Electronic copy available at: https://ssrn.

com/abstract=2886220
 Descrierea CIP / Description of CIP –
Biblioteca Naţională a României
Conferinţa Internaţională Educaţie şi Creativitate pentru o
Societate Bazată pe Cunoaştere – MEDICINĂ, MEDICINĂ
DENTARĂ ŞI FARMACIE, Bucureşti, Universitatea Titu Maiorescu,
2016
ISSN 2248-0048
Österreichische Nationalbibliothek Wien
The International Conference Education and Creativity for a
Knowledge – based Society – MEDICINE, DENTAL MEDICINE
AND PHARMACY, Vienna, Osterreichish Rumanischer
Akademischer Verein, 2016
ISBN 978-3-9503145-7-1

248 p.; 21 cm.

Referenţi ştiinţifici / Reviewers:

Dan-Florin Ungureanu
Daniel Cochior
Horia Mihail Barbu
Roxana Sandulovici

©
Universitatea Titu Maiorescu
ISSN 2248-0048
Osterreichish Rumanischer Akademischer Verein, 2016
ISBN 978-3-9503145-7-1
Bun de tipar / Signature for the press: 09.12.2016
Format: 21/29,7×100

Responsibility for content and originality of the text rests solely the author / the authors
Răspunderea pentru conţinutul şi originalitatea textului revine exclusiv autorului/autorilor

Electronic copy available at: https://ssrn.com/abstract=2886220

CONTENT

BILE DUCT STRICTURE – DIAGNOSIS, Dan Florin UNGUREANU, George MATEI,

Dorina UNGUREANU……………………………………………………………………… 6
VISIONS FOR RADIATION THERAPY (RT) 2020 AND BEYOND: STATE OF THE
ART AND FUTURE DIRECTIONS, Fabian FEHLAUER………………………………… 11
A CASE REPORT OF FAMILIAL ATENUATED ADENOMATOUS POLYPOSIS. A
SEVEN YEAR FOLLOW-UP, Septimiu C. ALEXANDRU, Cosmin A. MOLDOVAN,
Dan Florin UNGUREANU………………………………………………………………….. 13
RELEVANCE OF ADENOSINE DEAMINASE ASSAY IN THE PLEURAL FLUID
FOR THE DIAGNOSIS OF TUBERCULOUS PLEURAL EFFUSIONS, Daniel
GHEORGHITA, Mara BALTEANU, Nicoleta CIOBANU, Minerva GHINESCU………... 15
OPEN RADICAL RETROPUBIC PROSTATECTOMY SURGICAL TREATMENT OF
LOCALIZED PROSTATE CANCER - CASE REPORT, Florentina BEALCU…………... 20
STRUCTURAL ANALYSIS OF THE BLOOD VESSELS, Ioana Doretty CARPUS,
Carmen MIHAI, Dimitrie NANU…………………………………………………………… 26
HUMAN BODY AND INFRARED LONG WAVELENGTHRADIATION
INTERACTION, Cristina Daniela CRISTESCU, Elena RUSU, Mirela RADU…………… 31
MANAGEMENT OF SEPSIS: THE PIRO CONCEPT IN ICU, Gabriel GORECKI,
Daniel COCHIOR…………………………………………………………………………… 34
THE ART OF DOCTOR-PATIENT CONVENTION: NEW MEDICAL AND LEGAL
CONNOTATIONS, Lidia NICA-UDANGIU, Ana-Maria MIHĂLCESCU……………….. 38
PREVALENCE OF THE 35delG AND W24X MUTATIONS IN CHILDREN WITH
NON-SYNDROMIC CONGENITAL SENSORINEURAL HEARING LOSS,
H. MOCANU, A. NEAGU…………………………………………………………………. 41
TYPES OF CORONARY ARTERY STENTS AND THEIR USE, Alice MUNTEANU,
Irina FLORESCU, Cristina CALCAN……………………………………………………… 47
OSTEOID OSTEOMA OF THE HUMERAL SHAFT: A CASE REPORT IN A 37
YEARS OLD MAN, Mihai MARDARE, Manuel OPREA, Ancuta ZAZGYVA,
Marius NICULESCU………………………………………………………………………... 52
WHO ARE THE CANDIDATES FOR REINTERVENTION IN FAILED BACK
SURGERY SYNDROME? , Mihai MARDARE, Manuel OPREA, Iulian POPA,
Ancuta ZAZGYVA, Marius NICULESCU…………………………………………………. 58
OXYGENO THERAPY AT HOME AND ITS EVALUATION AS AN IMPORTANT
TREATMENT IN RESPIRATORY AND CARDIAC DISEASES, Costin POPESCU,
Liliana POPESCU, Dan MALAESCU, Lavinia OLAR, Dorina PUSCU.............................. 66
THE STUDY OF LUNG CANCER- DIAGNOSIS AND TREATMENT FOR A PERIOD
OF 8 YEARS, Costin POPESCU, Liliana POPESCU, Dan MALAESCU, Lavinia OLAR,
Lavinia PUSCU....................................................................................................................... 72
PHYSICIANS IN PAINTING, Mirela RADU, Eduard Said TRIFAN…………………….. 78
D.R. POPESCU BETWEEN MEDICINE AND LITERATURE, Mirela RADU,
Diana STOICA……………………………………………………………………………… 84
GNOSEOLOGY OF A PHYSICIAN-LITERARY MAN, Mirela RADU,
Liliana Florina ANDRONACHE…………………………………………………………… 89
BIOCHEMICAL EVALUATION OF PLASMA LIPIDS ON DIABETES MELLITUS,
Elena RUSU, Cristina CRISTESCU, Gabriela BURDUCEA………………………………. 92

3
ROAD TRAFFIC INJURIES – MEDICAL, INSURANCE AND LEGAL ASPECTS,
Ioana SOARE, Osama SALLOUM…………………………………………………………. 96
PSORIATIC ARTHRITIS, CLINICAL ASPECTS AND DIFFERENTIAL DIAGNOSIS,
Simona SOARE……………………………………………………………………………... 103
AUDITORY DISORDERS IN THROMBOPHILIA DIAGNOSIS, Cristina STOICA,
Gabriel BRÂNZOI.................................................................................................................. 115
THE HEALTHY SELF AND THE UNHEALTHY OTHER IN NADINE GORDIMER
GET A LIFE, Diana STOICA………………………………………………………………. 122
GENETIC EVENTS IN CHRONIC LYMPHOCYTIC LEUKEMIA,
Aurelian UDRISTIOIU……………………………………………………………………... 126
INFLUENZA AND SCHIZOPHRENIA (poster), Alexandra VLAD,
Viorel ALEXANDRESCU, Maria Elena MIHAI, Alexandru MATEI…………………….. 134
ASPECTS IN CONVENTIONAL IMPRESSION FOR CROWN AND BRIDGES,
Claudia Florina ANDREESCU, Andreea Mariana BĂNĂȚEANU, Cristina HĂINEALĂ,
Eugenia Diana RĂDULESCU………………………………………………………………. 140
CROWN RESTORATIONS WITH THE AID OF DIFFERENT INTRARADICULAR
DEVICES, Andreea Mariana BĂNĂȚEANU, Claudia Florina ANDREESCU,
Mariana BRIA, Eugenia Diana RĂDULESCU, Cristina Hăineală…………………………. 145
METAL-POLYMER BRIDGES-A VIABLE WAY OF TREATING PARTIAL
EDENTATION, Andreea Mariana BĂNĂȚEANU, Eugenia Diana RĂDULESCU,
Alexandru BARBU, Cristina Hăineală, Tudor IONESCU………………………………….. 150
THE ADVANTAGES OF PLATELET RICH FIBRIN IN DIFFICULT EXTRACTIONS:
RADIOGRAPHIC IMAGING OF THREE CASE REPORTS, Edwin Sever BECHIR,
Cherana GIOGA, Anamaria BECHIR, Mircea Marian BURUIAN………………………… 156
GIFTED STUDENTS IDENTIFICATION AND IMPROVING THE EDUCATIONAL -
PROCESS IN THEIR CASE, Gabriela CIAVOI , Anamaria BECHIR,
Edwin Sever BECHIR, Ioan TIG, Camelia DALAI, Ciprian DALAI……………………… 168
ANTIBACTERIAL EFFECT OF LASER ASSISTED PERIODONTAL THERAPY – A
CASE REPORT, Alin Alexandru ODOR, Deborah VIOLANT, Edwin Sever BECHIR,
Victoria BADEA……………………………………………………………………………. 172
CLINICAL OUTCOMES OF LASER SUPPORTED PERIODONTAL TREATMENT
CONCEPT USING ER,CR:YSGG (2780 nm) AND DIODE (940 nm),
Alin Alexandru ODOR, Deborah VIOLANT, Edwin Sever BECHIR, Ciprian BADEA,
Victoria BADEA……………………………………………………………………………. 178
COLOR PERCEPTION – AN UTTERLY IMPORTANT COMPONENT OF ESTHETIC
CERAMIC RESTORATIONS, Eugenia-Diana RĂDULESCU, Andreea Mariana
BĂNĂŢEANU, Claudia Florina ANDREESCU, Grigore LĂZĂRESCU…………………. 184
HEALING IN ENDODONTICS – A SERIES OF CASE REPORTS, Oana ROȘU,
Anna-Maria PANGICĂ, Dana COSAC, Stefan MANEA………………………………….. 189
EVOLUTION OF MANDIBULAR BODY FRACTURES ACCORDING TO THE
THERAPEUTIC APPROACH AND MATERIALS USED IN THEIR TREATMENT -
RETROSPECTIVE CLINICAL STUDY OVER A PERIOD OF 10 YEARS,
Paul Andrei ȚENȚ, Teodor Traian MAGHIAR, Florian BODOG, Liana MEȘTER,
Mihai JUNCAR……………………………………………………………………………... 196

4
EVALUATION OF METHODS AND MATERIALS USED FOR THE TREATMENT
OF FRACTURES OF THE ASCENDING RAMUS OF THE MANDIBLE – A
CLINICAL STUDY OVER A 10 YEAR PERIOD, Paul Andrei ȚENȚ, Teodor Traian
MAGHIAR, Raluca-Iulia JUNCAR, Liana MEȘTER, Mihai JUNCAR…………………… 202
THE BENEFITS OF USING ELECTROMAGNETIC FIELD THERAPY WITH
ELECTRONIC DOCTOR STEM GENERATOR: CASE PRESENTATIONS,
Bogdan VLADILĂ, Anamaria BECHIR, Cristian PETRESCU, Alexandru BURCEA,
Edwin Sever BECHIR............................................................................................................ 209
AUGMENTING THE BONE DEFECT RESULTING FROM THE EXTRACTION OF
SEMIINCLUDED WISDOM TEETH – CASE PRESENTATION, Silviu STĂNESCU,
Dana COSAC, Anna-Maria PANGICĂ…………………………………………………….. 215
THE PREVALENCE IN THE USE OF FOUR MINIMALLY INVASIVE THERAPIES
IN ROMANIAN DENTISTS: a preliminary study, Edwin Sever BECHIR, Anamaria
BECHIR, Gabriela CIAVOI, Carmen BIRIȘ, Ilinca SUCIU, Alexandru BURCEA, Roxana
MANU, Marius MARIȘ, Horia Mihail BARBU................................................................... 219
PROPOLIS-ACTIVE SUBSTANCE IN PHYTHOAPITHERPY RAISING SOME
TYPES OF DISEASES, Daniel CORD, Mariana POPESCU, Anca Daniela RAICIU…….. 226
STUDY OF GENETIC AND VIRAL MARKERS ASSOCIATED WITH NON-
RESPONSE TO TRIPLE THERAPY FOR PATIENTS WITH GENOTYPE 1 CHRONIC
HEPATITIS C, Gabriela OPRISAN, Sorin DINU, Laurentiu MICU, Georgiana MICU,
Monica ECOBICI, Sonia SPANDOLE, Georgeta CARDOS, Mihai VOICULESCU……... 231
PERSONALISED ANTI-INFECTIVE PHARMACOGENOMICS AND THERAPY,
Viorel ORDEANU, Mirela Claudia RIMBU, Roxana Colette SANDULOVICI…………... 234
DUAL BIOTECHNOLOGYS, Viorel ORDEANU, Mirela Claudia RIMBU,
Roxana Colette SANDULOVICI…………………………………………………………… 238
NEW MICROSCOPY TECHNIQUE FOR 3D STRUCTURAL BIOLOGY: FEI CRYO-
TEM WORKFLSOLUTIONSOW, Viorel ORDEANU, Iulian SÂRBU,
Alice PIPEREA……………………………………………………………………………... 242
MINT ESSENTIAL OIL - PHARMACEUTICAL AND USE ISSUES, Monica GAGIU,
Anca Daniela RAICIU………………………………………………………………………. 246

5
 BILE DUCT STRICTURE - DIAGNOSIS

Authors:. Dan Florin Ungureanu, Prof. Univ. dr., Titu Maiorescu University
George Matei, Student, Titu Maiorescu University
Dorina Ungureanu, Asist. Prof, PhD Cand., Titu Maiorescu University

Abstract: the paper “ Bile duct stricture – diagnosis “ shows the pathophysiology, benign stricture and
malign stricture, frequency, sex related demographics, morbidity and mortality, complications, patient
education, physical, diagnostic considerations, diagnosis and ends with conclusion that both types of bile duct
stricture need to be treated with maximum precaution.

Introduction

Bile duct stricture is caused by shrinking of the bile duct and management require a multidisciplinary
approach formed from surgeons, radiologists, oncologists and edoscopists. If the bile duct it`s untreated, will be
appear different complication, like bile duct infection, liver abscess, or gallstones.
Pancreatic cancer is the most common cause of malignant biliary stricture and risk of mortality is high,
because of complications of tumor invasion and metastasis.
Malign stricture and benign stricture are hard to distinguish and requires different diagnostic
techniques. Both types of strictures can be associate with painful symptoms and excessive morbidity.
Stenosis from chronic pancreatitis and nonanastomotic post liver transplant is still high, but endoscopic treatment
and technique called multistenting remain the standard procedure.

Pathophysiology

Exists two types of bile duct stricture malignant and benign, this types of stricture can be multiple, or
simple. Benign strictures evolved when the bile ducts are injured in some way during surgery, or the abdomen
trauma.
After the trauma an inflammatory response appears who`s followed by bile duct lumen narrowing,
fibrosis and deposition of collagen.
All this changes may evolved to portal hypertension and secondary biliary cirrhosis.
Malignant strictures are the results of bile ducts cancer in the adjacent organ, for example liver,
pancreas or gallbladder.

Etiology of benign biliary strictures

Causes of benign bile duct stricture are :

Approximately 80% of benign stricture apparition are post operative injury after cholecystectomy. The
incidence of bile duct stricture injury after classic cholecystectomy is about 0.2 – 0.3 % and incidence after
laparoscopic cholecystectomy is about 0.4 – 0.6 % .

Percentage of patients with unrecognized bile duct stricture at the time of surgery are approximately of
75 % and 30 % of them will present after than 5 years .
Majority of strictures after a laparoscopic procedure are short and appear more commonly in common hepatic
duct, distal to the confluence of the right and left ducts.

CBD strictures are more common after open cholecystectomy. The most iatrogenic injuries are
unrecognized at the time of operation. Clinical status of the patient with an unrecognized biliary tract injury,
because of sepsis or peritonitis can deteriorate rapidly, thus early diagnosis in urgent.

Lack of surgical experience is the cause of benign bile duct stricture, also failure to recognize abnormal
biliary anatomy, misplacement of clips, excessive use of cautery, excessive dissection around the major bile
ducts, congenital anomalies, acute inflammation, resulting in ischemic injury. A significant proportion of
strictures happen during the operations and are described as simple and uneventful.
Unexpected complication after other surgeries, such as gastrectomy, hepatic and portal vein surgery, or
pancreatic surgery can trigger the bile duct stricture.

Mirrizzi syndrome is observed in approx. 1 % of patients with cholecystectomies and extrinsic

compression of the common hepatic duct, due to a gallstone impacted in the cystic duct, or in the Hartmann
pouch results in jaundice and cholangitis. Episodes of repeated inflammation can lead to form type I stricture, or
pressure necrosis, who lead to the formation of a cholecysto-choledocal fistula ( type II) .

6
 Primary sclerosis ( PSC ), cause bile duct stricture, beading and irregularities of the intrahepatic and
extrahepatic bile duct. Inflammatory bowel disease can be associated with approx. 70 % of PSC cases.
Involvement of bile duct stricture distribution and extent is variable.

Orthotopic liver transplantation ( OLT ) : After transplantation approx. 30 % of patients develop biliary
stricture, which usually occurs 2 – 6 months after OLT.

Pancreatitis : Patients with chronic pancreatitis who manifest jaundice because of obstruction of the
intrapancreatic segment of the CBD are about 10 % of the patients with benign strictures. Uncommonly
associated with the development of bile duct stricture are pancreatic abscess, pseudocyst and acute pancreatitis.

Radiation therapy to the upper abdomen for cancer, or lymphoma, after years from treatment can
unleash bile duct stricture.

Blunt abdominal trauma can lead to bile duct stricture.

Tuberculosis and histoplasmosis are rarely reported to cause bile duct stricture on immunocompetent
individuals.

Polyarthritis nodosa and systemic lupus erythematosus ( SLE ) , involved small – to medium sized
arteries and its an autoimmune disease and can present extrahepatic biliary obstruction, secondary to biliary
stricture.

Sphincter of Oddi dysfunction, or papillary stenosis – biliary colic after cholecystectomy is usually
present, because of an abnormal basal sphincter pressure.

Chemotherapeutic drugs may cause bile duct stricture, for example hepatic artery infusion of 5-
fluorodeoxyuridine ( FUDR, FdUrd ), or other chemotherapeutic drugs.

Choledochal cysts are an uncommon anomalies of the biliary system and are manifested by cystic
dilatation of the intrahepatic biliary tree, or extrahepatic, or both. Frequently found on asian patients and
females. Hepatobiliary complications can be associated with bile duct stricture, cholelithiasis, recurrent
cholangitis, recurrent acute pancreatitis and choledocholithiasis.

Inflammatory stricture: choledocholithiasis can also cause chronic inflammation and fibrosis, conduct
to stricture of Oddi sphincter and CBD.

Endoscope- related stricture is possible post-endoscopic sphincterotomy stricture.

Idiopathic: a few cases have been reported.

Miscellaneous: Bile duct stricture was described in association with cholangitis, hepatic artery
aneurysm, Chron disease and duodenal diverticulum.

Etiology of malignant biliary strictures

Causes of malignant bile duct stricture are:

Mucinous cystadenocarcinoma is a pancreatic tumor who may invade the bile duct and cause
obstruction.

Gallblader neoplasm: neoplasm extension further the gallbladder, can have a poor prognostic sign and
can cause long obstruction and stricture.

Cholangiocarcinoma develop from biliary epithelium, usually is seen in association with chronic
ulcerative colitis, PSC, choledochal cysts and infection by liver flukes. The major clinical manifestation of
cholangiocarcinoma is obstructive jaundice. Cholangiocarcinoma can be located in the lower portion of the
biliary tree ( called distal bile duct cancer), the most common location is in the upper portion of biliary tree
(hilar).

7
 Pancreatic adenocarcinoma is the most common cause of malignant biliary stricture, appear in the sixth
and subsequent decades of life.

Adenocarcinoma of the ampulla of Vater is also named ampullary carcinoma and evolve from benign
adenoma. It`s less common than pancreatic neoplasm, but symptoms of pancreatitis or obstructive jaundice, are
observed early . Benign and malignant tumors of the ampulla of Vater can occur in the setting of genetic
syndromes, or sporadically.

Hepatocellular cancer is the third most common among men, the primary malignity of the liver and the
fourth leading cause of cancer related death in the world. It`s more common in the Far East than in U.S and
usually is associated with cirrhosis who results from hepatitis B or C.

Metastatic cancer and lymphoma of the liver and nodes in the transverse fissure of the liver (porta
hepatis )- sometimes can be cause of malignant bile duct stricture. Most common tumors who metastasize in to
the liver are : adenocarcinoma of the lung, pancreatic, renal and colorectal carcinoma. High-grade obstruction of
the common hepatic duct it`s cause by metastatic porta lymphadenopathy.

Sex-related demographics
Data on the overall sex ratio of bile duct strictures are lacking. Are some conditions who causing bile
duct strictures, for example PSC and chronic pancreatitis, are more common in men. The incidence of post-
cholecystectomy strictures are equal for the both sexes.

Morbidity/mortality
Indifferent of etiology, bile duct stricture can cause considerable morbidity from biliary stones,
recurrent episodes of ascending cholangitis, right upper quadrant abdominal pain, recurrent obstructive jaundice.
Patients mortality with bile duct stricture due to operative injury, chronic pancreatitis or trauma, have a good
prognosis. But the patients with bile duct stricture due to PSC and malignancy have an unfavorable outcome .

Complications
Complications of bile duct stricture are : pyogenic liver abscess due to recurrent episodes of ascending
cholangitis, development of stones in the gallbladder and bile ducts proximal to the stricture, secondary biliary
cirrhosis, weight loss and malnutrition from steatorrhea, with fat-soluble vitamin deficiency.

Patient Education
Patients with biliary stents should be teach by medical staff how to recognize the cholangitis and biliary
obstruction who indicate the blockage stent. Those with external drains should be taught how to flush their
catheters until the catheters are internalized and patients with alcoholic chronic pancreatitis may benefit from
counseling and alcohol abuse rehabilitation.

Physical
Patients with asymptomatic bile duct stricture may have unremarkable physical examination findings.
Skin excoriations may be seen on the patients with pruritus.
Patients presenting with cholangitis may also have right upper quadrant tenderness in addition to
jaudice, altered mental status, hypotension and fever.
Underlying cirrhosis and portal hypertension are indicated by the presence of gynecomastia, spider
angiomas, ascites, Dupuytren contracture, palmar erythema and portal hypertension.
On the patients with malignant obstruction are usually observed jaundice and a palpable, painless
gallbladder ,all these symptoms indicates the Courvoisier sign.
An enlarged nodular liver may indicate malignancy involving the liver or a large right upper quadrant
mass may indicate a malignancy involving the gallbladder and the presence of a friction rub or bruit may also
suggest malignancy.
The patients with a major surgical injury to the bile duct and those with recurrent strictures and
interventions may have evidence of a bile leak in the form of a biliary fistula, biliary peritonitis, or a biloma.
All these complications usually become evident early in the postoperative period, but sometimes appear
weeks to months later and attention should be given to the nutritional status of the patient.

Diagnostic Considerations
Patients presenting with acute ascending cholangitis should undergo urgent biliary drainage when an
appropriate response to antibiotic therapy is not achieved or when the initial presentation is severe.

Other conditions to consider in patients with suspected bile duct strictures include the following:

8
 autoimmune cholangiopathy
 colestasis associated with parenteral nutrition
 cholestasis associated with sepsis
 drug-induced cholestasis
 postoperative jaundice
 primary sclerosing cholangitis
 primary biliary cirrhosis

Diagnosis
To reach a conclusive diagnosis of biliary stricture, we need a varied diagnostic investigations, because
just the clinical features are insufficient. To confirm a diagnosis of biliary stricture and the possible cause, it`s
need to do some investigation like imaging studies, blood tests and biopsy.
Blood tests include : bilirubin, GGT and ALP ;
Imaging studies include: ultrasound, abdominal CT, MRCP, ERCP, PTHC and fistulography;
Biopsy : histologic examination.

Instead of conclusion:

Both types of bile duct stricture are need to be treated with maximum precaution.

Bile duct injury after cholecystectomy is a complication of a “simple” surgical procedure, to avoid this, surgeons
need to be better prepared.

The key to the successful management of these injuries lies on continued vigilance during and after the
cholecystectomy, hoping to early recognition.

Injuries should be early referred to tertiary centers with hepato-bilio-pancreatic surgery experience and expertise,
where a complete feld of diagnostic and treatment modalities are available, ensuring to the patient the best
opportunity for an good long-term result.

When the bile duct stricture starts to manifest, it`s an surgically emergency, because this can cause the patient
death from different complications, like mechanic jaundice, pancreatitis etc.

References:

1. Deviere J, Cremer M, Baize M, Love J, Sugai B, Vandermeeren A. Management of common bile

duct stricture caused by chronic pancreatitis with metal mesh self expandable stents. Gut. 1994 Jan. 35(1):122-6.
2. Kamisawa T, Tu Y, Egawa N, et al. Involvement of pancreatic and bile ducts in autoimmune
pancreatitis. World J Gastroenterol. 2006 Jan 28. 12(4):612-4. [Full Text].
3. Orons PD, Sheng R, Zajko AB. Hepatic artery stenosis in liver transplant recipients: prevalence and
cholangiographic appearance of associated biliary complications. AJR Am J Roentgenol. 1995 Nov. 165(5):1145-9.
4. Colonna JO 2nd, Shaked A, Gomes AS, et al. Biliary strictures complicating liver
transplantation.Incidence, pathogenesis, management, and outcome. Ann Surg. 1992 Sep. 216(3):344-
50;discussion 350-2.
5. Mansfield JC, Griffin SM, Wadehra V, Matthewson K. A prospective evaluation of cytology
frombiliary strictures. Gut. 1997 May. 40(5):671-7.
6. Gong Y, Huang ZB, Christensen E, Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis.
Cochrane Database Syst Rev. 2008 Jul 16. CD000551.
7. Bismuth H, Nakache R, Diamond T. Management strategies in resection for hilar
cholangiocarcinoma. Ann Surg. 1992 Jan. 215(1):31-8.
8. Lipsett PA, Pitt HA, Colombani PM, Boitnott JK, Cameron JL. Choledochal cyst disease. A
changing pattern of presentation. Ann Surg. 1994 Nov. 220(5):644-52
9. Moore AV Jr, Illescas FF, Mills SR, et al. Percutaneous dilation of benign biliary strictures.
Radiology. 1987 Jun. 163(3):625-8.
10. Nealon WH, Urrutia F. Long-term follow-up after bilioenteric anastomosis for benign bile duct
stricture. Ann Surg. 1996 Jun. 223(6):639-45; discussion 645-8.
11. Tocchi A, Mazzoni G, Liotta G, et al. Management of benign biliary strictures: biliary
enteric anastomosis vs endoscopic stenting. Arch Surg. 2000 Feb. 135(2):153-7.
http://reference.medscape.com/medline/abstract/10668872

9
 12. http://gastroenterology1.blogspot.ro/2007/11/bile-duct-strictures.html
13. Dumonceau JM, Deviere J, Delhaye M, Baize M, Cremer M.Plastic and metal stents for
postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc. 1998;47(1):8e17
14. Bismuth H, Majno PE. Biliary strictures: classification based on the principles of surgical
treatment. World J Surg. 2001;25:1241e1244.
15. Hintze RE, Adler A, Veltzke W, et al. Clinical significance of magnetic resonance
cholangiopancreatography (MRCP) compared to endoscopic retrograde cholangiopancreatogra
phy (ERCP). Endoscopy. 1997;29:182e187.
16. Schiano Di Visconte M. Analysis of pathogenic mechanisms of common bile duct iatrogenic lesion
during laparoscopic cholecystectomy. A review of the literature. Minerva Chir. 2002
Oct;57(5):663e667.
17. Schwartz DA, Petersen BT, Poterucha JJ, Gostout CJ. Endoscopic therapy of anastomotic bile duct
strictures occurring after liver transplantation. Gastrointest Endosc. 2000 Feb. 51(2):169-74

10
 VISIONS FOR RADIATION THERAPY (RT) 2020 AND BEYOND:
STATE OF THE ART AND FUTURE DIRECTIONS

Fabian FEHLAUER, M.D., Ass. Prof (Privatdozent Dr. med.),

Strahlenzentrum Hamburg, Germany (office.fehlauer@szhh.info)

Summery (Abstract and full text):

In recent years remarkable progress has been made towards the understanding of proposed
hallmarks of cancer development, diagnostics, imaging and treatment. With its increasing incidence,
the individual management of cancer patients according the physicians recommendation (e.g.
guidelines, expertise) continues to be a challenge for the 21st century.
The main treatment modalities in the fight against cancer today are state of the art radiation
therapy (RT), surgery, chemotherapy, immunotherapy and hormonal therapy, or in combinations.

Modern RT remains a very important component of cancer treatment with

approximately 60% of all cancer patients receiving radiation therapy during their course of
illness; it contributes towards 50% of curative treatment for cancer. The main goal of
definitive or adjuvant radiation therapy is to stop cancer cells of their multiplication potential
and to cure the patient. In patients with systemic cancer burden (metastatic stages)
radiotherapy remains a highly effective and safe tool for symptom and tumor growth control.
Psycho-oncologic support, use of integrative (and unconventional) medicine, nutrition
issues and second opinion will be demanded more by patients and their families in future to
improve the level of quality of life and justified hope for cure.
Technical innovations and advances in RT became state of the art treatments within
only few years: modern RT such as stereotactic body irradiation (SBRT, radio surgery, e.g.
robotic Cyberknife, LINAC-based), intensity modulated RT (IMRT, e.g. VMAT, rapid arc,
Tomotherapy), four-dimensional RT (4DRT, e.g. breath control, true beam) and image-guided
RT (IGRT, e.g. cone beam CT, integrated PET planning) have made it possible to deliver an
ideally distributed and biologically effective radiation dose to the target with great accuracy,
while sparing the surrounding organs of risk by respecting the normal tissue tolerance doses.
As a result, high tumor control rates by modern high precision RT (> 80-95%)
improved markedly and became excellent alternative to tumour surgery especially in patients
with (significant) co-morbidities, e.g. in asymptomatic or mildly symptomatic brain tumours,
early stage lung cancer or liver metastasis.
Robotic radio surgery (Cyberknife SBRT) delivered in only 5 treatments remains a
suitable and promising option in low- and intermediate risk prostate cancer with minor side
effects, but high tumour control rates equivalent to conventional IMRT (e.g. step and shot RT,
arc RT, Tomotherapy) brachytherapy (e.g. HDL, Seeds) or radical surgery. At five years
following SBRT, 97 percent of patients were free from prostate cancer progression.
In locally advanced stages of cancer, multiple randomized controlled trials established
the modern RT in combination with different compounds (chemoradiation therapy) as a
standard treatment option for patients with head and neck cancer, lung cancer, esophageal
cancer, pancreatic cancer, cervical cancer, bladder cancer and anal canal cancer. In curative
approaches of different organs and tumor stages, such as early stage breast cancer after breast
conserving operation or locally advanced rectal cancer before operation, the modern RT
remains the adjuvant or neo-adjuvant backbone for high local control rates. RT is also a
valuable treatment for palliation or re-irradiation (secondary radical RT) for palliation of local
symptoms caused by cancer with high response rates.
11
 Besides the priority use of photons in modern RT, other types of radiation will be used
to treat cancer, include particle beams (e.g. protons) - not only in academic setting and
protocols - in future.

In the background of increased elderly population the high demand, easy availability
and professional application of modern non-invasive cancer therapies has to be emphasized.
Moreover, data from European cancer registry (IARC) and others estimated the risk of getting
cancer before age 75 years in Romania of 23.1%. Every year about 70.000 newly diagnosed
cancer patients (cancer incidence) were registered in Romania.

Thus, a population-adapted number of modern RT facilities (e.g. public, private or

public private partnership) for hospital and ambulant treatment will increase the survival rates
and reduce treatment side effects for cancer patients. Standardized quality management
systems in modern RT, such as ISO 9001:2015, including risk-management, might reduce
errors and optimize workflow in modern RT centers.

Independent of the national reimbursement system, the purchase for novel technology
in the public healthcare system or potential investors in private centres should be aware of the
complexity of modern RT, and not expect short term profit.

The European Society for Radiotherapy and Oncology (ESTRO) evaluated the
radiotherapy staffing in European countries and concluded a very large variation between the
countries. Staff limitations in terms of quantity and quality prevent the delivery of state of the
art and safe RT, which restrict the potential of introducing new technologies and concepts
such as SBRT, IMRT and IGRT.

Therefore, an adequate number of RT professions will be needed in many European

areas to utilize highly-sophisticated state of the art RT technology. Substantiality
implementation of a robust and dedicated education system for radiation oncologist, RT
technologist, and medical physicist will be the future challenge.

Our common vision for 2020, published at ESTRO, is the following:

Every patient in Europe will have access to state of the art RT, as a part of a
multidisciplinary approach (e.g. tumour board) were treatment is individualized for the
specific patient’s cancer, taking in account of the patient’s personal circumstances.
References:
1. Baskar et al. Int J Med. Sci 2012
2. Fehlauer Dt Ärztebl Int 2009
3. Ikushima J Med Investig 2010
4. Lievens et al. Radiotherapy Oncol 2012
5. Meier et al. IJROBP ASTRO 2016
7. 6. Rosenblatt er al. Lancet Oncol 2013
8. Valentini et al. Radiotherapy Oncol 2012
9. www digi24.ro Romania furata: radioterapia 2015
10. www. Accuray.com
11. www. Elekta.com
12. www. Varian.com

12
 A CASE REPORT OF FAMILIAL ATENUATED ADENOMATOUS POLYPOSIS. A
SEVEN YEAR FOLLOW-UP

Alexandru C. Septimiu1, Moldovan A. Cosmin1,2, Ungureanu F. Dan1,2

1
Witting Clinical Hospital, General Surgery
2
Titu Maiorescu University of Bucharest, Faculty of Medicine

Corresponding author :
Moldovan A. Cosmin, Assistant Professor, Titu Maiorescu University of Bucharest, Faculty of
Medicine, moldovan.cosmin@gmail.com, +40723504207

DISCLAIMER
The authors declare no conflicts of interest. All authors have read and approved the final manuscript.

ABSTRACT
Background & Aims : The paper presents the follow-up of several attenuated familial adenomatous polyposis
cases. This study was placed integrally in the General Surgery Clinic from Witting Clinical Hospital. Methods :
The effects were recorded by monitoring for seven years a family with known antecedents of Attenuated Familial
Adenomatous Polyposis, the objective being to highlight the role of polypectomies in colon neoplasm prevention,
as opossed to untreated or unknown cases. Design : a seven year follow-up of three cases. Setting : Witting
Clinical Hospital, General Surgery Ward. Participants : three patients, brothers of the same parents.
Conclusion : The favorable evolution of these subjects clearly shows that the number of total colectomies
performed in the case of polyps that follow a malignization trend can be reduced, switching to a right
hemicolectomy just at the proper timing. Therefore, the life quality of the patients after the surgical interventions
will definitely increase.

Keywords : familial, adenomatous, polyposis, follow-up

Introduction
Familial Adenomatous Polyposis (FAP) is a hereditary disorder with multiple colorectal polyps that exhibit an
almost inevitable risk of colorectal cancer (CRC) in untreated patients. (1) FAP is an autosomal dominant
syndrome with a penetrance close to 100% at the age of 40 years. (2)

Objectives
This paper presents the case of three brothers with known Attenuated Familial Adenomatous Polyposis
antecedents on paternal line, where the father and an uncle died of colon neoplasm appeared from an unknown
Attenuated Familial Adenomatous Polyposis. Seven years ago, two of the three brothers presented themselves
for a colonoscopic control, while the youngest brother refused to be investigated.
The colonoscopies showed two cases of Attenuated Familial Adenomatous Polyposis. During several
interventions, all polyps situated in the left colon were extracted and the two brothers were anually checked for
possible relapses and for right colon polyps monitoring.
In 2016, after several rectal bleedings, the third brother presents himself for an investigation. The colonoscopy
presented numerous polyps, some of them having a 3 cm diameter. Moreover, at the sigmoid - descending colon
junction, a tumor with malignant characteristics was observed.

Methods
The present study consisted in a follow-up of the two brothers with a history of Familial Adenomatous Polyposis
with malignization and death on paternal line: S.G.B. (born in 1969) and S.C. (born in 1959). The first patient
(S.G.B.) was discovered in 2009 and during six sessions, until 2012, 26 polyps existent at the left colon level
were removed. The second patient (S.C.) was discovered in 2010 and during five sessions, until 2010, 29 polyps
existent at the left colon level were removed. The third brother S.D. (born in 1971) came to colonoscopic
investigation in 2016.
The interventions performed were as follows:
• Endoscopic resections:
Repeated every 6 months, in each session 5-7 polyps are removed, starting with the biggest ones,
keeping a 10 cm distance between two resections. The interventions are repeated until all existent
polyps are removed at the left colon level, also all possible removable polyps are operated at the
right colon level.

13
 • Biopsies for the remaining polyps which present macroscopic modifications.

The instrumentation used during the study:

• Pentax video endoscopy equipment with a 170 cm video colonoscope
• Cutting and electrocoagulation equipment with endocuter type ERBE ICC200
• Image recording system from the endoscopy laboratory of Witing Clinical Hospital
• The biopsies are processed in the pathologic anatomy laboratory of Witing Clinical Hospital or using
other facilities when necessary.

Results
All sessions consisted in total colonoscopies, polyp resections and right colon polyp monitoring, from where
biopsies were taken and polyps larger than 1 cm were removed when was possible. It is important to mention
that polyps situated at the right colon level are harder to remove because they appear in large numbers and many
polypoid agglomerations are present. After these sessions the two subjects (the two brothers) were monitored
through annual colonoscopies. No new polyps appeared at the level of the left colon.
The favorable evolution of these first two subjects lets us believe that the number of total colectomies effectuated
in the case of polyps that follow a malignization trend on the full length of the colon can be reduced, replacing
them at the suitable moment with right hemicolectomies. Therefore, the life quality of the patients after the
surgical interventions will increase. (3)
Of course, there is a high risk regarding the polyps that are chosen for a biopsy procedure, in relation with
existing macrosopic modifications, but the patients are fully aware of these risks and therefore gave their consent
for the surgical procedure that may be required at a given point in time.

Discussion
The fact that the third brother presented a malignant tumor and multiple large polyps at the left colon level (the
polyps found at the right colon level were smaller than 1 cm and similar to the right colon polyps of his brothers)
may suggest the possible evolution of the older brothers if they did not accept the investigations seven years ago.
The specific feature of this case is represented by the fact that the subjects come from the same family, having
the same pathology and the same possible evolution of the disease.
Because of the small number of Attenuated Familial Adenomatous Polyposis patients included in existent studies
(4), there is no specific protocol that should be followed in such cases. Therefore, the removal of all left colon
polyps during repetitive colonoscopies was considered appropriate because of the high percentage of malignant
tumors in the left colon as opposed to malignant tumors in the right colon, which also led to using the flexible
sigmoidoscopy as screening method. Morever, the left colon polyps are easier to remove by polypectomies. (2)

Conclusion
Performing endoscopy screenings and polypectomies (if possible) for tumor susceptible population represents a
good prevention method for colon cancer. Moreover, performing a smaller surgical intervention than in the case
of direct neoplasm discovery intervention offers higher life standards for operated patients.

Acknowledgement
This material is part of a larger retrospective and prospective study of a PhD studies thesis, currently under
development by Septimiu Cristian Alexandru, M.D., Ph. D. Candidate at Titu Maiorescu University of
Bucharest, Faculty of Medicine, with Univ. Professor Ungureanu Florin Dan, M.D., Ph. D., as thesis coordinator.

References

1. de Campos FG, Nicacio De Freitas I, Imperiale AR, Seid VE, Perez RO, Nahas SC, et al. [Colorectal cancer
in familial adenomatous polyposis: Are there clinical predictive factors?]. Cirugia espanola. 2010;88(6):390-
7.
2. Farinella E, Soobrah R, Phillips RK, Clark SK. Familial adenomatous polyposis (FAP) and gender. Does
gender influence the genetic transmission of FAP? Familial cancer. 2010;9(3):405-6.
3. Septimiu Cristian Alexandru MC, Ungureanu Florin Dan. The Role Of Repeated Polypectomy As
Prophylaxis Of Developing Left Colon Cancers In Patients With Attenuated Familial Adenomatous
Polyposis. International Conference “Education and Creativity for a Knowledge-Based Society” 9th Edition,
Medical Section. 2015;9(1):121-3.
4. Douma KF, Bleiker EM, Aaronson NK, Cats A, Gerritsma MA, Gundy CM, et al. Long-term compliance
with endoscopic surveillance for familial adenomatous polyposis. Colorectal disease : the official journal of
the Association of Coloproctology of Great Britain and Ireland. 2010;12(12):1198-207.

14
 RELEVANCE OF ADENOSINE DEAMINASE ASSAY IN THE PLEURAL FLUID
FOR THE DIAGNOSIS OF TUBERCULOUS PLEURAL EFFUSIONS
Daniel Gheorghita, Mara Balteanu, Nicoleta Ciobanu, Minerva Ghinescu, School of
Medicine, University “Titu Maiorescu”, Bucharest

ABSTRACT
TB pleural effusion develops as a delayed hypersensitivity reaction to a primary tuberculous infection.
TB pleural effusion diagnosis remains a challenge in clinical practice. Testing the pleural fluid for the Koch’s
bacillus with the Ziehl-Neelsen staining technique, according to the studies, turns positive results in less than 5%
of the cases and culture on the Lowenstein-Jensen medium in less than 40% of the cases 5. The
histopathological examination of the parietal pleura is positive in approximately 80% of the cases. 11
Consequently, diagnosis parameters with higher sensitivity and specificity must be used.
This study was aimed at demonstrating the correlation between ADA levels and the diagnosis of
tuberculous pleural effusion confirmed through a different diagnosis method. To confirm the diagnosis, we used
either pleural biopsy with needle aspiration or pleuroscopy, or the bacteriological examination of sputum.
The ADA test, correlated with the clinical tests (young patient, showing signs of tuberculous
impregnation) and paraclinical tests (exudate with lymphocytes prevalence) is highly relevant in diagnosing
tuberculous pleural effusion. Affordability and fast results recommend ADA assays as a mandatory step in the
diagnosis of tuberculous pleural effusions.

INTRODUCTION
Tuberculosis, an infectious/communicable disease, is caused by a mycobacterium of the Mycobacterium
tuberculosis complex, with contamination occurring by inhalation (>95%) and, rarely, by ingestion or
percutaneous inoculation. It seems that TB pleural effusion develops as a delayed hypersensitivity reaction to a
primary tuberculous infection [7]. Initially, we see a rapid inflammatory response with neutrophilia, followed by
an immune lymphocyte reaction with pleural granuloma formation and adenosine deaminase (ADA) release [7].
When diagnosing tuberculous pleural effusion, the anamnesis should be followed by clinical and
radiological investigations, biochemistry of the pleural fluid (protein, glucose, LDH, ADA assay), pleural fluid
cytology (lymphocytes prevalence) and pleural biopsy - the accurate diagnosis being given by the detection of
tuberculosis granuloma through histopathology. The examination of the pleural fluid in tuberculous pleural
effusion reveals: proteins > 30 g/l, pleural LDH/serum LDH > 0,6, glucose < 80 mg%, lymphocytes >80%,
adenosine deaminase (ADA > 60 u/l)
Microscopy of pleural fluid smear is positive in less than 10% of the cases, except for HIV positive and
empyema patients [3]. MTB culture has a rather low sensitivity of about 30% [3] and takes several weeks.
The histopathological examination starts with a pleural biopsy by thoracoscopy, a method that enables
the visualization of TB granuloma in the pleura.
Numerous studies assessed the relevance of ADA in TB pleural effusion diagnosis. The most extensive
study that included 2,796 patients with TB pleural effusion and 5,927 patients with non-TB pleural effusion
showed 90% specificity and 92% sensitivity of this test in TB pleural effusion [4]. Patients with non-TB pleural
effusion may have an ADA false positive. It has been demonstrated that ADA levels exceed 40 units/l in one
third of parapneumonic pleural effusion cases and two thirds of pleural empyema patients [9]. Increased ADA
levels may also be noted in some malignant conditions (lymphoma, bronchioloalveolar carcinoma,
mesothelioma), infectious diseases (Mycoplasma, Chlamydia etc.) and autoimmune diseases (systemic lupus
erythematosus, rheumatoid arthritis) [9].

PURPOSE

This study was aimed at demonstrating the correlation between ADA levels and the diagnosis of
tuberculous pleural effusion confirmed through a different diagnosis method. To confirm the diagnosis, we used
either pleural biopsy with needle aspiration or pleuroscopy, or the bacteriological examination of sputum.

MATERIAL AND METHOD

The study covered a group of subjects that comprised 84 patients hospitalized in the Pneumology I ward
at “Marius Nasta” Pneumology Institute between March and May 2016, diagnosed with pleural effusion of
etiology confirmed through pleural histopathology.

15
 The materials used for the study consisted of general clinical observation charts. For each patient, we
pulled out data from the observation charts, such as: demographics: age, gender, background, symptoms upon
admission: productive or dry cough, dyspnea, fever, side chest pain, sweating, living and working conditions:
occupational exposure to respiratory hazards, smoking, significant medical history (pulmonary tuberculosis,
frequent respiratory infections, neoplasms), X-ray results to establish the anatomical/clinical form and extent of
the disease, results of sputum microbiology upon admission, results of the pleural fluid biochemistry, results of
ADA assay in the pleural fluid, result of pleural fluid bacteriology, results of histopathological examination of
the pleural specimen obtained through pleural biopsy.
Based on the pleural histopathological examination, patients were split into two groups: first one
(G1=42 patients) made of patients with tuberculous pleural effusion, the second one (G2=42 patients) made of
patients with neoplastic pleural effusion.
This data was subsequently entered in an electronic database (Excel). The method of study was
clinical/statistical, retrospective, focused on mixed research: both analytical and descriptive. Program MedCalc
version 15.5 was used to statistically assess the data. The results were expressed as mean values ± standard
deviation, with a minimum-maximum range or as percentage points.
The Shapiro-Wilk test was applied to asses the normality of variables. The Spearman correlation was
used for correlations between variables with abnormal distribution and the Pearson correlation was used for
those with normal distribution. The results were considered to be statistically significant for a value of p <0.05.

RESULTS

In the G1 group, with confirmed tuberculous pleural effusion, the average age of patients was 36.8
years, with an 18.74 standard deviation. Patients’ age ranged between 19 and 86, but young ages below 30 were
prevalent. Split by age brackets, 24 patients were 19 to 35 years old, 10 patients were aged 35 to 55 and 8
patients were over 60.
In terms of gender distribution, 24 patients were male (57.1%) and 18 female (42.9%).
In the G1 group, 20 patients are smokers (active or former smokers) and 22 never smoked, 85.7% of the
patients worked in environments with no exposure to respiratory hazards, while 14.3% have been exposed to
respiratory hazards at their workplace.
39 (93%) of the patients in the first group had dry cough, 38 (91%) suffered weight loss, 27 (64%) had
pain and 18 (43%), fever.
By radiological site of the tuberculous pleural effusion, 52.4% were found in the right side and 47.6% in
the left, while 22 cases (52%) had associated pulmonary lesions. Split by associated pulmonary lesions, 8 of the
20 right-side pleural effusion cases were associated with parenchymal modifications and 14 of the 22 left-side
pleural effusion were associated with parenchymal modifications.
Hematology revealed anemia in 23.8% of the tuberculous pleural effusion patients; in most patients
(66.7%), lab tests indicated an inflammatory syndrome with normal leukocyte count, but an accelerated
erythrocyte sedimentation rate.
The sputum microscopy with the Ziehl Neelsen method revealed acid-alcohol resistant bacilli in 33% of
the cases, of which 50% had a conclusive histopathological examination.
The pleural fluid biochemistry revealed that all patients had high protein values, averaging at 49.7 g/l,
most of them within 45-55 g/dl; we found that all cases met Light’s criteria for the exudate diagnosis. The mean
glucose value in the pleural fluid is 83.40, with ± 14.27 standard deviation, with a minimum of 19 and a
maximum of 145 mg/dl. LDH in the pleural fluid ranged between 199 and 885, averaging at 599.
Pleural fluid cytology indicated a predominance of lymphocytes (50% of the patients), which is specific
to TB pleural effusion.
As for the ADA value in the patients from the tuberculous pleural effusion group, we found an average
of 71 U/l, with values ranging between 53 and 101.84 U/l; 62% of the patients had values between 58 and 80
U/l. In all patients, ADA was above 40 U/l, most of them staying within the 58-80 U/l range.
The tuberculous pleural effusion diagnosis was confirmed in 26.2% cases by sputum bacteriology alone
and in 73.4% of the cases by histopathology of the pleural specimen, which described Langhans multinucleated
giant cells with caseification necrosis.
In group G2, comprising neoplastic pleural effusion patients, among the 42 neoplastic pleural effusion
cases, an accurate diagnosis was set by histopathological examination of the pleural specimen in 26 patients
(61.9%), by bronchial biopsy in 8 cases (19.04%), by lymph node biopsy in 4 cases (9.52%) or by lung biopsy in
other 4 cases (9.52% of the patients).
The average age of the patients was 62, with an 18.74 standard deviation. The patients’ age ranged
between 26 and 86 years.
In terms of gender distribution, 32 patients were male (76.19%) and 10 were female (23.81%).
In the G2 group, 34 (80.95%) patients are smokers (active or former smokers) and 8 never smoked,
65.2% of the patients worked in an environment with no exposure to respiratory hazards.

16
 30 (71.42%) patients in the first group had dry or productive cough, 23 (54.76%) weight loss, 8
(19.04%) side chest pain and 15 (35.71%) dyspnea at medium/low effort.
Based on the radiological site of the neoplastic pleural effusion, 38 (90.47%) were unilateral, 52.4%
were on the right side and 47.6% were in the left pleura. Of the 42 patients in the group, 71.42% have suggestive
parenchymal lesions associated with pleural fluid effusions.
Hematology revealed anemia in 28.56% of the patients (12 patients) with neoplastic pleural effusion; in
18 patients (42.85%), lab tests indicated an inflammatory syndrome with normal leukocyte count and increased
erythrocyte sedimentation rate.
Pleural fluid biochemistry showed that 40 patients had high protein values above 3g/dl, with Light’s
criteria for exudate diagnosis being met.
We found a case where the neoplasm was associated with heart rate irregularities (fast rate atrial
fibrillation and decompensated heart failure), hence the cardiac origin of the transudate. The second case was
found in a pulmonary neoplasm with multiple liver metastases, causing liver failure and a transudate.
Mean LDH in the pleural fluid for the studied group is 458.10, with a standard deviation of ± 211.77, a
minimum of 101 and a maximum of 868 UI.
The mean value of glucose in the pleural fluid in patients where histopathology revealed neoplastic
etiology was 91, with a standard deviation of ± 29.42, a minimum of 60 and a maximum of 141 mg/dl.
Mean ADA in the pleural fluid in patients where histopathology revealed neoplastic etiology (ADK
metastases, either pulmonary or gastric, whether mesothelioma or lymphoma) was 54.66, with a standard
deviation of ± 29.07, a minimum of 22 and a maximum of 87 mg/dl. ADA values above 40UI/L were found in 4
cases, of which 3 with pleural mesothelioma and 1 with malignant lymphoma.
Pleural fluid cytology revealed neoplastic cells in 47.61% of the cases.

DISCUSSIONS

Tuberculosis is among the most common infectious diseases and a major public health issue worldwide,
given its high morbidity and mortality.
TB pleural effusion diagnosis remains a challenge in clinical practice.
Imagistic investigations in TB pleural effusion are crucial, as they show the presence of pleural fluid
with typical radiological aspect, the estimated quantity, the presence or absence of pulmonary lesions. CT scans
can diagnose potential pleural effusions and adenopathies [5].
Testing the pleural fluid for the Koch’s bacillus with the Ziehl-Neelsen staining technique, according to
the studies, turns positive results in less than 5% of the cases and culture on the Lowenstein-Jensen medium in
less than 40% of the cases 5
Pleural biopsy and pleural fluid examination are two important methods in TB pleural effusion
diagnostic. Pleural biopsy may reveal the presence of typical TB granuloma. In some 95% of the cases, they are
of tuberculous nature [5].
The histopathological examination of the parietal pleura is positive in approximately 80% of the cases.
11
Consequently, diagnosis parameters with higher sensitivity and specificity must be used.
Thus, the ADA assay in the pleural fluid seems to meet this criterion, but should be corroborated with
the other clinical and paraclinical elements.
ADA is an enzyme that fuels the conversion of adenosine into inosine and deoxyadenosine into
deoxyinosine. There are two isoenzymes - ADA1 and ADA2. ADA1 is an enzyme present in many cells in the
body, while ADA2 is produced mainly by monocytes/macrophages. The highest accepted value of ADA in the
pleural fluid is 40 U/l [8].
ADA relevance in TB pleural effusion diagnosis also depends on the local prevalence of TB. Thus, in
areas with high TB prevalence, increased ADA may indicate the need to start the anti-TB treatment. In these
areas, normal ADA levels are below 40 units/l [1].
Sometimes, in the early stage of the disease, ADA may be low, but at a biopsy repeat it may go up [11].
Some studies have shown that isoenzyme ADA2 increases in TB pleural effusion patients, while in
patients with empyema and non-infectious pleural effusion, ADA1 increases more [12].
Dooso recommends starting the TB treatment if ADA is higher than 70 u/l; pleural biopsy is a must
between 40 and 70 u/l, while at less than 40 u/l, TB can be ruled out [1]
Porcel et al. believe the presence of objective data (young age, fever), compounded with high ADA
levels may very accurately differentiate TB pleural effusion from malignant pleural effusion [9].
This study covered a group of 42 patients with tuberculous pleural effusion, with an average age of 36.8
years, most patients being in the >30 age group, which is in line with the data in the specialized literature.
In terms of gender distribution in the studied sample, male prevailed (57.1%), which is in line with the
WHO statistics.

17
 Among the patients in the group, only 52.4% were smokers and 14.3% worked in an environment with
exposure to respiratory hazards. It is fair to say that the external risk factors were present in a relatively low
percentage of cases, their relevance being higher in the case of pulmonary TB and older age, with longer
exposure.
The same applies to internal risk factors (comorbidities), with the charts showing that most patients
(66.7%) had insignificant comorbidities.
As young age is prevailing in the study, assessing the symptoms at onset shows in most cases the
following signs: dry cough (93% of the cases), chest pain (64% of the cases), fever (43% of the cases).
In this group, all patients had unilateral pleural effusion, mostly on the right side (52.4% cases), which
is in line with the specialized literature, where bilateral pleural effusion is uncommon 6.
In the studied patients, pleural effusion was associated with lung parenchymal lesions in 52% of the
cases, while the specialized literature describes a range of 20-50%. [10]. Lung involvement was prevalent on the
right side (63.6%).
Anemia is not a sign specific to the tuberculous disease; on the contrary, polyglobulia is often
associated. Only 23.8% of the studied patients had a certain degree of anemia.
In most patients (66.7%), lab tests revealed an inflammatory syndrome.
The pleural fluid assay indicates that all patients had high protein values, averaging at 49.7 g/l, most of
them staying within 45-55 g/dl.
Looking at the LDH values in the pleural fluid, the limits were between 199 and 885, averaging at 599.
We noted that Light’s criteria for the exudate diagnosis were met in all cases.
The specialized literature describes that the histopathological examination of the parietal pleura is
inconclusive in 20-40% of the cases. 2
26.2% of the studied group had inconclusive results and 63.6% of them also had lung parenchymal
lesions.
Regarding the sputum smear with Ziehl Neelsen staining, a positive result was present in 33% of the
cases, of which 50% had a conclusive histopathological examination.
This indicates that half of the tuberculous pleural effusion cases that were not confirmed through
histopathology were diagnosed by sputum smear microscopy.
When assessing the cytology of the pleural fluid, we see that lymphocytes prevail (50% of the patients),
which is specific to tuberculous pleural effusion.
The ADA value that most studies accept for the diagnosis of tuberculous pleural effusion is 40 U/l 4.
Looking at the ADA value in the patients from the group, we found: mean value 71 U/l, values ranging between
53 and 101.84 U/l, 62% of the patients had values between 58 and 80 U/l
We see that all patients had values above 40 U/l, most of them within the 58-80 U/l range.
When correlating ADA values with the pleural histopathological examination result, the values ranging
between 45 and 70 U/l were found in most patients with a positive TB histopathological examination (85%). Of
the 20 patients with ADA values between 45 U/l and 70 U/l, 17 (85%) had a positive result at the
histopathological examination and of the 22 patients with an ADA level higher than or equal to 70 U/l, 14 (64%)
had a positive histopathological examination result.
The mean ADA value for these patients was 70.3 U/l.
When correlating ADA values with the sputum bacteriology test with the ZN method, most patients
(64%) with ADA above 70 U/l had a positive result.
In those with a negative sputum bacteriology result, the prevailing ADA value ranged between 45 and
70 U/l (53.6%).
The mean ADA in patients with positive bacteriology tests was 73 U/l, 43% of the patients having an
ADA level in the range of 69-77 U/l.

CONCLUSIONS

Tuberculous pleural effusion is one of the most common extrapulmonary sites in TB.
An accurate diagnosis in pleural tuberculosis is given by the histopathological examination of the pleura
and, in a smaller number of cases, by the bacteriology test; both require a delay by 14 to 60 days in starting the
anti-TB therapy.
The ADA test, correlated with the clinical tests (young patient, showing signs of tuberculous
impregnation) and paraclinical tests (exudate with lymphocytes prevalence) is highly relevant in diagnosing
tuberculous pleural effusion.
Affordability and fast results recommend ADA assays as a mandatory step in the diagnosis of
tuberculous pleural effusions.

18
 REFERENCES

1. Dooso J. Tuberculous Pleural effusion. Tuberc Respir Dis 2014; 76; 153-1590
2. Ferrer J. Pleural tuberculosis. Eur Respir J.1997=10=942-947
3. Gopi A, Madhavan SM, Sharma TK, Shan SA. Diagnosis and treatment of tuberculous pleural effusion in
2006. Chest 2007= 131=880-889
4. Liang QL, Shi HZ, Wang K, Qin XJ. Diagnostic accuracy of adenosin deaminose in tuberculous pleural
effusion: a meta-analysis. Respir Med 2008; 102: 744-754
5. Light RW. Pleural disease.5 th ed.Baltimore:Lippincot, Williams and Wilkin;2007
6. Maskell NA, Butland RJA, BTS Guidelines for the Investigation of a Unilateral Pleural Effusion in Adults.
Thorax 2003: 58:8-17
7. Morne J, vorster MJ,Alwood B W, Diacon AH, Koegelenberg FN.Tuberculosis pleural effusions : advances
and controversies. J Torac Dis 2015,7 (6)=981-991
8. Porcel JM. Tuberculous pleural effusion. Lung 2009; 187: 263-270
9. Porcel JM, Aleman C, Bielsa S, Sarrapio J, Esguerda A. A decision tree for differentiating tuberculous from
malignant pleural effusions. Respir Med 2008; 102: 1159-1164
10.Seibert AF, Haynes J, Middleton R, Bass J B. Tuberculous pleural effusio: twenty year experience. Chest
1991/ 99/883-886
11.Valdes L, Pose A, San Jose E, Martinez Vazquez JM. Tuberculous pleural effusions. Eur J Intern Med 2003;
14: 77-88
12. Ungerer JPJ, Osthuizen MR, Retief JH, Bissbirt SH. Significance of adenosin deaminase activity and its
isoenzymes in tuberculous effusions.Chest 1994= 106= 33-37

19
 OPEN RADICAL RETROPUBIC PROSTATECTOMY SURGICAL TREATMENT
OF LOCALIZED PROSTATE CANCER - CASE REPORT

Florentina Bealcu Asist. Univ. Drd Titu Maiorescu University, Faculty of Medicine, Bucharest,
Doctorand of University of Medicine and Pharmacy “Carol Davila”, Bucharest, Center for
Uronephrology and Renal Transplantion of Fundeni Clinical Institute, Bucharest

Abstract
Objective of this case presentation is to point out the effectiveness and safety provided by surgical retropubic
radical prostatectomy with bilateral ilio-obturator limpho-dissection in a prostatic cancer patient.
Material and Method Patient M.V., aged 60, after having suffered an episode of highly retention of urine,
diagnosted by TURP 6 weeks behind with prostatic adenocarcinoma. We evaluated: General and clinical
information, examination, Disease history, Laboratory investigations, Indication for surgery, Preoperative
preparation, the surgical method, Describing the surgery, Post surgery nursing, complications,
Recommendations.
Results and discussed:
Patient presented in urology clinic after having suffered an episode of highly retention of urine, diagnosted by
TURP 6 weeks behind with prostatic adenocarcinoma ranged Gleason 7 (3+4), on PSA 1.52 ng/ml. The data
presented above is related to age, clinical exam, lab tests, therefor patient is aimed to be suffering from radical
prostatectomy the risk to develop the come back of prostate cancer depends on certain clinical and pathological
factors: PSA, stage T pathology and Gleason final scroring.
Conclusion: Radical retropubic prostatectomy (RRP) is the main therapeutically method used within patients
detected with early localized prostatic cancer (pT1-T2) having a more then 10 years life expectation ahead.

Keywords: ADKP, PSA, Gleason, radical retropubic prostatectomy

Introduction
Prostate cancer ranks third in men after lung cancer and gastric, representing the fourth leading cause
of cancer death.
The risk of getting a prostatic cancer grows along with aging process, so does the rate of mortality among
men due to this diagnostic. The risk factors are: age, heredity, endocrine factors, race, a diet highly based on
animal fats, prostatic adenoma, and sexual activity with multiple partners, specific and unspecific infections,
vasectomy.
Patients suffering of this disease can nowadays be more rapidly diagnosed at an early stage and so they can
get a proper curative treatment due to PSA – specific prostatic antigen. Prostatic cancer can now benefit from
different therapeutically strategies, in relation to the patient’s life expectation.[1]
Objective
Radical retropubic prostatectomy (RRP) is the main therapeutically method used within patients detected
with early localized prostatic cancer (pT1-T2) having a more then 10 years life expectation ahead (Fig. 1).
Objective of this case presentation is to point out the effectiveness and safety provided by surgical retropubic
radical prostatectomy with bilateral ilio-obturator limpho-dissection in a prostatic cancer patient.

Fig. 1 – Prostat cancer Fig. 2 - Prostate cancer stages of evolution

20
 General information
Patient M.V., aged 60, after having suffered an episode of highly retention of urine, diagnosted by TURP 6
weeks behind with prostatic adenocarcinoma Gleason score 7 (3+4), on PSA 1.52 ng/ml, gets admitted into our
clinic in February 2016 for estimation and specialty treatment.
Clinical information
A family history no comorbidities associated disorder that may have significance for the present. From
personal case history I remember of his hypertension. The patient doesn’t smoke, he is an infrequent alcohol
drinker and has one cup of coffee a day. He claims to have no allergies to known drugs or medical substances.
Disease history
The patient reports that the current suffering dates back about 4 months with an insidious onset by the
appearance of frequent urination during the night and difficulty in urination then six weeks ago.
Then six weeks ago it is diagnosed in another unit by T.U.R.P. (Transurethral resection of the prostate) with
histopathological result of Gleason score 7 (3+4) prostate adenocarcinoma, on PSA 1.52 ng/ml.
At the moment when admitted in hospital he was hemodinamical and respiratory stabilized, presented
physiological urinating, normal colored urine, no fever, blood pressure 148/85 mmHg, pulse rate 82
beats/minute.
General clinical examination devices and systems showed the following datas:
Tissue for cell-fat: normal rates; Muscular system: normal rates; Osteoarticular-system: mobility present;
Lymphatic system: no presence of pathologically lymph nodes palpable.
Respiratory system: bilateral normal sized thorax, bilateral presence of vesicular whisper, no over-added
rales, pectoral thrill present; Cardiovascular system: apex shock present in-between ribs line V on the left
medium-clavicle side, rhythmic heart noises, well defined, no pathologically whispers in the hearing spots;
Digestive system: normal abdomen, slim, flexible, no pain, no post operating scars, normal sized liver; Nervous
system: tendon reflexes present bilateral, temporal-spatial oriented patient.
Local exam of the uro-genital system: Inspection: lumbar and hypogastrium, no pathologically modifications;
Touch: renal lodges normal located bilateral, no pain, Giordano method negative, hypogastrium with no present
pain for superficial and deep touch; Auscultation: no pathologically blasts on renal-arteries; External genital
organs: normal sized, testes present in the scrotum, glands convertible; Rectal examination (RE): medium sized
prostate, no nodules present on touch.
Laboratory investigations for confirming the diagnostic: The usual lab tests were normal.
Urine culture: low rates of polymorphic flora ALT:11 U/L; AST:16 U/L; Total bilirubin: 0.9 mg/dL;
Creatinine: 0.9 mg/dL; GamaGT: 22 U/L; Glucose: 85.7 mg/dL, urea: 40.0 mg/dL, PT:13.3 sec; PT/INR (AP:94
%, INR:1.04 , PT:13.7 sec); The CBC : (WBC:9.31 103/ul, RBC:4.66 106/uL, HGB:14.3 g/dL, HCT:43.0 %,
MCV:92.3 fL, MCH:30.7 pg, MCHC:33.3 g/dL, PLT:312 103/ul, NEUT%:64.5 %, LYMPH%:26.6 %,
MONO%:7.3 %, EO%:1.3 %, BASO%:0.3 %, NEUT#:6.00 103/ul, LYMPH#:2.48 103/ul, MONO#:0.68
103/ul, EO#:0.12 103/ul, BASO#:0.03 103/ul, IG%:0.1 AUTOMATIC, IG#:0.01 AUTOMATIC, RDW-SD:46.1
fL, RDW-CV:14.0 %, PDW:12.0 fL, MPV:10.0 fL, P-LCR:25.5 %, PCT:0.31 %); Total SPA:0.638 ng/ml.
Urinary ultrasound: Right kidney – 115 cm, no hiperecogenic images of kidney stones, no dilation of
pielocaliceal system; Left kidney – 116 cm, no dilations, no hiperecogenic images; Bladder containing transonic,
regular contour, no images of stones, post-urinate residue – 50 ml; Prostate - 38/36/39 mm, volume: 28 cm3.
CT scan shows no detection of secondary adenopathologically regions, extraregions or metastases high
ranged. No isotope bone scan was performed because the patient has bone pain and PSA </ = 20 ng / ml studies
have demonstrated the absence of bone metastases.
Diagnostic positive
So, after having done the primary examination, the clinical exam and lab tests, the positive diagnostic was set
to be prostatic adenocarcinoma (ADKP), Gleason score 7 (3+4), pT2a pN0 pM0, essential hypertension stage
one. Having this histopathological result there is no need for differential diagnostic.
Indication for surgery:
In this stage the indication for this illness is surgical radical retropubical prostatectomy with pelvine
limphodisection. The illness’s evolution for not taking this indication into consideration is presented by death
and metastases. Patient agrees to do surgery and so it begins the preoperatory preparation.
Preoperative preparation is the first step surgical therapy applied to the patient and consists of:
- psychological preparation – looking for adapting to the hospital environment, re-establishing the psycho-
balance; psychotherapy – explaining the need for surgery, possible complications and other details; medication.
Getting an informed consent of the patient was presented after explaining the disease for the patient to fully
understand all terms regarding the intervention, complications, other therapies in place, date and signature
provided by patient.
- The biological preparation: due to clinical results and lab tests (background checks infectious, allergies,
cardiac stimulators and stopping anticoagulant/antiplatelet meds oral administered until then), cardiology consult
or any other side consult needed, blood type, order given due to fit patient blood type.
- Surgical preparation: the moment for proceeding with the surgery is set after having talked with an
anesthesiologist and after the patient was ok on respiratory, hemodynamic, psychic levels, no fever presented,
21
multiple vital signs present - prophylactic antibiotic, surgery risk 4 on Adriani Moore scale (old aged patient, big
surgery). Preanesthetic treatment the night before surgery on doctor’s indication. General and local preparation
proper done on a minimum acceptable operatory risk. Diet reduced by 18 hours – hidrical diet and 4-5 hours
before – completely stopped. Performing an enema 8-12 hours before surgery.
Prepping the tissues by shaving and disinfection using alcohol iodated (hair will be shaved widely 10-15 cm
regarding the limits of the incision). Shower in the morning and at night. In case of varies use tight socks.

Patient preparation in the operating room

The intravenous circuits were ensured in order to secure mentaining all the vital functions within the
procedure. All the vital signs were carefully observed, pulse, O2 saturation, blood pressure. Anesthesia was
general using oro-tracheal intubation (the complications of this anesthesia method were explained during the
informed consent procedure, such as: hipo/hiper blood pressure levels, rithm disorder, laryngospasm,
bronchospasm, teeth distruction, suffering of the lips, throat iritations, caugh, etc)

Intervenţia chirurgicală propusă:

Prostatectomie radicală retropubică cu limfodisectie loco-regională.

Surgery Proposed
Retropubic radical prostatectomy with loco-regional limpho-disection and anastomosis to the urethra and
bladder neck.

The surgical technique

The patient is set in Trendelenburg position, laying on his back. One surgeon on the left side of the patient,
first aid stand in front of the operator, the second stand to the right first aid and assistance instruments to the
surgeon left. Surgical instruments: high abdominal surgery for proper kit. Approach: pubo-abdominal umbilical.

Describing the surgery

An incision was performed pubical-ombilical located, of about 10 cm, the subcutaneous tissue was sectioned,
therefor entering extraperitoneal, with the dissection of the Retzius space and isolating the bladder anterior. Then
was performed the resection of the lymphatic tissue localized on the grand pelvine blood vessels, bilateral ilio-
obturator up to the level reaching the iliach arthery common bilateral and pre-sacral. In this area was located the
first station node, which could have been attacked by tumour cells from the prostate level. The fascial incision
bilateral endopelvine is done, (Fig. 3) digital dissection towards the prostatic apex and section of the pubical-
prostatic ligaments, prostate isolation on all sides and dorsal urethral complex.
Separate complex dorsal urethra using a specific forceps for prostatectomy surgery, tilted to the left and with
a length of 27 cm (type McDougal) (Fig. 4) [2]. Then sectioned between ligatures.

Fig. 3 - Disection prostate Fig. 4 - Specific forceps - type McDougal

22
 Bandeletele neurovascular, located posterolateral urethral separate and avoid sectioning (the "nerve sparing")
so they will be spared one or both packages vascular-nerve innervating the penis, helping the patient to maybe
continue his sex life and the ability to use his urethral sphincter.
The urethra is sectioned at the prostatic-membraneous junction, above and below. (Fig. 5)

Fig. 5 – Resection posterior prostate

The urethro-bladder anastomosis is done using 6 PDS II (poly p-dioxanone) special wires, 4/0 double
reinforced, 20 mm round needle, applied from the inside to the outside, locating hours 12, 1, 4,6, 8, 11. The 6
wires are mounted on the urethral wall for the next anastomosis procedure. The prostate is dragged out using the
urethral catheter previously mounted during surgery (type Foley no. 18), the urethral muscle is sectioned and the
dissection of the area between the rectum and Fascia Denonviliers is began, by releasing the rectal wall to be
presented the seminal vesicles and the vas deferens. (Fig. 6)
Such practice is prostatoveziculectomie by ligature complex vascular pedicles and deep venous prostatic
fascia and release the strip to the side pedicles, which is ligated near the prostate. Cut the bladder neck anterior
and posterior viewing ureteral orifices.
Then all is released and removed, from up to down, the prostate and the seminal vesicles from the rectum.
The bladder neck is sectioned above and beyond visualizing the urethral holes. The bladder neck is sutured
partially on the back side and then the anastomoses of the mucosis is made using Vicryl Rapid 4.0 wires, at the
end of the bladder neck, using the same directions, from the inside out, hours 12, 1, 4, 6, 8, 11.
Mounted special prostatectomy urinary probe with lavage 22 CH, through the urethra, carefully put the
threads for anastomosis, then continue carefully through the bladder neck into the bladder and inflate the balloon
with 15 ml physiological saline. (Fig. 7)

Fig. 6 - Dissection of the area rectum

23
 The table is adjusted on the back, punctual operating direction “0” (decubit dorsal). We count the compresses
and control the vital signs.
Drainage is made with two tubes mounted prevezical bilateral pelvic anatomy and parietorafie and then
suture the skin. Bandage
Total operating time: two hours, loss of blood – 400ml, without the need for intraoperative transfusion.
Possible intraoperative complications: skidding of ligatures or injury of to vessels resulting in bleeding or
damage rectum, ureter, obturator nerve.

URETRA

PROSTATA

VEZICULE
SEMINALE

Fig. 7 – Urethra, seminal vesicles and prostate

Postoperative care
Treatment with broad-spectrum antibiotic; Treatment anti-inflammatory painkiller for pain; Infusion fluid
intake to ensure diuresis 1.5-2 l / day; Supply units can be initiated after the resumption of normal bowel; The
patient can be mobilized in 48 hours postoperatively.

Early postoperative complications

Deep vein thrombosis - heparin prophylaxis by administration divided its; Urinary fistula (maintaining the
probe urethro-bladder for a longer period); Pulmonary embolism - by administering heparin prophylaxis its
fractional; Lymphatic drainage extended; Venous plexus bleeding or other sources of bleeding - requiring
reoperation; Wound infection - requires drainage, possibly secondary suture; Pelvic lymphocele - requires
drainage depending on its size; Persistent urinary infection - antibiotics according to antibiogram.

Late postoperative complications

Local recurrence (will require cancer treatment: radiation therapy and / or adrenergic blockade); Urinary
incontinence (pelvic floor rehabilitation, electrotherapy inside the rectum stimulation, TOT test strip for men, or
even artificial sphincter); Erectile dysfunction.

Recommendations hospital discharge

The patient was discharged with good general condition, afebrile, no other complaints; Hygienic-dietary
regimen recommended; Any intense physical activity is to be avoided for the next 6 weeks postoperator;
Carefully nursing the incision, daily using sterile compresses and betadine; Operative wound care, daily
dressings sterile compresses and betadine; Consult urological a month with histopathological result (of the
operative part) to determine subsequent therapeutic conduct and timing of control; Oncologic dispensary.

Discussions
Issues specific case
The patient presented in a urology service after complaints by the appearance insidious onset of frequent
urination during the night and difficulty in micturition. Deciding perform a resection T.U.R.P. (Transurethral
resection of the prostate).
Digital rectal examination revealed a medium-sized prostate, without palpable nodules and PSA was 1.52 ng
/ ml. The patient has lost weight and had no bone pain. Histopathologic outcome after resection showed Gleason
score 7 (3 + 4) prostate adenocarcinoma.
The above data associated with age, history, clinical examination, laboratory, and the absence of
comorbidities, patient turns in candidate for radical prostatectomy.
Radical prostatectomy is the "gold non standard" in the treatment of localized prostate adenocarcinoma.

24
 The relative risk for developing prostate cancer recurrence depends on various factors, preoperative and
postoperative clinical and pathological these being: prostate specific antigen (PSA), Gleason score and
pathological T stage final.

Prognosis
Vital, immediate (Qvo ad vitam) in case there are no other complications the disease can progress slowly so
that the patient may get cured, depends on the outcome histopathological result.
Health related (Qvo ad sanationem): localy cured.
The ability to work (Laborem ad Qvo): socio-professional reintegration after 6 weeks, 3 months to avoid
physical exertion; urologic control at 1 month, 3 months, 6 months, 1 year conducting PSA.

Control urological 1 month

The patient returns to control PSA = 0.001 ng / ml, with no major complications (lost a few drops of urine)
and histopathological result after radical prostatectomy: Adenocarcinoma acinar prostatic score histologic
Gleason 7 (3 + 4) group grade 2 pT3a PMX pN0.

Bibliography and References

1. www.ms.gov.ro/documente/1323%20Anexa%2014_8731_6689.doc
2. https: //catalog. Carefusion.com/vmueller/mcdougal-type-prostatectomy-clamps-gu8605.html
3. Br J Nurs. 2015 May 14-27;24(9):S24-8. doi: 10.12968/bjon.2015.24.Sup9.S24
Prostatectomy: information provision and education for patients.
http://www.ncbi.nlm.nih.gov/pubmed/25978470
4. Sinescu I., Glück G., Chibelean C., Surcel C., Tratat de Urologie, ISBN: 978-973-39-0655-1 / 978-973-
39-0659-9
5. Prostate Cancer EDITED BY: Gerald Andriole and Manfred Wirth An International Consultation on
Prostate Cancer Berlin, Germany, October 16–20, 2011Co-sponsored bySIU (Société Internationale
d’Urologie)ICUD (International Consultation on Urological Diseases) ISBN 978-0-9877465-3-5

25
 STRUCTURAL ANALYSIS OF THE BLOOD VESSELS

Ioana Doretty Carpus1; Carmen Mihai2; Dimitrie Nanu3

1
Univ. Assist., PhD,“Titu Maiorescu” University Medicine Faculty of Bucharest
2
Math., Eng. PhD, The Textile Research-Development Institute for Textile and Leather Bucharest
3
Prof. Univ, PhD,“Titu Maiorescu” University Medicine Faculty of Bucharest

Abstract
Immediately after the conception period, maternal cardiovascular system undergoes major changes with the
trend of progress during gestation and in some cases their maintenance for weeks or months after birth. Given
that pregnancy itself leads to an increase in the risk of thrombosis, convergent knowledge of the phenomenon, a
complex diagnosis and continuous monitoring of the dynamics of the phenomenon of thrombophilia to prevent
on the one hand problems of the fetus (abortion) and on the other hand those that put in serious danger the life
of the pregnant woman (pulmonary embolism associated with stroke, myocardial infarction, formaiton of clots in
the brain or abdomen) will help to establish more accurately the medication scheme, both during pregnancy as
and during lactation.
The study of phenomena associated with thrombophilia, using the integrative grahic software CATIA V5 has as
main directions of approach the development of virtual model of the phenomenon under study and its analysis in
static and dynamic conditions.
Using CATIA GENERATIVE STRUCTURAL ANALYSIS module, the paper shows the results of the study in
order to determine the state of tension and deformation of blood vessel tensioned due to the presence of
thrombus.

1. INTRODUCTION
Maternal physiological changes that occur in pregnancy are the result of hormonal changes, mechanical
effects of the gravid uterus, increased metabolic and oxygen needs, and the hemodynamic changes associated
with placental circulation.
Among the hemodynamic gestational changes there can be mentioend the physiological ones and [1-9] - 50%
volume expansion, decrease in systemic vascular resistance (SVR) by 21%, pulmonary vascular resistance
(PVR) by 34%, decrease in systolic BP (SBP) by 15 mmHg, decrease in diastolic BP (DBP) - both
differentiately according to the gestation month, resting heart rate increases by 10-20 BAT / min, resulting in a
30-50% increase in cardiac output (DC) etc. These changes are of particular importance to women with pre-
existing circulatory pathology.
Risk factors in the evolution of pregnancy and birth depend on the specifics of cardiovascular disease and the
clinical status of the patient [10].
Risk estimation due to cardiovascular complications associated with pregnancy is the subject of numerous
research in the field. CARREG risk score (CARdiac disease in PREGnancy) resulted from studies which include
pregnant women with cardiovascular diseases which are congenital or acquired and predictor score ZAHARA
(Zwangerschap bij Aangeboren HARtAfwijkingen), resulted from studies that include only pregnant women
with congenital cardiovascular disease have specific performances and limitations [11]. In 2011 ESC Guidelines
recommend to use for maternal risk assessment the changes proposed by the World Health Organization (WHO)
[12]. Classification is based on all existing knowledge in the respective field and include indications for pregnant
women who are not incorporated into the two scores mentioned.
It is known that hemodynamic changes during pregnancy can exacerbate the problems associated with
congenital heart disease. The result is influenced by the functional class (NYHA), the type of disease and
previous cardiac surgeries. Given the shortage of evidence regarding the management of pregnancy in such cases
further studies in the field using modern techniques of conception, design and analysis are necessary.

2. EXPERIMENTAL PART
The interactive graphic software Computer Aided Three Dimensional Integrative Applications is an
integrated system with a modular structure that allows on the one hand the transformation of the set of functional
specifications and requirements into a complete representation of the physical system, and on the other hand
performing the mathematical calculations and complex assessments (using libraries with computational
algebraic, statistical, automatic calculation for surfaces and volumes) in order to assess step by step the values of
sizes that vary continuously.
CATIA V5, used in the conception and design of the phenomena associated with thrombophilia in pregnant
women [13] through Generative Structural Analysis module allows evaluation of virtual model behavior under
static and dynamic stress conditions. Calculation and simulation of the process is done through FEM (Finite
Element Method), with specific assumptions, simplifications and generalizations for the basic concepts
(structure, calculation model, mesh - network of nodes and linear tetrahedra).

26
 This analysis was performed in order to determine the state of tension and deformation of blood vessel as a
result of thrombus presence.
Calculation and simulation [13, 14] were performed using the finite element method (FEM), and by setting
the constituent elements (input) of the mesh, namely:
- For mesh (fig. 1):
 Finite element size: 0.7 mm;
 maximum tolerance between the real model and the meshed model: 0.09 mm
 minimum size of the finite element: 0.1 mm
 tolerance: 0.01 mm
 type of element : linear (4 knots, 1 point Gauss, 3 degrees of freedom)

Fig.1 Mesh model – defining the network of nodes and elements (mesh)

Calculation and simulation conditions:

- blood vessel - considered as stable structure. The condition allowed on the one hand the representation of
the structural interface between the model analzyed (blood vessel) and its assembly, and on the other hand
it eliminates the numerical problems (singularities) that could cause impossibility of using the finite
element analysis;
- pressure – 3.3e+004 N/m2 – corresponding to the value of 250 mmHg considered as maximum possible
for the blood vessel, applied both on the surface of the thrombus and the vascular wall (the directions of
forces constantly exerted forces are permanently perpendicular to it);
- around the thrombus, blood vessel is subject to forces of magnitude 20 N, distributed in the area analyzed
(Fig. 2, Fig. 3). This value was imposed in close correlation with the value of malignant hypertension
(200/120 mmHg): 2.66 e+004N/m2. Additionally, it was found that the blood vessel is subjected to severe
dynamic loads (similar to impact or explosion), and requires taking into account an impact multiplier Ψ =
23.

Fig.2 Distribution of forces tensioning the blood vessel around thrombus –

image on the surface of the blood vessel – virtual model

27
 Fig. 3. Distribution of forces tensioning the blood vessel around thrombus –
image from inside of the blood vessel – virtual model

Finite element analysis performed for mesh showed that the values imposed for predetermined compund
loads tension the structure evenly (errors results fall within the limits of the software), as demonstrated by
change in yellow colour of the graphical representation of distributed loads (Fig. 4).

Fig. 4. Finite element analysis

Analysis of generated virtual model:

- the blood vessel does not show deformation, thus there is no danger of blood vessel cracking or
blocking. It should be emphasized that although tensions in the blood vessel in the thrombus area are at
maximum values, they manifest on infinitesimally short periods of time, with shock and not repeated,
in oscillator system. If one takes into account the phenomenon as a whole as being continuous, the
decrease in blood vessel diameter determines the narrowing of flow section and thus to increase the rate
of fluid through that section. According to Bernoulli's equation, increasing the rate detrrmines increase
in the dynamic pressure followed by decrease in static pressure, which causes blockage of the blood
vessel (Fig. 5, 6).

a b

28
 Fig. 5. Distorted representation of the virtual model
a – end view at a distance of 56 mm from thrombus – highlighting the nodes and mesh elements
b – Reduced representation of finite elements at subunit coefficient values (0.5)

a b

Fig. 6. Distorted representation of the virtual model

a - end view at a distance of 154 mm from thrombus - highlighting the nodes and mesh elements
b – Reduced representation of finite elements at subunit coefficient values (0.5)

- Over time, with the evolution of the phenomenon and development of thrombus, blood vessel is loaded
more in the location of thrombus, a fact demonstrated also by the distribution of pressure in the range [4.6e+005;
1.06e+006] N/m2. In this context, over time, the elastic deformation can be transformed into plastic deformation,
a phenomenon associated with increased risk of breakage of the blood vessel wall.
- Relative directions in which the model is in tension - were highlighted using the fields of components of the
main stress tensor (Fig. 7).

Fig. 7. Components using the main stress tensor- symbolization using nodal values

- The distribution error map of deformation energy (J) (which provides qualitative information on how the
estimated errors are distributed in the model) highlights that reduced estimated error rate (values ranging
between [3.29e-015; 2.76e-007] indicates viable solutions in both cases (Fig. 8).

29
 Fig. 8. Error distribution of strain energy for the virtual model

3. CONCLUSIONS AND OPEN PERSPECTIVES

- The pressure stored in the blood vessel walls (in the form of kinetic energy) and the elasticity of the
vascular walls determines a linearity of the flow regime of blood, the elasticity transforming the blood flow on a
discontinuous basis into the blood flow on a continuous basis).
- Screenshots obtained in the structural analysis further highlights that the blood flowing in the veins exerts in
turn forces on vascular walls.
- Because of the degree of elasticity, vascular walls are opposing to forces exerted by blood and cause the
compression of blood, the phenomenon being expressed through venous pressure (stress).
- Physically, the value of this pressure is dependent on the force of contraction of the heart and peripheral
resistance of the arterial and venous system.
- But realistically, this parameter is also dependent on: systolic volume, blood viscosity (which increases
friction forces), peripheral resistance (which depends on the radius and length of the vessel), the amount of blood
(which may have low values in bleeding).

References
[6] Katz R., Kaliner J.S., Resnik R., Effects of a natural volume overload state (pregnancy) on left
ventricular performance in human subjects. Circulation , 58:434-41, 1978.
[7] Ueland K., Novy M.J., Peterson EN, Metcalte J. Maternal cardiovascular dynamic.IV.The
influece of gestational age on the maternal cardiovascular response to posture and exercise. Am J
Obste Gynecol;104:856-64, 1969.
[8] xxx. Sarcina şi valvulopatiile. Seria Ghiduri clinice pentru obstetrică şi ginecologie. Ghidul 05/Revizia 0., 98
p, 2007.
[9] Kaleschke G., Baumgartner H., Pregnancy in congenital and valvular heart disease. Heart., vol. 97, no. 21,
p. 1803-1809, 2011.
[10] Regitz-Zagrosek V., Lundqvist C.B.,, Borghi C., ESC Guidelines on the management of cardiovascular
diseases during pregnancy. The Task Force on the Management of Cardiovascular Diseasesduring Pregnancy of
the European Society of Cardiology (ESC) European Heart Journal; 32: 3147–3197, 2011.
[11] Balci A., et al., Heart 2014;0:1–9. doi:10.1136/heartjnl-2014-305597, 2014.
[12] Thorne S., MacGregor A., Nelson-Piercy C. Risks of contraception and pregnancy in heart disease. Heart;
92:1520–1525, 2006.
[13] Carpus I.D., Mihai C., Nanu D., “Computer aided design of blood vessels”, Asian Academic Research
Journal of Multidisciplinary, 2015, volume 3, issue 4, online: ISSN-2319-2801, ISI 1,023, ISRA 1825, p 22-28.
[14] Carpus I.D., “Contributions to the study of pregnant women associated cardiovascular disordes” doctoral
thesis, 2015.

30
 HUMAN BODY AND INFRARED LONG WAVELENGTH RADIATION
INTERACTION

Cristina Daniela CRISTESCU1, Elena RUSU2, Mirela RADU3

1
Assist. Prof, PhD “Titu Maiorescu“ University of Bucharest, Faculty of Medicine
2
Assist. Prof, PhD “Titu Maiorescu“ University of Bucharest, Faculty of Medicine
3
Lecturer, PhD “Titu Maiorescu“ University of Bucharest, Faculty of Medicine
*Corresponding author: Lecturer PhD. Cristescu Cristina: cristescu.christin@yahoo.com Preclinical
Department, Faculty of Medicine, Titu Maiorescu University, Gheorghe Petrascu Street, no. 67A,
sector 3, Bucharest Romania
ABSTRACT
Infrared radiation is an electromagnetic emission with a wavelength ranged between 760 and 1,000
nanometers, located outside the human visible spectrum. FIR has beneficial influence on DNA and RNA,
increasing energy production and the cellular turnover and, consequently, cell rejuvenation.
Experimental studies demonstrate that the FIR resonance with water molecules constituent of the human
body produce heat, the immediate result is vasodilation and improving blood flow.
Consequently the FIR emission based systems can have pozitive effects in a number of osteoarticular and
cardiovascular diseases, etc.

INTRODUCTION

Infrared radiation is an electromagnetic emission wavelength ranged between 760 and 1,000 nanometers,
located outside the human visible spectrum. Infrared radiation with long wavelength (FIR) is the part of the
radiation that has a wavelength greater than 4-5 microns and a great power of penetration in the human body.
This type of energy enters the frequency of biophotons action [1] which can activate the vitality of DNA
and RNA cells, increasing ATP production and capacity of the body to produce energy, facilitating and
accelerating the turnover and multiplying cells even under the conditions of organ damage cell structures
existence.

MECHANISM OF ACTION

For a complete understanding of mechanisms of action it is necessary to consider three fundamental aspects of
the interaction between matter and energy.
1. The human body contains 70% water and inorganic and organic molecules.
2. The human body easily absorbs FIR
3. The human body behaves as a black body [5] in relation to the FIR, absorbing waves and retaining them
completely.

Figure1. FIR absorption by human body

31
 Under the action of vibration FIR energy aggregation form of water molecules (cluster) changes and there
is a concomitant increase in capacity of hydration.
All this, combined with increasing temperature of blood lead to a superior fluidity of body fluids (blood,
lymph) by improving microcirculation and eliminating increased accumulated toxins in the tissue matrix [3].
The more narrower blood vessels are and lower the fluidity is, the more it slows down circulation and
increase the risk of thrombus formation (deep vein thrombosis, stroke).
When FIR contact the human body, it is to be absorbed, in contrast to other electromagnetic waves which
will freely pass through the body or be reflected.
In order to understand how the human body which is subject to radiation FIR reacts, we will compare it to a
black body [5], obeying physical laws that govern black bodies. Black body is a body that absorbs all incident
radiation. However, it may issue a new radiation. For example, the sun behaves as a blackbody. According to the
above-mentioned law, the frequency at which there is maximum radiation emission is 9.5 microns-average
frequency infrared spectrum with long wavelength.
Increasing the temperature of a blackbody amplifies the total energy emitted and there is a decrease in the
maximum emission wavelength.

Figure 2. Total energy

If we consider that human body temperature is around 30 degrees, the curve will peak at a wavelength
between 4 and 16 microns and the maximum power emitted by the human body is about 95W. Making a
comparison, we can say that the human body behaves like a light bulb, noting that it does not emit in the visible
spectrum but in the infrared. So we can say that the human body absorbs and emits FIR radiation.
Reflection, penetration and resonance, the most important properties of FIR, induce wellbeing to the human
body [4].
Reflection: infrared rays generate heat, directly radiating bodies and are only partially reflected by them.
Penetration: FIR penetrate deeply into organic tissue.
Resonance: by penetrating living tissue, rays belonging to FIR activate (resonate with) water molecules,
producing rotary movement and an overall increase in body temperature.
This aspect is interesting and important if we consider that the body temperature is one of the parameters
which directly influence the gelling of the extracellular matrix, accompanied by diminishing transmission
capacity both of nutrients especially photonic biocybernetic communication [2].
Experimental studies have shown that FIR resonance with water molecules of the human body produce
heat, generating a pleasant sensation of heat in the skin and subcutaneous tissue, the immediate result is a
vasodilation irrigation followed by an improvement in blood circulation, which has as a consequence a number
of beneficial effects.
FIR ensures better oxygenation of tissues, improved intake of nutrients in tissues, stimulates cell
metabolism and bone turnover cell (rejuvenation of tissues), quicker elimination of metabolic wastes and toxic
substances from the body, breaks clusters of water molecules and facilitates the exit of water from fat cells,
stimulates the sweat glands, thereby increasing perspiration and elimination of excess water and toxins, reduce
the accumulation of lactic acid in the muscles and stimulates its elimination, relaxes muscles, it is an effective
painkiller, improves wellbeing, reduces hypertension.
32
CONCLUSIONS
Systems based on emission of FIR, having beneficial effects on tissue oxygenation, intake of nutrients to
tissues as well as on the faster elimination products of catabolism and excessive water, can be successfully used
in osteoarticular afflictions, peripheral circulatory failure, hypertension, nutrition diseases, improving physical
appearance, increase quality of life and self-esteem (obesity, cellulitis), physiotherapy, postoperative neuromotor
rehabilitation or after prolonged immobilization in a cast, recovering from paresis or paralysis, increase exercise
capacity in athletes.

REFERENCES

1. Popp FA, Cohen S Biophoton Emission of the Human Body. J Photochem Photobiol B. 1997 Sep; 40(2): 187-
9
2. Popp FA, Biofotoni, Nuove basi per la compresione della medicina biocibernetica moderne. EAV. 8,
Dicembre 2000: 17-21.
3. Sclauzero E, Studio Osservazionale-Longitudinale-Prospettico delle modificazioni dei disturbi del sonno,
degli stati ansiosi, delle disfunzioni del microcircolo, delle algie e delle contratture moscolari e di ulteriori
parametri clinici e psicofisici correlati mediante l’utilizzo di uno stuoino a Fibre di Carbonio caratterizzato
dalla emissione di onde del lontano infrarosso.
4. Sharkey BJ. Fisiologia del benessere, Edra Publishing House. 1996
5. Spaggiari P, Tribbia C. Medicina quantistica: La medicina attraverso la fisica dei quanti. Tecniche Nuove
Publishing House, Milan 2008.

33
 MANAGEMENT OF SEPSIS: THE PIRO CONCEPT IN ICU

Authors: Dr. Gorecki Gabriel, Prof.Dr. Cochior Daniel

Sepsis is a relatively frequent pathological occurrence in the Intensive Care Unit and has
therefore become a global health issue that has a great impact, both on resources and on the financial
aspect of the Health System.
The current definition and classification of sepsis dates back to 1991 when the American
College of Chest Physicians and the Society of Critical Care Medicine first introduced the notion of
‘systemic inflammatory response syndrome’ (SIRS). At least two of the following values must be
present in order to diagnose SIRS:
 The body temperature must be over 38oC or under 36oC
 The heart rate must be over 90 beats per minute
 The respiratory rate must be over 20 breaths per minute or the patient must show signs
of hyperventilation with the partial pressure of arterial carbon dioxide (PaCO2) level
below 32 mmHg
 The leucocyte count must be over 12000/mm3, under 4000/mm3 or the number of
immature leucocyte circulating should be over 10%.
Sepsis is defined as infection caused SIRS and is a major health issue. Just like in the case of
polytrauma, acute myocardial infarction and stroke, the faster treatment is applied the greater the
chances of a positive outcome.

The PIRO (predisposition, insult, response, organ dysfunction) score is similar to the TNM
staging system (tumor, lymph nodes, metastasis) used in Oncology, devised by Pierre Denoix in 1946.
The TNM staging system is used to identify subgroups of patients with different prognosis and to
assign the correct course of action. Theoretically, the PIRO model can be used to evaluate the
condition of the patient and to estimate their recovery.

The PIRO system offers the possibility to form homogeneous subgroups of patients who will
be able to receive personalised treatment. The chance of recovery is thus greatly improved.

The potential use of the PIRO concept consists in the ability to differentiate between infection
cause morbidity and morbidity caused by the response to the infection. The problems the patient had
before sepsis mark an underlining condition independent of the infection. The process that needs to be
influenced is the evolution towards organ failure.

The studies used to test the PIRO system focused on determining the accuracy of the
prediction of the diagnostic and less on the prediction of the response to therapy. Patients with an a
priori diagnostic of sepsis were used in the studies.

Just like in the case of the TNM classification, a long period of time is necessary to develop a
PIRO test that will successfully classify the stages of sepsis.

An interesting and unexplored perspective is that of bedside testing of PIRO and the structural
evaluation of the patient based on this concept

The objectives of the study consisted in the analysis of various clinical factors present in
sepsis diagnosed patients while taking in consideration the correlation with their prognostic and the
selection of clinical and paraclinical indicators relevant to the PIRO system that have an impact on
the prognostic of septic patients from the ICU. At the end of the study a PIRO score was made that
can be used when treating patients.

The study was prospective. It included 152 patients (78 men, 74 women of the average age of
69,9 years). It spanned over 2 years and it included patients diagnosed with sepsis/ sever sepsis/ septic

34
shock in the first 24 hours after being admitted to the ICU and that have survived at least 48 hours
after being admitted.

The following data has been collected:

1. Demographics: age, sex

2. Location previous to admission to the ICU( hospital, health clinic, community)
3. The duration of the previous hospital stay before the admission to the ICU
4. Underlining condition present before admission to the ICU:
- Cronic obstructive bronhopathy, congestic heart failure, diabetes mellitus, cronic
renal deficiency, ischemic heart disease ( including history of myocardic
infarction) peripheral vascular disease( including the absence or presence of aortic
aneurism), cerebrovascular disease( including stroke with or without hemiplegia),
dementia, diseases of the conjunctive tissue, gastric and duodenal ulcer
- Cronic hepatic disease (cronic hepatitis, hepatic cirrhosis)
- Leukaemia, lymphoma
- Neoplasia ( including the presence or absence of metastasis)
- Prior use of chemotherapy or radiotherapy
- Immunosuppression: corticotherapy used for a short period of time – doses of
over 1 mg/kg/day of prednisolone for at least a week in the last 3 months
- Immunosuppression: corticotherapy used for a long period of time – doses of over
0,2 mg/kg/day of prednisolone for at least 3 months in the last 12 months
- The presence of HIV (Human Immunodeficiency Virus)
- AIDS ( Acquired Immune Deficiency Syndrome)
5. The value of the Charlson Comorbidity Index on admission to the ICU
6. The place where the sepsis originated, the origin (community acquired or nosocomial
infections), the extent of the infection, the presence of the bacteria during the stay in the ICU
7. The etiology of the sepsis (viral, Gram positive or Gram negative bacteria, fungi)
8. Imagistic proof of the presence of sepsis taken in the first 24 hours (radiology, echography,
computer tomography, nuclear magnetic resonance)
9. Antibiotherapy taken in the first 24 hours
10. The value of the body temperature, the heart rate, the arterial systolic tension and the
leucocyte count taken on admission to the ICU
11. The number of organ dysfunctions present on admission to the ICU
12. The value of the serum lactate in dynamics: taken after 24, 48 and 72 hours
13. The dynamic measurement of the SOFA and APACHE scores after 24, 48 and 72 hours
14. The determination of the SAPS3 score on admission to the ICU
The studied variables have been put in four categories that correspond to the PIRO model:
- In Predisposition we included: demographic dates of the patients, the associated
pathology, the Charlson comorbidity index, the prior location of the patients, the
number of days of prior admission to hospitals
- In Infection we included: the origin of the infection (community or nosocomial),
the extent of the infection, the point of development, the presence of the bacteria,
the etiology of the infection (viral, Gram positive or Gram negative bacteria,
fungi)
- In Response we included: the number of leucocyte (including the number of
neutrophilia), the systolic arterial tension, the heart rate and the procalcitonin
level on admission to the ICU
- In Organ Dysfunction we studied the number of organ dysfunctions present on
admission, the lactate value, the hypoxic index, and the SOFA score after 24, 48
and 72 hours.

35
 The first prognostic was the survival of the patient after being taken out of the ICU. The
second prognostic was the time spent in the ICU. We made an univariate analysis of each factor taken
in consideration the prognosis. We tried to identify those that were correlated positive with mortality.
We compared each studied variable with the risk models used in therapy: SOFA, APACHE II and
SAPS3. The ones that impacted the prognostic were included in the PIRO test.
The study has identified a group of variables associated to each PIRO component that
predicted mortality in the patients present in the study.
The death rate wasn’t much different between the community and the nosocomial origin of the
infection. The mortality was much lower in the surgical cases compared to the medical cases. This can
be explained by the possibility of more specific therapeutical interventions in the surgical cases. The
length of the stay in the ICU was not important and did not influence whether the patient died or lived.
Prior admission to hospitals did not influence mortality.
There wasn’t an important difference in the survival rate between sexes. Women did not
present any correlation between age and mortality but for men the age of 61,5 proved to be important.
The death rate for men under the age 61,5 was lower than that of men over the age of 61,5. This study
confirms the results present in the literature and it that proves the higher mortality of elderly men.
The mortality rate grew considerably in the presence of comorbidity, the difference between
the mortality of cases without pathologic association and those with pathologic association being
considerably different.
The study confirmed the results from prior literature studies, such as the higher mortality in
the case of nosocomial infections versus community infections.
The most frequent place of origin of the sepsis in this study was the abdominal region. Men
presented the most cases of abdominal sepsis, followed by infections of the inferior respiratory tract.
There weren’t important differences between survival rates taking in consideration the site of the
initial infection location.
The most frequent infections were those with Gram negative bacteria (48%). The mortality
rate was the highest with this etiogy. The data matches the one from the EPIC II study (European
Prevalence of Infection in Intensive Care), published in 2009. In this study 62,2% of infections were
with Gram negative bacteria. The extent of the infection was associated with the prognostic but with
modest specificity and sensibility. Bacteremia was more frequent in men.
The etiologic agent, identified or not, the extent of the infection and the presence of
bacteremia were taken in consideration for the construction of the first component of the PIRO score.
None of the variables studied in the Response component (tachycardia, hypotension,
temperature, leucocyte count) had any correlation with the prognostic. The value of procalcitonin was
the only one that differed between survival and death, basically being the only variable to be taken in
consideration when constructing the Response component.
In this study we observed that regarding organ dysfunction, the mortality rate grew
statistically between patients that had 1 or 2 organs affected and those with 3 or 4 organs affected.
Mortality levels reach 100% for those with more than 4 organs affected. These patients were analysed
separately, being excluded from the models generating the PIRO test. In this situation there was a
higher number of cases with unidentified etiology and with a higher number of days spent in hospitals
prior to admission to the ICU. The patients of this group had higher scores on the SOFA test, on
admission and after 48 hours. They also scored higher on the SAPS 3 test. This was explained by the
presence of organ dysfunction criteria both in the SOFA and the SAPS3 test.
Regarding the dynamics of the seric lactate we concluded that the value of the seric lactate
after 48 hours and, more importantly, the lactate clearance is strongly correlated with the prognostic.
The value of Procalcitonin had statistically important differences between those who died and
those who lived, being correlated with the prognostic.
The hypoxemic index after 24 and 72 hours was correlated with survival rates, the value after
48 hours having statistic importance. Alongside the number of organ dysfunctions, the Lactate
clearance, the hypoxemic index was taken in consideration in the generation of the PIRO model.
In this study we also characterised the patients following the risk models used in intensive
therapy: the SOFA, APACHE II and SAPS 3 scores, taking in consideration the static values ( after
24, 48 hours and for survivor 72 hours) and the dynamic values ( the trend determined by delta-SOFA
and delta-APACHE II). The negative values of delta-SOFA and delta-APACHE were strongly
associated with survival.
36
References:
1. Jawad I, Lukšić Ivana, Rafnsson Snorri B: Assessing available information on the burden of
sepsis: global estimates of incidence, prevalence and mortality. Journal of Global Health 2012: 2(1)
010404.
2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR:
Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated
costs of care. Crit Care Med 2001, 29:1303-1310.
3. Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, et al. Epidemiology
of sepsis syndrome in 8 academic medical centers. JAMA 1997; 278:234-40.
4. Vincent JL, Ocampos Martinez E: Evolving Concepts in Sepsis Definitions. Crit Care Clin
2009; 25665–675.
5. ACCP-SCCM Consensus Conference: definitions of sepsis and multiple organ failure and
guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20:864–74.
6. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM,
Vincent JL, Ramsay G for the International Sepsis Definitions Conference: 2001
SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med
2003; 29:530–538.
7. Dellinger RP, Levy M, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung
C, Douglas IS, Jaeschke R, Osborn TM, Nunnally M, Townsend SR, Konrad Reinhart K, Kleinpell
R M, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL,
Moreno Rand the Surviving Sepsis Campaign Guidelines Committee including the Pediatric
Subgroup: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and
Septic Shock: 2012; Critical Care Medicine, February 2013,Vol 41, Number 2: 580-637.
8. Vincent JL, Ocampos Martinez E: Evolving Concepts in Sepsis Definitions. Crit Care Clin
2009; 25665–675.
9. Moreno RP, Metnitz B, Adler L, Hoechtl A, Bauer P, Metnitz PG; SAPS 3 Investigators.
Sepsis mortality prediction based on predisposition, infection and response. Intensive care Med 2008;
34: 496-504.
10. Lisboa T, Diaz E, Marcio S B et al. The Ventilator Associated Pneumonia PIRO Score Chest
2008; 134; 1208-1216; DOI 10.1378/chest.08-1106.
11. Rello J, Rodriguez A, Lisboa T, Gallego M, Lujan M, Wunderink R. PIRO score for
community-acquired pneumonia: a new prediction rule for assessment of severity in intensive care unit
patients with community-acquired pneumonia. Crit Care Med 2009; 37:456-62; PMID:19114916;
http://dx.doi. org/10.1097/CCM.0b013e318194b021
12. Rubulotta F, Marshall J C, Ramsay G et al: Predisposition, insult/infection, response, and
organ dysfunction: A new model for staging severe sepsis. Crit Care Med 2009 Vol. 37, No. 4: 1329-
1335.
13. Reade MC, Yende S, D’Angelo G, Kong L, Kellum JA, Barnato AE, Milbrandt EB, Dooley
C, Mayr FB, Weissfeld L, et al.; Genetic and Inflammatory Markers of Sepsis Investigators.
Differences in immune response may explain lower survival among older men with pneumonia. Crit
Care Med 2009; 37:1655-62; PMID:19325487; http://dx.doi.org/10.1097/ CCM.0b013e31819da853.
14. Angele Chaudry I M K, Pratschke S, Hubbard W J, H. Gender differences in sepsis
Cardiovascular and immunological aspects. Virulence January 1, 2014; 5:1, 12–19.
15. Offner PJ, Moore EE, Biffl WL. Male gender is a risk factor for major infections after
surgery. Arch Surg 1999; 134:935-8, discussion 938-40;PMID:10487586;
http://dx.doi.org/10.1001/archsurg.134.9.935
16. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J,
Gomersall C, Sakr Y, et al.; EPIC II Group of Investigators. International study of the prevalence and
outcomes of infection in intensive care units. JAMA 2009; 302:2323-9; PMID:1995219;
http://dx.doi.org/10.1001/jama.2009.1754.

37
 THE ART OF DOCTOR-PATIENT CONVENTION: NEW MEDICAL AND LEGAL
CONNOTATIONS

Prof. PhD Lidia Nica - Udangiu

Chief of works – Dr. Ana - Maria Mihălcescu
Titu Maiorescu University of Bucharest, Faculty of Medicine

Abstract: The development of medical psychology and of the medical law has substantially altered the doctor-
patient relation, which must consider the new coordinates that sciences bring to discussion. The authors
underline the main elements of the doctor-patient dialogue in the shown context, underlining, by using the notion
of art, the complex, interdisciplinary character of this endeavor.

From the beginning of medical practice, which is situated in ancient times, the doctor-patient dialogue has been
an intrinsic part of any medical deed, even of the simplest one, the inter-human relation being inherent, we
would say even similar to the doctor-patient relation.
However, the special human contact established between the person who suffers and the person who brings
comfort has been subject to many changes through the evolution of medical sciences, but of legal sciences as
well, that have led to the professionalization, almost ,,standardization,,, of this dialogue, to correspond to the new
theoretical approaches.
From this point of view, we must note, on the one hand, the appearance of medical psychology, as applicative
branch of psychology, and, on the other hand, the outline of the standards of medical law, both developments
bringing more precise, more standardized contents, to the dialogue between doctor and patient.

In terms of traditional medicine, the dialogue between doctor and patient aimed at, mainly, investigating the
patient through anamnesis, in order to word the diagnosis and to follow the evolution of the disease.
Once medical psychology has developed and the bio – psycho - social model of the disease has been set, the
disease, the suffering appears to be structured on various levels, beginning with the molecular one up to the
social one, any of these levels being able to influence the psychic functions and, implicitly, the patient-doctor
dialogue.
Therefore, a complex of causal factors, of molecular, genetic or social nature, by their interaction, generate the
disease. Equally, it is impossible to separate the subjective feelings and experiences, expressed by the patient,
from the psychic or somatic suffering, seized by the examiner, thus rendered objective by clinical examination.
Departing from this theoretical model, clinical psychology has set, as a therapeutic need, an approach of the
patient by the doctor, based on data known by science, observing the patient’s personality, in order to build a
therapeutic alliance between doctor and patient.
The doctor-patient alliance is, after all, a specific and complex inter-human relation, where there is a double
emotional transfer, whose effect is to harmonize and humanize the relation between doctor and patient, to have
empathy with the patient, to build his trust for his doctor.
Such relation of transfer differs according to the respective pathology, to the perspective of the sick man
concerning the disease and to the type of psychotherapy used.
Usually, the transfer is positive, and the patient develops feelings of empathy and confidence for the doctor,
even exacerbating and idealizing his doctor. On other occasions, the transfer becomes negative, and the patient
develops a suspicious attitude and antipathy.
Naturally, the doctor-patient relation is not spontaneous, it is an evolutional process, with several stages, from
the patient’s call to the doctor, rendering objective the relation through the medical act of diagnoses and
treatment in itself, until the personalization or maturity of the therapeutic relation.
We may say that the doctor-patient relation has known fundamental differences, in terms of the same disease,
according to the typology of the sick person’s personality. In medical psychology, several types of patients are
known: hyper-expressive, anxious, depressive, obsessional, antisocial, the patient with high social statute; these
are totally different types of reaction facing the disease and the doctor.
There may appear role conflicts, as a result of the resistance developed by patients towards the doctor’s
authority or by contradictory feelings that the patient may have towards the doctor, and, sometimes, even by the
doctor towards the patient.
In this complex landscape, previously outlined, it is obvious that communication is essential, both the verbal,
and the non-verbal one.
The doctor must have an efficient communication with the patient, by choosing a suitable place and moment to
talk, paying attention to the elements of the non-verbal language (gestures, visual control, attitude, mimic,
posture), and of the verbal language (voice tone, verbal type).

38
 An efficient verbal communication supposes credibility for the doctor, he is the professional with experience in
treating similar patients, he is sure of what he says, the tone of his voice excludes fear or anxiety for a possible
failure, he presents messages in a logical and correct order, in a clear speech, that the patient understands,
allowing him to say his opinion, making sure that he understands the meaning of the medical terms that have
been used, exploring in detail the discussed topic, making sure that he remains focused on it, encouraging the
patient to express his feelings and emotions.
The doctor must be and must remain master of this relation, however without becoming a tyrant. The
„Patronizing” that he exercises based on his professionalism and on knowing the proper communication
techniques used in medical practice, allowing him to make an action plan adapted to the situation, to provide
enough information on a given topic, to consciously transmit messages, suggesting at the same time the idea of
cooperation in order to establish a therapeutic alliance.
It is inappropriate to advise the patient on the actions he is going to take, and the doctor must not disclose his
agreement with the patient’s thoughts and feelings, nor his disagreement with the patient’s ideas or behavior, he
must never disregard the patient’s emotions, he must not reject or refuse to take the patient’s ideas into
consideration, he must not display a despising or superior attitude towards the patient.
In any case, the patient will be communicated the diagnosis without postponing or avoiding to talk with him,
without using hard words and expressions in inappropriate circumstances, distantly, possibly in the hallway or in
front of other patients.

These imperatives of medical psychology are overlapped with elements of legal nature resulting from the
unprecedented legal regulation of medical actions, that has outlined and imposed the medical law, which
includes the standards applicable to the exercise and organization of medical professions such as those applicable
to the legal relations generated by the exercise of medical professions, during which the doctor-patient legal
relation occupies a central place.
The development of medical law is a consequence of the multiple faces of the present medical act, which is no
longer limited solely to the therapeutic alliance between doctor and patient, a relation during which the patient is
weak and dependent, and the doctor is strong and omniscient.
The modern, European patient is a user of public health services, a taxpayer for health services, an insured
contributing to mandatory or voluntary heath securities.
All this gets the „consumer” closer, as beneficiary of organized or authorized public services, therefore he has
rights that the law expressly recognizes. 1
Beside this approach, from an economic point of view, so typical for the current societies, the patient’s rights
appear as a development, as a corollary, of the fundamental human rights, a perspective which is, of course,
more accepted by the jurists.
At the same time, it would be unfair not to mention the contribution of the common law system to the
development of this field, which was the first to recognize the patient’s right to be asked for his consent
regarding a medical maneuver.2
We may state with certainty that the era of medical paternalism, whose milestone was Hippocrates’s oath, has
ended. The doctor who makes decisions on behalf of his patient and based on the professional deontology that he
undertakes when he starts practicing is anachronic and risks to be sanctioned at any time, even criminally.
Therefore, the doctor-patient dialogue inevitably acquires legal dimensions, that include the recognition of the
patient’s right to be informed, as well as, at a later stage, the patient’s consent for treatment or investigations.
The paternalist model was therefore replaced with the model of partnership between doctor and patient, during
which the previously described principles of medical psychology must be completed and increased by the
compliance with the legal requirements.
A correct and complex information of the patient supposes the actual communication of data concerning the
investigations that have been or should be carried out, elements of diagnosis, therapeutic alternatives, prognosis
of the disease with and without treatment, as well as the risks associated to every medical procedure, even the
exceptionally rare risks.
The patient is considered to have been properly informed if he actually understood what the doctor said, and
the doctor must make sure that it is so.
Only based on correct, complex, objective information, according to the recognized data of medical science,
perceived as such by the patient, the doctor may move on to the next stage, respectively to obtain the consent for
a certain treatment or investigation, or to take notice of the patient’s refusal to follow the doctor’s indication.
The doctor must accept the patient’s possible refusal and, in this case, he must abstain from any medical act,
even if this refusal endangers the patient; naturally, provided that the patient is in full control of his faculties and
discernment during the refusal.

1
The recitals of the legislative initiative of the law on patient’s rights mentions ”the more and more frequent use of the term
of consumer instead of patient”, www.senat.ro
2
Slater v.Baker and Stupleton, 1767
39
 In conclusion, we may state that the doctor – patient dialogue has acquired new dimensions in the past

years, not known to the medical practice so far, particularly set by the development of medical psychology

and of the medical law. The doctor – patient partnership is today an undisputed reality, and for its

achievement, the doctor plays a central part.

The actual building of this partnership is a complex endeavor, and the doctor must possess serious theoretical

knowledge of medical psychology and medical law but, equally, the art to combine this theoretical knowledge

in a conversation with the patient, that should preserve the specific humanity of the profession of doctor.

40
 PREVALENCE OF THE 35delG AND W24X MUTATIONS IN CHILDREN WITH
NON-SYNDROMIC CONGENITAL SENSORINEURAL HEARING LOSS

H. Mocanu, MD. PhD,1,§ A. Neagu, MD. PhD2,§

1
Titu Maiorescu University– Bucharest, Romania, Faculty of Medicine
ILFOV County Clinical Emergency Hospital, ENT Department
2
Children’s Clinical Emergency Hospital “Marie Sklodowska Curie” – Bucharest, Romania,
ENT Department
§: Both authors contributed equally to this work.

ABSTRACT:
During the last decade, due to outstanding progress in understanding the molecular bases of
sensorineural hearing loss (SNHL), it became clear that 50 to 80% of all such afflictions result from mutations
in a single gene, GJB2, which encodes the protein Connexin 26. One mutation of this gene, the 35delG allele, is
particularly common in white populations. Studying this matter within the Romanian population is still in its
early stages. In order to, at least partially clarify this problem, we searched for the two most common variations
of this gene, 35delG and W24X in children with positive diagnosis of bilateral severe - profound sensorineural
hearing loss.
KEYWORDS: Connexin 26, GJB2, 35delG, W24X, congenital non-syndromic hearing loss, genes

INTRODUCTION:
According to data reported by the World Health Organization, over 250 million people currently suffer
from hearing loss of variable etiology, which represents 4.2% of the world’s population. 4,5,19,22 Congenital
hearing loss is relatively frequent, with a prevalence reported by different sources in literature as varying between
1-3/1000 newborns28 and 1/500 newborns.35 Although etiologically heterogeneous, at least 50% of all early on-
set hearing losses have a genetic cause and of these, the large majority are most probably autosomal recessive
(75-80%)35 and non-syndromic (70%)28,35,13,25. Due to the etiological heterogeneity of the disease, genetic
evaluation and council become difficult, especially for very small children. Recent discoveries indicate the
mutations of the GJB2 and GJB6 genes on the 13q11-q12 chromosome as responsible of more than 50% of all
types of non-syndromic autosomal recessive congenital hearing loss in certain populations. This information
facilitates, to some extent, the genetic diagnosis and gives families increased information regarding this genetic
affliction.
The GJB2 and GJB6 genes encode the Connexin 26 (Cx26) and Connexin 30 (Cx30) membrane proteins
which form the intercellular heteromeric channels called gap-junction. These structures have an important role in
the cochlea homeostasis and insure the influx of potassium ions from the internal and external hair cells to the
cochlea supporting cells. The GJB2 gene has over 100 alleles, especially for the autosomal recessive forms of
hypoacusis. The deletion of a single guanine, 35delG, is responsible for over 50% of the non-syndromic
sensorineural hearing loss in Europe, North-America and Asia.23,27,41 The common deletion 342-Kb of the GJB6
gene (GJB6-D13S1830) appears in up to 20% of all SNHL cases in the U.S.A. and could be responsible of
approximately 10% of all the DFNB1 alleles, since it has a very wide action range, based on ethnic origin and is
frequently associated with the 35delG/GJB2 mutation.11,14,27
Some of the most recent studies have stated that the GJB6 mutations have no active role in the etiology
of congenital non-syndromic SNHL and that the Connexin 30 protein would only modulate the action of the
Connexin 26 protein. This would mean that in the case of a SNHL with a GJB6 deletion, the hypoacusis would
be, in fact, the result of a GJB2 deletion modulated by the presence of the GJB6 deletion. 6

MATERIAL AND METHODS:

The study took under evaluation a cohort of 34 children (20 female and 14 male), ages between 2 and 10
(mean age 4.62 years), coming from 33 nonrelated families. All cases were diagnosed with severe or profound
bilateral congenital SNHL, in the ENT Department of the Children’s Clinical Emergency Hospital “Marie
Sklodowska Curie”, in Bucharest, between October 2014 and April 2015. After establishing a complete family
and personal history, the patients underwent a thorough ENT examination which excluded the syndromic forms
of hypoacusis and other associated diseases. A personal interview of the parents provided essential information
regarding the pregnancy period (mother’s health, pollution, use of ototoxic drugs, alcohol, smoking during
pregnancy), birth (premature child, hypoxia, cranial trauma, extended ICU care after birth > 5 days) and
evolution of the SNHL (when and how it was discovered).
After excluding any middle ear pathology, the audiological diagnosis was established by using
Otoacoustic Emissions (OAE), Brainstem Auditory Evoked Response (BAER) and Auditory Steady State
Response (ASSR) for children under 4 years of age (following the current international guidelines)2 and Pure

41
Tone Audiometry for children over 4 years of age. Syndromic or acquired hypoacusis were excluded from the
study. Patients with a suggestive SNHL family history (deaf parents) were also excluded but we kept the patients
with suggestive risk factors (ototoxic treatments, hypoxia at birth, prematurity etc.) since it has been shown that
the presence of such factors does not exclude a genetic etiology of the SNHL.
None of the patients benefited from neonatal screening even though some of them presented doubtless
risk factors for congenital SNHL. The mean age for diagnosis was 2.7 years.
After obtaining the informed, written consent of the parents, a blood sample was taken for molecular
testing and establishing a possible genetic cause for the hearing loss. The blood was collected in EDTA tubes.
The DNA was extracted from peripheral blood by in-vitro growth of lymphocytes. The cultures were stopped
with colchicine during the metaphase. The molecular analysis was made using AS-PCR and multiplex-PCR
techniques by directly amplifying the DNA with specific primers.

RESULTS:
Since genetic testing is an expensive method and the financial means of our study were limited, a
selection of patients was necessary. We initially evaluated a cohort of 58 cases with severe or profound bilateral
SNHL. Of these, 34 cases were selected, children that had no other health issues (non-syndromic cases) and had
no family history of SNHL (normal hearing parents). The 34 subjects underwent a genetic screening for the
35delG and W24X mutations of the GJB2 gene.
26.6% of cases (10/34) were homozygotic for the 35delG mutation (35delG/35delG), also known as
genotype Δ/Δ (the Greek letter Δ preceding the name of a gene, signifies that the gene has a chromosome deletion
whilst the letter N represents the lack of a deletion). No case of heterozygosity 35delG/N (Δ/N) was present for
the 35delG mutation whilst 5.88% of cases (2/34) belong to the heterozygotic bigenic group 35delG/W24X.
The W24X mutation was present in 5.88% of cases (2/34) as homozygotic genotype (W24X/W24X) and
in 2.94% of cases (1/34) as heteozygotic genotype (W24X/N). Results can be seen in
Table 1.
The overall prevalence of the mutant allele was 32.35% for 35delG and 10.29% for the W24X (see
Table 3).

DISCUSSION:
SNHL represent one of the most frequent human disabilities and the genetic factor plays a central role in
its research and diagnosis. Until now, more than 130 loci for human nonsyndromic SNHL were identified and it
is estimated that more than 100 mutations of the Cx26 encoding genes could be involved. 1 This variety of
mutation makes the genetic diagnosis extremely difficult and even more, the prevalence of certain genes varies
for different population groups.
The 35delG mutation of the GJB2 gene remains, however, the main cause of genetic SNHL in the
Caucasian population. The prevalence of mutation carriers varies from 1/35 for the south European population to
1/79 in Northern Europe.10,12 The maximum prevalence is recorded in countries arround the Mediterranean.1,8,18
This mutation has also one of the highest pathogenic potential in humans, with a frequency of carriers similar to
that of the deltaF508 mutation of the cystic fibrosis gene (CFTR). 10,40 It can be found both in homozygosis and
heterozygosis state and it can also be associated to other mutations of the GJB2 gene or of the GJB6 gene such as
D13S1830, which is the second ranking mutation involved in the etiology of SNHL in Europe. In certain
population groups such as the Japanese, the Chinese, Ashkenazi Jews and the rroma populations, the 35delG
mutation is very rare and is replaced by other mutations such as 235delC, 167delT or W24X. 15
The present study evaluates the prevalence of the 35delG and W24X mutations within the Romanian
population suffering from congenital non-syndromic SNHL. Although the number of studied cases was relatively
small and all diagnosed in the same clinic, the results showed that the screening for known mutations and a
rigorous selection of cases can pinpoint the presence of the genetic factor in almost 50% of cases of severe or
profound congenital SNHL.
The prevalence of the 35delG mutation was 29.4% in accordance with similar studies that report 13.6%
in Jordan, 14% in Palestine1,34, 16% in Egypt1,24, 5.66% in Iran1,23, 94% in Lebanon1,16 and 60-80% in European
populations1,38 (see Table 2) whilst the relative frequency of the 35delG mutant alleles was also in line with
previously published studies (see Table 3). Extensive research done in the Middle East determined that the
frequent presence of the 35delG mutation is directly linked to the high level of consanguinity of the studied
populations, which does not apply to the European and therefore the Romanian population.
The frequency of the 35delG mutation carriers varies in different studies from 1,1% in Jordan to 1,66%
in Syria and up to 3,2% in Italy, the highest known frequency so far. 1
Concerning the presence of the homozygotic genotype 35delG/35delG in the Romanian population, our
study is in accordance with those of our colleagues in Bucharest (36%), Craiova (24%) and Transylvania
(25.33%) 20,26,37 – see Table 4. A particular feature of our results is the total absence of the heterozygotic
genotype, 35delG/N. This result had been reported only once before by Romanian researchers, in a 2010 study by
Lazăr et al., on 75 patients from Transylvania.20

42
 The results of the present study suggest that the high prevalence of the 35delG mutation within the
studied population could represent enough reasons to implement genetic diagnosis and council on a larger scale
and also continue the research on this subject. However, the techniques used for detecting mutations are still very
expensive and sometime prone to sequencing errors.10
The W24X mutation is another relatively common cause for the non-sydromic SNHL, especially in
populations from Northern and Southern India.1,21,32 A study on the rroma population of Slovakia reports a
relatively large prevalence of W24X carriers (26.1%), probably in close correlation to the Indian origin of these
populations. Our study found a 10% prevalence of the homozygotic genotype (W24X/W24X) and a 6.66%
prevalence of the digenic heterozygotic genotype (35delG/W24X) for this mutation, similar to the study by Lazăr
et al. which reports a 1.33% prevalence for the W24X/W24X genotype a 2.66% prevalence for the 35delG/W24X
genotype 20 (see Table 4).
The diagnosis of SNHL in children is very complex and requires a number of specialized tests for
establishing the etiology 9,28 but testing for GJB2 mutations is currently recommended as an initial test 2,28,
followed by GJB6 testing in the case of a negative result. 28,29 Genetic testing has become a very useful tool for
the ENT specialist in the attempt of explaining the etiology of the SNHL. The main benefit of genetic testing is
that it can explain the hypoacusis without any additional exams 28,33 and it can also bring information on the way
the mutation was transmitted and the probability of appearance in other possible offspring.28,33,39
Although genetic diagnosis is very expensive and is not routinely done in developing countries,
investigating the mutations of the GJB2 gene is essential in clarifying the problem of congenital hypoacusis. This
type of diagnosis leads to genetic council for family members and facilitates the quick rehabilitation of the child.

CONCLUSIONS:
The genetic affliction of a child also brings social and psychological consequences on the family
(concern for the child’s wellbeing, stigmatization, guilt for passing the disease on to the child) which can affect
the parent’s capabilities of coping with the situation. After the birth of a deaf child, the parents don’t usually
know the etiology and most of them do not anticipate a genetic factor, especially without a suggestive family
history.
The present study confirms the relatively high prevalence of the 35delG and W24X mutations in cases
of congenital non-syndromic severe of profound bilateral SNHL, in accordance with previously published
studies. Two of the patients presented a double mutation 35delG/W24X (bigenic heterozygosity). These results
confirm the importance of genetic testing in clarifying the etiology and implementing a precocious recovery
program for the patient. The purpose of such a program is the optimal hearing and linguistic rehabilitation. The
prevalence of the 35delG mutation within the European population also suggests the necessity of a genetic
screening which would facilitate the early identification of mutation carriers and would bring the genetic council
accordingly.

Table 1 - Results of genetic testing in the present study

Genotype Nr.of subjects/Total nr.of
patients

35delG/35delG 10 / 34 (29,4%)

35delG/N 0 / 34 (0%)
35delG / W24X 2 / 34 (5,88%)

W24X/W24X 2 / 34 (5,88%)
W24X/N 1 / 34 (2,94%)
N/N 19 / 34 (55,88%)
N – absence of mutation (35delG or W24X)

43
 Table 2 – Prevalence of genotypes in the present study compared to other published studies

Genotype Present Cordeiro- Pfeilsticker Piatto Battisoco Nogueira Al- Khushvakova

study Silva et.al. et.al.200430 et.al. et.al.20093 et.al.201127 Achkar et.al. 2010
20107 200431 et.al.
20111

35delG / 10/34 3/77 2/75 5/33 22/300 4/95 15/50 146/374 (39%)
35delG (29,4%) (3,9%) (2,66%) (15%) (7,3%) (4,2%) (30%)
35delG/N 0/34 5/77 2/75 3/33 12/300 8/95 9/50 57/374 (14%)
(0%) (7,8%) (2,66%) (9%) (4%) (8,4%) (18%)
35delG / 2/34 1/77 N.A. 1/33 3/300 6/95 2/50 23/374 (6%)
Other (5,88%) (1,35%) (3%) (1%) (6,3%) (4%)
mutation
N – absence of mutation (35delG or W24X); N.A. – Not analized

Table 3 – Prevalence of mutant alleles (35delG and W24X) in the present study
compared to other published studies

Genotype Present Lazăr Corde Pfeilstick Piatto Battissoc Nogueir Al- Khushvako Hamid Frei et.al.
study et al. iro- er et.al. et.al. o et.al. a et.al. Achka va et.al. et.al. 200210
201020 Silva 200430 200431 20093 201127 r et.al. 2010 200915
et.al. 20111
20107

35delG 32,35% 33,33 7.8% 4% 21% 9.8% 40% 42% 53% 40.9% 77%
%
W24X 10,3% 5,3% N.A. N.A. N.A. N.A. 2% 0% N.A. N.A. N.A.

N.A. – Not analized

Table 4 – Prevalence of genotypes in the present study compared to other published studies from Romania

Genotype Present study Neagu 201326 Totolin 201137 Lazăr 201020

35delG/ 10/34 (29,4%) 30/84 (36%) 6/26 (24%) 19/75 (25,33%)

35delG
35delG/ 0/34 (0%) 15/84 (18%) 5/26 (19%) 0/75 (0%)
N
N/N 19/34 (55,88%) 39/84 (46%) 15/26 (57%)
W24X/W24X 2/34 (5,88%) N.A. N.A. 1/75 (1,33%)
W24X/N 1/34 (2,94%) N.A. N.A.
35delG/W24X 2/34 (5,88%) N.A. N.A. 2/75 (2.66%)

N.A. – Not analized

44
 REFERENCES:

1. Al-Achkar W., Moassass F., Al-Halabi B., Al-Ablog A. Mutations of the Connexin 26 gene in families
with non-syndromic hearing loss. Molecular Medicine REPORTS, 2011, 4: 331-35.
2. American College of Medical Genetics. Genetics evaluation guidelines for the etiologic diagnosis of
congenital hearing loss. Genet Med 2002;4:162–171. [PubMed: 12180152]
3. Batissoco AC, Abreu-Silva RS, Braga MC, Lezirovitz K, Della-Rosa V, Alfredo T Jr, et al. Prevalence
of GJB2 (connexin-26) and GJB6 (connexin-30) mutations in a cohort of 300 Brazilian hearing-impaired
individuals: implications for diagnosis and genetic counseling. Ear Hear. 2009;30(1):1-7
4. Bochkov N. Clinical genetics: Manual, Moscow 2002.
5. Bork J., Peters L., Riazuddin S. Genetic and metabolic hearing disorders. American Journal of Human
Genetic, 2001, 68:1; 26-37.
6. Boulay AC, del Castillo FJ, Giraudet F, Hamard G, Giaume C, Petit C, Avan P, Cohen-Salmon M.
Hearing is normal without Connexin 30. The Journal of Neuroscience. 2013, 33(2): 430-34.
7. Cordeiro-Silva MdF, Barbosa A, Santiago M, Provetti M, Rabbi- Bortolini E. Prevalence of
35delG/GJB2 and del (GJB6-D13S1830) mutations in patients with non-syndromic deafness from a population
of Espírito Santo – Brazil. Braz J Otorhinolaryngol. 2010;76(4):428-32.
8. Cryns K, Orzan E, Murgia A, et al: Agenotype-phenotype correlation for GJB2 (connexin 26) deafness.
J Med Genet 41: 147-154, 2004.
9. Duncan RD, Prucka S, Wiatrak BJ, Smith RJH, Robin NH. Pediatric otolaryngologists’ use of genetic
testing. Arch Otolaryngol Head Neck Surg 2007;133:231–236. [PubMed: 17372079]
10. Frei K., Szuhai K., Lucas T., Weipoltshammer K., Schofer C., Ramsebner R., Baumgartner WD.,
Raap AK et.al. Connexin 26 mutations in cases of sensorineural deafness in eastern Austria. European Journal of
Human Genetics 2002, 10, 427 – 32.
11. Fuse Z., Doi K., Hasegawa T., Sugii A., Hibino H., Kubo T. Three novel connexin26 gene mutations in
autosomal recessive nonsyndromic deafness, NeuroReport, 1999; 10(9), 1853–57.
12. Gasparini P, Rabionet R, Barbujani G et al: High carrier frequency of the 35delG deafness mutation in
European populations. Eur J Hum Genet 2000; 8: 19 – 23.
13. Gorlin, RJ.; Toriello, HV.; Cohen, MM, Jr. Hereditary Hearing Loss and Its Syndromes. New York:
Oxford University Press; 1995.
14. Grifa A. , Wagner C.A., D’Ambrosio L. et al., Mutations in GJB6 cause nonsyndromic autosomal
dominant deafness at DFNA3 locus, Nature Genetics, 1999; 23(1), 16–18.
15. Hamid M, Karimipoor M, Hashemzadeh Chaleshtori M, Taghi Akbari M. A novel 355–357delGAG
mutation and frequency of connexin-26 (GJB2) mutations in Iranian patients. Journal of Genetics, 2009, 88.3,
359-62
16. Hashemzadeh Chaleshtori M, Hoghooghi Rad L, Dolati M, et al: Frequencies of mutations in the
connexin 26 gene (GJB2) in two populations of Iran (Tehran and Tabriz). Iranian J Publ Health 34: 1-7, 2005.
17. James, C., Hadley, D., Holtzman, A., Winkelstein, A.. How does the mode of inheritance of a genetic
condition influence families? A study of guilt, blame, stigma, and understanding of inheritance and reproductive
risks in families with X-linked and autosomal recessive diseases. Genetics in Medicine, 2006, 8, 234–42.
18. Janecke AR, Hirst-Stadlmann A, Günther B, Utermann B, Müller T, Lӧffler J, Utermann G and
Nekahm-Heis D: Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2
mutations – phenotypic spectrum and frequencies of GJB2 mutations in Austria. Hum Genet 111: 145-153,
2002.
19. Koroleva I., Grigoreva I., Petriga E. Modern methods of differential diagnoses of hearing disorders.
Materials of scientific-practical conference, 1999 Suzdal.
20. Lazăr C, Popp R, Trifa A, Mocanu C, Mihut G, Al-Khzouz C, Tomescu E, Figan I, Grigorescu-Sido P.
Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss
from North-West Romania. Int J Pediatr Otorhinolaryngol. 2010; 74(4):351-5. doi: 10.1016/ j.ijporl.
2009.12.015. Epub 2010 Jan 21.
21. Maheswari M, Vijaya R, Ghosh M, Shastri S, Kabra M and Menon PSN: Screening of families with
autosomal recessive nonsyndromic hearing impairment (ARNSHI) for mutations in GJB2 gene. Indian Scenario.
Am J Med Genet 120: 180-184, 2003.
22. Markova T., Shagina I., Megrelishvilli el al. DNK-diagnostics congenital and early childhood hearing
loss and deafness, Bulletin of otorhinolaryngology, 2002; 6, 12-15.
23. Mustaapha BM, Salem N, Delague V, et al: Autosomal recessive non-syndromic hearing loss in the
Lebanese population: prevalence of the 30delG mutation and report of two novel mutations in the connexin 26
(GJB2) gene. J Med Genet 38: E36, 2001.
24. Mustafa MW: Prevalence of the connexin 26 mutation 35delG in non-syndromic hearing loss in Egypt.
Internet J Otorhinolar 3: http://www.ispub.com/ostia/index.php ?xmlFilePath=journals/ijorl/vol3n1/ connexin.
xml, 2004.

45
25. Nance WE. The genetics of deafness. Ment Retard Dev Disabil Res Rev 2003;9:109–119.
[PubMed:12784229]
26. Neagu A. Studiu genetic şi clinic în hipoacuziile neurosenoriale non-sindromice congenitale. UMF
„Carol Davila” Bucureşti, Lucrare de doctorat 2013
27. Nogueira C, Coutinho M, Pereira C, Tessa A, Santorelli FM, Vilarinho L. Molecular Investigation of
Pediatric Portuguese Patients with Sensorineural Hearing Loss. SAGE-Hindawi Access to Research Genetics
Research International Volume 2011, Article ID 587602, 5 pagesdoi:10.4061/2011/587602
28. Palmer C.G.S., Lueddeke J.T., Zhou J. Factors influencing parental decision about genetics evaluation
for their deaf or hard-of-hearing child, Genet Med. 2009 April; 11(4): 248. doi:10.1097
/GIM.0b013e318195aad9
29. Pandya A., Arnos KS, Xia XJ et al. Frequency and distribution of GJB2 (connexin 26) and GJBG
(connexin 30) mutations in a large North American repository of deaf probands. Genetics in Medicine, 2003,
5(4), 295–303.
30. Pfeilsticker LN, Stole G, Sartorato EL, Delfino D, Guerra ATM. A investigação genética na surdez
hereditária não-sindrômica. Rev Bras Otorrinolaringol. 2004;70(2):181-6.
31. Piatto VB, Bertollo EM, Sartorato EL, Maniglia JV. Prevalence of the GJB2 mutations and the
del(GJB6-D13S1830) mutation in Brazilian patients with deafness. Hear Res. 2004;196:87-93.
32. Ramshankar M, Girirajan S, Dagan O, Ravi Shankar HM, Jalvi R, Rangasayee R, Avraham KB and
Anand A: Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in
India. J Med Genet 40: E68, 2003.
33. Schimmenti LA, Martinez A, Fox M, Crandall B, Shapiro N, Telatar M, et al. Genetic testing as part of
the Early Hearing Detection and Intervention (EHDI) process. Genet Med 2004;6:521–525. [PubMed:
15545749]
34. Shahin H, Walsh T, Sobe T, Lynch E, King MC, Avraham KB, and Kanaan M: Genetics of congenital
deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. Hum
Genet 110: 284-289, 2002.
35. Smith, R., Hildebrand, M., Van Camp, G. (2010). Deafness and hereditary deafness overview.
http://www.ncbi.nlm.nih.gov/pubmed/20301607.
36. Steinberg, A. G., Kaimal, G., Bain, L., Krantz, I., Li, Y. (2007). Parental narratives on genetic testing
for children with deafness: a qualitative inquiry. American Journal of Medical Genetics, 143(A),1533–1545.
37. Totolin M. Metode clinice, audiologice şi genetice moderne de investigare a hipoacuziei neuro-
senzoriale congenitale. UMF Craiova, Lucrare de doctorat 2011
38. Wilcox SA, Osborn AH and Dahl HH: Simple PCRtest to detect the common 35delG mutation in the
connexin 26 gene. Mol Diagn 5: 75-78, 2000.
39. Withrow KA, Burton S, Arnos KA, Kalfoglou A, Pandya A. Consumer motivations for pursuing
genetic testing and their preferences for the provision of genetic services for hearing loss. J Genet Counsel
2008;17:252–260.
40. Worldwide survey of the delta F508 mutation: Report from the cystic fibrosis genetic analysis
consortium. Am J Hum Genet 1990; 47: 354 – 359.
41. Zelante L., Gasparini P., Estivill X. et al. Connexin26 mutations associated with the most common
form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Human
Molecular Genetics. 1997; 6(9); 1605–09.

46
 TYPES OF CORONARY ARTERY STENTS AND THEIR USE

Alice MUNTEANU MD, University assistant, Dr. Carol Davila Central Military Emergency
University Hospital
Irina FLORESCU MD, National Institute of Gerontology and Geriatrics "Ana Aslan"
Cristina CALCAN MD, Dr. Carol Davila Central Military Emergency University Hospital

Abstract
Obstructive coronary disease is one of the most important causes of death worldwide. Percutaneous
coronary intervention is one of the most important treatments of this pathology and its evolution in the last years
developed many different options for intervention with new benefits for the patient evolution. The using of
coronary artery stents represented a major advance in interventional cardiology. While bare metal stents (BMS)
set the reference point for improved safety over angioplasty, intimal hyperplasia and subsequent restenosis were
important limitations. First-generation drug-eluting stents demonstrated significant improvements in efficacy,
but not necessarily safety, and further technologic developments have focused on optimizing both. Current
advances and understanding in stent design continue to improve on these concepts.

HISTORY
The history of PCI begin in 1977 with the first successful transluminal coronary angioplasty in men by
Andreas Gruentzig at University Hospital Zurich using balloon catheter.[5] In 1986 was launch the first self-
expanding stent by Puel and Sigeart in order to prevent coronary occlusion during PTCA and reducing restenosis
rate (the restenosis rate was 30-40% before introducing the stents). In 1993 FDA approve the first coronary stent,
developed by Cesar Gianturco, radiologist, and Garry Roubin, cardiologist. They developed a stent made of a
stainless steel wire type spool expandable with balloon and in 1994 it approves the second coronary stent,
developed by Julio Palmaz, vascular interventional radiologist, and interventional cardiologist Richard Schatz.
They conceive a BMS type grooved-tube, expandable with balloon [1]. In 1999 PTCA with BMS implantation
represents 84,2% in all PCI [9]. 2002 is the year when DES covered with Serolimus were approved in Europe.
Clinical trials showed a 0% restenosis rate at 6 months, comparing with BMS which have a high rate of
restenosis and late thrombosis in stent.[2] In 2011 the first bioresorbable stent (Absorb – Abbot) start being used
in Europe, and in 2012 bioresorbable stents were used for the first time in Romania at Bucharest and Cluj. In
2013 a new bioresorbable stent was approved in Europe – DESolve, covered with Novolimus.

INDICATION AND CONTRAINDICATION OF INTERVENTIONAL MYOCARDIAL

REVASCULARIZATION
Indications for interventional myocardial revascularization are: STEMI, NON-STEMI, stable angina, angina
equivalent – dyspnea, arrhythmias, syncope, asymptomatic patients or moderately symptomatic with a medium-
large surface of viable myocardia, or moderately-severe myocardial ischemia on noninvasive tests, angiographic
– hemodynamically significant lesions on myocardia arteries which irrigate a viable myocardia and have a
diameter higher than 1.5 mm.[12]
Relative contraindications for interventional myocardial revascularization are: relevant comorbidities, small
diameter coronaries or venous grafts with diffuse stenosis, LAD stenosis in a patient with CABG
recommendation (surgery remains the preferred therapy method for such cases), PCI unsuitable coronary
anatomy. [12]
Contraindications for interventional myocardial revascularization are: patients with contraindications for
antiplatelet or anticoagulant therapy, coronary lesions which prevent fully inflating the balloon and properly
implanting the stent. [12]

BMS – EFFECTIVENESS AND SAFETY

The major limitations of balloon angioplasty have been represented by the acute obstruction and restenosis of
blood vessels. Early studies of intracoronary stents have shown that these devices are very effective in treating or
preventing acute blood vessel obstruction, thus avoiding emergency surgical bypass interventions. Two
randomized trials – the Benestend[8] and STRESS (Stent Restenosis Study)[3] have shown that stenting lesions
de novo on native coronary have reduced angiographic restenosis by about 30% compared to conventional
balloon angioplasty. Implanting stents leads to a luminal diameter larger than balloon angioplasty, both right
after the surgery and in the follow up, thus to a lower restenosis rate.

47
 Two trials – Benestent study[8] and STRESS (Stent Restenosis Study)[3] proved that stenting new lesions on
native coronary artery reduced intrastent restenosis with almost 30% comparing with balloon angioplasty. A
stent implanted on coronary determine a higher diameter of the artery comparing with balloon angioplasty, also
immediately and at follow up, so the restenosis rate is reduced.
Using BMS was compared with coronary artery bypass grafting (CABG) in the treatment of obstructive
multicoronary disease in ARTS trial (A rterial Revascularization Therapies Study)[10]. The 1 year follow up
showed that the mortality, myocardial infarct and stroke rate was similar in the two groups. Survival rate without
cardiovascular events was higher in CABG group (87.8% vs 73.8%). Also less surgery patients needed a second
revascularization procedure (3,5% vs 16,8%).
Stone et al, studying the safety and effectiveness of BMS and DES on 3006 patients with STEMI with
immediate PCI noticed that in DES group the restenosis in stent and recurrent ischemia needing
revascularization procedure in 1 year follow up was significant lower than in BMS group.[11] Although,
mortality and in stent thrombosis rate were similar for the 2 groups.

DES – DRUG ELUTING STENTS

Drug eluting stents are a newer coronary stent category, superior to BMS. This keeps the mechanical pros of
BMS metallic stents while also having anti restenosis proprieties.

Effectiveness and safety

The RAVEL trial[7] was one of the first studies which compared the safety profile and effectiveness of
metallic stents with that of drug eluting stents covered with Sirolimus. Results at 6 months have shown a
significant reduction of intra-stent restenosis, a significant decrease of major adverse cardiac events, as well as
target lesion revascularization in those patients which benefited from DES. Results at 5 years have demonstrated
a similar rate of intrastent thrombosis between the two groups, but a significant lower incidence of major adverse
cardiac events in the DES group.
A trial managed by Hsieh and co [4] compared post procedure results on artery with different diameters in
patients with DES vs. BMS. They also proved that incidence of major cardio-vascular events was significant
lower in DES group, but the benefits are limited if the diameter is under 3.7mm.
CE-approved new generation DES recommended for clinical use based on randomized trials with a clinical
end-poind (alphabetical order)[12]:

CE-approved DES with angiographic efficacy data from randomized or non-randomized studies (in
alphabetical order)[12]:

48
BIO-ENGINEERED STENT
Bio-engineered Stent is also known as antibody-coated stent. This type of stent differs from DES because it
does not contain a polymer and does not use a drug. As a result, it helps to speed up the cell lining of the artery
(endothelialization), promoting natural healing.
The antibody on the stent's surface attracts circulating Endothelial Progenitor Cells (EPCs) which come from
human bone marrow and help speed up the formation of healthy endothelium. This provides rapid coverage over
the stent's surface helping to reduce the risk of early and late thrombosis (blood clots).[6]

BIORESORBABLE STENTS
The latest in interventional cardiology are Bioresorbable stents, which are incorporated in the blood vessel,
then are dissolved all the way to carbon dioxide and water, allowing the artery to resume vasomotricity and
eliminating the risk of inflammation, a process which takes about two years after implantation.
Bio-resorbable stents providing drug elution with angiographic efficacy date from randomized and non-
randimized trials (in alphabetical order)[12]:

DUAL THERAPY STENT

Dual Therapy Stent (DTS) is the latest type of coronary stent. It is a first-of-its-kind stent therapy designed to
not only reduces the likelihood of the re-narrowing of the artery or of having to undergo a repeat procedure, but
also help the healing process of the artery. It combines the benefit of DES and bio-engineered stents and is the
only stent to contain a drug with active healing technology.
The DTS has coating both inside and outside, which reduces the likelihood of blood clots, inflammation and
helps the healing process of the artery.

49
 The stent surface facing the artery wall contains a drug that is released to help stop the artery blocking again
without the worry of swelling or an inflammatory response. The drug is delivered from a bioresorbable polymer
that will degrade over time.
The side of the stent which faces blood flow is coated with antibodies, which promote natural healing and
helps the healthy artery function properly.

GUIDELINES INDICATIONS [12]

Primary PCI for myocardial reperfusion in STEMI: procedural aspects

Recommandations Class Level

50
 CONCLUSIONS
Both PCI and CABG have undergone continued advances, especially by using of arterial conduits for CABG,
and the advent of stents. Since it`s first use 19 years ago, PCI has become one of the most frequently performed
therapeutic interventions in medicine, and progress has resulted in a steady decline of periprocedural adverse
events, resulting in excellent outcomes with both revascularization techniques. Coronary stents aim at restoring
normal blood-flow of the native coronary arteries by local treatment of obstructive lesions without offering
protection against new disease proximal to the stent, in constrast with the CABG witch offers protection against
proximal obstructive disease and witch offers extra sources of blood flow to muscle cells.[12]
Various stents are currently available, differing from each other with respect to composition (eg, stainless
steel, cobalt chromium, or nickel chromium), architectural design, and delivery system (ie, the balloon catheter
that delivers the stent).
The best possible revascularization approach, by taking into consideration the social and cultural context,
require interaction between cardiologists and cardiac surgeons. Patients need help with taking informed
decisions about their treatment and the most valuable advice will probably be provided to them by the „Heart
Team”.[12]

References

1. Butany J., Carmichael K., Leong SW, Collins MJ. Coronary artery stents: identification and evaluation.
J Clin Pathol. 2005 Aug 58(8):795-804
2. FDA Approves Drug-Eluting Stent for Clogged Heart Arteries". U.S. Food And Drug Administration.
April 24, 2003. From http://fda.gov Retrieved 2007-04-08
3. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and
balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N
Engl J Med. 1994 Aug 25. 331(8):496-501
4. Hsieh MJ, Chen CC, Chang SH, Wang CY, Lee CH, Lin FC, et al. Long-term outcomes of drug-eluting
stents versus bare-metal stents in large coronary arteries. Int J Cardiol. 2013 Jul 2
5. King SB 3rd, Schlumpf M. (1993). Ten year completed follow-up of percutaneous transluminal
coronary angioplasty: the early Zurich experience. J Am Coll Cardiol 22 (2): 353-60
6. Lim W-H, Seo W-W, Choe W. et al. (2011) Stent Coated With Antibody Against Vascular Endothelial-
Cadherin Captures Endothelial Progenitor Cells, Accelerates Re-Endothelialization, and Reduces
Neointimal Formation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011; 31: 2798-2805
7. Morice MC1, Serruys PW, Sousa JE et. al. A randomized comparison of a sirolimus-eluting stent with a
standard stent for coronary revascularization. N Engl J Med. 2002 Jun 6;346(23):1773-80.
8. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation
with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J
Med. 1994 Aug 25. 331(8):489-95
9. Serruys PW, Kutryk MJB, Ong ATL. Coronary-artery stents N Engl J Med 2006; 354:483-95
10. Serruys PW, Ong AT, van Herwerden LA, et al. Five-year outcomes after coronary stenting versus
bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial
Revascularization Therapies Study (ARTS) randomized trial. J Am Coll Cardiol. 2005 Aug 16.
46(4):575-81.
11. Stone GW, Lansky AJ, Pocock SJ, et al. Paclitaxel-eluting stents versus bare-metal stents in acute
myocardial infarction. N Engl J Med. 2009 May 7. 360(19):1946-59
12. 2014 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal Advance
Access 2014 August 29.

51
 OSTEOID OSTEOMA OF THE HUMERAL SHAFT: A CASE REPORT IN A 37
YEARS OLD MAN

Mihai MARDARE1, Manuel OPREA1, Ancuta ZAZGYVA2, Marius NICULESCU3

1.
University of Medicine and Pharmacy „Victor Babes“ Timisoara, Romania
2.
University of Medicine and Pharmacy Tîrgu Mure , Department of Cell and Molecular Biology, Tîrgu Mure ,
Romania
3.
Colentina Clinical Hospital, Clinic of Orthopaedics and Traumatology I, Bucharest, Romania// Titu Maiorescu
University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Bucharest, Romania

Corresponding author :
Mihai MARDARE
Email : mihai_mardare@yahoo.com

Abstract
Osteoid osteoma is a small and painful osteoblastic tumor, accounting approximately 10% of symptomatic
beningn bone tumors and 5% of all primary bone tumors (1). It can occur anywhere, affecting only one bone or
several bones but in 80% - 90% of the cases, osteoid osteoma is reported to occur in the cortex of the shaft of the
long bones. In 50% - 60% of the cases the femur and tibia are involved (2,3). The humeral shaft is not a common
location for the osteoid osteoma. We present a case of osteoid osteoma of the right humeral shaft in a 37 - year -
old patient, who had a 10 months history of pain in the right arm, with distinct night pain, that responded to
salicylates. The key of diagnosis in this patient was observing the night increasing character of the pain and
performing bone scan.

1. Introduction

Osteoid osteoma is a benign bone tumor, described for the first time by Bergstrand in 1930 (4) and defined as
a clinical – pathological entity by Jaffe in 1935 (5). In the literature there have been published numerous
descriptions of the incidence, localization and therapeutic options. The osteoid osteoma accounts 10% of all
benign bone tumors (1), more commonly affects males, with an approximate male/female ratio of 2 to 1 and the
highest incidence occurs in the first three decades of life (6). The incidence at the humerus is between 2% (7)
and 6.3% (8).
The most common location for the osteoid osteoma is the proximal femur, followed by the tibia, posterior
elements of the spine and the humerus (9).
When located in uncommon locations, the osteoid osteoma presents a diagnostic challenge and the time delay
elapsed from the symptom initiation and diagnosis is significant due to the lack of clinical signs and radiographic
features that exists in the well – established classical hallmarks of an extra – articular lesion (11-15).
Pain can usually be the only symptom of disease presented in patients and it’s character can help establishing
the diagnosis of a benign bone tumor. The history of a dull aching pain for weeks to months, which is more
intense at night and relieved by aspirin or non-steroidal anti-inflamatory drugs (NSAID’S) is very common
associated with osteoid osteoma (5,10).
The classic radiological presentation of an osteoid osteoma is a radiolucent nidus surrounded by a dramatic
reactive sclerosis in the cortex of the bone. The center can range from partially mineralized to osteolytic to
entirely calcified. There are four features relevant for the diagnostic: an oval or sharp round lesion less than 2cm
in diameter which has a homogeneous dense center and a 1-2 mm peripheral radiolucent zone (9)
The differential diagnosis of cortical osteoid osteoma includes: brodie abscess, stress fracture, eosinophilic
granuloma, intracortical hemangioma, bone island, intracortical osteosarcoma, Ewing osteosarcoma,
osteoblastoma, osteomyelitis, arthritis and enostosis.
A nidus can be difficult to see on a plain radiography, even if radiographic findings include sclerosis.
CT remains the best imaging modality for the diagnosis of osteoid osteoma (16).
MRI is inferior to CT scan in revealing the nidus, surrounding bone sclerosis and precise localization of the
tumor but is very good in detecting the nidus in cases of intra-articular lesions (17).

52
 2. Case report
A 37-year old man was referred to our hospital due to on-going pain of his right arm. The symptoms began 10
months ago when he had a sports accident (tennis). He already undergone conservative treatment until he was
referred to our clinic.
The pain was decreased with daily activity and increased at night and subsided partially with anti –
inflammatory drugs, especially salicylates.
On physical examination, he reported persistent pain in the 2/3 distal arm on the posteromedial side, with the
preservation of the movement in the elbow joint.
Conventional radiographs of the right humerus in anteroposterior and lateral views showed in the 2/3 distal
humerus a partially radiolucent, partially sclerosing area with normal adjacent cortical bone (Figure 1).
This particular radiologic finding triggered a battery of tests which gathered: firstly a scintigraphy in order to
study any other possible metastatic lesions, a CT scan for a more precise study of the osseous lesion, and, finally,
an MRI to assess the tumor staging, the cortical involvement and intramedullary and soft tissue spread (18).
The CT scan showed a thickening of the posteromedial side of the humeral shaft, with a smooth and regular
surface, and homogeneous intense radiodensity (Figure 2).
The bone scan showed focal uptake of radioisotope corresponding with the site of radiographic abnormality
with no other focus (Figure 3).
Evaluation of the radiographs, in addition to the CT and the scintigraphy, suggested an osteoid osteoma of the
humeral shaft.
Surgical treatment was performed with the patient under general anaesthesia in the beach chair position. A
posterior approach to the humerus was performed and after exposure, the sclerotic bone covering the nidus was
removed, performing an “en bloc’’ resection. The posterior 1/3 of the cortex was involved and it was removed
and the cavity was completely curetted. The excised fragment was 2/8 cm and the macroscopic evaluation during
surgery, revealed the nidus within the cortical bone, surrounded by cortical sclerosis and thickening (Figure 4,5).
Subsequently, antegrade nailing of the humerus was performed, in order to support the osteosynthesis (Figure 6).
After the surgery, the patient reported complete pain relief.

3. Discussion
The humeral shaft is a rare site for the osteoid osteoma and it is not often included in the differential diagnosis.
Osteoid osteoma of the arm often mimics other etiologies; the tendency of the patients to relate their symptoms
to trauma is an important factor that easily lead to misdiagnosis or delay in the diagnosis. A high index of
suspicion is essential and the diagnosis is based on accurate clinical assessment and careful selection of imaging
studies (19).
The patient associated the beginning of his symptoms 10 months ago, with a sports accident in tennis. The
conservative treatment could not subside the pain, which have increased in intensity.
The character of the pain who was increased at night, decreased by daily activity and subsided partially by anti
– inflammatory drugs, especially salicylates, was the leading symptom, the key guide of diagnosis.
Radiologically, as much as 25% of all osteoid osteomas are not detected by simple radiographs (20,21).
A nidus can be difficult to see on a plain radiography, even if radiographic findings include sclerosis.
CT remains the best imaging modality for the diagnosis of osteoid osteoma(16).
MRI is inferior to CT scan in revealing the nidus, surrounding bone sclerosis and precise localization of the
tumor but is very good in detecting the nidus in cases of intra-articular lesions(17).
When facing an osteoid osteoma, medical and/or surgical treatment may be attempted. Medical prostaglandin
suppression with NSAID’s has proven successful, nevertheless the duration of the treatment is 2 – 3 years (22).
When opting for surgical treatment, total excision is considered the state of the art and should be done in order
to avoid recurrence. The “en bloc” resection is the surgical technique which allows the total resection of the
nidus (23), therefore the healing.
Operative complete excision of the osteoid osteoma may be done openly, percutaneously or arthroscopically.
The minimally invasive techniques form an important part in the therapeutic arsenal of the osteoid osteoma,
especially the radiofrequency coagulation (24-26). The inconvenient of these nidus destroying techniques is the
impossibility to have an histopathological examination.
In our case, the “en bloc” resection permitted us to achieve a histhological confirmation, necessary for our
diagnosis.
If the ostheosynthesis with the antegrade nailing will be unsuccessful and no bone formation will be noticed,
then an ostheoplasty will be made per secundam.

4. Conclusion
The osteoid osteomas of the humeral shaft are very rare and often their diagnosis is difficult but is possible
with the contribution of the medical imaging. A high index of suspicion is essential and the diagnosis is based on
accurate clinical assessment and careful selection of imaging studies (19).
The complete excision of the lesion allows total healing and avoids recurrences.
53
Figure 1. AP / Lateral plain radiograph: partially radiolucent, partially sclerosing area with normal adjacent
cortical bone.

Figure 2. CT scan showing a thickening of the posteromedial side of the humeral shaft, with a smooth and
regular surface, and homogeneous intense radiodensity

54
Figure 3. Bone scan shows focal uptake of radioisotope corresponding with the site of radiographic
abnormality with no other focus.

Figure 4. The excised fragment 2/8 cm; cortical sclerosis and thickening.
55
Figure 5. The nidus within the cortical bone, surrounded by cortical sclerosis and thickening.

Figure 6. Post op lateral humerus plain radiograph.

56
 References:

1. Swee RG, Mcleod RA, Beabout JW. Osteoid osteoma. Radiology 1979; 130: 117 – 123
2. Barei DP, Moreau G, Scarborough MT, Neel MD. Percutaneous radiofrequency thermal ablation of
osteoid osteoma. Operative Tech Orthop. Apr 1999;9(2):72-8.
3. Sproule JA, Khan F, Fogarty EE. Osteoid osteoma: painful enlargement of the second toe. Arch Orthop
Trauma Surg. Jun 2004;124 (5):354-6.
4. Bergstrand H. Uber eine eigenartige, warscheinlich bisher nicht beschriebene osteoblastische
Krankheit in den langen Knochen in der Hand und des Fusses. Acta Radiol 1930; 11: 596-613.
5. Jaffe HL. Osteoid osteoma. A benign osteoblastic tumor composed of osteoid and atypical bone. Arch
Surg. 1935;31:709-728.
6. Dahlin DC. Bone tumors: general aspects and data on 6,221 cases. Spring field, Illinois: Charles C
Thomas, 1978: 43 – 569 75 – 85.
7. Marcove RC, Heelan RT, Huvos AG, et al. Osteoid osteoma. Diagnosis, localization, and treatment.
Clin Orthop Relat Res. Jun 1991;197-201.
8. Lenke LG, Sutherland CJ, Gilula LA. Osteoid osteoma of the proximal femur: CT-guided preoperative
localization. Orthopedics. Mar 1994;17(3):289-92.
9. Bloem J. Kroon M. Osseous lesions, Radiologic clinics of North American, 1993; 31(2):261-277.
10. Frassica FJ, Waltrip RL, Sponseller PD et al. Clinicopathologic features and treatment of osteoid
osteoma and osteoblastoma in children and adolescents. Orthop Clin North Am 1996; 27 : 559 – 574.
11. F.H. Sim, D.C. Dahlin, and J.W. Beabout, ‘’Osteoid osteoma: diagnostic problems’’, Journal of Bone
and Joint Surgery. American, vol.57, no.2, pp. 154-159, 1975.
12. V.N. Cassar-Pullicino, I. W. McCall, and S. Wan, ‘’Intraarticular osteoid osteoma’’, Clinical
Radiology, vol.45, no.3, pp.153-160, 1992.
13. R.C. Marcove and R.H. Freiberger, ‘’Osteoid osteoma of the elbow – a diagnostic problem. Report of
four cases, “Journal of Bone and Joint Surgery’’. American. Vol.48, no.6, pp. 1185-1190, 1966.
14. P.Gille, P. Gross, P. Brax, J. M. Carcopino, D. Aubert, and H. Giordan, “Osteoid osteoma of the
acetabulum: two cases”, Journal of Pediatric Orthopaedics, vol.10, no.3, pp. 416-418, 1990.
15. J. M. Lamo – Espinosa, A. Gonzalez, and S. Amillo, “Osteoid osteoma mimicking triangular
fibrocartilage complex injury: diagnosis and review of treatment, “Case reports in Surgery”, vol.2012,
Article ID 612106, 4 pages, 2012.
16. Assoun J, Richardi G, Railhac JJ et al. Osteoid osteoma: MR imaging versus CT. Radiology 1994; 191
: 217 – 223.
17. Barbierra F., Bartolotta TV, Lo C stro A et al. Intra-asrticular oteoid osteoma: diagnostic imaging in
three cases. Radiol Med 2002; 103: 464-473.
18. Orzincolo C, Ceruti S, Cardona P et al. Diagnostic imaging of osteoid osteoma. Radiol Med 1995; 92:
351-357.
19. Themistocleous GS, Chloros GD, Benetos IS, Efstathopoulos DG, Gerostathopoulos NE, Soucacos PN,
Osteoid osteoma of the upper extremity. A diagnostic challenge Chir Main, 2006 Jun; 25(2):69-76.
20. O. Zupanc, N. Sarabon, and K. Strazar, “Arthroscopic removal of juxtaarticular osteoid osteoma of the
elbow”, Knee Surgery, Sports Traumatology, Arthroscopy, vol. 15, no.10, pp. 124-1243, 2007.
21. F. J. Frassica, R.L. Waltrip, P. D. Sponseller, L. D. Ma, and E. F. McCarthy Jr., “Clinicopathologic
features and treatment of osteoid osteoma and osteoblastoma in children and adolescents, “The
Orthopaedic Clinics of North America”, vol. 27, no. 3, pp. 559-574, 1996.
22. I. Ilyas and D. A. Younge, “Medical management of osteoid osteoma”, Canadian Journal of Surgery,
vol. 45, no. 6, pp. 435-437, 2002.
23. Saidi H., El. Bouanani A., Ayach A., Fikry T. Osteom osteoide du lunatum: a propos d’un cas. Chir
Main. 2007; 26(3): 173-5.
24. Osteome osteoide et osteoblastome. Les cahiers d’enseignement de la SOFCOT; Conferences
d’enseignement.
25. Papagelopoulos PJ, Mavrogenis AF, Kyriakopoulos CK, Benetos IS. et al. Radiofrequency Ablation of
Intra-articular Osteoid Osteoma of the Hip. The Journal of International Medical Research. 2006; 34:
537-544.
26. Rosenthal DI, Hornicek FJ, Torriani M, Gebhardt MC, Mankin HJ. Osteoid osteoma: Percutaneous
treatment with radiofrequency energy. Radiology. 2003; 229(1): 171-5.

57
 WHO ARE THE CANDIDATES FOR REINTERVENTION IN FAILED BACK
SURGERY SYNDROME?
Mihai MARDARE1, Manuel OPREA1, Iulian POPA1, Zazgyva Ancuta2, Marius NICULESCU3
1.
University of Medicine and Pharmacy „Victor Babes“ Timisoara, Romania
2.
University of Medicine and Pharmacy Tîrgu Mure , Department of Cell and Molecular Biology,
Tîrgu Mure , Romania
3.
Colentina Clinical Hospital, Clinic of Orthopaedics and Traumatology I, Bucharest, Romania// Titu
Maiorescu University, Faculty of Medicine, Department of Orthopaedics and Traumatology,
Bucharest, Romania
Corresponding author :
Iulian POPA
Email : medexpe@gmail.com
Abstract
A very common problem encountered in the surgical spine patients is an unsuccessful back surgery.
Due to the natural evolution of a spinal disorder with previous surgery, revision surgery may become
necessary but most often, a failure of the initial procedure may need revision. Some of the identifiable
explanations for a failed back surgery consist in recurrent pathology, poor surgical technique, misdagnosis and
inappropriate candidate selection for surgery.
Revision after failed back surgery syndrome is a very complex and demanding surgery with significant
complications. Only the failure of a well conducted conservative treatment in the presence of severe or
progressive neurological symptoms and instability can justify the reintervention.
Keywords: laminectomy, recurrent disc herniation, degenerative spine, fusion
INTRODUCTION
Failed back surgery syndrome or “failed back syndrome”, is a clinical condition in which patients who
undergo one or more surgical procedures for lumbosacral disease, obtain unsatisfactory long term relief of
symptoms, with persistent or recurrent low back pain [6].
Unfortunately, even whith appropriate surgical technique and precise indication, failed back surgery
syndrome may occur . As listed by various authors, the reasons for failure of lumbar surgery are: inadequate
diagnosis, improper patient selection, inadequate surgery, recurrent disk herniation, secondary instability or
related degenerative changes (Table 1) [1, 2].
Table 1. Causes for pain in failed back surgery syndrome
Causes for persistent postoperative
Causes for reccurent back/leg pain
radicular/back pain
Wrong segment decompression Recurrent or adjacent herniated disk
Failure to recognise degenerative stenosis and Facet syndrome (secondary facet joint arthritis)
inadequate decompression (microdiskectomy)
Insufficient removal of disk material, failure to Instability due to aggressive decompression without
notice a second herniated disk fusion
Traumatic retraction of a nerve root Transitional stenosis (new stenosis above the fused level)
Failure to address a symptomatic Injury to neural tissue with faulty screw or cage
spondylolistesis or deformity placement
No/incomplete foraminotomy Epidural scarring, arachnoiditis
Failure to address a “far out” compression Spondylodiscitis
Other causes (tumours, peripheral neuropathy Meralgia paresthetica
Decompression without fusion for discogenic Pars fracture after extended decompression
pain associated with leg pain
Pseudomeningocele
Due to the high rate of complications after revision back surgery, the surgical indication should be
carefully considered. The surgeon must bear in mind that any revision will likely have poorer results than the
initial surgery [4, 5] and therefore prevention of a failed back surgery is the best patient management.
The majority of patients are not surgical candidates; they should be protected from ineffective surgical
procedures, surgery being helpful only in two conditions: nerve compression and instability. When the patient’s
complaints are compatible with the compression seen on the imagistic exam, surgical decompression is
indicated. The other problem in which surgery is indicated is instability. Spinal fusion is used to stabilize spinal
segments that have been damaged to such a degree that normal physiological forces will cause damage to neural
structures or loss of biomechanical integrity. Objective criteria that are indicated for fusion are: demonstrated
motion on dynamic X-rays, progressive spinal deformity in any direction and spondylolisthesis [3, 7].
58
 MATERIAL AND METHODS
In this study we have analyzed the postoperative results in 14 consecutive cases of reintervention for
lumbar stenosis performed between 2007-2014 in the Spine Surgery Department from Timisoara.
All patients had at least 6 months of conservative treatment before the reintervention was decided. An
improvement in symptoms with epidural steroids injections, even on short term, was considered to be a strong
argument for revision surgery.
Two patients suffered iatrogenic dural tears during revision (14.28%), repaired by direct suture with
Nurolon 4-0. One patient has developed adjacent level disc disease which needed reintervention.
Results after 12 months of follow-up were good in all cases, with significant pain decrease and
increased walking distance. 13 patients (92.85%) declared satisfied with the surgical result at 1 year, and 1
patient has characterised the result as poor.
Below there are a few representative cases regarding etiology, diagnosis and treatment.
Case 1. 63 y.o. woman complaining of severe back pain (7 points on visual analogic scale - VAS) and
neurogenic claudication (VAS = 8 for leg pain, walking distance = 50m), 12 months after her primary operation
for lumbar stenosis (L4 laminectomy and diskectomy, L5 laminotomy). The L4-5 space was identified as the
potential cause of pain due to inadequate foraminal decompression. We performed L4-L5 left facetectomy, L4-
S1 stabilization, L4-L5 TLIF and L4-S1 PLF (Figure 1).

Figure 1 A. Preoperative x-ray; B. Intraoperative picture showing fibrous scarring of the dura mater; C and D.
Postoperative x-rays – L4-S1 fusion with L4-5 interbody titanium cage.
At 1 year follow-up, leg pain was greatly decreased (VAS = 2) with back pain moderate amelioration (VAS = 5).
59
 Case 2. A 48 y.o. male suffering from severe neurogenic claudication (maximum 50 m walking
distance, right leg pain (VAS=9) and severe back pain (VAS=8). He underwent a L4 right diskectomy 2 years
prior to revision and followed a conservative treatment for 18 months with no satisfactory results. On
examination: positive bilateral straight leg raise sign, paresthesias on L4 and L5 right dermatomes and decreased
right knee reflexes with no weakness; no long tract signs were found. The lateral X-ray shows the collapse of
L4-5 disc space and osteosclerotic changes to L4-5 endplates. Anteroposterior X-ray shows a reducible right
concave scoliotic deformity of the lumbar spine with no rotational deformity, incongruence of the L4-5 disc
space. MRI of the lumbar spine shows evidence of ligamentum flavum and facet hypertrophy, together with a
L4-L5 right recurrent disc herniation with right lateral recess and foraminal stenosis. We performed a L4-L5
laminectomy, L4 right diskectomy, L4-5 PLIF and L4-L5 PLF (Figure 2). In the early postoperative course the
leg and back pain resolved. Starting with 7th day the patient was febrile in the evenings and was complaining of
slight back pain and testicular pain. Inflamatory markers were raised: CRP:150, ESR:100 mm/h, with normal
WBC. MRI revealed a liquid collection with contrast dye take-up which was surgically drained, showing white,
creamy puss. No microorganism could be identified. The patient underwent 4 weeks of antibiotherapy with
normalisation of the inflamatory markers. Immediately after the collection was drained, the symptoms have fully
resolved. The patient was pain free at 12 months follow-up.

Figure 2. Preoperative MRI and x-ray images (above) showing re-herniated L4 disk, and scoliosis with loss of
parallelism between L4-L5 endplates; postoperative x-rays (below) – L4-L5 instrumented fusion.
60
 Case 3. 42 y.o. male suffering from severe neurogenic claudication (maximum 100m walking distance,
right leg pain graded as 9 on VAS) and severe back pain (8 on VAS) underwent twice (in November 2010 and in
February 2013) L5 left diskectomy, first for L5 left disc herniation and second for L5 left recurrent herniation.
Clinical examination shows left foot-drop, a positive bilateral straight leg sign, paresthesias on L5 left and S1
right dermatomes. The dynamic X-ray showed L5-S1 instability.

Figure 3. Dynamic x-rays showing L5-S1 instability

Anteroposterior X-ray demonstrated a reducible left concave scoliotic deformity of the lumbar spine
with no rotational deformity.

Figure 4. AP x-ray demonstrating a reducible left lumbar concave scoliotic deformity

MRI of the lumbar spine demonstrated L5 right disc herniation and left epidural fibrosis correlated with
subjective complaints and objective findings (fig.5).

61
 Figure 5. MRI axial image at the L5 disc level showing L5 right disc herniation and left epidural fibrosis

We performed L5 hemilaminectomy, L5-S1 facetectomy, L5 right diskectomy and L5-S1 TLIF (Figure
6). The patient was pain free at 12 months follow-up.

Figure 6. Postoperative AP and lateral view x-rays demonstrating good scoliotic correction and sagittal balance
after L5-S1 instrumented fusion

Scoliosis is often the cause of failed back surgery syndrome being a source of biomechanical imbalance
and back pain. The complexity of these interventions is enhanced by altered anatomy and fibrosis. Scoliotic
curve correction is a secondary objective of the intervention, and after correction is mandatory to check the
foraminal decompression.
For stabilization we used in most cases a hybrid implant which associates pedicle screws, sublaminar
hooks LSZ (Signus Medizintechnik – Germany)

Case 4. 57 y.o. female presented with severe bilateral neurogenic claudication (maximum 100 m
walking distance (VAS=9) and severe back pain at 10 years post L4-L5 right diskectomy. Anteroposterior X-ray
shows a rigid right concave scoliotic deformity of the lumbar spine with torsional deformity. MRI proved
multilevel spinal stenosis, L3 right stenosis being responsible for radicular simptomatology according to EMG.
She responded well to epidural injections for a short period of time. The options have been discussed with the
patient and extensive decompressive surgery at L3-L4-L5 level was performed (fig. 7 a, b and c). Immediately
after surgery the symptoms improved, with noticeable decreased leg pain (VAS = 3) and increased walking
distance.

62
 a b

c
Figure 7
a. Degenerative scoliosis with lumbar stenosis in a 57 years old patient operated 10 years ago for L4 an L5
herniated disc.
b. Preoperative coronal IRM, b. Preoperative AP X-ray
c. AP x-ray after decompression by L2-L3 right facetectomy and left L3-L4 TLIF L3-L4, scoliosis correction
and stabilization using a hybrid implant based on pedicular screws and sublaminar LSZ hooks (Signus
Medizintechnik – Germany).

Case 5. 61 y.o. female had L4-L5 decompression 8 years ago for L4-L5 right disc herniation. Clinical
exam shows bilateral neurogenic claudication with significant bilateral progressive neurological deficit of L4 and
L5 myotomes and severe back pain (10 on VAS). Anteroposterior X-ray shows a rigid right concave scoliotic
deformity of the lumbar spine with torsional deformity (fig.8a). MRI proved multilevel spinal stenosis and the
patient responded well for short periods of time to epidural injections.
An extensive decompression by L3-L4-L5 laminectomy and L3-L4 left facetectomy and instrumented
posterolateral T12-L5 fusion was performed (figure 8b). Postoperative evolution was favourable with marked
decrease of back and leg pain (4 points for back and 3 for leg pain on VAS) and the patient is able to perform her
daily activities comfortably.

63
 a b

Figure 8
a. Preoperative AP x-ray of a patient with degenerative scoliosis due to previous L4-L5 hemilaminectomy
b. Postoperative AP x-rays of a patient with degenerative scoliosis after surgical decompression by extensive
laminectomy, left L3-L4 facetectomy, right L2-L3 facetectomy and T12-L5 stabilization with a hybrid system
sublaminar hooks and a left pedicle screw on L5

DISCUSSIONS
Revising a previous surgery on the lumbar spine provides a series of issues and technical difficulties
that need serious consideration regarding surgical indication and preoperative planning. The rate of dural tears
expected for revision lumbar surgery is high (30% according to Hamill et al. 8), thus adding time and blood loss
to the procedure. Due to the collapse of disk space after diskectomy, and instability due to facet joint arthritis and
posterior wall disruption after decompression, secondary deformity (spondilolystesis, lumbar kyphosis, scoliosis)
is common among patients with failed back surgery.
Technical challenges in revised decompression of the lumbar spine are mainly tied to extensive scarring
around the dura mater and the nerve roots and change of the local anatomy. This makes decompression very
difficult and meticulous. One of the main problems is to identify cleavage planes and to differentiate structures.
In order to allow a better access to neural structures and increase the odds of avoiding and if necessary
repairing a dural tear, a significantly wider decompression during revision is recommended due to the extent
fibrosis and adherences consequent to primary procedure.
In one case of our series an adjacent level disease quickly developed - a classic complication of lumbar
fusion.

CONCLUSION
A revision after a failed back surgery could have a significant complications rate. The poor patients
selection will increase the complications rate. The need for a reintervention could be justified only by the failure
of a well conducted conservative treatment in the presence of severe or progressive neurological symptoms and
spine instability. Prior to any revision surgery, it is paramount to obtain a detailed history, clinical examination
and appropriate preoperative imaging studies. Also any occult infection needs to be rule out by blood tests. Due
to the fibrosis and adherences secondary to the initial procedure, a wider decompression and often fusion of the
segment involved may be needed. Revisions should be performed only by experienced surgeons and only when
appropriate implants for an instrumented fusion are available.

64
 REFERENCES

1. Fritsch E., Heisel J., Rupp S.: The Failed Back Surgery Syndrome: Reasons, Intraoperative Findings,
and Long-term Results: A Report of 182 Operative Treatments. Spine 1996, 21(5): 626-633
2. Guyer R.D., Patterson M., Ohnmeiss D.D.: Failed back surgery syndrome: diagnostic evaluation.
JAAOS 2006, 14(9): 534-543
3. Hamill L.C., Kowalski J.M.: Lumbar spinal stenosis: operative and nonoperative treatment. In:
Vaccaro, Betz, Zeidmann :Principles of spinal surgery, Mosby 2003, 355-363
4. Jonsson BS. Repeat decompression of lumbar nerve roots: A prospective two-year evaluation. J Bone
Joint Surg [Br] 1993; 75:894-7
5. Keskimaki I, Seitsalo S., Osterman H., Rissanen P.: Reoperations After Lumbar Disc Surgery: A
Population-Based Study of Regional and Interspecialty Variations. Spine 2000, 25(12: 1500-1508
6. Long DM: Failed back surgery syndrome. Neurosurg Clin North Am 1991;2:899
7. Malter A.D., McNeney B., Loeser J.D., Deyo R.A.: 5-Year Reoperation Rates After Different Types of
Lumbar Spine Surgery. Spine 1998, 23(7): 814-820
8. OstermanH., Sund R., Seitsalo S., Keskimaki I.: Risk of Multiple Reoperations After Lumbar
Discectomy: A Population-Based Study. Spine 2003, 28(6): 621-627

65
 OXYGENO THERAPY AT HOME AND ITS EVALUATION AS AN IMPORTANT
TREATMENT IN RESPIRATORY AND CARDIAC DISEASES

Authors; Dr. Popescu Costin*,Dr. Popescu Liliana *, Professor Dan Malaescu**, Dr. Olar
Lavinia**, Dr, Puscu Dorina**
* Caracal Municipal Hospital;** University Titu Maiorescu of Bucharest**

Material and Methods

This study was realised simultaneously in Caracal and Targu-Jiu cities for a three years period,
precisely from 2010 to 2012, on a sample of 229 patients. We tried to demonstrate the efficiency of the oxygeno
therapy at the patients with lung diseases, some of them being associated with heart diseases.

TABLE 1. O2 Saturation at T0

60
>90%
40 80-90
<80 <80
20
80-90
>90%
0
NR %

SAT O2% >90 80-90 <80 TOTAL

Nr. 8 43 21 72
% 11,1 59,7 29,2 100

TABEL 2 Varsta bolnavilor

30-40

41-50

51-60

61-70

>70

Ani 30-40 41-50 51-60 61-70 >71 TOTAL

Nr. 3 17 21 15 16 72

% 4,2 23,6 29,2 20,8 22,2 100

66
TABLE 3 Lung Diseases at T 0

Lung diseases B.P.O.C. Severe Lung Neo Tuberculosis Total

asthma suppurations lung sequelae
Sat O2 >90 1 2 1 2 2 8
Sat O2 80-90 17 4 5 6 11 43
Sat O2 <80 9 3 3 0 6 21
Total nr 27 9 9 8 19 72
Total % 37,5 12,5 12,5 11,1 26,4 100

20

15

10
>90 80-90 <80
5

0
B.P.O.C. Supuratii pulm
TBC sechelar

20

15

10
>90 80-90 <80
5

0
B.P.O.C. Supuratii pulm
TBC sechelar

TABLE 4 Heart related diseases

SAT O2 % >90 80- <80 TOTAL TOTAL%

90 No

HTA 4 6 3 13 18,9
B.C.I.ND 3 5 3 11 15,3
B.C.I. D 1 2 1 4 5,5
TOTAL 8 13 7 28 38,8

67
TABLE 5 TIME/h/oxygeno therapy at home
6

4
>90

2 80-90

<80
0
H.T.A. B.C.I. D
14
12
10
2-5 ore
8
6 6-10 ore

4 11-15 ore
2 15-18 ore
0
B.P.O.C. Astm br Supuratii Neo pulm TBC
pulm sechelar
6
5
4
>90
3
2 80-90

1 <80

0
H.T.A. B.C.I. B.C.I.
ND D
2-5 3 3 2 1 9
6-10 14 3 2 3 8
10-15 7 3 2 4 2
15-18 3 0 1 1 0

TABLE 6 Saturation O2 at T3 (3 months)

Sat O2 B.P.O.C. Severe Lung Neo Tuberculosis total Total%
asthma suppurations lung sequelae

>90 9 4 3 4 5 25 34,7
80-90 14 4 4 4 8 34 47,2
<80 4 1 2 6 13 10,1
Total 27 9 9 8 19 72

14
12
10
8 >90
6
80-90
4
<80
2
0
B.P.O.C. Astm sever Supuratii Neo pulm TBC
pulm sechelar

68
TABEL 7 Saturation O2 at T 6 (6 months)
Sat O2 B.P.O.C. Severe Lung Neo Tuberculosis total Total%
asthma suppurations lung sequelae
>90 12 6 4 5 7 34 47,2
80-90 13 3 4 3 8 31 43
<80 2 0 1 0 4 7 9,8
Total 27 9 9 8 19 72 100

14
12
10
8 >90

6 80-90

4 <80

2
0
B.P.O.C. Astm sever Supuratii pulm Neo pulm TBC sechelar

TABLE 8 Saturation O2 at T 9(9months)

Sat O2 B.P.O.C. Severe Lung Neo Tuberculosis total Total%
asthma suppurations lung sequelae
>90 14 5 4 4 9 36 50
80-90 11 4 3 3 6 27 37,5
<80 2 0 2 1 4 9 12,5
Total 27 9 9 8 19 72 100

14
12
10
8 >90
6 80-90
4
<80
2
0
B.P.O.C. Astm sever Supuratii Neo pulm TBC
pulm sechelar

69
TABLE 9 Saturation O2 at T 12( 12 months)
Sat O2 B.P.O.C. Severe Lung Neo Tuberculosis total Total%
asthma suppurations lung sequelae

>90 15 6 5 3 10 39 54,2
80-90 11 3 2 3 5 24 33,3
<80 1 0 2 2 4 9 12,5

Total 27 9 9 8 19 72 100

15

10
>90
80-90
5
<80

0
B.P.O.C. Astm sever Supuratii Neo pulm TBC
pulm sechelar

The saturation of studied patients was involved in a great majority below 90%, requiring specialized
treatment from the beginning.
Regarding the age of the patients , it was between 40-80, the number of patients being constant in
each decade of age.
Most COPD patients were 37.5% and after those were the patients with pulmonary sequelae
tuberculosis -about 26%. These two groups had the lowest saturation.
There were presents at the patients who were administered oxygeno therapy at home and heart disease
predominantly HTA and then the cardiopathies.
The time spent at home for the oxigeno therapy was 10-15 / day being used more intensively by the groups with
BPCO, bronchopulmonary cancer, tuberculosis sequelae

CONCLUSIONS

The evaluation realised by this study led to the conclusion that the oxygen therapy at home improves the
evolution of patients with chronic lung disease, and also has a profit when they are associated with heart disease.
The progress achieved with the oxygeno-therapy at home occurs rapidly but remains almost constant in
evolution during the studied period by measuring the arterial oxygen saturation.

BIBLIOGRAPHY
1. Bennett PB, Elliott DH, eds. The Physiology and Medicine of Diving. 4th ed. London, England: Saunders &
Company; 1993. A major reference textbook in the field of diving medicine.
2. Peirce EC. Cerebral gas embolism (arterial) with special reference to iatrogenic accidents. HBO Review.
1980;1:161. An excellent review of the pathophysiology and incidence of air embolism.
3. Kindwall EP, Goldmann RW. Hyperbaric Medicine Procedures (rev.). Milwaukee, Wis: St. Luke's Medical
Center; 1995. An excellent handbook guide for the use of HBO therapy; contains numerous, timely references.
4. Davis JC, Hunt TK, eds. Hyperbaric Oxygen Therapy. Bethesda, Md: Undersea and Hyperbaric Medical
Society; 1977. This reference established state-of-the-art status of hyperbaric medicine in 1977 and serves as a
basis for all further work.

70
5. Davis JC, Hunt TK, eds. Problem Wounds—The Role of Oxygen. New York, NY: Elsevier; 1988. This
comprehensive review of wound healing presents basic physiology on the role of oxygen in the normal sequence
of wound closure and its application in the problem wound.
6. Kindwall EP, ed. Hyperbaric Medicine Practice. 2nd ed. Flagstaff, Ariz: Best Publishing; 1999. A state-of-the
art reference, with heavy emphasis on physiology, basic mechanisms, and patient management; a must for the
practicing hyperbarist.
7. Bakker DJ. The Use of Hyperbaric Oxygen in the Treatment of Certain Infectious Diseases, Especially Gas
Gangrene and Acute Dermal Gangrene. Wageningen, Holland: Drukkerij Veenman BV; 1984. A comprehensive
review of adjunctive HBO in the treatment of gas gangrene and necrotizing fasciitis. Written by an experienced
surgeon.
8. Hart GB, Lamb RC, Strauss MB. Gas gangrene I, a collective review. J Trauma. 1983;23:991. The definitive
review of the subject. Written by surgeons experienced in the application of HBO to this disorder.
9. Kindwall EP, Gottlieb LJ, Larson DL. Hyperbaric oxygen therapy in plastic surgery: a review article. Plast
Reconstr Surg. 1991;88:898. An excellent review of the applications of HBO in the field of plastic and
reconstructive surgery.
10. Niezgoda JA, Cianci P, Folden BW, et al. The effect of hyperbaric oxygen therapy on a burn wound model in
human volunteers. Plast Reconstr Surg. 1997;99:1620. A randomized, controlled study with normoxic controls
demonstrating a reduction in wound size, inflammation, and wound exudation in human volunteers.
11. Thom SR. Leukocytes in carbon monoxide-mediated brain oxidative injury. Toxicol Appl Pharmacol.
1993;123:234. In this paper, oxidative brain injury after carbon monoxide was shown to occur in the following
sequence: leukocyte sequestration in the microvasculature, B2 integrin-dependent adherence, protease-mediated
conversion of endothelial xanthine dehydrogenase to xanthine oxidase, O 2 radical-dependent lipid peroxidation.
12. Siddiqui A, Davidson JD, Mustoe TA. Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy:
a new physiologic concept. Plast Reconstr Surg. 1997;99:148. Ischemic tissue may actually store oxygen.
13. Hehenberger K, et al. Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation.
Wound Repair and Regeneration 1997;5:147. The authors describe stimulation of fibroblast activity in human
cell cultures in diabetic patients.

71
 THE STUDY OF LUNG CANCER- DIAGNOSIS AND TREATMENT FOR A
PERIOD OF 8 YEARS

Authors; Dr. Popescu Costin*,Dr. Popescu Liliana *, Professor Dan Malaescu**, Dr. Olar
Lavinia**, Dr. Puscu Lavinia**
* Caracal Municipal Hospital;** University Titu Maiorescu of Bucharest**

THE ANALYSIS PURPOSES

The increased incidence of cancer lung in Caracal city and a tardive detection of this disease existing early
detection and staging ways;
- computerized tomography
-fibrobronchoscopy

MATERIAL AND METHODS

This study was conducted within the period 2006-2013 on a sample of 81 patients diagnosed with
cancer lung and then studied over several years.
All these patients were then confirmed by anatomo-pathological examination made bronchoscopy and
thoracic CT performed in a particularly high percentage by M. Nasta Pneumology Institute of Bucharest and
1SPAD Craiova

RESULTS

EVALUAREA NEOPLASMULUI BRONHOPULMONAR

PE GRUPE DE VARSTA -CAZURI NOI-
IN PERIOADA 2006-2014 PE TERITORIUL CARACAL-

ANI/ <30 31-40 41-50 51-60 61-70 >70 TOTAL

VARSTA
2006 0 1 1 2 3 2 9
2007 0 0 2 3 1 4 6
2008 0 0 0 4 3 1 8
2009 0 1 2 5 4 4 16
2010 0 0 1 3 2 3 9
2011 0 0 1 5 3 2 11
2012 0 2 0 3 4 3 12
2013 0 0 2 4 3 1 10
TOTAL 0 4 9 29 23 20 81

TABEL 1

4
31-40 ANI
3 41-50 ANI
51-60 ANI
2
61-70 ANI
1 peste 70 ani

0
2006 2007 2008 2009 2010 2011 2012 2013

Figura 1

72
 NEOPLASM BRONHOPULMONAR

EVALUARE PE SEXE

ANI 2006 2007 2008 2009 2010 2011 2012 2013 TOTAL
SEX M 8 4 5 13 7 7 9 7 60
SEX F 1 2 3 3 2 4 3 3 21
TOTAL 9 6 8 16 9 11 12 10 81

TABEL 2

14
12
10
8 MASCULIN
6 FEMININ
3-D Column 3
4
2
0
2006 2007 2008 2009 2010 2011 2012 2013

MEDIUL DE PROVENIENTA AL BOLNAVILOR CU CBP

ANI 2006 2007 2008 2009 2010 2011 2012 2013 TOTAL TOTAL
NR %
URBAN 4 5 3 6 5 3 6 7 42 59.9
RURAL 5 1 5 7 4 8 6 3 39 48.1
TOTAL 9 6 8 16 9 11 12 10 81 100

TABEL 3

URBAN
RURAL
Slice 3
Slice 4

Figura 3

8
7
6
5
4 URBAN
3 RURAL
2
1
0
2006 2007 2008 2009 2010 2011 2012 2013

Figura 4

73
 ANTECEDENTE LA BOLNAVII DEPISTATI CU CBP

FUMAT CONSUM TBC MEDIU BOLI PULMONARE ALERGII

CRONIC CU CRONICE(EXCEP.
ALCOOL NOXE TBC)
NR 69 53 7 21 31 15
% 85.1 65.4 8.6 25.9 38.2 18.5

FUMAT

CONSUM
CRONIC
ALCOOL
TBC

NOXE

BOLI PULM
CRONICE(EXCE
P. TBC)
ALERGII

SIMPTOME SI SEMNE CLINICE PRECOCE LA DEPISTAREA CBP

SIMP- DISP INAPE- SCADERE TUSE FEBRA HE WHEE ASTE TRANS

TOME NENE TENTA PONDE- SEACA/ +FRI- MOP ZING NIE PIRATII
RALA PRODUC- SON TIZIE
TIVA
NR 48 59 48 71 32 30 16 64 28
% 59.2 72.8 59.2 87.8 39.5 37 19.6 79 34.6

TABEL 5

74
 EXAMENE PARACLINICE LA DEPISTARE

CBP

NR %
LEUCOCITOZA 31 38.2
>10.000/mmc
ANEMIE 29 35.8
HB<10g/dl
VSH>30/1h 41 50.6
FIBRINOGEN 63 77
>400 mg/dl
ASLO >200 UI/ml 19 23.4
PROTEINA C REACTIVA 17 21
>6 mg/L
AST/TGO 31 38.2
>50 U/L
ALT/TGP 44 54
>50U/L
ALFA 1 GLOBULINA 16 19.6
>6

TABEL 6

TRATAMENT CBP

CHIR+RADIOTE
RAPIE+CHIMIO
TERAPIE
CHIR+CHIMIOT
ERAPIE

CHIMIOTERAPI
E

PALEATIV

Figură 2
TRATAMENT CBP

TRATAMENT TRATAMENT CHIMIOTERAPIE TRATAMENT

CHIRURGICAL+ CHIRURGICAL+ SIMPTOMATIC
RADIOTERAPIE+ CHIMIOTERAPIE PALEATIV
CHIMIOTERAPIE
NR 28 18 25 10
% 34,6 22,2 30,9 12,3

TABEL 2

75
 Typical image of lung cancer in the frame. Enlarged image of the same neoplasm

Image of a bronchoalveolar lung cancer surgery left upper lobectomy .On the enlarged image we can observe a
secondary pulmonary fibrosis installed

The number of patients taking out and confirmed anatomo- pathological varied annually around 10
cases, but it must be said that this number was probably double as the patients detected had very serious forms of
fast mortality while others were not able to be diagnosed with the disease and their anatomo-pathological
confirmation. So, the cohort included a total of 82 patients studied. Males predominated 60/21 male / female.
Regarding their origin rural / urban, that wasn’t important but we observed at the patients who had smoked a
percentage of 85% of all cases.
The contamined environement had a great importance in triggering the disease.Among the symptoms
and signs at the beginning of the disease, their inapenta and their weight loss were important at the patients
presenting the advanced stages of the disease.
Regarding the laboratory analyzes, VHS and the fibrinogen were relevant
sometimes.Unfortunately,surgery followed by roengenterapie and chemotherapy was conducted in a small
number of patients which is why the survival rate was particularly low in its detection.
The radiological images are from the detection of the patients except the patient who has survived operated for 8
years.

76
CONCLUSIONS

1. Tardive detecting of bronchopulmonary cancer.

2. Age 50 and after, male gender, smoking and alcohol consumption were factors favoring the occurrence of
disease.
3. There weren’t predominant symptoms and signs of the disease
4. Paraclinically, the fibrinogen is a good indicator of the disease and its evolution.
5. The Radiography is important for the diagnosis and the further evolution.
6. The Survival is small because of the extension of the disease when it is detected.

REFERENCES

1.Ambrosone CB, Rao U, Michalek AM, et al.: Lung cancer histologic types and family history of cancer:
Analysis of histologic subtypes of 872 patients with primary lung cancer. Cancer 72:1192–1198, 1993.
2.Auerbach O, Saccomanno G, Kuschner M, et al.: Histologic findings in the tracheobronchial tree of uranium
miners and non-miners with lung cancer. Cancer 42:483–489, 1978.
3. Balsara BR, Testa JR: Chromosomal imbalances in human lung cancer. Oncogene 21:6877–6883, 2002.
4. Bennett WP, Colby TV, Travis WD, et al.: p53 protein accumulates frequently in early bronchial neoplasia.
CancerRes 53:4817–4822, 1993.
5. Burke L, Flieder DB, Guinee DG, et al.: Prognostic implications of molecular and immunohistochemical
profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma. Clin Cancer
Res 11:232–241, 2005.
6. Campiglio M, Tagliabue E, Srinivas U, et al.: Colocalization of the p185HER2 oncoprotein and integrin alpha
6 beta 4 in Calu-3 lung carcinoma cells. J Cell Biochem55:409–418, 1994.
7. Cannon-Albright LA, Thomas A, Goldgar DE, et al.: Familiality of cancer in Utah. Cancer Res 54:2378–
2385, 1994. Clements NC Jr, Nelson MA, Wymer JA, et al.: Analysis ofK-ras genemutations in malignant and
nonmalignant endobronchial
tissue obtained by fiberoptic bronchoscopy. Am J Respir Crit Care Med 152:1374–1378, 1995.
8. Cordon-Cardo C: Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia.
Am JPathol 147: 545–560, 1995.
9. D’Amico D, Carbone DP, Johnson BE, et al.: Polymorphic sites within the MCC and APC loci reveal very
frequent loss of heterozygosity in human small cell lung cancer.
Cancer Res 52: 1996–1999, 1992.
10. Daya-Makin M, Sanghera JS, Mogentale TL, et al.: Activation of a tumor-associated protein kinase
(p40TAK) and casein kinase 2 in human squamous cell carcinomas.

77
 PHYSICIANS IN PAINTING

Lecturer PhD. RADU Mirela, Faculty of Medicine, „Titu Maiorescu” University, 67A Gheorghe
Petraşcu Street, Bucharest, Romania
Student TRIFAN Eduard Said, Faculty of Medicine and Pharmacy „Carol Davila”, 8 Eroilor
Sanitari Boulevard, Bucharest, Romania

Abstract

The current study aims at analyzing several physicians who were eager to spend their imagination in
aesthetic values creations, namely in painting. Throughout mankind history, physicians were representatives not
only of scientific knowledge, promoters of science and rationality but also missionaries of art and culture in its
larger sense. Beginning with the Renaissance, several personalities bound themselves to serve human being,
both scientifically and artistically. In Romania, one of the most known doctors who devoted himself to painting
as well, influencing further generations of painters was Ion Ţuculescu. Another example, this time from the
world culture, is the Frenchman George Chicotot who not only painted exquisite works of art but also blended
this with revealing medical techniques as well. David Solot is another instance of how medicine influenced the
world of aesthetics.

Key words: medicine, aesthetics, painting, anatomy, dissection

History of world painting abounds in examples of painters who embraced medicine and brushwork or
vice versa. One of the most famous examples was Leonardo da Vinci (1452-1519) who blended sculpture,
painting, architecture, music and anatomy. His painting which offers the best understanding on how da Vinci
perceived the man, both anatomically and aesthetically, is without doubt, Le proporzioni del corpo umano
secondo Vitruvio (The Vitruvian Man) (1490) drawing which frames the human being within the univsal
knowledge. Permanently searching for perfection, in La Gioconda, da Vinci applied what science today calls
“the golden share” which aimed ideal relationships in building physiognomies. His contact with anatomy
occured during apprenticeship with the painter Verrocchio. Numerous sketches of da Vinci describe anatomical
relationships and more precisely how the musculature and skeletal system work together. Precisely to improve
the realistic nature of his paintings, da Vinci performed numerous dissections in hospitals in Florence, Rome and
Milan. His work in the medical field was boosted by working with physicians, Marcantonio della Torre among
them. His drawings, beyong the great veracity, were accompanied by detailed descriptions of the anatomical
components. To his anatomical studies, science owes the description of the maxillary sinus as well as studies and
sketches of the circulatory system, heart, guts and embryos. Besides dissections, da Vinci was performing
experiments on animals even anatomical moulds by wax injection.

Leonardo Da Vinci’s drawings on anatomic studies

Almost in parallel with da Vinci’s work, the Flemish physician Andreas Vesalius (1514-1564)
published De humani corporis Fabrica, a treaty accompanied by numerous anatomical sketches which brought
as novelty the approach, almost plastic, of representing human body parts. His works represented the first ones to
present the human body both artistically and objectively: “The aura of the body is no longer searched, at least

78
starting with Vesalius and with the development of anatomical science. Science and technology, faithful to their
project of eventually winning the world are trying, in a paradoxical gesture, to remove the body and at the same
time to emulate it. On the one hand, to overcome their limits, to rebuild it, to intervene in its processes.” 3

Andreas Vesalius's De humani corporis fabrica

If the vast majority of physicians have found their safety valve of their artistic inventivity in literature,
some representatives of Hippocrates found other ways to live aesthetically. One of the most illustrative examples
in Romania is Ion Ţuculescu (1910-1962). Born in Craiova, Ţuculescu had an early affinity to painting. He
studied drawing with Freda Tribalsky, schooled in Münich, and he had as teacher of painting Eugen Ciolac but
he was a disciple of Eustaţiu Stoenescu as well. The entire Ţuculescu family had high moral values they instilled
to their son. For Ţuculescu family come first: “love and respect for traditions, appreciation of beauty, of national
and universal culture.”4 This passion to painting was to take the form of participation (in 1925), at an early age,
only 15 year-old, at a painting exhibition held in the Administrative Palace in Dolj County. Large majority of the
paintings displayed at the exhibition were landscapes or still life. The obvious talent the future physician had
from the very age of adolescence was translated in that most of those paintings were also bought. A year later he
would continue the series of exhibitions by attending the first exhibition of painting, sculpture and drawing of
Artistic Oltenian Circle. In the same year, Ţuculescu signs his first portrait: Portrait of actress Aura Fotino.
But, in 1927 the feeling of failure occurred, of not being able to and of not having the artistic value
needed to paint Faust inspired by Goethe’s work. This would echo in the choice of the future profession:
medicine. Disillusioned, Ţuculescu opted for the Faculty of Natural Sciences of the University in Bucharest. He
graduated in 1936 but meanwhile he attended also the Faculty of Medicine which he graduaded with a doctorate
in medicine in 1939. Even a year before obtaining this title, Ţuculescu organised his first own exhibition at the
Romanian Athenaeum. During the Second World War he had such exhibitions where he had the chance to
display brushworks with certain artistic value. Practitioner of medicine only during the war years, his real
scientific passion was biology and he continued his scientific career as a researcher and a doctor in Brâncovenesc
Hospital. His paintings, mostly landscapes were inspired either by Romanian folklore or the beauties that nature
offered. Aesthetic values offered him the way to calm that medicine could not give him “Frankly, in everyday
life I cannot live happiness. I live it only in art, especially in painting and music.”5 But medicine and painting
have not occupied all of his time and he found the energy for one year, between 1936-1937, to teach at the
Theological Seminary at Cernica Monastery. “Ţuculescu synthesized elements of expressionist substance with
those derived from Romanian folk art (Oltenian); they were associated existence of figurative «short-circuited»

3
David Le Breton, The human body anthropology and modernity, Cartier Publishing House, Chişinău, 2009, p. 17
4
Paul Rezeanu, Ion Ţuculescu in Craiova, in Ramuri, no. 7/2010
5
Ion Țuculescu , The Contemporary, Bucharest, no. 8, 1965 of 19th February1965
79
by «escapes» in abstract gestualism; stylistic data whom he added symbolism and totemic configurations
reminding (I would be tempted to say) of a phase similar to Pollock, but produced in another cultural context....” 6
His influence on the new talents appeared in the 60’s is recognized by great painters. Thus, strongly
influenced by Ţuculescu were painters such as Theodore Rusu, Şerban Epure, Mircea Milcovici, Horia Bernea.
The physician’s influence had wide reverberations on the next generation of painters: “From the mid-60’s, an
expressionist trend made its presence felt in our painting and sculpture - perhaps partly due to Ţuculescu «case»,
but nourished by other sources as well; it was extended partly along the next decade. This trend is reflected in
works by artists who frequented Poiana Mărului.”7
Folkloric inspiration played an important role in the artistic creation of the biologist: “I had gathered a
collection of old rugs from Oltenia. Living surrounded by them, I was so penetrated by their spirit that all I could
see were only them everywhere. I had come to be more interested in Calu's Round Dance than in the Ninth
Symphony. Painting done before deeply displeased me. I felt I was alienating from my great predecessors,
Grigorescu, Andreescu, Luchian. Romanian painting line, moderate before, was no more convenient to me. I
wanted to look for something else. The folklore I worked at that time, a series of several dozens of landscapes in
which I replaced with rugs themes trees, clouds, flowers. The soil was laid out with themes from Oltenia, also
the sky was also on the rugs model and that was a special kind of interpreting folklore. When you looked better
you could see that, in spite of all the popular motifs and quotations, nature was not subject of the rugs pattern,
but peasant themes were subjected to a force of nature and a lyric that was stronger than them.“ 8
What impresses about Ţuculescu is the ability of being original. By not undertaking the framing into a
certain, the physician from the heart and soul: “Everything that Ţuculescu painted orders in a hostile universe of
the others, opposing the «school» or «manners.» His art means a victory of the subjective world - the essence of
authentically living the segment of living in the huge thread of time – unlike «approved» art or requested at that
time from here or elsewhere.”9 The human being as a singular entity came first for both Ţuculescu the painter as
much as Ţuculescu the physician:”monads of Ţuculescu’s eyes not order in a pyramidal way but also structure
totemically, based on the totem which gains its «life» from the caly pitcher filled with living water, to the totem
raised towards exaltation, worship and glorification and up to the rotem collapsed horizontally as a sign of
transition and passing into death. The artist Ion Ţuculescu thought that through artistic knowledge by revelation
can reach the supreme monad. Between the totemic ascension of worship and glorification of deity and the
totemic all, passing into death from Together, Countless Months, The Apocalypse, or The Testament, lives the
world of images created by Ion Ţuculescu. He wanted artistically, to be with the Son, the Father and the Holy
Spirit.”10
In 1955, in the memory of this physician who lived both as a practitioner of the chosen profession as
well as in the aesthetic plan, there was set up the Cenacle of Fine Arts of Physicians, circle that bears his name
even today. The cenacle, with certain artistic values, brings together doctors from different specialties: internal
medicine, surgery, pharmacy, bacteriology, gastroenterology, pediatrics, hematology, psychiatry, dentistry,
microbiology, histology, etc. This is another proof that pleasure of painting, of creating art, in general, knows no
boundaries and can be practiced even by neophytes. If science tries to respond in a practical manner, that
exfoliates reality layer after layer, to eternal questions which bother human beings, art, in any of its forms of life,
comes to throw a veil of mystery. Art has the task to connect to the knowledge the individual to the world
knowledge in an abstract manner. Like any other form of human knowledge, art tries to establish the link
between creative consciousness and the one who gives life to it. Ion Ţuculescu’s work, especially in the last
seven years of life, 1955-1962, period in which «the secret painter» - as he observed himself in a letter of 1956 -
headed towards the surprise of «cosmic mystery. » Thus, his art became purely subjective, art of a conscience
and not a painting of a painter.”11
Ion Ţuculescu’s artistic development went hand in hand with his professional becoming as a
practitioner. Actually, this stage, of professional growth, is the one that riped the value of his paintings as well, is
phase in which the health professional gained the safety “over his owan intellectual capacities of knowledge of
the universe. It is the period of attending and graduating two faculties, biology and medicine, in 1936 and in
1939 respectively, the period of his scientific research beginnings, of total trust the possibilities of reasoning to
reach the ultimate truths of life and, in existential field, this coincided with the dream of a lasting and deep love
to Mary Fotiade who would become his wife.” 12

6
Adrian Guţă, Considerations about the School from Poiana Mărului, in Şchool from Poiana Mărului, Publishing House of
the Art Braşov, 2013, p. 50
7
Idem, p. 51
8
Radu Bogdan, interview with Ion Ţuculescu About the mutations of my vision, in The Contemporary, Bucharest, no. 8, of
19th February1965
9
Florin Rogneanu, Inner sights of Ion Ţuculescu, in The Romanian writing, Year VIII, no. 7 (83) July 2010, p. 31
10
Ibidem
11
Idem, p. 32
12
Ibidem
80
 If his scientific formation answered partially to certain dormant questions in the physician’s soul, his
aesthetic side remained in expectation of that thrill to wake him up to the true reality: “Each «encounter» with
Ion Ţuculescu’s sights, either it is the «sight – leaf», «sight - spiral» or «ovoid», «line sight», «fish- sight» or
«triangle-sight», awakens a painful sense of loneliness, of unique living with a sharp note of questioning: why ?,
how ?, can it be like this ?, who am I?, what for ?, up to where ?, towards what? and the series of questions can
go on.”13 The questions that science could not answer, the thrills of knowledge that Ţuculescu felt, he tried to
overcome in artistic field, living the hope that art would enlighten some existential enigmas.
The phase in which he approached folklore motifs seems to have
been the most fruitful, bringing the creator of art closer to the fund artistic of the people, to the essence of
creative soil from which he drew the intellectualist sip: “Coming through the period of folklore was for Ion
Ţuculescu the covering the deep structures of plastic, decorative grammar of folk origin, understanding the
semantics of symbolic-formal thereof , that is how it is encoded in a sign some sort of feeling the world, to
synthesize the coordinates of a universe that the Romanians always felt close to and friendly.” 14
The are also other physicians and practitioners who blended their profession with the artist one. Thus,
Louis Thomas Jérôme Auzoux (1797-1880) was a French physician known internationally as the creator of
anatomical models used in teaching human medicine and in veterinary education. He was noted both in fine art
and in medicine for these anatomical models. The method used was an innovative one: paper paste and cork
molded and pressed using the paper mache technique and in order to create viscera the doctor used plaster molds
on which he successively stuck several layers of colored paper. Moreover, Auzoux created anatomical models of
horses. They are exposed currently at the Museum of Anatomy of the National Veterinary School in Toulouse.
The artistic novelty brought about by him is not only the amazing ability to render anatomical details but also the
ability to isolate individual components of models.
Thomas Cowperthwait Eakins (1844- 1916) was the son of a weaver. He started by studying drawing
and anatomy at the Pennsylvania Academy of the Fine Arts beginning in 1861. Afterwards, he joined courses in
anatomy and dissection at Jefferson Medical College between 1864 and 1865. For four years he studied painting
in Paris with Jean-Léon Gérôme. During a trip in Spain he discovered his enthusiasm towards realism. When
coming back home, he took up teaching in Pennsylvania Academy. He dared his students study anatomy in depth
as he was himself mesmerized by the study of the human body from anatomicl point of view as well as
dissections. He managed to blend the study of anatomy and painting in a unique way. In order to avoid taking his
students in dissection rooms all the time, he took casts made of plaster after the dead bodies which he used as
teaching aids. His methods of teaching body movements were considered unorthodox and he was forced to
resign from his teaching career.

The Gross Clinic The Agnew Clinic

One of his most important paintings depicting medical environment is In The Gross Clinic (1875). Dr.
Samuel D. Gross was a famous surgen in Philadelphia at the time. The painting shows Gross running an
operation in which part of the patient’s femur is removed. Gross used to teach students in large lecture halls at
Jefferson Medical College. Eakins was innovative not only by chosing subjects dealing with medicine but by
showing the breakthrough of the latest experiments in the field, a sort of testimony of the newest medical
procedures and discoveries in medicine.
Another well-known painting with medical subject was devoted to D. Hayes Agnew. The surgeon is
portrayed watching his students in the University of Pennsylvania's Medical Departmen performing an operation,
a mastectomy. The two paintings manage to c apture even the way the two doctors viewed the medical act.
While Gross did not have a clear system of maintaining aseptic environment, Agnew is portrayed wearing white
gowns and using sterile fields while perforing surgery.

13
Ibidem
14
Ibidem
81
 Another famous example is George Chicotot (1868-1937). He had attended the courses of School of
Fine Arts. He exhibited regularly at the Salon of French Artists from 1877 to 1913. But he proved to be
fascinated by anatomy and dissections (Subject on the dissecting table - 1882), he attended medical school
starting with 1892 which he graduated in 1899. He began his medical career in Broca hospital, where he became
the head of the radiology lab in 1908, then to the Boucicau hospital. In 1904 he signed another painting called
Tubing in croup.

George Chicotot’s Subject on the dissecting table

Until the beginning of the twentieth century infectious diseases (such as scarlet fever, measles,
diphtheria, whooping cough, tuberculosis) were the most terrible scourge that decimated young children,
especially those from poor families. Croup or laryngeal diphtheria was another disease that was killing thousands
of children at the beginning of last century. Chicotot’s painting presents the physician Albert Josiah performing
an intubation on a child suffering from respiratory distress, held in her arms by a nurse, and on right side of the
picture we can see another doctor preparing an anti-diphtheria vaccin. On the left of the composition, behind the
physician, there are students pursuing the medical operation carefully. In order to avoid tracheotomy, a more
invasive technique, Dr. Josias was practicing intubation to prevent death due to asphyxiation. Chicotot’s
paintings come to offer not only art but also a realistic picture of the time of health care system, placing
emphasis on objectivity and scientific rigor. Chicotot, trained in methods of clinical observation and discipline
necessary for the use of new medical techniques, presents in this picture an objective view of medical progress.
Chicotot specialized in radiotherapy and in 1907 he painted a self-portrait during a session of
radiotherapy. The doctor appears in foreground and in the background there is electrical equipment - tables, pilot
lights and electronic tubes in a Crookes tube, the transmitter X-rays symbolizing the supremacy of this
innovative therapy technique. The doctor portraited himself having in his right hand a gas torch high to regulate
the voltage through the bulb (the cable that connected to the device of radiotherapy) and in his left with hand
timer. Having in view that the technique was a new one, what strikes the modern viewer is the lack of
methodological rigour of the operation, consisting in the total lack of protection for patients and patricians, such
as screens and lead aprons. This lack of protective screens was to be regulated with booths and screens lined
with lead, aprons, gloves and goggles which began to appear in Germany. These rules become mandatory until
1922. Chicotot himself would be victim of irradiation. Chicotot received the Cross of Officer of the Legion of
Honour for his work on the battlefield as a doctor.15
An example of how art and medicine came across and used each other is David Solot (1909-1985) who
was both a painter and successful dentist of French lands. In his expressionistic and surrealistic paintings prevail
dental tools and even molars. The dentist found a way to turn these harmless objects into ones of high artistic
expression. School graduate from Dental Surgery and Dentistry Faculty of Paris, in 1933, the Jewish Solot
hailing from Vaslui, was practicing the profession of private practice dentist in the private office that he had
opened in Choisy-le-Roi. The reclusion generated by the fact that he had Jewish origins led his steps to Brive la
Gaillarde. The period, although bad from the career point of view, proved to be conducive to the artistic creation.
That was the phase in which he painted a lot and exhibited his works at the Salon of Bas-Limousin. After the war
he returned to the career in dentistry.
But he owes his the international fame to an American producer of drugs (Lederle Cy) who used the
physician’s paintings to promote their products. The period in which art galleries, discovering a new artistic
breath, call for his presence more and more. He reached to exhibit in Stockholm (1960), Dublin and Belfast two
years later in Helsinki. He even got in Israel and when coming back to his adoptive country, France, he received
for the painting titled Jerusalem the Medal of Honor award. No even the art was writing was foreign to him,
because, in 1967, he signed a film scenario for Près de Colette by Maurice Goudeket. Two years later he signed
a personal drama, Le procés du Docteur Tabart that blends elements of autobiography with fiction. In 1975 he
made a short film entitled Revolt of the molars, inspired by one of his paintings.

15
See F. Jayle, George Chicotot in La Lettre de l’Adamap no. 12 - 20 December 2008 – p. 36
82
 To conclude, physicians have been, along history, able to approach various field of mankind
knowledge. Either we speak of literary works or painting, these devouted practitioners have proven capable of
embracing not only the narrow field of medicine but the larger one or fine arts as well. Even if the painting
having medical subjects have not been all the time the work of physicians, those who devoted their lives to
creating a clearer image to posterity concerning medical personalities and experiments have the laudability of
having blended fine art with medical knowledge.

BIBLIOGRAPHY

1. Le Breton, David The human body anthropology and modernity, Cartier Publishing House, Chişinău, 2009
2. Guţă, Adrian Considerations about the School from Poiana Mărului, in Şchool from Poiana Mărului,
Publishing House of the Art Braşov, 2013
3. Jayle, F. George Chicotot in La Lettre de l’Adamap no. 12 - 20 December 2008
4. Radu, Bogdan interview with Ion Ţuculescu About the mutations of my vision, in The Contemporary,
Bucharest, no. 8, of 19th February1965
5. Rezeanu, Paul Ion Ţuculescu in Craiova, in Ramuri, no. 7/2010
6. Rogneanu, Florin Inner sights of Ion Ţuculescu, in The Romanian writing, Year VIII, no. 7 (83) July 2010
7. Țuculescu , Ion The Contemporary, Bucharest, no. 8, 1965 of 19 th February1965

83
 D.R. POPESCU BETWEEN MEDICINE AND LITERATURE

Lecturer PhD. RADU Mirela, Faculty of Medicine, „Titu Maiorescu” University, 67A Gheorghe
Petraşcu Street, Bucharest, Romania
Assistant Professor PhD, STOICA Diana, University POLITEHNICA of Bucharest, 164 Ion
Mihalache, Bucharest, Romania

Abstract

The current study aims at analyzing the writings of D.R. Popescu from another perspective. If the
author has been reviewed by scholars by connecting him with the political era he wrote in, we propose an
analysis of his writings from the perspective of medical studies that D.R. Popescu abandoned in favour of
literature. Even if there was not a palpable impact, scientific training of the writer has put its touch on his
literature through the “angle gnoseological angle in assessing reality.”16 Intellectual beginnings of D. R.
Popescu were, therefore, marked by other milestones. Feeding on a scientific source of reality approximation
was going to have a strong influence on the further ability of the writer to address topics most diverse: processes
of consciousness, deep psychological exploring, fantastic and even mythological, all came to form an astounding
picture: “World History as well as the national one, the immediate actuality, the village, the town or the science
fiction future, everything seems to fit the writer perfectly.”17 His style itself seems to suffer from chameleonic
character.

Key words: medicine, realism, naturalism,polysemantic, conscience dissection

Dumitru Radu Popescu (1935-) was an alternate member of the RCP in 1968, deputy in the Grand
National Assembly in 1975. As a dramatist, he wrote Shakespeare The Bird, These sad angels and The dwarf in
the summer garden. He enrolled in the Faculty of Medicine but abandoned it in the third year. Between 1956 -
1969 he was editor of the magazine Steaua in Cluj, between 1969 - 1982 he was editor-in-chief of Tribuna from
Cluj and in 1982 became editor of the journal The Contemporan. He received the award on behalf of the Writers
Union of Romania (1964, 1969, 1974, 1977, 1980). He wrote a lot of short stories: The escape (1958); The girl
from the south (1964); The Sleep of the Earth (1965); Dor (stories) (1966); Sun umbrella (1967); Too small for
such a big war (1969); Anastasia endearingly passing (1967); White Rain (1971); The Applecart (1974); The
Blue Lion (1981). But he headed his writer’s steps towards novels as well: Weekdays (1959); Oltenians’ summer
(1964); F (1969); Royal Hunt (1973); The two next to Ţebea(1973); A beer for my horse (1974); Rains beyond
the time (1976); The King of clouds (1976); The Life and work of Tiron B. I. Limping rabbit (1980); Life and
work of Tiron B .; II, The Ice Bridge (1982); City of Angels (1985). In addition to working as a novelist, D. R.
Popescu has signed plays. He also tried his talent in lyrics by writing The Phosphorus Dog (1981) as well as
essays Commas (1978).
From mimicry, symbolism, realism and up to naturalism all of these steps have represented milestones
in forming the talent of a complex writer. Innovative combination between real and fabulous and has led some
commentators to propose a unique interpretation of this Romanian writer, through the filter of Gabriel García
Márquez’s literature.18 And the language by this prose writer comes, through multi-poly-semantism to
emphasize this great ability to adapt the stylistic needs to the formal means of conveying ideas. This ability to re-
invent permanently, fear of the ankylosing tradition and following the same path, was discovered by other
commentators: His narrative formula has changed and is still changing - subtle, yet significantly - with each
book, entitling us of either talk about the conceptual background which self-generates its shape or of a
programmatic writer periodic reinvention.”19 By using medical terms which could not be strange that to the
author, we can conclude that the syndrome that D.R. Popescu suffered from at literary level was a homeostasis of
means and styles, homeostasis which continually adapted him to the environment. From folk themes to the
burlesque style and up to apophthegms, D.R. Popescu’s style manages to surprise the reader permanently, as
“Converting popular motifs, the vernacular of magic and human relations in the world's greatest symbols is a
way to communicate.”20

16
Dan Stoica, The writer and the era. A case study, in The Literator, no. 193-194, July-August 2015, p. 9
17
Ibidem
18
See Valeriu Cristea, To write, to read, Dacia Publishing House, Cluj, 1992, p. 112
19
Răzvan Voncu, Dumitru Radu Popescu – The journalist prose writer and the synthesis of genres, in The Literator, no. 193-
194, July-August 2015, p. 12
20
Anemona Pătrulescu, The comedy of existence at Dumitru Radu Popescu, Sitech Publishing House, Craiova 2012, p. 55
84
 Fecundity and multiplicity of D.R. Popescu's work prompted some critics to parallel it with
Sadoveanu’s.21 The innovation brought about by the writer in the Romanian literary landscape is the creation of a
novel F- by the juxtaposition of three short stories apparently autonomous but which create a novelistic triptych.
The first short story that makes up cycle, Snowing in Jerusalem, phantasmagorical story, put in question the
connection between objective and material. This occurs by tracing some of the noemes that make up the cycle:
aversion towards the vacuity of objective reality and the accumulation of epic events. The next mini-novel is The
ox and the cow which lays emphasis on guilt. Finally, the third writing, The seven windows of the labyrinth, “an
interesting novel of ideas”22 by sending to Daedalus, focuses on identifying contortions of consciousness specific
to human beings, having as “its own theme the man as a labyrinth.”23 The author himself confesses about the
twisted structure designed by Daedalus: “I have been long obsessed with the idea of a labyrinth as a space of
lack of rationality in which the monster eagerly swallows lives and people.”24 And the only one who can defeat
the ugliness of the world is rationing. The way to reason, we would say, passes-even if the writer has not
realized-through scientific knowledge. If his case, medical studies had the effect of lifting the veil of darkness
that covered the reality. The novelist’s own vision on the act of literary creation reveals the analogy done
subconsciously with his early studies: “(...) I consider the writer as a continuous laboratory, as a great plant that
takes the raw materials in the world, processes and eliminates always looking and always finds or does not find,
assimilating the world as an organism (...).”25
Prone to identification of unusual and expressive features, D.R. Popescu appeals to medical knowledge,
gained during the years spent in Medical School which he later abandoned, in order to probe his characters’
mental disorders. Moreover, the author has a linking to stories of fabulous with sacred character by setting a
ratio of coexistence between “general human eternal conflicts (myths) with the power of tradition, history,
stability of a nation, but also with the questions and problems of the modern human being.”26 But it is precisely
this mix between old and new, myth and modernity, burlesque and sacred, sociology and psychology, individual
and general which makes D.R. Popescu’s prose to occupy a special place in the panoply of the Romanian novel
in the seventh and eight decades. The author has a twofold role: theorist and philosopher and from this duality
his literature itself won, literature which augments, by agglutination, different perspectives of knowledge. The
permanent sliding on the trajectory of the real world and the invented one is achieved by a swinging mechanism,
through the “serious, sententious tone” which “turns suddenly towards parody, the story plunging into the
fantastic.”27 Parables, the labyrinth, bizarre conflicts approach D.R. Popescu to the exponent of expressionism:
Kafka. The world of the Romanian author as well as the German one is “that lacks reason and that establishes the
absurd, hence its tragic dimension.”28 Other commentators put him in lineage of Faulkner, admitting that there is
a “strong literary family ties with the magic realism, with Russian writers of the time or narratives of Mircea
Eliade and Vasile Voiculescu.”29
The reference that Paul Cernat makes to another doctor-literate-Vasile Voiculescu- even if achieved
only in a formal manner, by analyzing Popescu’s fantastical prose, we believe to have a much deeper meaning.
Both Voiculescu and D.R. Popescu attended, even if partially in the case of the second one, the Faculty of
Medicine. Scientific training they received did not entirely meet the spiritual needs and the questions the two
asked and to which science remained silent. The steps of these doctors-literates were in route for magic and
unreal because it was the only way to transcend the tangible world of objects. Approximation of values,
overturning the ordinances merely amplifies the feeling of disintegration that their characters live. And the
dissolution of conventional forms leads to tragedy Allegories, open endings and equivocation come to replenish
the feeling of decomposition of the objective world with well-defined hierarchies, throwing the entire action in
the abyss of chaos. The reader is left to unravel the threads of amphiboly that governs the universe of D.R.
Popescu novels: “The writer always proposes several possible solutions, each duly substantiated, but leaving the
reader the freedom of choice by keeping intentionally a certain ambiguity.” 30

21
See Cristian Vieru, Dumitru Radu Popescu-Unsuspected resources of the writing, in The literary movement, Year IX, no.
1-2 (33-34), 2010, Bistriţa, p. 10
22
Gheorghe Glodeanu, The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa, p. 2
23
Mioara Apolzan, D.R.Popescu. A novelistic cycle, in The House of fiction. Novels and novelists of the 8 th decade, Dacia
Publishing House, Cluj-Napoca, 1979, p. 120
24
D.R. Popescu, Commas, Dacia Publishing House, Cluj-Napoca, 1978, p. 240
25
D.R.Popescu interview given to Vasile Rebreanu-Miron Scorobete, in Interviws in the Romanian literature. Confessions of
several generations. Study, anthology and notes by Vasile Netea, Junimea Publishing House, Iaşi, 1983, p. 185
26
Mioara Apolzan, D.R.Popescu. A novelistic cycle, in The House of fiction. Novels and novelists of the 8 th decade, Dacia
Publishing House, Cluj-Napoca, 1979, p. 124
27
Gheorghe Glodeanu, The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa, p. 4
28
Idem, p. 6
29
Paul Cernat, Seas under deserts. Notes about D.R. Popescu’s literature, in Academica, no. 8-9, August-September 2015,
Year XXV, 298-299, p. 19
30
Gheorghe Glodeanu, The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa, p. 6
85
 Driven by the sheer fever of authenticity, D.R. Popescu accesses to non-quantifiable methods of the
most diverse: legendary, mythical “self-referentiality, irony, burlesque” 31 being only means to achieve the
ineffable. D.R. Popescu owes his medical studies the ability of probing conscience because he “rather explores
obscure zones of human psychology, those that verge on pathological and bestial instincts buried in the human
subconscious, bursting out sometimes with great violence to the surface.”32 Excessive rationalising from which
the author suffers penetrates the shell of the outside world and exposes its core: “D.R. Popescu's pen pierces
moral and social bolgias of the Romanian reality, and raises them by writing to the dignity of topics for
reflection.”33 For the writer it is a tool to measure social tensions, as the proseman has the duty to “take roots in
life, he cannot live above ground, he must start from life towards writing, towards himself, and, through his own
barometer his and his power of understanding, he has the duty to judge life.” 34
The special relationship that D.R. Popescu had with medicine, which he abandoned, is also recalled by
a collaborator of his in magazine Tribune “he was not a graduate of the Faculty of Medicine, but only of
Philology in Cluj, he attended only the first three years of medicine, preclinical stage, as they say, and told me
once, or I dreamed that he confessed that stopped there, in the third year, because he could not stand up blood
and dissections, but he will describe them wonderfully, by enumerating the fight between senses, smells and all
the details throughout his prose. For his writing is a continuous prose which mixes all the structures and means
of expression in voluptuous and greedy way.”35 We could deduce that, what literary critics saw in Popescu’s
writings as realism, could actually be the influence of his started but unfinished studies. An author’s biography,
even without him realizing it, leaves deep scars into his subsequent literary development. And in the present
case, this influence translates into dissecting consciences by fleshing pathological mechanisms that make up
characters. Even the nickname he had among the other writers bears the mark of his medical studies: “Frankly
about Doctor Popescu, as we called him down the alley, I heard intensively during the faculty years from a
lecturer of Romanian, language former assistant of Professor Coteanu.”36 Even the writer’s own personality was
going to be shaped by medical studies. From here he got the meticulousness, pedantry and ability to work. And
this portrait is sketched by one of his literary co-workers: “'Dumitru Radu Popescu is firstly, a man equipped
with a brilliant and unique intelligence, passionate and mere worker on the field of literature, generous, straight,
fastidious and extremely prudent, very gifted.” 37 Although furious manufacturer of novels, the author declares
his attachment to small species of the epic genre. This is able to show the true art of a writer “because it seems to
the happiest lab for a writer.”38
Characters, as exponents of the author, try to identify the mechanisms of social life by spying inner life.
These alter egos of the writer's mind try to understand the habitus of the objective world. And the chosen path for
introducing self-analysis is the background of a detective novel “Crime is an excellent excuse to probe the depths
of the human psyche, to present some extreme situations that people have had to face throughout history.”39 Not
accidentally, the author sees in evil a tumor coming to choke the innocence of the world as an “outgrowth of a
complex process.”40 The method of knowledge suggested by the author is a deductive one. Conservative, by his
intellectual formation, D. R. Popescu felt drawn towards the fabulous, tragedy and theater. The world woven by
author is an ornamental and grandiose one “his own Baroque perspective on existence, and from the events and
fictional characters (which always become symbolic) realities are made.”41 But, unlike the ancients, Popescu’s
characters do not fall in dramatic and this very feature makes his literature to gain the traits of “the modern
theater, of the anti-theatre.”42
Even the writer’s heroes are reversed: “Through all his «anti-heroes», the author not only disputes the
limits of reasoning, but reveals a resistance to rational explanation of reality.”43 This expressionist feature
approaches the writer to the Romanian predecessors playwrights concerned about moral values imprecision in

31
Răzvan Voncu, Dumitru Radu Popescu – The journalist prose writer and the synthesis of genres, in The Literator, no. 193-
194, July-August 2015, p. 21
32
Idem, p. 22
33
Idem, p. 27
34
D.R.Popescu interview given to Vasile Rebreanu-Miron Scorobete, in Interviws in the Romanian literature. Confessions of
several generations. Study, anthology and notes by Vasile Netea, Junimea Publishing House, Iaşi, 1983, p. 182
35
Nicolae Iliescu, How I spent my necessary youth, in Academica, no. 8-9, August-September 2015, Year XXV, 298-299, p.
29
36
Idem, p. 30
37
Idem, p. 32
38
D.R.Popescu interview given to Vasile Rebreanu-Miron Scorobete, in Interviws in the Romanian literature. Confessions of
several generations. Study, anthology and notes by Vasile Netea, Junimea Publishing House, Iaşi, 1983, p. 183
39
Gheorghe Glodeanu, The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa, p. 3
40
D.R. Popescu, Royal hunt, Eminescu Publishing House, 1973, p. 203
41
Rodica Mureşan, History and myth at Dumitru Radu Popescu, in Literary movement, Year IX, no. 1-2 (33-34), 2010,
Bistriţa, p. 7
42
Mioara Apolzan, D.R.Popescu. A novelistic cycle, in The House of fiction. Novels and novelists of the 8th decade, Dacia
Publishing House, Cluj-Napoca, 1979, p. 136
43
Ibidem
86
the modern world, about the uncertainty generated by the grotesque, writers such as E. Ionescu, Beckett S., B.
Brecht, Dürrenmatt.44 Behavioral deviations and of psychological structure of Popescu’s characters are mirrored
in the structuring of the objective world, individual psychoses having their repercussions in the social one.
Raisonneurs, those that detach best from the real world and accedto the forms of knowledge beyond the capacity
of those society considers normal, are the alienated ones. Heterogeneity of D.R. Popescu’s characters was noted
by many critics: “he debates in his creation the ideas and problems of the contemporary world, he is inspired by
the rural world, cultivating a prose of atmosphere, where preferred heroes are those people with oddities, with
twisted natures, original, eccentric types from the village world, youth struggling with absolute desperation.”45
Modernity of Popescu’s writing brought him about his progeny in line with Ezra Pound and Ferdinand Céline.46
The novelty that D.R. Smith brought into the Romanian prose has not remained unnoticed by colleagues
of generation and even by literary rivals as the writing of this author: “is part of the profound, expressive
experience of our prose, and not only a value that will be added to the Romanian pantheon still recent of our
novel , and not only a value that will be added to the pantheon another recent Romanian novel, a mirror of not
only the feeling and the Romanian Sub-Carpathian nature, an essential capability of ours to provoke the mystery
hiding us, as Lucian Blaga would have said.” 47
D. R. Popescu the unreal reality cannot emphasize reality. His writing is a mix between two opposites:
“the trivial alternates with the diaphanous, the grotesque, the tragic, cruelty with innocence.”48 Just by being
presented with the two forms of possible existence, the reader can decide which he stops on, having in view that:
“the fantastic” is “a unique way of reflecting reality.”49 The practice of counterpoint, inner introspection and
permanent query about the surrounding world that are privileges which the writer acquired as a result of the
scientific unfinished studies. Only a spirit hardened in the flame of science and of perpetual questioning is able
to bring such a fresh perspective in Romanian literature. On the same principle is built the detective short story
Dor. And the same happens in Royal Hunting that blends: “the fantastic, the miraculous, the symbolic, detective
element, the chronic of recent events and the imperfect chronic of the facts in the past.”50 The unbelievable takes
the form of schizophrenia generalized to entire communities. Confabulation characterizes most of his characters:
“all of them fable, gossip around, announce disasters (deaths) and then deny them, jump from one time to
another and rarely say what they really think. Truth comes out, when it happens, from the amount of those
confessions twisted and unfinished.”51 The author has the rare ability to hide mysteries in their most
mundane forms: “the word is a deck and an abyss, is the door that opens perspectives and where you lose in
thicket of happenings, it is a curtain that reveals and conceals people, characters, meanings. (...) The texts of
D.R. Popescu become by reading a confrontation of the reader with himself. (...) Marshes attract you to
suffocate, the jungle ofdrpopescien literature accepts you to fill you with sense, of ideas and conflicts that change
you, make you stronger, make you know who you are and what you are capable of.”52
The originality of his writings singularize DR Popescu, without saying, within the Romanian literary
landscape. He brings on local literary lands, a fresh air which mixes the tragic, the absurd and the jovial. The
writer has the ability to reinvent Romanian style by “leaning towards parable, the desire to introduce new
dramatic constructions and the Romanian robust, catchy, humor; qualities that not only imprint originality to his
creation, but also a special distinction.”53
Another physician-literate, Augustin Buzura, makes the connection between the moment he came to
know D.R.Popescu with his medical studies: “I heard of D.R. Popescu from the very first year of Medicine. It
was said at that time that a student, after, I think, two years of Medicine, switched to Philology and devoted to
literature. There was no any hint, I had not written a line yet, I had only attended different courses of some great
names in Cluj university and look at walks of a few who, today, have become statues, without whom the city
seems unthinkable.”54 The same physician turned into man of letters saif about DR Popescu: “I treasured his
prose and his unconventional theater, the new special note and the special touch which have raised him very
high, not only in literature but also in social life.”55

44
See Mioara Apolzan, D.R.Popescu. A novelistic cycle, in The House of fiction. Novels and novelists of the 8th decade, Dacia
Publishing House, Cluj-Napoca, 1979, p. 136
45
Florea Firan, Dumitru Radu Popescu, in Romanian writing, no. 7 (83), July 2010, p. 3
46
See Ion Moise, D.R.Popescu-An emperor of Romanian prose, in Literary movement, Year IX, no. 1-2 (33-34), 2010,
Bistriţa, p. 16
47
Nicolae Breban, To an anniversary, in Academica, no. 8-9, August-September 2015, Year XXV, 298-299, p. 14
48
Eugen Simion, Trivial and diaphanous, grotesque and tragig, cruel and innocent,iȋn Academica, no. 8-9, August-
September 2015, Year XXV, 298-299, p. 8
49
Gheorghe Glodeanu, The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa, p. 3
50
Eugen Simion, Trivial and diaphanous, grotesque and tragig, cruel and innocent,iȋn Academica, no. 8-9, August-
September 2015, Year XXV, 298-299, pp. 8-9
51
Idem, p. 10
52
Dan Stoica, The writer and the era. A case study, in The Literator, no. 193-194, July-August 2015, p. 5
53
Augustin Buzura, The winter of the blue lion, in Academica, no. 8-9, August-September 2015, Year XXV, 298-299, p. 13
54
Ibidem
55
Ibidem
87
 BIBLIOGRAPHY

1. Apolzan, Mioara The House of fiction. Novels and novelists of the 8 th decade, Dacia Publishing House, Cluj-
Napoca, 1979
2. Breban, Nicolae To an anniversary, in Academica, no. 8-9, August-September 2015, Year XXV, 298-299
3. Buzura, Augustin The winter of the blue lion, in Academica, no. 8-9, August-September 2015, Year XXV,
298-299
4. Cernat, Paul Seas under deserts. Notes about D.R. Popescu’s literature, in Academica, no. 8-9, August-
September 2015, Year XXV, 298-299
5. Firan, Florea Dumitru Radu Popescu, in Romanian writing, no. 7 (83), July 2010
6. Glodeanu, Gheorghe The world as a show, in The literary movement, Year IX, no. 1-2 (33-34), 2010, Bistriţa
7. Iliescu, Nicolae How I spent my necessary youth, in Academica, no. 8-9, August-September 2015, Year XXV,
298-299
8. Moise, Ion D.R.Popescu-An emperor of Romanian prose, in Literary movement, Year IX, no. 1-2 (33-34),
2010, Bistriţa
9. Mureşan, Rodica History and myth at Dumitru Radu Popescu, in Literary movement, Year IX, no. 1-2 (33-
34), 2010, Bistriţa
10. Pătrulescu, Anemona The comedy of existence at Dumitru Radu Popescu, Sitech Publishing House, Craiova
2012
11. Popescu, D.R. Royal hunt, Eminescu Publishing House, 1973
12. Simion, Eugen Trivial and diaphanous, grotesque and tragig, cruel and innocent,iȋn Academica, no. 8-9,
August-September 2015, Year XXV, 298-299
13. Stoica, Dan The writer and the era. A case study, in The Literator, no. 193-194, July-August 2015
14. Vieru, Cristian Dumitru Radu Popescu-Unsuspected resources of the writing, in The literary movement,
Year IX, no. 1-2 (33-34), 2010, Bistriţa
15. Vlad, Ionel-Valentin In honorem Dumitru Radu Popescu, in Academica, no. 8-9, August-September 2015,
Year XXV, 298-299
16. Voncu, Răzvan Dumitru Radu Popescu – The journalist prose writer and the synthesis of genres, in The
Literator, no. 193-194, July-August 2015

88
 GNOSEOLOGY OF A PHYSICIAN-LITERARY MAN

Lector PhD. RADU Mirela, Faculty of Medicine, „Titu Maiorescu” University, 67A Gheorghe
Petraşcu Street, district 2, Bucharest, Romania;
Assistant PhD. Liliana Florina ANDRONACHE, „UMF” Carol Davila, 8 Eroilor Sanitari
Boulevard, Bucharest, Romania

Abstract

Vasile Voiculescu (1884-1963) was awell- known and revered practitioner of medicine and equally a
writer. His entire religious belief system is based on the pillars of science, mysticism and religion. Devoted to
both patients and lifting by faith, Voiculescu did not leave any spiritual values even during hard moments that
life gave him. As concerns his literature, it was strongly influenced by his own system that agglutinated popular
superstitions and beliefs, fantastic, popular religious beliefs and customs. The eclecticism of this vision brought
to which the physician added the contribution of science would characterize not only his poetry but prose as
well. Theosophy, pseudosciences and metaphysical did not express better than in the unique voice of the
voiculescian literature.

Key words: medicine, fabulos, occultism, religious dedication, spirituality

As the profession practiced got him closer to people, Voiculescu’s lyric has, undoubtedly, its starting
point in his social life. His poetry is placed at the confluence between human and nature:“His inner matrix, of
large gestures, the sovereign effects, the elemental unleashing phenomenal.” 56 The poet’s classical and even
medical formation make their presence felt by being a follower, even camouflaged sometimes, of the biological
vitalism on which he applies “the fresh layer of Christian iconography.” 57 Voiculescu’s lyric, as observed by
some critics, does not find its source in the prosody gift but in the enormous work done by the author to polish
the word and to subjugate it to the poetic purpose. Incomparable artificer, Voiculescu is a “homo faber” 58 in that
he transforms reality through “dignity and devote work.”59 And who could have these characteristics more than a
dedicated physician in the fight against human suffering?
Principles that have guided the physician can be seen in his poetry as well, as he “has a poetized ethics,
ȋn operanting from the bottom to the up, from the «the sole of the country» to the absolute heaven. Not the
mystical ecstasy is his instrument, but the principle of Enlightenment admiration towards labor and its products,
an affectionate expansion of a logical trait plugged to phraseology (...).”60 This cerebral poet has the ability to
transform the conceptual into concrete and this comes from his openness towards the sciences he studied and
practiced. Some exegetes found him even from the lyric period to be a true believer. Only with the Burning Pyre
we can realize how much dedication Voiculescu had in searching for answers that, throughout life, he did not
receive either from science or from writing: “In dramatic moments of life (war, prevention of contagious
diseases, loss of his wife, loneliness, detention) Voiculescu used the Creator's name with great moderation and
wisedom and, therefor, we cannot stop our conscience ask to what extent his faith was a life philosophy and an
61
ethical system? To what extent his Christianity is based on knowledge and to what extent on faith?”
If his poetry is charged with the Christian thrill, the doctor-literate’s short writings breathe the heavy air
of the fantastic “Voiculescu, clearly, is interested in superstitions, magic symbols, in one word in the occult
existence. His short stories touch more or less this superficial or deep this reality of unseen things. Even when
the epic detaches from symbols and works freely by its own mechanisms, there is sufficient evidence pointing to
a magic substrate.”62 However, unable to abandon entirely religious faith that guided his steps even from his
childhood, Voiculescu, even in his short stories, adopts a hybrid formula, found at the crossroads between hard
scientific explanation and fabulous: “Voiculescu does not raise the question of obscurantism, popular mysticism,
his interest goes to a magic substrate in Romanian spirituality which he does not hurry to approve or condemn.
More importantly for him - and of course for the reader - is the way ȋn that defines a particular human condition

56
Gheorghe Grigurcu, A mediator through substance: Vasile Voiculescu in From Mihai Eminescu to Nicolae Labiş, Minerva
Publishing House, Bucharest, 1989, p. 189
57
Idem, p. 190
58
Idem, p. 192
59
Ibidem
60
Idem, p. 193
61
Gheorghe Postelnicu, Preface to Life and literary work of Vasile Voiculescu, EuroPress Group Publishing House, 2012, pp.
1-2
62
Eugen Simion, Romanian writers of today, Vol. I, Litera Internaţional Publishing House, Bucharest-Chişinău,2002, p. 203
89
in relation to these old beliefs.”63 The narrator-doctor’s digressions into fantastic are merely stages. Sometimes,
the storyteller tries to give an explanation of the religious side, avoiding fantasmagoric which he replaces with
rationalization. This amalgam between religious, mystical, imaginary and fabulous b rought Voiculescu’s lineage
with an illustrious predecessor: Edgar Allan Poe.
Voiculescu's structural religiosity emerges from the end of the novel Zahei The Blind. The character
expects his redempţiunea as a practicant believer: “The fact that the central character is a blind man searching for
vision (salvation) emphasizes the idea of an evangelical symbolism.”64 Zahei seeks for his salvation, as did his
life the author of the novel, either by medicine, or through art. The poem Fifty years dedicated to the poet and
theologian Nichifor Crainic is, even if was not meant to, a history of the physician-literate himself, who ought to
overcome the humble condition of the human being in order to access the Creator.
The fact he was a doctor brought Voiculescu into the Royal entourage. The seriousness with which he
treated all his patients, unusual diagnostic capabilities and, not infrequently, use of traditional medicines brought
an excellent professional reputation. In her turn, Queen Mary inspired the physician, by her commitment to the
poor and the unhappy, a great respect “The rural origin and family education have enhanced the respect of the
poet towards the Royal Household. Queen involvement in the care of the wounded from the frontline in
supporting widows, orphans and infirm impressed him and decided to write three odes: «Soldiers, wanderers,
wounded in a heap to disperse all comfort; / On the front, in the country, hospitals struggled reap torment, / And
taking everyone’s pain Yours was growing up. / Your soul carries so many tears they shed by your subjects.”(M.
S. Queen Mary)65
Revealing on how religious felt Voiculescu is an analysis of Christian prayer Our Father. The words
themselves of the poet leave the reader enter his faith universe and make the reader understand how the
physician perceived the Creator: “God has no name, what is meant by the name of God (IHVH) is all science and
our knowledge of Him. It includes our minds and sanctifies, that worships and adores him knowing God in this
way. His name is wisdom. Service are the laws of universal harmony, arts fruitful principles of the universe,
confidences of the physical and hyper physical world, lights of reason, rigors of logic, Splendora of the truth, the
power of numbers, ordinances knowledge, traits soul, mysteries of the body, goodness, beauty, order,
consummation toward which all and that everything will reach. On some we pray and ask to be given to us the
strength and the ability to sanctify, to adore. These are divine rays of light which reveal the name of the writing
and creation.”66
This globalizing vision joins into the concept of the Godhead both religion and science, making us think
about the searches both aesthetic and creative man made in the service of man. Eclecticism of the voiculescian
system as regards the Christian thought and feeling is evident when, by free will, sending to the theory whose
foundations were laid by Saint Augustine, the poet believes that God gave people full freedom: “freedom is
God's will ... through and by this large, unrestrained will, God allows us deviations to sin, abomination, that is
our will, our human freedom. Here is the great, original creator infinity mirrored in us; reckoning us free, we are
limited by our will as a false infinity. Our freedom is a denial of freedom, because it is not free, hung to the sin.
But we have the freedom from God to be unfree God.”67

63
Idem, p. 211
64
Idem, p. 211
65
Gheorghe Postelnicu, Preface to Vasile Voiculescu and the Royal House, in Ȋntrezăriri, Year II, nr. 6, July 2014, p. 2
66
Vasile Voiculescu, Our Father, in Ȋntrezăriri, Year II, nr. 6, July 2014, p. 4
67
Idem, p. 4
90
 Voiculescu divided his soul between the profession, literary passion and family duties: “(...) he daily
changed the hospital ward with the literary salon, without neglecting the least to his own duties as a father of
four children.”68 And being a doctor was in those times of the century one of the most difficult profession. Lack
of medicine, lack of hygiene made his work devoted to getting the sick healthier even harder. Respite which
allowed himself was of participating in literary circles that were organized by Academy of Bârlad; they were
those respire he needed from the medical careerr, that welcome break from the harsh realities of impoverished
Romanian village. They were the only times that abundance sensitivity found refuge from the shackles of
everyday life. This messianism which the doctor dedicated his life path was chosen to salvation. In fact, this
sinuous route has been classified as “his way from the simple to the profound faith, called isihasta.”69
Voiculescu proved a constant seeker of transcendence either in drama or in his novels. A possible
explanation for this constant thirst for metaphysical religion can be sought either in literary works or in the
answers to which science, specifically medicinewhose fervent practitioner was, could not provide. The doctor
had declared himself in a continuous search for a fountain of knowledge that would quench thirst, moving from
scientific study, at the religious doctrines to pseudo-sciences: “I went through all the stages of mystical
experience, from Buddhism to theosophy and a curiosity that does not know how to explain it pushed me
towards the occult and even to books of palmistry.”70But his true testament are words to paper:”True religious
inspiration, which may together art and faith, remained only the prayer.”71

BIBLIOGRAPHY

1. Acterian, Arșavir Portraits and three jailman memories, Ararat Publishing House, Bucharest, 2004
2. Gheorghe Grigurcu, A mediator through substance: Vasile Voiculescu in From Mihai Eminescu to Nicolae
Labiş, Minerva Publishing House, Bucharest, 1989
3. Postelnicu, Gheorghe Preface to Life and literary work of Vasile Voiculescu, EuroPress Group Publishing
House, 2012
4. Postelnicu, Gheorghe Preface to Vasile Voiculescu and the Royal House, in Ȋntrezăriri, Year II, nr. 6, July
2014
5. Postelnicu, Gheorghe Vasile Voiculescu and Academy from Bârlad, in Academia Bârlădeană, Year XXI,
4(57), Sem. IV, 2014
6. Simion, Eugen Romanian writers of today, Vol. I, Litera Internaţional Publishing House, Bucharest-
Chişinău,2002
7. Sorescu, Roxana Vasile Voiculescu’s chronology of life and work, in vol. V. Voiculescu, Entire literary
prose, Anastasia Publishing House, Bucharest, 1999
8. Voiculescu , Vasile interview with Nicolae Crevedia, in Universul literar, 18 May 1930
9. Voiculescu, Vasile Confessions of a writer and physician, in White thoughts, Cartea Românească Publishing
House, Bucharest, 1986
10. Voiculescu, Vasile Our Father, in Ȋntrezăriri, Year II, nr. 6, July 2014

68
Gheorghe Postelnicu, Vasile Voiculescu and Academy from Bârlad, in Academia Bârlădeană, Year XXI, 4(57), Sem. IV,
2014, p. 9
69
Gheorghe Postelnicu, Preface to Life and work of Vasile Voiculescu, EuroPress Group Publishing House, 2012, p. 2
70
Vasile Voiculescu in interview with Nicolae Crevedia, in Universul literar, 18 May 1930
71
Vasile Voiculescu, Confessions of a writer and physician, in White thoughts, Cartea Românească Publishing House,
Bucharest, 1986, p. 45
91
 BIOCHEMICAL EVALUATION OF PLASMA LIPIDS ON DIABETES MELLITUS
Elena RUSU1, Cristina CRISTESCU2, Gabriela BURDUCEA 3

1
Lecturer PhD. Preclinical Department, Faculty of Medicine, Titu Maiorescu University,
Gheorghe Petrascu Street, no. 67A, sector 3, Bucharest Romania
2
Lecturer PhD., Preclinical Department, Faculty of Medicine, Titu Maiorescu University,
Gheorghe Petrascu Street, no. 67A, sector 3, Bucharest Romania
3
Lecturer PhD. Preclinical Department, Faculty of Medicine, Titu Maiorescu University,
Gheorghe Petrascu Street, no. 67A, sector 3, Bucharest Romania

*Corresponding author: Lecturer PhD. Rusu Elena: elenarusu98@yahoo.com Preclinical Department,

Faculty of Medicine, Titu Maiorescu University, Gheorghe Petrascu Street, no. 67A, sector 3,
Bucharest Romania

Abstract
Risk factors for type 2 diabetes and cardiovascular disease are including obesity, insulin resistance,
hyperglycemia, dyslipoproteinemia, and hypertension. Insulin resistance have been identified as a major
contributor to the development of type 2 diabetes mellitus and metabolic syndrome since it increases the delivery
of fatty acids into the circulation, which modulate the ability of the heart to use glucose as a source of energy
leading to a cellular stress.
Lipoproteins are comprised of proteins (apolipoproteins), phospholipids, triglycerides, and cholesterol.
Lipoproteins contain several classes VLDL, LDL, and HDL. The presence of elevated cholesterol level is known
to play a key role in both the initiation and progression of atherosclerosis as well as in the clinical consequences
such myocardial infarctation, stroke, peripheral vascular disease, and heart failure. Diabetic dyslipidemia is
characterized by high fasting and postprandial triglycerides levels, low HDL level and slightly elevated LDL-
cholesterol with domination of atherogenic small dense LDL. Despite the improvement observed in recent years,
the leading cause of morbidity and mortality of diabetics are cardiovascular diseases.

INTRODUCTION
Diabetes mellitus is a major metabolic disease; its prevalence is increasing exponentially. World-wide,
type 2 diabetes mellitus is constitutes for about 90% of all cases and is more in men than women. Risk factors
for type 2 diabetes mellitus and cardiovascular disease are including obesity, insulin resistance, hyperglycemia,
dyslipoproteinemia, and hypertension. Persistent hyperglycaemia causes glycoslation of proteins, mainly
collagen cross linking and matrix proteins of arterial wall. This eventually leads to endothelial cell dysfunction
and further to atherosclerosis.
Dyslipidaemia is one of the major risk factors for cardiovascular disease in diabetes mellitus [13].
Diabetic dyslipidaemia is characterized by increased serum low-density lipoprotein (LDL), tryglicerides (TG)
and decreased high/density lipoprotein (HDL). Cardiovascular disease is a significant cause of morbidity and
mortality in patients with diabetes mellitus. The increased risk of coronary heart disease in type 2 diabetes is due,
in part, to lipid abnormalities often present in the diabetic patient. Current guidelines for the prevention of
coronary heart disease in diabetic patient identify elevated level of LDL-cholesterol as the primary target of
lipid-lowering therapy, and recommend statins as the first-line treatment for diabetic dyslipidaemia [10].

METABOLISM OF TRIGLYCERIDES
After a fatty meal, dietary triglycerides are hydrolyzed in the intestine to free fatty acids and
monoglycerides. Fatty acids and monoglycerides are then absorbed by enterocytes and resynthesized to for
triglycerides. Triglycerides within the intestinal enterocytes are assembled within apolipoprotein into large
chilomicrons which are released from the cells into the lymphatic system. They have access to plasma via the
toracic duct and are rapidly metabolized by lipoprotein lipase to yield chylomicron remnants .

92
 Figure 1. Lipoproteins transport
The presence of elevated cholesterol level is known to play a key role in both the initiation and progression of
atherosclerosis as well as in the clinical consequences such myocardial infarctation, stroke, peripheral vascular
disease, and heart failure. After fatty acids are taken up by target tissues, they have three major fates in the cell.
They can be esterified into triglycerides, diglycerides, or phospholipids, converted to sphingolipids or oxidized
for energy [7]. The majority of patient with type 2 diabetes exhibit a dyslipidemia which presents a major link
between diabetes and cardiovascular disease. It is well known that good glucose level control improves
dyslipidemia but doesn’t eliminate it. Elevated levels of triglycerides leads to elevated levels of free fatty acids
which may induce insulin resistance and β-cell dysfunction. The fact that hypertriglyceridemia can worsen
glucose metabolism is clinically important as it explains why it is more difficult to control hyperglycemia in
patients with hypertriglyceridemia compared to those with normal triglycerides values [15].
Dyslipidemia is a common feature of diabetes. There is an association between atherosclerotic
cardiovascular disease and serum cholesterol and triglyceride levels in both type 1 and type 2 diabetess. The risk
of coronary heart disease is greater at any given level of serum cholesterol in patients with diabetes and its
association with hypertriglyceridemia is stronger than in general population.
Lipoproteins are the particles that transport cholesterol and triglycerides. These compounds are essential to cell
structure and metabolism and are not soluble in aqueous solutions. Lipoproteins are comprised of proteins
(apolipoproteins), phospholipids, triglycerides, and cholesterol. Lipoproteins contain several classes VLDL,
LDL, and HDL. VLDLs are produced by the liver with a primary function of supplying free fatty acids to
tissues. They are normally the predominant carries of circulating triglycerides. LDLs are by-products of VLDL
metabolism and, in the normal state, are the primary carriers of plasma cholesterol. Nascent HDLs are produced
by the liver and intestine and then mature and become enriched with other apolipoproteins and lipids by
enchanges with chylomicrons and VLDL [5]. These are taken up by remnant receptor and by LDL receptors in
the liver. Free fatty acids liberated by the action of LDL are available to adipose tissue for storage and so other
tissues for us as energy substrates (skeletal muscle, heart). Lipids derived from de novo synthesis, chylomicron
remnants, and from lipolysis of adipose tissue are reassembled in the liver as very-low-density lipoprotein
(VLDL) particles, which are secreted into the plasma. VLDL particles are metabolized by lipoprotein lipase to
yield intermediate density lipoprotein (IDL) particles, which are metabolized by lipoprotein lipase and hepatic
lipase to yield low-density-lipoprotein (LDL) particles. Small VLDL, IDL and LDL molecules may be taken up
by peripheral tissues to deliver nutrients, cholesterol and fat-soluble vitamins [19].
Diabetic dyslipidemia is characterized by high fasting and postprandial triglycerides levels, low HDL
level and slightly elevated LDL-cholesterol with domination of atherogenic small dense LDL. Despite the
improvement observed in recent years, the leading cause of morbidity and mortality of diabetics are
cardiovascular diseases [12]. Dyslipidemia is much closed linked with insulin resistance thus causing glycemic
disorders. Based on this pathophysiological pathaway, effective management of dyslipidemia plays a key role in
preventing cardiovascular disease. The current guidelines broaden the spectrum of statin usage, which is mainly
indicated in patients with diabetes mellitus aged 40 to 75 years of age, as moderate-intensity statin usage to
provide a decrease of 30% to 49% in LDL-C [18]. Some studies which investigated relationship between aging
and lipid profile in diabetic and non-diabetic atherosclerotic patients shown that dyslipidemia increases with
increase in age and female are more prone to diabetic dyslipidemia and have more risk of developing
atherosclerosis with increasing age [3].

93
 Hypertriglyceridemia is accordingly to recent recommendations categorized as mild, moderate and
extreme [8]. Mild to moderate values are most often associated with cardiovascular events and non-alcoholic
steatohepatitis while extremely elevated values are most associated with pancreatitis and lipemia retinalis.
Several genetic and non-genetic factors are included in regulation of triglycerides levels. Extremely elevated
triglycerides not provoked by dietary factors, especially by high alcohol intake are more likely to have a
monogenic cause. On the contrary, mildly to moderately elevated triglycerides have mostly polygenic origin and
often coexist with other metabolic disturbances, mainly with central obesity, insulin resistance and diabetes
mellitus [16].
Type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia, which may be due to a
defect in insulin secretion of pancreatic β cells, insulin resistance is peripheral tissues, and/or and excessive
accumulation of triglycerides and fatty acid derivates in skeletal muscles. This pathology remains a leading
cause of cardiovascular disorders, such as microvascular (retinopathy, nephropathy, and neuropathy) and
vascular disease/complications. This is also associated with increased risk of cancer, psychiatric illness,
cognitive decline, chronic liver disease and development of arthritis.

INSULIN RESISTANCE AND FATTY ACIDS

Insulin resistance have been identified as a major contributor to the development of type 2 diabetes
mellitus and metabolic syndrome since it increases the delivery of fatty acids into the circulation, which
modulate the ability of the heart to use glucose as a source of energy leading to a cellular stress. This stress is
characterized by an excessive radical oxygen species production, impaired state of nitric oxide vaso-relaxation,
production of inflammatory cytokine, mitochondrial dysfunction, increased advanced glycation and products,
and dysfunction of endothelial progenitor cells, as the inhibition of the anti-atherogenic adipokine adiponectine
[1]. The treatment of type 2 diabetes mellitus has been directed toward the reduction of hyperglycemia and
glycosylated hemoglobin in order to prevent cardiovascular and other long term risks. Glucose deficiency is
adipose tissue induces metabolic compensation, leading to the hydrolysis of triglycerides and release of fatty
acids, which are oxidized by the liver and transformed to ketonic derivates. In patient with type 2 diabetes
mellitus, besides controlling blood pressure and lipid levels, the major therapeutic goal is to optimize glycemic
control in order to reduce the development and/or severity of long-term diabetic complication.
Although oral anti-diabetic agents may initially control hyperglycemia, most patients with type2
diabetes mellitus will require insulin therapy, as β-cell function progressive decline [6].
Circulating free fatty acids contribute to the development of insulin resistance via a number of
mechanisms. Circulating concentrations of plasma free fatty acids are determinate to a large extent by the release
by lipolysis of adipocytes triglyceride stores by adipose triglyceride lipase and hormone-sensitive lipase [11].
Hormone-sensitive lipase-stimulated release of free fatty acids from triglyceride store in adipose tissue is tightly
controlled by hormones that are regulated by the metabolic status. During conditions such as fasting, when blood
glucose level is low when energy demands are increased, glucagon, glucocorticoids and cathecholamines lead to
activation of hormone-sensitive lipase to promote hydrolysis of triglycerides to free fatty acids. By contrast, in
the fed state, insulin inactivates hormone-sensitive lipase and inhibits lypolysis.
Improved glycemic control generally has favorable effects on lipoprotein levels in diabetes, with a
reduction in cholesterol and triglyceride levels through deceased circulating very-low density lipoprotein and by
increased catabolism of LDL trough reduced glycation and up regulation of LDL receptors [17].
Hydroxymethylglutaril-coenzyme A reductase inhibitors (statins) are first-line lipid-lowering therapy for patients
with type 2 diabetes mellitus. In these patients, statins generally reduce LDL-cholesterol levels by 24-52%,
depending upon the statin and dose (atorvastatin, fluvastatin, lovastatin, and rosuvastatin). Although the efficacy
of statins is well established, a considerable proportion of patients do not achieve lipid goals with statin
monotherapy and may require add-on or alternative therapies to statins to better achieve LDL-cholesterol
treatment goals [4].
In fasting conditions, the glucose in blood is provided by liver that is used by the brain, without any
dependency on insulin. Beside the storage of glucose, insulin also inhibits the secretion of glucagon and lowers
the concentration of serum fatty acids leading to a decline in liver glucose production [9]. Insufficient insulin or
resistance to insulin in the body results in intracellular hypoglycemia causes hyperglycemia. The intracellular
hypoglycemia causes gluconeogenesis that leads to fats breakdown and decreases protein synthesis and γ-
globulins while extracellular hyperglycemia leads to hyperglycemic coma and osmotic diaresis [14]. One major
role of insulin is to stimulate the storage of food energy in the form of glycogen in hepatocytes and skeletal
muscle, following the consumption of a meal. In addition, insulin stimulates hepatocytes to synthesize and store
triglycerides in adipose tissue. In uncontrolled type 1 diabetes mellitus there is a rapid mobilization of
triglycerides leading to increased levels of plasma free fatty acids. The free fatty acids are taken up by numerous
tissues (except the brain) and metabolized to provide energy. Insulin has an overall effect on protein metabolism,
increasing the rate of protein synthesis and decreasing the rate of protein degradation. Thus insulin deficiency
will lead to increased catabolism of protein. The increased rate of proteolysis leads to elevated concentration of
amino acids in plasma.

94
CONCLUSION
Dyslipidaemia is one of the major risk factors for cardiovascular disease in diabetes mellitus and
hypertriglyceridemia is common in type 2 diabetes. Hypertriglyceridemia associates with a spectrum of cardio-
metabolic risk factors and increases cardiovascular disease risk in type 2 diabetes. Statins are the first-line of
lipid-lowering therapy to target LDL-cholesterol and triglycerides.

REFERENCES

1. Abel ED., O’Shea KM., Ramasany R., Insulin resistance: metabolic mechanisms and consequences in
the heart. Arteriosclerosis, Thrombosis and vascular Biology, 2012, 32(9):2068-2076
2. Aleman-Gonzalez-Duhart D, Tamay-Cach F, Alvarez-Almazan S, Medieta-Wejebe J.E., Current
advances in biochemical and physiological aspect of the treatment of the type 2 diabetes mellitus this
thiazolidinediones PPAR Res.2016,2016:7614
3. Ali F., Jamil H., Anwar SS., Wajd N. Characterization of lipid parameters in diabetic and non-diabetic
atherosclerotic patients. J Geriatric Cardiol, JGC, 2015, 12(1):37-43
4. Bays HE. Lowering low-density lipoprotein cholesterol level in patients with type 2 diabetes mellitus. Int
J Gen Med, 2014, 7:355-364
5. Brunzell J.D, Davidson 19., Furbeng CD, et.al. Lipoprotein management in patients with
cardiometaboli risk: consensus statemen from the American Diabetes Association and the American
College of Cardiology Foundation.Diabetes Care.2008,31(4):811-22
6. Cagatay P, Susleyici-Damian B,Alasya H, Ipbuker A. Effect of oral antidiabetic drugs over lipid
parameters in Turkish type 2 diabetes patients. Acta Media Academina,2009,38(2):77-85
7. Chavez JA., Summers SA. Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular
mechanisms. Biochim. Biophys. Acta, 2010, 1801(3):252-65
8. Hegele RA, Ginsberg HN, Chapman Mj, Nordestgaard BG,et.al. Lancet Diabetes Endocrinol,2:655-
666,2014
9. Kangralkar VA, Partil SD, Bandivadekar RM. Oxidative stress and diabetes: a review. Int J Pharm.
Appl, 2010, 1(1):38-45
10. Karalis DG. The role of liid-lowering therapy in preventing coronary heart disease in patients with type
2 diabetes. Clin. Cardiol., 2008, 3(6):241-8
11. Lass A., Zimmermann R., Oberer M., Zechner R. Prog. Lipid Res. 2011, 50(1):14-27
12. Mark L, Dani G, Diabetic dyslipidaermia and the atherosclerosis.Orv.Hetil.2016,157(19):746-52
13. Mooradian D. Dyslipidemia in type 2 diabetes mellitus. Nat. Clin. Pract. Endocrinol. Metab, 2009,
5(3):150-9
14. Ozougwu JC. Obimba KC, Belowu CD., Unakalamba CB. The pathogenesis and pathophysiology of type
1 and type 2 diabetes mellitus. J Physiol Pathophysiol., 2013, 4(4):46-67
15. Parhofer KG. Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia.
Diabetes Metab. J, 2015, 39(5):353-62
16. Pitha J, Kovar J, Blahora T, Fasting and monfasting triglycerides in cardiovascular and other
diseases.Physiol.Res.2015,66,Suppl.3:5323-30
17. Schofield JD, Liu Y, Rao-Balakrishna, Malik P, et al. Diabetes dislypidemia, Diabetes Therapy, 2016,
7(2):203-219
18. Stone NJ, Robinson JG, Lichtenstein HA,et.al.2013 Acc/AHA guideline on the treatment of blood
cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of
Cardiology/ American Heart Association Task Force on Practice Guidelines.ciculation,2014,129(25
suppl.2)51-45
19. Tannock L, Bhat A. Risk assessment and guidelines for management of triglycerides. In De Groot LL,
Beck-Peccoz P, et al Editors. Endotext (Internet). South Dartmounth MA: MDText.com 2015

95
 ROAD TRAFFIC INJURIES – MEDICAL, INSURANCE AND LEGAL ASPECTS

Dr. Ioana SOARE, insurance medical expert, lecturer UTM

Dr. Osama SALLOUM

Abstract
Children, pedestrians, cyclists and older people are among the most vulnerable of road users. Over 3400 people
die on the world's roads every day and tens of millions of people are injured or disabled every year. The most
frequent injuries encountered are head trauma, fractures and psychological consequences.
These accidents cause medical problems, medical insurance problems, and multiple legal problems related to
work accidents, life insurance, fault and damages, death.
Key words: road traffic injuries, trauma, head injury, fracture, short term sick leave, disability, pension, life
insurance, death

Children, pedestrians, cyclists and older people are among the most vulnerable of road
users. Over 3400 people die on the world's roads every day and tens of millions of people are
injured or disabled every year. The most frequent injuries encountered are head trauma,
fractures and psychological consequences. But we encounter also a lot of work accidents, in
professional drivers, policemen, couriers, selling agents. Work related accidents are road
accidents happening on the way to and from work to home, and in this cathegory we are all
included.
Given the high costs generated by the medical expenses of the victims of road
accidents in the European Union, 2% of GDP per year, it was made a plan to reduce them at
EU level by 2020.
Preventing various accidents that occur daily, both nationally and worldwide, is one of
the key priorities of the institutions because road accidents are among the main causes of
death among adults (about 1/3 of the total number of deaths recorded annually in Europe).
We conducted the study on a group of 42 patients who suffered various accidents in between
2008-2015. Patients came to the insurance medical expert to assess their functional deficit in
order to obtain some insurance rights.
For this study, we considered outlining and defining the impact of road crashes. Goals:
• trama caused by road accidents;
• identify those populations that have a serious risk of injury in case of an accident;
• an assessment of the impact on the functionallity by various injuries that occur when
involved in a road accident.
The main goals envisaged were following the evolution of these 42 patients,
identifying those damages that were caused by trauma suffered by them as a result of
involvement in various road incidents, taking into account the number of days they have been
granted short term sick leave, as well as the functional deficit, the invalidity pension.
The most common injury reported in patients who were included in the study group
was craniocerebral trauma, with different degrees of severity. Basically, of the 42 patients
who were followed in 2008-2015, two thirds have suffered TCC, falling in the age group 21-
40 years, the gender distribution of cases being equal.

96
 Fig. 1. Distribution of pacients with craniocerebral trauma (5)

Besides craniocerebral trauma patients have suffered vertebral fractures. Out of the 42
patients, one-third were diagnosed with various vertebral fractures, the gender distribution in
this case being equal (i.e. by 7 cases), the most affected beeing people aged between 21-40
years.

Fig.2 Vertebral fractures statistics (5)

Broken legs, as upper limb fractures were found in almost half of patients in the study,
the vast majority of which are included in the same age category mentioned.
12% of all patients who underwent this research presented simultaneously leg
fractures and fractures of the upper limb, which reflected mainly not only at the level of the
number of days of short term sick leave, but especially on the current functional deficit. In
these cases, the most affected were patients in the age group 31-40 years.

97
 Fig. 3 Total limb fractures (5)

Pelvic fractures were diagnosed less often if the enrolled patients, below 20%.
The most affected patients were between 41-50 years.

Fig. 4 Total basin fractures (5)

Worthy of mention is the fact that due to traffic incidents they have been involved in,
over 80% of all these patients experienced immediatly a functional deficit of 100%. Many of
them remained with various sequelae, which are reflected in the actual functionality.
Fewer than 5% of the total number of patients now present a functional deficit in the
range of 5-10%, while 20% of the patients still show a functional deficiency of 70% and
nearly 40% of patients still have a functional impairment ranged between 30% -40%.
The lesions found had different degrees of severity, something that was reflected
especially in the functional deficit and in the number of days of short term sick leave.
Most cases were within 51-100 days of short term sick leave. Most patients were aged
between 20 and 40 years, took sick leave up to 90 days and returned to work, had low and

98
middle income. Even if they had a functional deficit, they did not take more sick leave
because of low incomes.

Fig. 5 Total short term sick leave days (5)

Only 36% of all patients went on disability pension, because of reduced income during
retirement. Immediately functional deficit caused by multiple trauma was observed in most
patients as being caused by head trauma and fractures.

Fig. 6 Functional deficit (5)

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 A novelty of this work is the study of polytrauma by road accidents in terms of the
damage caused to the patient: functional deficit, sick leave and disability retirement.

Insurance aspects

Following involvement in a road accident victims may be located in one of the

following cases and may die, may suffer a temporary disability or suffer a permanent work
incapacity (disability). Sometimes you can see a work accident (on the way to work or back
home or for work performed as professional driver, courier).
By law, all persons who are insured under the Romanian mandatory insurance are
entitled to benefit from various services and benefits as:
• obtaining compensation for temporary incapacity (short term sick leave);
• medical rehabilitation and recovery of work capacity;
• return to work and retraining;
• obtain an allowance for moving to another job, temporarily;
• obtain compensation for the reduction of working time;
• Miscellaneous compensation to achieve integrity;
• compensation - in case of death;
• reimbursement of expenses.

Regarding the calculation of temporary disability allowances dedicated, it is calculated

taking into account the average gross income per month obtained by the employee during the
last six months prior to the event.
By law, all insured persons are entitled to receive various medical services for
investigation, diagnosis and restore health, and for recovery of work capacity, taking into
account the legal provisions.
Also by law, the insurer is obligated to pay for various medical services which are
awarded for:
• restoring health or to improve various health deficiencies that arose from the insured risk;
• prevention of reduction or loss of work capacity in the evolution of the sequelae, as well as
the prevention of need for permanent care.

In medical rehabilitation, as well as the recovery of work capacity, all insured persons
benefit from various individual rehabilitation programs, set by the physician, taking into
account both the diagnosis and the nature of the disease. Depending on the type of disease,
this program may include periodic cures of individual recovery and balneophysiotherapy, 15
days - 21 days.
By law, insured persons are obliged to follow the recovery programs, otherwise the
insurance rights beeing suspended.

All insured persons (regardless if they have an employment contract for an indefinite
period / determined period, part time- 2, 4, 6 hours / day), same as the disability retired
patients (grade III), persons who are included in free professions, unemployed or retirees
rehired (which cumulat pension and salary) are eligible for compensation for short term sick
leave if they prove that they are temporarily incapacitated, having obtained a medical
certificate issued under the conditions provided by law.

Regarding the revenues that are obtained during short term sick leave, their value is a
percentage ranging between 75% -100% of the monthly income of the person. Short term sick
leave / temporary disability allowance may be granted for a maximum duration of 183 days /
365 days / 548 days, which are calculated from the first day of incapacity, depending on the

100
condition. Temporary work incapacity certificates (which are issued monthly, for a period of
31 days) can be given at an interval of more than 24 hours after onset of the disease in
hospital admission, plaster appliances, in quarantine situation, as the accidents happening
abroad. After 90 days of sick leave, it can be extended with the approval of the social
insurance medical expert. At the end of 183 days of short term sick leave a doctor may apply
for a further 90 days to recover the patient or for another disease that has appeared in the
meantime.
For people who have lost partially or totally the work capacity, the law grants a
disability pension.
By disability we mean a functional deficit greater than 50%.
Inclusion in a certain degree of disability is accomplished considering the expanded
medical criteria. Thus, a functional deficit in the range of 50-69% is required for classification
in grade III of disability (the person has the possibility of part time work).
A functional deficit between 70-89% leads to a classification in grade II disability (the
patient has lost full work capacity) and functional deficit in the range 90-100% leads to
admission to the degree I of disability, the person having lost the ability to self-service, self-
conduction or capacity of spatial orientation, situations which require permanent care or
supervision by another person.
In order to determine the degree of disability, the person must report to the service of
medical expertise with the report issued by the treating physician and all the medical records.
In case of confirmation, the insurance medical expert will complement the medical report,
issuing a medical decision what will be sent to the regional pensions office.
The damage is evaluated based on:
- Altering health emergence of a functional deficit
- Decrease in quality of life after recovery (by sequelae, psychological trauma, retirement)
- Decrease in revenues during illness and disability pensioners.

Analyzing data that was collected during the course of research, it was able emphasize
that the populations that may be at serious risk of injury in case of a road accident is included
in the age group 21 - 40 years. Worthy of mention is the fact that the distribution by age of the
patients included in the periods considered (ie 21-30 years, 31-40 years and 41-50 years) was
approximately equal, the only major differences being in the range 17-20 and 51-56 years
respectively. Much of the patients in the study group came from families with low and middle
income, which may have particular relevance in the process of recovering the loses, recovery
can be not only cumbersome and difficult, but expensive.

Legal Aspects

Patrimonial damage compensation has dedicated levels (aimed at the suffering

endured by the person who was injured in a road accident) and can be adjusted based on
various existing samples, depending on the specifics of the case. According to law, those
damages diminish when:
• the victim did not use mandatory safety elements provided for by law (such as wearing seat
belts, wearing helmet, winter tires, etc.) due to which it was produced, or merely expanded
that harm;
• the victim agreed to be transported by a vehicle or on a seat that was not intended to
transport people;
• the victim agreed to be transported in a vehicle and it knew that it is led by a person who
was under the effect of alcohol or other substances (drugs or narcotics);
• the victim intentionally or negligently contributed to the damage or to its development, as
where he had the opportunity to avoid injury in part or in whole and had not done so.

101
 If bodily injury or health-patrimonial damage is determined through various forensic
act, we consider the total number of days of medical care.
If the victim is still living, the prosecutor will make a mandatory penal trial.
The victim can choose a mediator or a lawyer to obtain his/her insurance rights from the
insurance company, based on the RCA compulsory insurance of the driver.
In case of a death in a work accident, the family receives up to 4 medium salaries.
If the person had a life insurance, the family will receive the amount insured.
If the person had only the usual insurance (state insurance for all) the family will receive only
1 medium salary, as a help for funerals, and only if he was retired.
The compensation for death shall not be granted to the driver in the situation where he was
found liable for the accident or if the accident occurred due to his health.
Manslaughter victim was crossing the street in an illegal place, Art. 192 Manslaughter, Penal
Code:
1. art. 31 Cp - As the act was committed in unforeseeable circumstances, the driver was
found not guilty. (Curtea de Apel Bacău, Penal Decision nr. 611/2015, www.rolii.ro)
2. The common fault of the accused and the victim/pedestrian in the road traffic accident
was 30% the accused and 70% the victim. (Judecătoria Sectorului 1 Bucure ti, Penal
Sentence nr. 29/2015, portal.just.ro)
3. a higher degree of contribution of the victim to the accident , setting its fault rate of
75% and 25% the driver.(ICCJ, Secţia penală, Decision nr. 352/A din 30.10.2014,
www.scj.ro)

References

1. Law 236/2010, Pension Law

2. Law 346/2002, Work accidents and occupational diseases Law
3. GEO 158/2005 on short term sick leave and health insurance benefits,
4. Ioana Soare, International Pensions, Insurance Medicine, Etna Publishing House, 2010
5. Osama Salloum, Trauma Injury Evaluation in Road Accidents, license paper, UTM, 2016
6. Penal Code, law 286/2009
7. Penal procedure code
8. Civil Code, law 287/2009
9. Civil procedure code
10. Penal Decision nr. 611/2015, www.rolii.ro
11. Penal Sentence nr. 29/2015, portal.just.ro
12. Decision nr. 352/A 30.10.2014, www.scj.ro

102
PSORIATIC ARTHRITIS, CLINICAL ASPECTS AND DIFFERENTIAL DIAGNOSIS

Dr. Simona SOARE, Medic primar medicina interna si reumatologie, sef de lucrari UTM

Abstract
Psoriatic arthritis is an musculoskeletal disease, both autoimmune and inflammatory occurring in individuals
with psoriasis.
This paper aims to describe psoriatic arthritis as a distinct entity within psoriatic disease (2-3% of the general
population), which is a systemic inflammatory disease currently considered.
Patients with psoriasis should be carefully checked and investigated by entesial ultrasound, MRI, for the
detection of joint damage in early stages, for a correct and quick diagnosis and appropriate, more aggressive
treatment in the presence of psoriatic arthritis, which will help prevent disability.
Differential diagnosis in psoriatic arthritis will be done with rheumatic fever at a young age, rheumatoid
arthritis, atritele crystal or septic arthritis, lupus, arthritis.
It presents comorbidities and we need to identify the patient's at risk for metabolic disorders and cardiovascular
diseases, to correct and to treat risk factors the associated conditions.
There is not a consensus among family doctors Currently, dermatologists, rheumatologists, orthopedic doctors
and rehabilitation doctors, Concerning the algorithm for diagnosis and treatment of psoriatic arthritis with the
patient's. The author enhances the idea That we Need a Multidisciplinary team.

Key words: psoriasis, psoriatic arthritis, diagnosis, differential diagnosis

Psoriatic arthritis (PsA) is framed in seronegative Spondylarthropathies family

together with ankylosing spondylitis, reactive arthritis, undifferentiated spondyloarthritis and
enteropathic arthritis.
APs initially was considered as rheumatoid arthritis in context of psoriasis.
Considering the radiological studies, the absence of rheumatoid factor and based on clinical
examination, rheumatoid arthritis and psoriatic arthritis were considered two separate entities.
The classic features of psoriatic arthritis were described by Wright in 1959, which
together with Moll published the criteria for classification in 1973. (Moll & Wright, 1973)
These criteria were used in clinical to poliarthritis (similar rials until recently. The five
clinical patterns of psoriatic arthritis described are: asymmetric oligoarthritis, symmetric
poliarthritis( simmilar to rhumatoid arthritis), distal interphalangeal arthritis, axial involvment
(spine and sacro-iliac joints) and destructive arthritis (mutilans).
APs was considered a more severe phenotype of the psoriatic disease based on several
susceptibility genes and several environmental factors present in these patients. APs starts,
according to most studies, every one to two decades after the onset of skin manifestations of
psoriasis.
Epidemiologically APs occurs in 7-25% to 30% of patients with psoriasis (arthritis
prevalence in the general population is 2-3%); It has an equal distribution by gender and
affects mainly white race. Psoriasis occurs in teens and young adults; tip of developing
psoriatic arthritis is between 22-40 years. (O. Fitzgerald, 2013)

30%
70%

Psoriazis artropatic Psoriazis fara artropatie

Fig. 1 The prevalence of PsA in patients with psoriasis

103
 40

30

20

10

0
Psoriazis Artropatie
psoriazica

Varsta de debut

Fig. 2 Age of onset psoriasis and PsA

Icelandic patients have been sudied in large genetic studies in five generations in order to
establish the rate of risk of developing psoriatic arthritis at descendents. The results confirmed
a strong and complex relationship with the genetic factor, which extends up to the 4th
generation. (Karason, et al, 2009)
CD8 + T cell supports the central role in the mechanism of this arthritis and manifests an
independent role towards the presence of CD4 + T lymphocyte. A proof of this is that HIV
infection is characterized by lymphocytic depletion of CD4 + and is often associated with
severe psoriatic arthritis. (Njobvu P and P McGill, 2000)
In the synovial fluid is found clonal expansion of CD8 + lymphocytes.
Classical aspects of pathogenesis of the APs take into account the characteristics of the host (
intrinsic factors) and extrinsic factors.

Factori genetici

Trauma
Stress fizică

Factori infecțioși
(viral/bact)

Fig. 3 Environmental factors involved in the occurrence of PsA

1. Intrinsic factors
Among the inhereted factors, genetic factors play an important role in the development of the
disease. There is a genetic susceptibility to develop psoriasis and psoriatic arthritis. Family
studies have shown a risk of psoriatic arthritis rate 55 times higher in first-degree relatives of
these patients compared with controls and only 8-10 times higher for psoriasis. (Parker H)
Studies of monozygotic twins have shown an increased rate of concordance in patients with
psoriatic arthritis than those dizygotic. (CJ Eastmond, 1994). Descendants of psoriatic arthritis
patients are more likely to develop the disease if the sick parent is father, versus those whose
sick parent is the mother; currently it is not known why the risk is greater for paternal than
maternal transmission, in the risk of developing psoriatic arthritis in offsprings. (Rahman et
al., 1999)
Genetic studies in regions HLA B and C of psoriasis patients and of those with psoriatic
arthritis showed significant differences, suggesting that psoriatic arthritis can not be regarded
as a subset of the genetic psoriasis, but as a separate entity.

104
 Fig. 4 The presence of HLA-12, HLA-B 38 and 39 favors the onset of arthritis.
(Eder L et al., 2012)

The spinal injury is important when associated with HLA-B27, but this combination is
uncommon compaired with ankylosing spondylitis or reactive arthritis. There are psoriatic
spondilarthritis in negative for HLA-B27 patients.. (Gladman DD, et al., 1995)
Genes Il-23, TNFAIP3 (TNF alpha induced protein3) TNIP1 (TNFAIP3 interaction protein
1), genes involved in auto-immunity and general occurring in rheumatoid arthritis, in systemic
eritematous lupus appear in patients with psoriatic arthritis. (Plenge et al., 2007; Graham et
al., 2008; J Bowes, Barton A, 2010)

2. Extrinsic factors
The influence of environmental factors on the onset of arthritis was assessed mainly through
clinical trials.
The trauma was proposed as trigger for episodes of synovial inflammation, called deep
Koebner phenomenon. Arthritis can be triggered by sprains, dislocations, lifting weights. (A
Fitzgerald, 2013 Antoni C, 2003)
Infectious factors were also involved in the onset of psoriatic arthritis, mainly Streptococcus
group A or B. (Wilbrink B et al., 1998)
HIV infection is associated with psoriasis and psoriatic arthritis and leads to aggressive forms
of the disease. HIV infection produces a particularly depleted CD4 + and increased CD8 +
105
ratio / CD4 +. In Zambia, where HIV is endemic, occurring in approximately 30% of the
population, those who develop psoriatic arthritis have a HIV infection rate of 94%. (Njobvu P,
P McGill, 2000) Consequently, HIV can be considered a powerful viral trriger of the psoriatic
arthritis.
Stress is a trigger for the disease, many patients declaring the presence of a stressful event
before the onset or exacerbation of the disease, perhaps by neuro-peptides released by
psychological stress, activating the immune system who releases proinflammatory cytokines.
Smoking is a risk factor for developing psoriasis, but there is an inverse association with
psoriatic arthritis. (L Eder et al., 2012 b)
Targets of the inflammatory process in PsA are synovial joints, enthesis, articular cartilage,
bone joint and skin.
In psoriatic arthritis, at synovial level there is a more developed vascularisation, with a larger
number of vessels than in rheumatoid arthritis, due to neo-angiogenesis. The synovial
hyperplasia and infiltration with macrophage cell line are less obvious in APs compaired to
PR.
At synovial level were found pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-6 and IL-
10 and cytokines of innate immunity: Il-18 and Il-15. (A Fitzgerald, 2013) Patients with
psoriatic arthritis have an increasing number of Th 17 cells and an increased level of IL-17 in
the synovium, synovial fluid and the skin affected by psoriasis. (Jandus C et al., 2008;
Raychaudhuri et al., 2010)
IL-12 and IL-23 are associated with susceptibility to psoriasis and psoriatic arthritis. (Filer et
al., 2008)
TNF-alpha cytokine plays a key role in the pathogenesis of PsA and is found in high
concentrations in synovium, synovial fluid and the skin of patients with psoriatic arthritis.
(Ritchlin, C. et al., 1998)
3. Clinical Features
PsA is heterogeneous in terms of skin rash and joint pain, the severity of each these features
and the coexistence of different types of disease.
The clinical features of psoriatic arthritis are:
• peripheral and axial arthritis
• enthesitis
• dactylitis
• nail injury
• psoriasis.
There is a temporal relationship between the development of PsA and the cutaneous lesions in
most cases (approximately 75% of arthritis the patients already are clinically diagnosed with
psoriasis and is regarded as an evolutive form of psoriatic disease. There are situations when
the impairet of skin and joints occur simultaneously - 10% of cases. The most difficult
diagnostic appears when arthritis precedes skin lesions - 15% of cases, delaying the diagnosis
of psoriatic arthritis. (Gladman et al., 1987)
Clinical onset can be mono, oligo or polyarticulary.
Moll and Wright have established a classification of clinical features in joints:
• asymmetric oligoarthritis
• symmetric polyarthritis
• damage to joints mainly distal inter-phalangeal (DIF)
• predominant axial involvement (spondilarthritis)
• Hand destructive arthritis (mutilans).
The oligoarticular form is asymmetrical and affects the small joints of the hand and a big joint
-knee. The ssociation with dactylitis and skin lesions are often modest.
The polyarticular form is symmetrical. Women are particularly affected. Like rheumatoid
arthritis, PsA affects the small joints of the hands and feet, but unlike it, are affected

106
simultaneously the distal joints inter-phalange. So all joints of the finger are affected, giving
the characteristic appearance of "sausage". There are also joints of the fingers unaffected by
the inflammatory process. In rheumatoid arthritis the damage appears horizontally, affecting
all meta-carpo-phalangeal (MCF)andproximal inter-phalangeal (PIF) joints.
The CASPAR study, conducted for classification APs, revealed a net predominance of the
polyarticular to form versus oligoarticular form (63% vs 13%). The form with predominant
involvement of DIF joints meets low percentage (5% of cases). (Helliwell et al., 2007)

Forma mutilanta 4
5
Forma spinala 40
13
Forma poliarticulara 63

0 10 20 30 40 50 60 70

Fig. 5 Main forms of APs and their frequency

Peripheral arthritis is characterised by pain, swelling, local erythema, local temperature rise
and functional impairement. The clinical aspects are the result of synovitis. The most
commonly affected joints are PIF and DIF of the hands and feet, joints MCF, metatarsal
phalange (MTF), radio- cubito-carpal (RCC), tibial-tarsus, knees and elbows.

Fig. 6 Seat of the inflammation in PsA

107
DIF arthritis is a hallmark of PsA and an important element for the differential diagnosis with
rheumatoid arthritis which does not affect these joints.
In prospective studies concomitant flare of arthritis and skin damage was observed only in
35% (Gladman et al., 1987) although most studies are linking the severity of flares of arthritis
to the severity of skin lesions.
It is described a severe form of peripheral joint damage, erosive arthritis, a destructive form
due to the osteolysis of the distal phalanx and the pathognomonic radiography gives the
appearance of "pencil holder" (in pencil cup). This form occurs in situations where treatment
has not been established or were are aggravating factors, such as HIV.
Important to keep in mind is that the clinical form is not immuable, clinical pattern may
change over time: it can worsen without TREATMENT form oligoarticular arthritis passing
in a poliarticular form, or in reverse after treatment, the polyarticular form goes to the
oligoarticular form.
Mainly axial form is rare. Its frequency is increased when judged in the presence of other
clinical forms of psoriatic arthritis and when spinal damage is assessed and withX-ray
examination (40% -70%). (Battistone et al., 1999) Risk factors for spinal damage are the
presence of HLA-B 27 and the peripheral severe arthritis. (Chandran et al., 2010) 30% of
psoriasis patients have back and neck pain.
Clinically, the axial disease begins with deep buttock pain, difficult to locate and has insidious
onset and is due to sacroileitis. The pain radiates towards the region of the greater trochanter
and posterior region of the thigh. Coughing and sneezing can exacerbate the pain. At the
onset, the pain is unilateral and intermittent. In a few months it becomes persistent,
comprising the lumbar region and is accompanied by stiffness, most severe in the morning.
Both pain and stiffness may improve with movement, gym, hot showers, non-steroidal anti-
inflammatories and are not improved by rest.
As a result of persistent pain, stiffness of the spine in the lower region, the patient wakes up in
the second half of the night and has chronic fatigue syndrome.
Psoriatic arthritis can affect both the lumbar and the dorsal spine, with stiffness and impaired
mobility. Damage of the cervical segment of the spine is responsible for pain and morning
stiffness at this level.
CASPAR Study proposed The Classification of psoriatic Arthritis (Helliwell et al., 2007). The
study included 588 patients versus 536 witnesses, considered subtypes of arthritis and defined
as inflammatory joint disease when minimum 3 points of the following were accumulated:
Criteria Score
Manifest Psoriasis 2pct
Personal history of psoriasis objectified by the doctor 1pct
Family history of psoriasis 1pct
dactylitis 1pct
Juxta articular new bone formation 1pct
FR negative 1pct
One nail dystrophy 1pct

Enthesis represents the place where tendons, ligaments, joint capsules and sheaths are fixed
on bone surfaces. They are designed to reduce bio-mechanically stress at this level and are
subjected to repeated micro-trauma.
Enthesitis is the inflammation of the enthesis. Enthesitis are the hallmark of spondilarthritis.
They express local tenderness and swelling. They are located mainly in the lower limbs,
probably due to higher stress, and are easilly accessed to ultrasound diagnosis. Their
diagnosis is important because sometimes the only clinical features of the disease are the
enthesitis. Their prevalence is about 38%. (Kane et al., 2003) The subclinical damage is
diagnosed by ultrasound. The most common locations of enthesitis are the Achilles tendon,

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plantar fascia, but also: inserts on the iliac crest, rotator cuff, epicondilii humeri, enthesitis of
the ribs, elbow.

Fig. 7 Achilles Tendinitis (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology,

Hospital Elias)
Dactylitis like enthesitis is a characteristic feature of psoriatic arthritis. It has a prevalence of
29% -33.5% upon presentation to a doctor, in patients with psoriatic arthritis. (Kane et al.,
2003; Brockbank et al., 2005) It manifests itself through diffuse swelling of the fingers, hand
or foot and can be acute and chronic. In the acute form of inflammation dislays the classic
signs: tumor, rubor, calor, dolor and functional impairment. In the chronic form lasts only the
diffuse swelling of the fingers. Dactylitis is a characteristic sign of psoriatic arthritis, but not
pathognomonic and can be found in other spondylarthropathies and other diseases such as
gout, tuberculosis, sarcoidosis, sickle cell anemia and beta-hemolytic streptococcal infections.
The appearance of sausage finger is given by flexors tenosynovitis, peritendinous edema,
joint synovitis PIF, DIF, MCF, MTF, juxtaarticular periosteal reaction.

Fig. 8 Dactylitis (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology, Hospital Elias)
The patterns of nail involvment are: pitting (dystrophic depressions), horisontal Beau lines,
onycholysis, yellowish discolouration, dystrophic hyperkeratosis , splinter haemorrhages. Nail
psoriasis occurs generally in the presence of skin lesions of psoriasis (in 10-55% of patients),
but in rare cases is the only manifestation of the disease. It is very common in patients with
psoriatic arthropathy.

Fig. 9 Nail psoriasis (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology, Hospital Elias)
The most frequent skin lesion is psoriasis plaque. Psoriasis plaque is an erythemato-squamous
injury, well defined, scaly, pearl white, multi-layered, easily removable and is located mostly
on the knees, elbows, back, buttock and in locations less visible, such as the scalp, ombilicus,
folds of the skin (buttocks, armpits, groin, underbreasts).

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 Fig. 10 Psoriasis vulgaris (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology, Hospital
Elias)
In much smaller proportion psoriasis occurs as pustular, guttate, erythrodermic.
Guttate psoriasis is between 1.6-44% of psoriasis cases, the second frequenct form of
psoriasis in children. Streptococcal group A β-hemolytic pharyngeal disease often precedes
the onset by 2-3 weeks and is considered a precipitating factor. (Nahary et al., 2008) It affects
both sexes equally and more frequently individuals aged under 30 years. Papules and plaques
appear as erythemato-squamous small (1-10 mm) with fine scales, disseminated on the
surface. Particularly affected are the trunk and proximal extremities, but can be generalized.
Rarely it has a chronic course, but it can turn to plaque psoriasis.

Fig. 11 Psoriasis guttata (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology, Hospital
Elias)
Pustular psoriasis is a rare form of psoriasis, which may arise de novo or amid chronic
psoriasis plaques. It manifests itself as small sterile pustules on an erythematous base and
presents two clinical forms:

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- Generalized pustular psoriasis von Zumbusch: erythematous areas and disseminated pustules
that can confluent in large lakes of pus. It may be complicated by sepsis, hypoalbuminemia,
hypocalcemia, renal tubular necrosis, hepatic disease, malabsorption, malnutrition, death from
cardio-respiratory failure;
- Pustular psoriasis can be located: palmar-plantar pustulosis and acro-suppurative dermatitis
Hallopeau.
Pustular psoriasis may develop into psoriatic erythroderma. It requires close monitoring
because generalized form can be fatal without prompt treatment.

Fig. 12 Plantar pustular psoriasis (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology,
Hospital Elias)
Erythrodermic psoriasis is manifested by erythema and generalized desquamation, affecting
more than 90% of the body, often accompanied by fever, chills or hypothermia, sometimes
cardiovascular instability and hypotension. It can be associated with fluid or electrolyte and
metabolic imbalance.
Most often it occurs due to a worsening of pustular psoriasis plaque.

Fig. 13 Erythrodermic psoriasis (courtesy of Prof. Dr. Calin Giurcaneanu, Dermatology,

Hospital Elias)

The severity of skin lesions in psoriasis is measured by the index PASI (Psoriasis Area and
Severity Index) indicator combining the severity of lesions and of the size of the area affected
into a single score, between 0 and 72.
Each region of the body is measured. By the size of the affected area:
• impairment 0
• <10% of impaired Grade 1 skin area analyzed
• 10-29% grade 2
• 30-49% grade 3
• 50-69% grade 4
• 70-89% grade 5
• 90-100% grade 6

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Each affected lesion area is analyzed by severity of erythema, induration and desquamation
on a scale from 0 to 3: 0 -without damage, impaired 1- slight, 2 - moderate impairment 3 -
severely impaired.
The amount of severity parameters for each area obtained are multiplied by the
predetermined coefficient for each area of the body: head - 0.1; upper limbs - 0.2; trunk - 0.3;
legs - 0.4.
The extraarticular manifestation outside skin and nail lesions is the eye disease:
conjunctivitis, iritis, uveitis. The acute form is the red eye, itchy local pain and a marked
decrease in visual acuity. Iritis or uveitis occurr with greater frequency than in ankylosing
spondylitis, are bilateral and occur mainly in the axial pattern. Uveitis prevalence is lower in
patients with psoriatic arthritis, ankylosing spondylitis compared to reactive arthritis. (Queiró
et al., 2002)
Psoriatic arthritis is most frequently associated with inflammatory bowel disease, particularly
Crohn's disease. Peripheral psoriatic arthritis correlates with inflammatory bowel disease.
(Williamson et al., 2004)
Psoriatic arthritis is associated with edema or lymphedema of distal lower limbs.

4. Diagnosis
The diagnosis of PsA can be done easily when we are faced with a patient with psoriasis and
peripheral arthritis, but the rhumatoid factor is absent. Skin lesions and nail dystrophy may
occur after developing arthritis or enthesitis. To overcome the difficulties of diagnosis in the
latter two situations and to have homogenous populations in clinical trials, CASPAR group
has developed diagnosis criteria with high sensitivity and specificity. (Taylor et al., 2006)
CASPAR classification criteria for psoriatic arthritis:
Inflammatory joint disease - joint, spinal, joint enthesitis- 3 of the following:
1. Psoriasis (a, b or c)
a. psoriasis diagnosed at the time of dermatologist or rheumatologist
b. psoriasis personal history obtained from the patient, family physician, dermatologist,
rheumatologist, other carers
c. family history of psoriasis (first or second degree relatives) reported by the patient
2. psoriatic nail dystrophy including onycholysis, hyper-keratosis, nail depressions observed
on physical examination
3. rheumatoid factor negative (ELISA or nephelometry, latex no method after local laboratory
values)
4. dactylitis (a or b)
a. swelling of an entire finger when examined
b. dactylitis history confirmed by a rheumatologist
5. radiological evidence of juxtaarticular new bone formation (joint ossification at the edges
of the hands or feet - excluding osteophytes)
Diagnosis algorithm for the patient with a possible psoriatic arthritis (amended Fitzgerald A,
2013):

5. Differential Diagnosis
The shape of the peripheral psoriatic arthritis:
To form the predominant damage to joints hands or feet, differential diagnosis of PsA include:
• rheumatoid arthritis
• gout
• systemic lupus erythematosus
• peripheral form of SPAs
• septic arthritis
• DIF joint arthrosis.

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In rheumatoid arthritis joints affected by inflammatory process are PIF, MCF, but never DIF
joints of the hands. Arthritis is symmetrical, affecting mainly the hands and be accompanied
by morning stiffness. The inflammatory process is carried horizontally (MCF and PIF).
DIF joint inflammation is an important sign for differential diagnosis between the two
arthritis, as the presence or enthesitis, dactylititis, also arguments for psoriatic arthritis. The
sacro-ileitis changes in X-ray or MRI, advocate for psoriatic arthritis.
Other affected joints are RCC , elbow, and in legs - PIF, MTF, tibiotarsian, knees.
The microcrystals arthritis (gout, pseudogout or chondrocalcinosis, ochronosis) is determined
by increasing uric acid, pyrocalcium phosphate, respectively phenols (homogentizic acid and
hydroquinone) hydroxyapatite deposits.
Gouty arthritis is usually monoarticular, a disease of the lower extremities The impaired joint
is mainly meta-tarso-phalange I (toe). 90% of patients had the first attack of gouty arthritis at
this level. In descending order of frequency the joints affected are meta-tarso-phalangeal,
tibio-tarsal, heel, knee, RCC, DIF, elbows. Usually it occurs in older age, 40-60 years in men
and after 60 years women. The differential diagnosis ia made by the analysis of synovial fluid
which highlights uric acid crystals in gouty arthritis. Serum uric acid may be increased in
patients with psoriatic arthritis too. It can be accompanied by tenosynovitis, bursitis.
Arthritis in systemic lupus disease is characterized by inlammation of the small joints of the
hands, knees. The inflammatory phenomena on these joints are less marked than in
rheumatoid arthritis. The synovial fluid is in a lesser amount. Deformations occur mainly due
to ligament laxity or subluxation at this level, like Jaccoud arthropathy. Changes are
reversible. Unlike rheumatoid or psoriatic arthritis, the radiologic imaging or MRI reveals no
bone erosions. When highlights bone erosions, they are usually associated with the presence
of antibodies to cyclic citrullinated antipeptide. It appears also juxta-articular teno-synovitis.
Septic arthritis is usually monoarticular. Hematogenous dissemination occurs through
inoculation or local accident or unsterile maneuvers. It has sudden loud onset, fever, local
pain, redness and symmetrical swelling of joints, local periarticular soft tissue edema,
synovial hypertrophy and increased amount of synovial fluid. It is accompanied by functional
impairment. The germs involved are usually Staphylococcus aureus, Streptococcus,
Haemophilus influenzae. Septic arthritis after treatment appears due to decreased immunity,
such as in anti-TNF therapy. Radiological examination and initial MRI reveals osteopenia and
joint space widening, then, shortly after, appear bone erosions and joint space narrowing by
cartilage destruction. Joint ankylosis occurs in late stages. Septic arthritis changes are
nonspecific. MRI is also used to highlight complications: abscess and osteo-myelitis. Etiologc
diagnosis is established by arthrocentesis: cloudy liquid with increased number of leukocytes
in the synovial fluid, with predominance of neutrophils.
Heberden and Bouchard nodules are the characteristic element for hand osteoarthritis.
Heberden nodules are bony growths that appear in the DIF joints. At the ondset the nodules
are red, swollen, painful and associated with impaired hand function. They are situated at the
edge of the dorsal-lateral or medial phalanges. Bouchard nodules develop in the PIF. Nodule
development occurs in weeks, months or years. Their presence is accompanied by pain and
morning stiffness. Simple radiography is considered the "gold standard" for assessing changes
in osteoarthritis of the hand, providing a two-dimensional image for thinning of bone and
articular cartilage (indirect); subchondral bone sclerosis, forming cysts and bone spurs at the
lateral edge of the joints DIF and PIF. MRI is more sensitive in early detecting changes in
articular cartilage and bone erosions, early detection of osteophytes. (Ionescu R)
Differential diagnosis for the axial form of PsA is made with other seronegative
spondylarthropathies: ankylosing spondylitis (bilateral sacroiliac damage, bilateral
sindesmofite), Reiter's syndrome (urethritis, Chlamydia coexistence, ocular damage) and
Crohn's disease.

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The differential diagnosis can be made and depending on the patient's age:
1. up to 20 years:
a. rheumatic fever,
b. juvenile arthritis,
c. Infectious arthritis,
d. osteo-Calvé Perthes Condrita distorting Legg-.
2. 20 to 40 years:
a. discopathies vertebral
b. spondylo-listezis,
c. inflammatory arthritis,
d. septic arthritis,
3. over 40 years:
a. discopathies vertebral
b. spondylo-listezis,
c. inflammatory arthritis,
d. osteoporosis,
e. metastases.
There is not currently a consensus among family doctors, rhumatologists, dermathologists,
orthopedicand rehabilitation doctors concerning the algorithm for the diagnosis and
treatement for the patients with psoriatic arthritis. It is obvious that we need a
multidisciplinary team or a specialised center as in other rare diseases.

References
1. Battistone MJ, BJ Manaster, Reda DJ, et al: The prevalence of psoriatic arthritis in sacroiliitis:
new perspectives from a large, multicenter cohort. A Study Department of Veterans Affairs
Cooperative. Skeletal Radiol 1999; 28: 196-201.
2. JE Brockbank, Stein M, Schentag CT, et al: Dactylitis in psoriatic arthritis: a marker for
disease severity ?. Ann Rheum Dis 2005; 64: 188-190.
3. V Chandran, Tolusso DC, Cook RJ, Gladman DD: Risk factors for axial inflammatory
arthritis in psoriatic arthritis Patients with. J Rheumatol 2010; 37: 809-815.
4. Gladman DD, Antoni C, Mease P, et al: Psoriatic arthritis: Epidemiology, clinical features,
course, and outcome. Ann Rheum Dis 2005; 64 (Suppl 2): ii14-ii17.
5. Gladman DD, Shuckett R, Russell ML, et al: psoriatic arthritis (PSA) -an analysis of 220
Patients. Q J Med 1987; 62: 127-141.
6. Fitzgerald O. Kelley Textbook of Rheumatology, 9th Edition, 2013, pp. 1232-1250
7. Helliwell PS, G Porter, Taylor WJ: Polyarticular psoriatic arthritis psoriatic arthritis is more
like Oligoarticular, rheumatoid arthritis than. Ann Rheum Dis 2007; 66: 113-117.
8. Ruxandra Ionescu, C. Constantinescu, Psoriatic arthritis, Essential in rheumatology, Publisher
Amaltea 2013
9. Kane D, L Stafford, Bresnihan B, et al: A prospective, clinical and Radiological study of
psoriatic arthritis early: an early synovitis clinical experience. Rheumatology 2003; 42: 1460-
1468.
10. Nahary L, Tamarkin A, Kayam N, Sela S, L Fry, Baker B, et al. An Investigation of
antistreptococcal antibody Responses in guttate psoriasis. Arch Dermatol Res. 2008; 300 (8):
441-9
11. Liliana Gabriela Popa, Psoriasis and cardiovascular disease, Thesis, Bucharest, 2012
12. Queiró R, Torre JC, Belzunegui J, et al: Clinical features and predictive factors in psoriatic
arthritis-related uveitis. Semin Arthritis Rheum 2002; 31: 264-270.
13. Taylor W, Gladman D Helliwell P, et al: Classification criteria for psoriatic arthritis:
development of new criteria from a large international study. Arthritis Rheum 2006; 54: 2665-
2673.
14. L Williamson, JL Dockerty, Dalbeth N, et al: Gastrointestinal disease and psoriatic arthritis. J
Rheumatol 2004; 31: 1469-1470.

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 AUDITORY DISORDERS IN THROMBOPHILIA DIAGNOSIS

Cristina STOICA, Assist. Prof., PhD, “Titu Maiorescu” University – Faculty of Medicine,
Bucharest, Clinical Hospital CF1 Witting – Bucharest
Gabriel BRÂNZOI, Stud., “Titu Maiorescu” University – Faculty of Medicine, Bucharest

ABSTRACT

The aim is to underline the importance of complete clinical and paraclinical evaluation (including
interdisciplinary collaboration) of the patient with auditory disorders to identify the etiopathogenic mechanism
and the proper treatment.
Method consist in identifying and presenting eloquent cases for this type of pathology.
Results are finalised with establishing diagnostic and therapeutic strategies for patients with SSNHL,
helping to identify those likely to repeat ischemic vascular manifestations both at cochlear level but also in other
territories and preventing their recurrence.
Conclusions. Highlighting the etiopatogenic mechanism will help adjust the therapeutic strategy; all
patients with SSNHL and no other etiopathogenic findings should undergo a comprehensive hematologic
investigation of inherited and acquired prothrombotic factors, to identify a subset of patients at high risk of
recurrent HL [4].
Key words: SSNHL, thrombophilia, auditory

1. INTRODUCTION
Sudden hearing loss raises many etiopathogenic problems, often being unable to identify the mechanism of
generation [1]. The primitive mechanism is vascular producing ischemia at cochlear level [2]; there are
recognized like pathogenic mechanisms:
- spastic mechanism: angiospasm, oscillating arterial hypertension, effort, emotions, à frigore, spasm by
sympathetic nervous system irritation;
- thrombosis: varicose disease, atherosclerosis, coagulation disease - thrombophilia;
- embolisation: mitral stenosis, atrial fibrillation
- hemorrhagic: high blood pressure, stroke – cochlear ictus.
Most often in medical practice it is hard to demonstrate the etiopathogenic mechanism, this is thought-out in the
patient's clinical and paraclinical context and is confirmed by the patient response to treatment.
The treatment for sudden deafness is adapted to each case depending on the suspected etiopathogenic
mechanism, so drug combinations are particularized for each patient [2].
Thrombophilia is a multifactorial disorder, involving both genetic and acquired risk factors that affect the
balance between procoagulant and anticoagulant factors and lead to increased thrombotic tendency.
Thrombophilia screening require level measurements of: antithrombin III, protein C, protein S, factor V
Leiden and APC resistance test, antiphospholipid antibodies, fibrinogen, factor VIII and homocysteine.
Molecular tests for thrombophilia screening: MTHFR polymorphisms, prothrombin gene analysis for the
G20210A variant, factor V Leiden mutation, factor XIII mutation, PAI 1 (Plasminogen activator inhibitor 1)
gene mutation [7].
Thrombophilia – Clinical manifestations (venous and arterial thrombosis):
- deep veins thrombosis, pulmonary thromboembolism
- migraines, ischemic stroke
- pregnancy complications: recurrent loss of pregnancy, pre-eclamsia, eclamsia, placental disorders,
premature birth, congenital malformations
- cardiovascular diseases – acute myocardial infarction (hyperhomocysteinemia risk factor for
atherosclerosis) [10]
- retinal circulation thrombosis (central retinal vein occlusion) [9]
- SSNHL (sudden sensorineural hearing loss)
Thrombophilia and SSNHL
Factor V Leiden and MTHFR gene polymorphisms were found to occur more frequently in patients with
SSNHL in several studies, suggesting these inherited prothrombophilic mutations could be independent risk
factors of SSNHL. A low level of serum folate may also be implicated as a risk factor [5]. T allele of MTHFR
C677T could be associated with susceptibility to SSNHL, and even imply that this mutation could be a risk
factor that is independent of blood folic acid and homocysteine [8]. Deficiencies of antithrombic, protein C or S
taken together, high factor VIII and hyperhomocysteinemia were significantly associated with SSHL, whereas no
association was found with the remaining thrombophilia markers. The increased risk of poor clinical outcome is
directly proportional with homocysteine levels [6].

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 2. CASE RAPORT/METHOD
Going from these theoretical aspects we consider interesting and useful to present two clinical cases of
patients that make us to take in the discussion some issues regarding the pathogenic mechanism.

The first patient FA 28y.o. was admitted in our clinic for headache, bilateral nasal obstruction, posterior
rhino rhea, no hearing loss complain, aural fullness sensation on the left ear.
The patient is known with pollen and cat allergies, asthma and neurologic evaluation for the headache.
The first step paraclinical evaluation at that time showed:
- audiogram –left ear mild sensorineural hearing loss on high frequencies (4000, 8000 Hz) (fig.1)

Fig.1 Audiogram – left ear mild sensorineural hearing loss

- impedance - type A tympanogram right ear

- type C tympanogram left ear
Conclusion: ET dysfunction
- RFL Video-endoscopy: important obstructive syndrome most by inflammatory rhinosinusal lesions and septal
deviation (fig.2)

Fig. 2 Video-endoscopy – septal deviation, obstructive syndrome; peritubar inflammation

The next step paraclinical evaluation:

- BERA (click) - latency and intervals between peaks within normal limits bilateral
- The cerebral CT scan showed a well defined cystic formation suggestive for retention cyst in the apex of right
temporal bone, chronic rhino sinusitis – right maxillary and ethmoid sinuses and a septal deviation on the right
side (fig. 3).

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 Fig.3 CT scan – retention cyst in the apex Fig. 4 Brain MRI – retention cyst in the apex
of right of right temporal bone temporal bone

- The patient performed a brain MRI (pontocerebellar angle, temporal bone, internal auditory canal) and revealed
a well defined homogenous oval formation, 7/6 mm, signal changed due to protein content in a liquid secluded in
the apex of right temporal bone – retention cyst and therefore cochlear nerve lesions were totally excluded
(fig.4).
- Hematological evaluation: screening for thrombophilia – positive: hyperhomocysteinemia and high levels for
proteins C and S. MTHFR C677T molecular analysis – heterozygous (one mutated allele genotype) (fig.5).

Fig. 5 Hematological evaluation – positive: hyperhomocysteinemia

and high levels for proteins C and S; MTHFR C677T molecular analysis

Etiopathogenic mechanisms for Case 1:

- thrombophilia – vascular mechanism for sensorineural hearing loss on the left ear. It may also explain the
persistent headache.
- accidental imaging discovery of a temporal bone retention cyst – no etiopathogenic mechanism related with
the hearing loss on the left ear. It explains the extention of the inflammatory lesions of the upper airways.
The therapeutic strategy for Case 1: hematologic treatment, surgical treatment for the upper airway obstructive
syndrome to prevent association of other pathogenic mechanisms for hearing loss (like inner ear barotraumas)
on auditory structures already sensitized.

The second patient IR 33y.o. was admitted in our clinic ( July, 2015) for acuphene on left ear, bilateral
nasal obstruction, posterior rhino rhea, no hearing loss complain. From the family history we underline: sister
with hearing aid (no etiopathogenic information) and the father deceased of brain neoplasia.
The first step paraclinical evaluation:

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 Fig.6 RFL Video-endoscopy – obstructive syndrome by septal deviation

- RFL Video-endoscopy: obstructive syndrome by septal deviation and inflammatory rhinosinusal lesions
(fig.6)
- Audiogram: bilateral mild sensorineural hearing loss on high frequencies (2000, 4000 Hz), left ear is
more affected (fig.7).
- Impedance: bilateral type A tympanogram and present bilateral stapedius reflexes

Fig. 7 Audiogram – bilateral mild sensorineural hearing loss on high frequencies;

left ear is more affected.
The next step paraclinical evaluation:
- BERA (click) revealed latency and intervals between peaks within normal limits bilateral (fig.8).

Fig. 8 BERA – latency and intervals between peaks within normal limits bilateral

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- The patient performed a brain MRI: cochlear nerve lesions were totally excluded and pontocerebellar
angle, temporal bone and internal auditory canal are within normal limits (fig. 9).

Fig. 9 Brain MRI - pontocerebellar angle, temporal bone, internal auditory canal within normal limits

- At the hematologic evaluation it was made the screening for thrombophilia – positive:
hyperhomocysteinemia, 677 C>T mutation in MTHFR gene – heterozygous and 1298 A>C mutation in
MTHFR gene – heterozygous. Conclusion: Hyperhomocysteinemia and MTHFR double heterozygous
(Fig. 10).

Fig. 10 Hematologic evaluation – positive: hyperhomocysteinemia, MTHFR double heterozygous.

Etiopathogenic mechanisms for Case 2:

- Thrombophilia – vascular mechanism for bilateral sensorineural hearing loss (left ear > right ear) and
acupheneon left ear. The aim of the hematologic treatment is to improve the hearing (fig. 11) and to
reduce the tinnitus (intensity and duration) parallel to decreasing homocysteine level.

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 Fig. 11 Improved Audiogram after 1 year

The therapeutic strategy for Case 2:

- Initial treatment with betahistinum 48mg/d, acid alfa-lipoicum 600mg/d, vitamin therapy – B1,B6 and
B12 vitamins for 30 days.
- After hematologic evaluation – hematologic treatment: acid acetylsalicylic 75 mg at two days, vitamin
therapy with B6 and B12 and folic acid.
- Medical and surgical treatment of the upper airway obstructive syndrome to prevent association of
other pathogenic mechanism (like inner ear barotraumas) for hearing loss on auditory structures
already sensitized.

3. CONCLUSIONS

A complex and phased investigation of a patient with auditory disorders must be initiated in the same
time with the first step therapy adapted to the clinical case. Highlighting the etiopathogenic mechanism will
adjust the therapeutic strategy.
The suspected etiologies for patients suffering of sudden sensorineural hearing loss includes idiopathic
(71.0%), infectious disease (12.8%), otologic disease (4.7%), trauma (4.2%), vascular or hematologic (2.8%),
neoplasia (2.3%) and other causes (2.2%). Establishment of a direct causal link between SSNHL and these
etiologies remains elusive. Imagistic diagnosis is a useful method for identifying temporal bone or intracranial
pathology that can present with SSNHL as primary symptom [3].
The association between inherited and acquired prothrombotic factors and sudden HL suggests that the
microvascular impairment causing SSNHL may be caused by a multifactorial mechanism. All patients with
ISSNHL should undergo a comprehensive hematologic investigation of inherited and acquired prothrombotic
factors, including MTHFR polymorphisms, the prothrombin transition, and the platelet and V Leiden mutations,
to identify a subset of patients at high risk of recurrent HL [4].
The interdisciplinary collaboration proves its importance also in this type of pathology: ENT, Imaging,
Hematology, Neurology and Cardiology.

4. REFERENCES

1. Ataman T., Otologie, Ed. TehnicaBucharest 2002, 605-608; 639-643

2. Cummings CW, Flint PW, Haughey BH, et al, eds. Otolaryngology: Head & Neck Surgery. 5th ed.
Philadelphia, PA: Mosby Elsevier; 2010, Sensorineural hearing loss in adults, chap 149
3. Justin K. Chau MD, FRCSC, June R. J. Lin BSc, Shahnaz Atashband MBBS, MS, MHSc, Robert A.
Irvine MD, FRCSC, Brian D. Westerberg MD, MHSc ,FRCSC, Systematic review of the evidence for
the etiology of adult sudden sensorineural hearing loss, Laryngoscope May 2010 ,Volume 120, Issue 5,
Pages 1011–1021
120
4. Pasquale Capaccio MD, Francesco Ottaviani MD, Valeria Cuccarini MD, Alessandro Bottero MD,
Antonio Schindler MD, Bruno Mario Cesana MD, Salvatore Censuales BS, Lorenzo Pignataro MD,
Genetic and Acquired Prothrombotic Risk Factors and Sudden Hearing Loss,Larygoscope March 2007,
Volume 117, Issue 3, Pages 547–551
5. Rui Jun Lin MD, Randall Krall, Brian D. Westerberg MD, MHSc, Neil K. Chadha MD, MPH, Justin K.
Chau MD,Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss
in adults, Laryngoscope March 2012, Volume 122, Issue 3, Pages 624–635
6. Serena M. Passamonti, Federica Di Brardino, Paolo Bucciarelli, Valentina Berto, Andrea Artoni,
Francesca Giannillo, Umberto Ambrosetti, Antonio Cesarani, EmanuelaPappalardo, Ida
Martinelli, Risc factors for idiopathic sudden sensorineural hearing loss and their association with
clinical outcome, Thrombosis research, March 2015, Volume 135, Issue 3, Pages 508-512
7. Victor Hoffbrand, Paul A. H. Moss, Essential Haematology 2016, 6th Edition, Chapter 27, Page 369-
370
8. Yasue Uchida MD, PhD, SaikoSugiura MD, PhD, Fujiko Ando MD, PhD, Hiroshi Shimokata MD,
PhD, Tsutomu Nakashima MD, PhD ,Association of the C677T polymorphism in the
methylenetetrahydrofolate reductase gene with sudden sensorineural hearing loss , Laryngoscope April
2010, Volume 120, Issue 4, Pages 791–795
9. C. D. Fegan, Central retinal vein occlusion and thrombophilia, Department of Haematology
Birmingham Heartlands Hospital, Eye Journal, 2002
10. Paul Schick, Barbara P. Schick, Francisco Talavera, Ronald A. Sacher, Srikanth Nagalla, Pradyumna
D. Phatak, Hereditary and Acquired Hypercoagulability,
http://emedicine.medscape.com/article/211039-overview#a4 , 2016

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 THE HEALTHY SELF AND THE UNHEALTHY OTHER IN NADINE
GORDIMER GET A LIFE

STOICA Diana, Assistant Professor PhD, University POLITEHNICA of Bucharest, 164

Ion Mihalache, Bucharest, Romania

Abstract
The anxieties caused by unknown or unfamiliar territories, whether these are geographical or human,
physical or psychological, are universal. In these territories, at the borders of the known world, the Other
resides, maintaining the boundaries between the self and the other, between ‘us’ and ‘them’. These
Others may have different physical forms and unusual attributes. Such an example is the unhealthy Other,
as presented by Gordimer, which is the result of the projection of misunderstandings and fears of healthy
bodies on the perception of illness as difference. If we accept that all bodies have social and symbolic as
well as physical features, the unhealthy Other offers an illustration of the processes all people undergo
when perceiving healthy or diseased others, and also when perceiving themselves as the Other.
Eventually, the Others are either integrated (by healing after treatment, or by adoption, in Gordimer’s
novel) or rejected. The argument of this paper is that health and disease are used as tropes for a
redefinition of private and public relationships and as the means to explore new issues that arise in the
South African society.
Key words: health, identity, self, other, illness

The concepts of health and self have been intertwined since the development of medicine in the 20th
century. Health has become a marker of self-identity, a means for self-recognition and acknowledgment
of self-realization by others. Individuals are no longer at the mercy of doctors or healers; they have access
to detailed information and have the possibility to choose the type of treatment from a series
recommended to them. We may state that individuals are increasingly responsible for their health. This
paper explores how the Self is constituted in relation to health and medicine, and in opposition to the
unhealthy Other. My analysis is situated in the context of cancer invasion followed by a radiation
treatment that has a number of troubling effects on a person’s sense of self, including fear of self-
destruction when becoming the Other, alienation and enforced solitude which leads to meditation on
different aspects of life. The implicit aim of this type of treatment is to reconstruct and secure the
independent Self, with an emphasis on health as an enterprise of energetic Self and on illness as a location
for the meditative and lethargic Other. In exploring the healthy Self and the unhealthy Other, this paper
uncovers a number of the binary concepts on which contemporary discourses of illness and health rely,
such as exposure and immunity, insecurity and dependability, vulnerability and potency, solitude and
public life, other and self. These concepts are related to Nadine Gordimer’s novels The House Gun and
Get a Life and her latest volume of short stories Beethoven Was One-sixteenth Black. After having
explored the social and the racial Other, the cultural and the sexual Other, the violent Other, all connected
to South African life and the politics of the country, Nadine Gordimer turns to the unhealthy Other, not
necessarily diseased, as it is affected not only by AIDS, cancer and medical testing but also by the
ordinary phenomena of aging and dying. The experience of the body in illness or health is thoroughly
depicted and analyzed in her latest writings, as the healthy or diseased body is a metaphor of the diseased/
healthy state of South Africa. However, it has to be noted that stereotyping people as ill and healthy
triggers discrimination and isolation, on the one hand, and protects the healthy community from
contamination, while identifying the indispensable treatment, on the other.
In his 1986 essay, “The Rediscovery of the Ordinary: Some New Writings in South Africa”,
Njabulo Ndebele (1992:436) considers that South African authors “have a penchant for the spectacular”,
for the dramatic presentation of the injustices of the Apartheid system. He suggests that they should
“rediscover the ordinary,” by focusing more on the details of the everyday lives of the South African
people. They should turn away from the “crude and too political” writings (440) and thus, produce a type
of literature that can “break down the barriers of the obvious in order to reveal new possibilities of
understanding and action” (446). Nadine Gordimer has presented both sides of the story: the spectacular
and the ordinary, focusing both on the political, racial and social aspects of South African life and on
various expressions of ordinary life, thus, paralleling microcosm and macrocosm.

Susan Sontag (2001:3) maintained in Illness as Metaphor that illness is the night-side of life, a most
onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the
kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is
obliged, at least for a spell, to identify ourselves as citizens of that other place.
Nadine Gordimer’s latest novel, Get a Life, presents two cases of “dual citizenship” - a man diagnosed
with cancer and a little girl infected with HIV – who manage to escape that ‘other place’ which is the
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kingdom of the sick either by defeating the disease or by obtaining acceptance to be integrated in the
community of the healthy Other. Their bodies become the markers of individuals who are quarantined
before they are accepted by the healthy community.
At the surface, Get a Life appears to deal with the lives of comfortably situated characters surviving
various threats to middle-class life: disease, loneliness, marital discord. Yet, the novel explores and
reflects on environmental issues in South Africa, viewed as a small part of the ‘global village’, narrating
the place and its history while examining a white middle-class family that has to isolate one of its
members.
In this 2005 novel, Nadine Gordimer examines how the healthy caregivers structure their
relationships with the ill, the unhealthy Other, using as a specific example cancer and AIDS. The novel
focuses on how the professional and personal Self is identified and defined in relation to the suffering
Other, through the development of concepts such as fear (of radiation and isolation), body self-image,
illness and family relationships, disease and health, nature, memory and survival. The threat to the young
man’s body posed by an aggressive group of cells is used to delineate the threat posed to South African
territories: the exploitation of its resources, at any cost. She examines the body scarred and cured by
treatment for serious diseases, and seeks the answer to the question about the possibility and necessity to
depict the sick body in order to render illness and health experiences tangible. The body is invested with
the capacity to heal itself with the help of extreme treatment (radiation) so that it may return to normality
and order may be restored. The disease is eliminated by therapy and the positive outcome, in Gordimer’s
case, is not only the healed body but also the multiple transformations that actually take place when
human bodies and medical treatments converge. As Asha Persson (2004:45) remarks “medicine and
therapy have the capacity to reconfigure bodies, diseases and identities in multiple and unpredictable
ways”.
Gordimer uses some key images in Get a Life in order to reconstruct the healthy Self. Thus, the
diseased and contagious other (along with the sexual other) are becoming important issues in the South
African society, still concerned with the politics of race and social inequality. As health becomes “a
medium for expressing what is believed to be essential about the self”, disease - as the mark of outsiders -
signifies the otherness of the self. The diseased Other is perceived as lacking willpower to restore health,
as not exhibiting self-control to integrate in the ‘ordinary society’. Other categories of people who are
characterized as undisciplined and lacking self-control are homosexuals, addicts and minorities and they
are also seen as diseased or as agents of disease (Crawford 1994:1348). Gordimer has introduced them in
her post-Apartheid writings, as they are part of the new South Africa.
Gayatri Chakravorty Spivak (2003:24) defines the subordinate Other as “the Self’s shadow” and the
same can be noticed when we speak about the diseased Other: there is a latent particle in every healthy
body that may activate itself and, thus, the healthy Self becomes an unhealthy Other. In her 1985 essay,
“Can the subaltern speak?” Spivak (27) asks two main questions: “How can we touch the consciousness
of the people, even as we investigate their politics? With what voice-consciousness can the subaltern
speak?” Indeed, the silent subaltern can speak and they do it when they are offered the proper conditions.
It is the situation of the diseased body, rendered silent by the healthy Self when the former is isolated,
quarantined so that order should be maintained. Paradoxically, the voice of the diseased Other is the
healthy Self, who nurses the ill or adopts an HIV-positive child. If we replace the subaltern with the
unhealthy Other, the question receives its answer: due to the fact that it is impossible for the unhealthy
Other to find their own voice, it is the duty of the caregiver to represent them, as it is the duty of
intellectuals to represent the subaltern, as Spivak suggests. The ‘consciousness of people’ can be touched
by the voice of the healthy Self who is able to direct attention towards the diseased Other and to the fact
that the latter may become marginalized at any moment.
As Robert Crawford (1994:1348) observes, “the subordinate or marginalized other is a physical
danger to the healthy individual and a symbolic danger to the social self”. The threat posed by the
marginalized Other manifests itself in opposition to the self. Thus, the ‘ordinary’ Self is opposed to the
unhealthy/ diseased Other and only when the former becomes a caregiver, will the latter be accepted. The
unhealthy Other is a threat to the well-being of healthy Self due to the risk of contamination and also to
its constantly being a reminder of what the latent particle might cause when it is activated. By extension,
the healthy Self may represent the healthy family, race, or country, the so-called ‘safe side’ of the
Western civilization. Critical diseases, such as cancer and HIV/AIDS, are regarded as invisible
destructive forces that bring chaos, disorder and disintegration of ordered society, family life and
interpersonal relationships.
Moreover, as Crawford (1350) points out, societies are preoccupied with control and at the same
time, are anxious about its loss. Thus, contagion is the opposite of control, as it “evokes images of
violating boundaries, wildness, and nature untamed. In contagion, categories are shattered. If the
symbolic logic of health suggests purification, locating threatening elements to the outside, then disease,
along with associated images of contagion, provides a model for all feared threats. The pure inside is
contaminated by the impure outside”.
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 The diseased Other, in its representation outside the domain of control, is untouchable, dangerous,
contagious and overtaking the ordinary. Consequently, it is identified as the undisciplined element that
has to be isolated, quarantined so that order should be reestablished. The result of the isolation process is
the difficulty to reintegrate into the ordinary when the body is healed and it should return to its former
safe Self. The healing process is brought about not only by medical treatment and radiation therapy but
also by persons who behave as nurses: family members or outsiders. The success of the treatment consists
in the ability to reunite the patient with his own body and make him understand the disrupted or even
disturbed relation of the self with the body, which characterizes the experience of illness or injury. The
unhealthy Other is untouchable, yet they try to ‘touch’ the public conscience.
In Get a Life, medical and ecological issues are brought forward instead of Gordimer’s favourite
theme - racial politics. Paul Bannerman, the white ecologist in South Africa, one of the main characters,
is diagnosed with papillary carcinoma of the thyroid at the age of 35 and has to undergo surgery to have
his malignant thyroid gland removed. Four weeks after the surgery, he is treated with radioactive iodine
to obliterate any residual cancerous cells. Paul remains radioactive for 16 days and has to avoid any
contact with his family - the healthy Self. From this moment on, he starts to consider himself as a present-
day leper, a diseased citizen of that other country represented by illness.
The lives mentioned in the title are those of the Bannermans, a white family confronting a series of
personal crisis. Lyndsay and Adrian, a successful couple in their 60s, and their son, Paul, with his wife,
Berenice, are focused from the moment when their lives are changed by the fact that Paul develops
serious cancer requiring intense radiation treatment, forcing him to quarantine himself at his parents’
house. These South African characters become the means for exploring the word ‘life’, and they all
contribute with a different meaning to it. The significance of life for every character in the novel is mostly
personal. As a result, the political involvement that used to be dominant in Gordimer’s earlier fiction
seems peripheral. Illness, death, sexual and emotional betrayal, the attempt to bring into being a child,
adoption of a sick child, all these topics add “crucial layers of significance to personal choice”, whereas
political activity that used to contribute to the shaping of personal identity, “represents choices already
made, settled into” (Vital 2008:92).
Paul Bannerman works on environmental issues and the irony is that he is being cured by the same
kind of science that he is trying to stop in South Africa. His main project at the time he is diagnosed with
cancer is fighting against a nuclear power plant in an ecologically protected area. The ecologist speaks
against highways and dams that would permanently damage major ecological systems and transform rural
life. When he becomes radioactive, he perceives the impact of radiation both on a large scale – the fragile
South African environment – and on the miniature ecosystem of his family. Moreover, South Africa is the
representative microcosm of the complex structure that is the Earth. Thus, a form of cancer that takes
over a man’s body, a man who is concerned with the health of his country provides Gordimer with the
opportunity to draw attention to global politics.
The novel is the story of a family’s progress through life, with an emphasis on shifting emotions,
between selfishness and empathy. These emotions are caused by the diseased body rather than by the
characters’ attitudes and actions. The progress towards a happy conclusion is partly due to the characters’
decision to think life through and to come to terms with the unhealthy body. Cancer has been removed
along with Paul’s thyroid, and Paul and Berenice’s new baby is not affected by his father’s radiation
treatment. The project of the nuclear plant has been “halted…Pending further environmental assessment”
(Gordimer 2005:187). Lyndsay’s request to adopt an HIV positive child is approved and the little girl,
Klara, is playing with Lyndsay’s healthy grandson in “an unexpected form of relationship, unnamed”
(171).
The effects of illness on self and family require a reexamination of the Self and the Other, as disease
often segregates individuals from the healthy community and ordinary life. Referring to his illness and
treatment with radioactivity, the protagonist “cannot trust his body. It remains the stranger that was made
of it” (119). The result of this reexamination is metamorphosis, another major theme in Gordimer’s novel.
The radioactive treatment of the disease forces transformation upon the ordinary life of this white South
African family, transformation that starts from the body and mind and continues to marriage, career, and
eventually reflects upon the environment.
In essence, the individual health crisis parallels a family crisis and the threat that South Africa faces:
exploitation of its resources and disregard for its people and environment. Two of Paul’s black colleagues
- Derek and Thapelo - are also rejecting any development that could threaten rural areas, and, in an ideal
world, they would struggle to find another job instead of the well-paid one that implies the exploitation of
the nation’s natural and human resources. Gordimer’s activists are involved in three different projects
(opposing the development of a pebble-bed nuclear reactor, the dams in the Okavango Delta, and the
Pondoland national toll road and mining scheme) and regard their work as having broad-based social
consequences. Paul and his fellow activists have strong connections with their social circle and, although
they oppose the Australian mining company’s projects, they are considering various international
agencies (including those that use culture for profit) as an opportunity to raise funds. Healthy bodies have
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 long been considered as beautiful and erotic and they used to oppose diseased and, hence, ugly and
unappealing bodies. The numerous outbreaks of diseases during the twentieth century made scholars
reconsider their theories about the beauty and ugliness of healthy bodies. Cancer and AIDS are two of the
diseases that allow the body to be beautiful and erotic for some time before they manifest themselves.
These diseases do not mark the body from the beginning and this is the reason why ‘beautiful’ is no
longer a synonym of ‘healthy’. If the healthy Self used to rely on skin to tell the story of the Other, now
“visible beauty no longer [offers] any protection” (Gilman 1955:146). Illness is perceived to be dangerous
to the collective and, consequently, it must be isolated and stigmatized as it does not belong to the model
of beauty.
According to David Morgan and Sue Scott (1993:10), “the body in its sexual mode is supposed to
be a source of pleasure/power, not a source of disease and danger”. They also note the lack of a “good
sociology of health and illness to take thorough account of the body in a state of change, flux and
interaction with other bodies, and as a site of contradictions in relation to both collective and individual
strategies of health care”. In this respect, bodies that are diseased fail to maintain social order, and thus,
they are identified as a menace to the social order. The restoration and preservation of order implies that
restrictions and boundaries must be drawn so that the diseased bodies should be prevented from
contaminating the healthy community. Nevertheless, isolating/ hiding the diseased in order to maintain
the taboo subject of illness does not stop the disease from spreading. An effective strategy of health care
must include raising awareness and using the body as a text that provides information about the disease.
In Get a Life, Paul experiences the benefits of the healthy body before he undergoes surgery and
radiation treatment by making love to his wife. His parents use the act of physical love to bury their fear
of illness and death: “He stroked her hair, her shoulder, […] a signal they would have to meet, kiss. […]
They made love, as Paul and his woman had buried their fear when the judgment came by telephone, and
they were not aware of their son without this resort, this brief haven from fearful solitude” (2005:28). The
sensual experience enables the two couples to hide their anxieties and return to their ordinary lives. At the
same time, it provides the opportunity to get in touch with their inner selves and, in Paul’s case, come to
terms with the diseased body, although his greatest ambition is “to go back to touch and be touched” (54).

The healthy body can also be described as a social body and the proof that a diseased body has been
restored to its healthy condition is the welcoming of others. For Paul Bannerman, the return to ordinary
life as a ‘natural expression’ (110) is marked by the afternoons spent with his two black friends and their
families. The white man searches for the closeness of Black families with four children each, swarming
around and not allowing a single moment for privacy and meditation to which he was used in his parents’
garden. The ordinary life of South Africans is no longer defined by people’s skin colour and the new
white person enters into new relationships with the others. Distance is no longer the defining element for
relations within the white society, and frequent contacts with blacks and ‘in-between colours’ (112) are
shaping the post-Apartheid South African society. Gordimer’s description of children’s games is a small-
scale picture of different races interacting on the South African territory: they “race about in rivalry, covet
one another’s toys, invent games, hug lovingly, tussle savagely and have to be parted” (112). To
paraphrase Susan Sontag, we might say that the way societies perceive illness and regard the unhealthy
Other is what makes illness ‘the evil’ of all times. Yet, “there are new beginnings, in place” (Gordimer
2005:176) and the breaking of taboos will transform the reading of the diseased body from a text that
differentiates and stigmatizes into a palimpsest that may be interpreted to uncover the circle of health,
illness and recovery.

BIBLIOGRAPHY
1. Crawford, R. 1994. ‘The Boundaries of the Self and the Unhealthy Other: Reflections on Health, Culture
and AIDS’ in Social Science and Medicine 38(10): 1347-1365.
2. Gilman, S. 2004. Health and Illness: Images of Difference. London: Reaktion Books.
3. Morgan, D.H.J., S. Scott (eds.). 1993. Body Matters. London and Washington: The Palmer Press
4. Ndebele, N. 1992. ‘The Rediscovery of the Ordinary: Some New Writings in South Africa’, in M.
Chapman, C. Gardner, E. Mphahlele (eds.) Perspectives on South African English Literature.
Johannesburg: Donker, pp. 434-453.
5. Persson, A. 2004. ‘Incorporating Pharmakon: HIV, Medicine, and Body Shape Change’ in Body &
Society, Vol. 10, No. 4, pp. 45-67.
6. Sontag, S. 2001. Illness as Metaphor and AIDS and Its Metaphors. New York: Picador.
7. Spivak, G. Ch. 2003. “Can the Subaltern Speak?” in Bill Ashcroft, G. Griffiths, H. Tiffin (eds.) The Post-
colonial Studies Reader, London: Routledge.
8. Vital A. 2008. ‘Another Kind of Combat in the Bush: Get a Life and Gordimer’s Critique of Ecology in a
Globalized World’ in English in Africa, 35, No. 2 (October 2008) pp. 89-118

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 GENETIC EVENTS IN CHRONIC LYMPHOCYTIC LEUKEMIA

Aurelian UDRISTIOIU - Fellow PhD, Molecular Biology, Medicine Faculty, Titu Maiorescu
University, Bucharest, Romania

Abstract

Aim of this study is to present the latest researches in the field of molecular medicine, in
terms of Chronic Lymphocytic Leukemia (CLL), emerged from the P53 gene deletion in
human lymphoma genome.
Method
In recent years proved that the best technique in the investigation of malignant lymphocytes
is the Fluorescence in situ hybridization (FISH). This method is used as an alternative to
chromosomal banding, a conventional application in molecular medicine.
Previous results:
In the literature it was registered, in previous years, on an international study, conducted
on 109 cases of CLL, 79 cases (72.5%) who had more genetic abnormalities: the remaining
30 cases (27.5%) had normal results, using FISH technology. The majority of patients, 67%
(53.79) had a single anomaly and the remaining 33% had two or three genetic abnormalities.
The chromosomes 14q32 /17p translocations in LLC genome, which appeared similar to some
common, had demonstrated abnormalities involving IGH gene, located on
chromosome14q32.
Discussion
Recent, endogenous somatic gene therapy research is a basic of trial clinical and
therapeutic trial. The DNA, is used to treat a disease arising as a result of mutations in
chromosomal regions. In the past few years, this method has been included in the treatment of
CLL, acute lymphocytic leukemia, [ALL], or multiple myeloma [MM].
Conclusion
The frequencies of P53 gene mutations and deletion in CLL can be categorized as
individual biomarkers in proteomic and genomic profile for this type of leukemia that can be
implemented in targeted patient treatment of personalized medicine.

Keywords: P-53 Gene, Lymphocytic Leukemia, Apoptosis, Fluorescence in Situ Hybridization

GENETIC EVENTS IN CHRONIC LYMPHOCYTIC LEUKEMIA

Introduction
Chronic lymphocytic leukemia (CLL) is a malignancy of B cells of unknown etiology. CLL is a clinically
heterogeneous disease characterized by the accumulation/expansion of a clonal population of small mature B
lymphocytes in blood, bone marrow, and lymphoid organs.
Although initial genetic events are considered primarily responsible for the first step(s) of neoplastic
transformation, the development and progression of the CLL clone are thought to be affected by various micro-
environmental signals that regulate proliferation and survival of malignant B cells. Most CLL tumor cells are
inert and arrested in G0/G1 of the cell cycle and there is only a small proliferative compartment; however, the
progressive accumulation of malignant cells will ultimately lead to symptomatic diseases [1].
The diagnosis of CLL can be established initially by optical microscopy morphology combined with immune-
phenotyping: monoclonal antibodies in the panel receptors CD5 +, CD20 + and CD23 +, CD28 + B lymphocytes
color, to intensely positive for CD20, FMC7 and / or CD79b, or coloring negative for CD23 immuno-
phenotyping which was seen as an atypical LLC. The receptor CD38+ is considered positive if a population
distinct lymphocytes exhibit a greater intensity of staining than granulocytes in the sample and in association
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with proteins ζ model (ZAP-70) were confirmed cases of malignancy aggressive with bad prognosis. The protein
ZAP70 is a member of the protein-tyrosine kinase family. ZAP70 is normally expressed in T cells and natural
killer cells, and has a critical role in the initiation of T-cell signaling. ZAP70 in B cells is used as a prognostic
marker in identifying different forms of chronic lymphocytic leukemia (CLL), [2].
Various biological and genetic markers also have prognostic value. Patients with a del (17p) chromosome or
P53 gene mutation are refractory to repeated chemo-immuno-therapies. [3]. The product of gene P53, protein
p53 can arrests the growth cells by holding the cell cycle at the G1/S regulation point on DNA damage
recognition. If the P53 gene is damaged, tumor suppression is severely compromised. People who inherit only
one functional copy of the P53 gene will most likely develop tumors in early adulthood, a disorder known as Li-
Fraumeni syndrome [4]. The P53 gene can also be modified by mutagens (chemicals, radiation, or viruses),
increasing the likelihood for uncontrolled cell division. More than 50 percent of human tumors contain a
mutation or deletion of the TP53 gene. Loss of p53 creates genomic instability that most often results in an
aneuploidy [5].

Aim
The objective of this study is to present the latest researches in the field of molecular medicine, in terms of
Chronic Lymphocytic Leukemia, emerged from the P53 gene with deletions, translocations in human lymphoma
genome and, the prognostic and treatment of this diseases, in function of damages of P53 gene.
Previous results
In the previous literature it was registered, in previous years, on an international study, conducted on 109 cases
of CLL, 79 cases (72.5%) who had more genetic abnormalities; the remaining 30 cases (27.5%) had normal
results, using the technique Florescence in situ Hybridization, (FISH). The majority of patients, 67% (53.79) had
a single anomaly and the remaining 33% had two or three genetic abnormalities. The band chromosomes 14q32 -
17p translocations in LLC genome, which appeared similar to some common, had demonstrated abnormalities
involving IGH gene, located in 14q32 region [6].
Of the 90 CLL cases, which were analyzed for CD38, 81 were placed in bad prognostic groups. Nineteen
(23%) of the 81 were CD38+. A similar percentage of CD38+ cases was present in cases with 17p [33%]) and
11q deletion [36%]) and cases with normal FISH results [33%]). CLL cases with trisomy 12 and isolated 13q-
had the lowest percentage of CD38+ cases; 15% (2/13) and 8% (2/24), respectively. ZAP-70 was tested in 36
cases; 10 were positive [7].
Deletions of the chromosomal region 13q14 are commonly associated with CLL, with monoclonal B cell
lymphocytosis (MBL), which occasionally precedes CLL, and with aggressive lymphoma, suggesting that this
region contains a tumor-suppressor gene. Was demonstrated that deletion in mice of the 13q14-minimal deleted
region (MDR), which encodes the micro ARN, miR-15a/16-1 cluster, causes development of indolent B cell-
autonomous, clonal lympho-proliferative disorders, recapitulating the spectrum of CLL-associated phenotypes
observed in humans [8].
CLL and Hodgkin Lymphoma (HL), are particularly dependent on their microenvironment and have
associated signaling pathways and deletion of miR15/16 locus, common in specially, in CLL. Was showed that
micro ARN, miR15 and miR16 are located at chromosome 13q14, a region deleted in more than half of B cell
chronic lymphocytic leukemia (B-CLL). Detailed deletion and expression analysis shows that miR15 and miR16
are located within a 30-kb region of loss in CLL, and that both genes are deleted or down-regulated in the
majority (approximately 68%) of CLL cases.

Discussions
Identification of P53 gene mutations in regions of 17 chromosome of hematological neoplasm is important
because these mutations have an impact on the clinical course of patients and requires an attitude adjustment
therapeutic adequate [12]. In the last decade it became clear that CLL does not constitute a uniform disease, but,
based on the prevalence of mutations in the BCR heavy chain (IgVH), can be classified into two distinct
subgroups. Several molecular markers correlate with IgVH mutations..
Some of them, like zeta-chain associated protein kinase, are also involved in BCR signaling and influence cell
cycle. If, the primary pathogenic event leading to increased proliferation and survival in CLL is difficult to
ascertain. Molecules involved in BCR signaling pathways and cytoplasmic pro-survival players probably act in
concert to confer resistance to apoptosis [Figure 1].

127
 Figure 1. In a normal cell, p53 is inactivated by its negative regulator, mdm2.

Upon DNA damage or other stresses, various pathways will lead to the dissociation of the p53 and
mdm2 complex. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell
or apoptosis to discard the damaged cell. How p53 makes this choice is currently.
Increasing the amount of p53 may seem a solution for treatment of tumors or prevention of their spreading.
This, however, is not a usable method of treatment, since it can cause premature aging. Restoring endogenous
normal p53 function holds some promise.
Research has shown that this restoration can lead to regression of certain cancer cells without damaging
other cells in the process. The ways by which tumor regression occurs depends mainly on the tumor type. For
example, restoration of endogenous p53 function in lymphomas may induce apoptosiss while cell growth may be
reduced to normal levels. Thus, pharmacological reactivation of p53 presents itself as a viable cancer treatment
option [18].
Many of the tumor-suppressor functions and the counteracting oncogenic functions by mutant p53 are
represented as mirror-image pairs: cell death/cell survival; cell cycle arrest/cell proliferation; DNA-
repair/genomic instability; senescence/invasion and metastasis; metabolic homeostasis/Warburg effect;
restriction of angiogenesis.[Figure 2].

128
 Figure 2. Mirror-image pairs: cell death/cell survival; cell cycle arrest/cell proliferation in cancer; DNA-
repair/genomic instability; senescence/invasion and metastasis. [Sabapathy K, Contribution mutant p53
proteins in oncogenesis. Sci. Republication beyond 2015; 5,E-mailgs.moc.sccn@bskrmc.com

The large spectrum of cancer phenotypes due to mutations in the TP53 gene is also supported by the
fact that different isoforms of p53 proteins have different cellular mechanisms for prevention against cancer.
Mutations in TP53 can give rise to different isoforms, preventing their overall functionality in different cellular
mechanisms and thereby extending the cancer phenotype from mild to severe [19] [Figure 3].
Acetylation of p53 is an important means of post-translational modifications and is indispensable for its
activation that is a reversible enzymatic process. Both acetylation and deacetylation of p53 are involved in the
fine regulation of cellular responses to DNA damage and genotoxic stress [20] .

129
 Figure 3. Three dimensional structure of p53 protein in its tetrameric isoforms in cancer. [Rangueil,
Toulouse, France, Jean-Christophe Bourdon, Email: ku.ca.eednud@nodruob.j].

Elevated glucose levels feed into metabolic anabolism to provide the increased demand for the molecular
building blocks required to support rapid cancer cell proliferation, inherent in the Warburg effect. Reciprocally,
glucose maintains mutant p53 stability and promotes cancer cell growth generating a positive regulatory loop.
Reliance on a mutant p53-dependent enhanced supply of glucose to foster cell proliferation defines a unique
point of vulnerability in cancer cells. This appetite for glucose identifies a potential therapy target which is
currently being extensively investigated [i.e., ketogenic diets and repurposing of the widely used diabetic
metformin. [21]
The critical event leading to the activation of p53 is the phosphorylation of its N-terminal domain. The N-
terminal transcriptional activation domain contains a large number of phosphorylation sites and can be
considered as the primary target for protein kinases transducing stress signals [22].
Encoded by the mutated variants of the TP53 tumor suppressor gene, mutant p53 proteins are getting an
increased experimental support as active oncoproteins promoting tumor growth and metastasis. Previous studies
have suggested that the expression of clock genes have circadian rhythms, and many cell cycle genes are
regulated by clock genes.
The disruption of circadian rhythms appears to be associated with the acceleration of cancer development. To
investigate the circadian patterns of the clock gene Per2 and of cell cycle genes p53, Cyclin D1, CDK1 and
Cyclin B1 in different stages of carcinogenesis, the daily mRNA profiles of these genes were detected by real-
time RT-PCR P21 protein no longer bind DNA in an effective way, and, as a consequence, the p21 protein will
not be available to act as the "stop signal" for cell division [Figure 4}.

130
 Figure 4. Mutant p53 functions during the evolution of a cancer cell. P53 mutations are not present in the
normal case and are induced upon genotoxic exposures in one allele. Hence, in the intermediate stage, the mutant
p53 co-exists with the wild-type (WT) p53, until the loss of the wild-type allele by loss-of-heterozygozity
(LOH).

Current models can also be useful for modeling the mutations in p53 isoforms and their effects on p53
oscillation, thereby promoting de novo tissue-specific pharmacological drug discovery and farmakinetics of
chemotherapy in treatment of LLC [25]. Somatic gene therapy is a basic research of clinical mass and the
therapeutic DNA (either integrated into the genome or episome plasmid external) is used for the treatment of a
disease. In gene therapy, for example, on line blood stem cells fenotyping cells is modified by introducing of
functional genes in their genomes.
The dynamics of p53 proteins, along with its antagonist Mdm2, indicate that the levels of p53, in units of
concentration, oscillate as a function of time. This "damped" oscillation is both clinically documented and can be
presented as mathematically model. Mathematical models also indicate that the p53 concentration oscillates
much faster once teratogens, such as double-stranded breaks (DSB) or UV radiations [Figure 5].

131
 Fig 5. The p21protein functions as a regulator of cells cycle progression at G1 to S phase, controlled by the
tumor protein p53.[11. Udristioiu A. Bioenergia celulara normala si maligna. Cap, Interferenta bioenergetice
intre normal si malign, pg: 125-135. Tipografia Everest, Bucuresti, Editura Academica Brancusi, Targu . Jiu,
2002.; 12. Hamada, Tomoko Niki, Norio Ishida. . Role of p53 in the entrainment of mammalian circadian
behavior rhythms. Genes to Cells Volume 19, Issue 5, pages 441–448, May 2014].

Conclusion
The most common form of therapy using DNA encoding, is using a functional gene to replace a mutated
gene. Polymer molecule is packaged in a "vector" molecule within the cells bearing. [26, 27]. In the recent
researches were included this method to treat (CLL), [28, 29, 30], acute lymphocytic leukemia (ALL), [] or
multiple myeloma [MM] [31].
The frequencies of P53 gene mutations, deletions or translocations, in CLL, can be categorized as the
individual biomarkers in proteomic and genomic profile for this type of leukemia and can be implemented in
chooses of targeted treatments from personalized medicine.

Refernces
1.Zenz T, Mertens D, Küppers R, Döhner et al. From pathogenesis to treatment of chronic lymphocytic
leukaemia. Nat Rev Cancer .2010 ; 10(1): 37-50.
2.Udristioiu A, Florescu C, Popescu MA, Cojocaru M. High Concentration of anaerobic ATP implicated in
aborted apoptosis from CLL. LabMed 2010; 41: 203-208.
3. Hallek M. Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment.
Cancer Cell. 2010;17(1):28-40.
4. Gonzalez DK, Buzin HC, Dongqin Gu et.al. Beyond Li Fraumeni Syndrome: Clinical Characteristics of
Families With p53 Germline Mutations. JCO 2009; 29 (8): 1250-1256.
5. Read AP, Strachan T. Human molecular genetics 2. New York: Wiley, ISBN 0-471-33061-2, Chapter 18:
Cancer Genetics 2009.
6. Nelson BP, Gupta R, Dewald GW, Paternoster SF et al. Chronic Lymphocytic Leukemia, Panel FISH: Impact
about diagnosis. Am J Clin Pathol 2007; 128 (2): 323-332.
7. Zerdoumi Y, Kasper E, Soubigou F, Adriouch S. A new genotoxicity assay based on p53 target gene
induction. Mutat Res Genet Toxicol Environ Mutagen. 2015; 789-790:28-35.
8. Wang F, Lv P, Liu X, Zhu M, et al. MicroRNA-214 enhances the invasion ability of breast cancer cells by
targeting p53. Int J Mol 2015 ; 35(5):1395-402.
9. Klein U, Lia M, Crespo M, Siegel R et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and
its deletion leads to chronic lymphocytic leukemia. Proc Natl Acad Sci 2002; 99(24):15524-9.
132
10. Zhu J, Zhang S, Jiang J, Chen X. Definition of the p53 functional domains necessary for inducing apoptosis.
The Journal of Biological Chemistry 2000; (51): 39927–34.
11. Oncogenetic Tests, FISH panel LLC . MedLife Genetica]. https:/ www.medlife.ro/genetics/teste-
disponibile/teste-de-oncogeneticaa , accesat in/03/2016.
12. Isobe M, Emanuel BS, Givol D, Oren M, Croce CM. Localization of gene for human p53 tumour antigen to
band 17p13. Nature 1986; 6057: 59.
13. Kern SE, Kinzler KW, Bruskin A, Jarosz D, et a. Identification of p53 as a sequence-specific DNA-binding
protein. Science 1999; 235: 1708–11.
14. Hollstein M, Sidransky D, Vogelstein B, Harris CC. P53 mutations in human cancers. Science 1991; 253
(5015): 49–5
15. Josephy PD. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2015; 790:28-35.

133
 INFLUENZA AND SCHIZOPHRENIA

Alexandra Vlad - student anul III, Univ. Titu Maiorescu , Facultatea de Medicina Generala,
Bucuresti
Viorel Alexandrescu - Univ. Titu Maiorescu, Bucuresti & INC Cantacuzino
Maria Elena Mihai - INC Cantacuzino
Alexandru Matei - asistent univ. , Univ. Carol Davila , Bucuresti

I . INTRODUCTION

Schizophrenia is a disease known since ancient times, but despite the unprecedented development of medicine,
its causes still remain mysterious.
Clinical manifestations of schizophrenia are well established , and effective therapeutic procedures have been
implemented for some of its forms, but two etiologies are in dispute: cerebral organic disease and functional
psychosis.
Over time, several risk factors have been identified, factors that cannot trigger the disease separately, only
associated.

II. RISK FACTORS

1. Place and time of birth : urban / winter

2. Infections during pregnancy : influenza, respiratory , rubella , with polivirus , of CNS
3. Prenatal factors : hunger , floods, unwanted/ unexpected child , maternal depression , maternal distress ( eg
mourning etc. )
4. Obstetrical factors : Rh incompatibility , hypoxia, low birth weight , preeclampsia, CNS damage
5. Family History : +/- genetic mutations

RISK FACTORS AND ODDS-RATIO

Figure 1. Source = Sullivan; 2005. PLos Medicine , 2.pp.0614-0618

134
INTERPRETATION (increased risk propotion)
o The average growth of relative risk regarding schizophrenia is 1.

- OR ( odds ratio ) = 1, exposure does not affect the result

- OR ( odds ratio ) > 1, exposure is associated with bigger effects on the results.
- OR ( odds ratio ) < 1, exposure does not affect the results
o A child born in winter months ( January to March / April in the northern hemisphere ) has a 10% higher
risk of schizophrenia than the average 1.
o A person born in the urban area has a 50 % higher risk of developing schizophrenia.
o A child born to a mother who had rubella, has an increased risk of schizophrenia close to 500%.
o In the case of family history , the rate of expanded risk is difficult to estimate , depending on genetic
factors , the level of interrelation with a member who had schizophrenia and the existence of other brain
disorders in the family.

III. SCHIZOFRENIA - CHARACTERISTICS

o The disease occurs at young age ( 15-30 years ).
o It affects both sexes, but onset is prior in men than in women.
o Disease severity is more advanced in men.
o Frequency of schizophrenia is between 0.5 – 1 % , with an annual incidence rate of approx. 0.05 %.
o The probability of disease in the general population : 1%.
o In families with existing schizophrenia patients there is a higher prospect of illness.
o At univitelino twins , the concordance rate is 50 %.

IV. INFECTIONS DURING PREGNANCY AND SCHIZOPHRENIA

Risk factors for schizophrenia have been documented for decades.
In 1988 , Mednick and colleagues ( Finland ) have published a study that highlights an increased risk of
schizophrenia in individuals who were " fetuses " during the 1957 flu pandemic .
Another study in 2008 ( Denmark ) , with a broader database ( national longitudinal registry of medical records )
again confirmed the increased risk of schizophrenia associated with an influenza mother during pregnancy.
During these 20 years , over 25 epidemiological studies have examined this issue, using various sources of
information regarding infection, ranging from a simple correlation with known dates of epidemics memories of
the mother , hospitals records and the archives in the national register on the documented occurrence of the flu .
Almost half of them have confirmed the outcome of the research , and the other half did not. These failures could
lead to inaccurate information on the role of infections or other factors or may represent true results of the
association between maternal flu and schizophrenia in some populations.
But the increased rates of diagnosis for major affective disorders have also been reported after exposure to
influenza epidemic during the second trimester of pregnancy , which indicates that the effects may not be
specific to schizophrenia.
Besides the flu, a variety of other maternal infections during pregnancy were associated with increased risk of
schizophrenia. These include viral infections ( rubella , measles , varicella - zoster, polio ), native
bronchopneumonia ( mainly bacterial ), maternal infections with parasites ( toxoplasmosis ) and genital &
reproductive system infections.
Studies covering rubella demonstrated that more than 20 % of the subjects exposed to the virus ( serologic
confirmation ) in the first trimester , have developed schizophrenia in adulthood .
The observations presented above , support the hypothesis that maternal infection with various agents could
likely increase the risk for schizophrenia and that the common factors of these infections are responsible for this
effect .
In recent years, some labs have tried to confirm maternal infection by analyzing antibodies for viral infections in
maternal serum which had been stored for a period of 30-40 years until the children have grown and developed
schizophrenia. These studies are difficult because of the test object size limit , storage availability and stability of
the samples.
Brown and collaborators have found a correlation between the disturbances of schizophrenia and mother’s
influenza during the first trimester, which lost statistical significance ( p = 0.08 ) and during the first half of
pregnancy which also lost statistical connotation ( p = 0.052 ).
The first epidemiological studies suggested flu as a risk factor in the second trimester of pregnancy, while
studies conducted by Brown with archived maternal serums, concerned flu in the first trimester through mid-
pregnancy.
If the association between influenza and schizophrenia will be confirmed in other studies , then influenza, which
is an extremely widely distributed disease that affects considerable groups of people (including pregnant women)
in the annual out breaks, could be a relevant risk factor in the development of schizophrenia.

135
Other serologic studies have found elevated titers of antibodies to type 2 Herpes virus in late pregnancy ,
associated with an increased incidence of psychosis in children born to mothers with herpes infection during
pregnancy, but Brown and collaborators have refuted this association.
The effects of these associations between infections and schizophrenia are comparable to the magnitude of
genetic polymorphisms linked to schizophrenia.
Except for the studies of influenza , most epidemiological studies involving prenatal infections with various
agents have beem reported only by single groups, without being replicated by other researchers.
Disorientation factors management ( Sorensen and colleagues ) revealed that maternal exposure to analgesics (
ASA and other anti-inflammatory drugs , codeine and morphine ) in the II trimester of pregnancy is associated
with a higher risk of schizophrenia .
If maternal infection is indeed a risk factor , then the epidemiological studies do not clearly define the main
period of vulnerability.
In both first and second trimester, pregnancy can be altered by infections.
Since 2000 more studies on pregnant animals have been published, to illustrate the effects of infections on brain
development , demonstrating the risk of schizophrenia .
Living influenza viruses , viral RNAs and bacterial endotoxin were used in the analysis.
In a substantial number of studies in rodents, it was demonstrated that maternal infection during pregnancy can
cause CNS changes and structure, functions and descendants behavior disturbances.
These changes may be relevant to schizophrenia , such as deficits in : startle reflex inhibition, latency inhibition,
memory and social interaction, and the expansion of amphetamine and locomotion induced by MK -801,
changes in the CNS of dopamine and tyrosine hydroxylase , cell death , cell atrophy or decreased volume of the
hippocampus .
In conclusion, these studies support the belief that maternal infection can alter brain development in several ways
, but each laboratory work / has worked with various species ( mouse , rat , etc. ) , different doses and different
infectious agents ( viruses , nucleic acids, endotoxin bacterial ) and highlighted certain effects on offsprings .

V. THE ACTION MECHANISMS OF MATERNAL INFECTIONS ON THE FETAL BRAIN

1. The living virus can act directly and affect the fetal brain . One experiment ( performed on a pregnant mice -
intranasal inoculation of influenza virus ) describes the mechanism .
2. Chemical mediators of the infection can facilitate changes in brain development. During maternal infections,
chemical mediators of inflammation, particularly cytokines , interleukin- 1β ( IL- 1β ), IL-6 and tumor necrosis
factor - α are elevated in maternal blood and placenta.
It is not yet clear whether these are normally excessive in fetal brain after maternal infection .
Cytokines can affect fetal brain development , by compromising placental function or by effects mediated
through maternal injuries .

3. Fever caused by increased removal of maternal cytokines can affect fetal neuro-development .
Physiological researches studying the increased body temperature of the mother during pregnancy displayed that
the short exposure of pregnant rodents at temperatures of 40 ° C to 43 ° C temperatures can lead to fetal
resorption and CNS anomalies .
Khan and Brown indicated that keeping pregnant rats to 42 ° C for 45 min on day 17 of gestation , generates
apoptosis in the cerebral cortex of fetal brain .
Some experts believe that similar effects can occur in the current situation , where global warming can determine
sizable temperature changes .

4. The assumption that antibodies against infectious agents can cross- react and damage the fetal brain structures
exists, but that is not yet an evidence that an autoimmune mechanism develops in schizophrenia.
An example might be in favor of self- immune mechanism : the fact that β -hemolytic streptococcal throat
infections ( group A) can cross- react with basal ganglia causing Tourette syndrome ( motor tics + a vocal tic ) or
obsessive compulsive disorder.

5. Drugs such as analgesics and some anti-inflammatory drugs used for infection during pregnancy can affect
fetal development.

VI. CONCLUSIONS
 If maternal infection is a definit risk factor for schizophrenia , then there are more aspects to prevention.
 If the flu is an important factor in increasing the risk of schizophrenia in descendants , then influenza
vaccination has a clear target of high vaccination coverage in pregnant women.
 Must be mentioned what other risky maternal infections can be prevented by vaccination.
 Can you use anti-inflammatory/ anti-pyretic drugs in maternal infection? Which ones?
 Is bringing down the fever sufficient or the growth and elimination of cytokines in maternal infections has to
be inhibited by other therapeutic measures ?
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VII. PARTICULAR ASPECTS OF INFLUENZA ASSOCIATED WITH SCHIZOPHRENIA
A study by Lauren Ellman revealed that the risk of schizophrenia increases 1.5- 7 times in children born to
mothers who suffered from flu. Exposure to influenza during childbirth triggers heightened production of
immune proteins that cause brain changes in fetuses. The study was conducted on archived blood samples
collected between the 1950-1960 from 12,000 pregnant women in each trimester . Women and their descendants
were followed , so descendants who developed schizophrenia were easily identified.

The study showed a direct correlation between structural brain changes in offsprings diagnosed with
schizophrenia and the increased levels of interleukin - 8 (IL -8), active proinflammatory cytokine response
against infection during pregnancy. The brain abnormalities found were similar to those regularly seen in
schizophrenia.

Recent studies have shown significant raises in the risk of schizophrenia, by over 700 % in children born to
mothers who suffered from flu during pregnancy.
An increased risk of approx. 700 % is observed when the flu hit the mother in the first trimester , while maternal
influenza in the third quarter resulted in a 300% increase in risk.

Although the vast majority of studies that have examined the association of risk concerning schizophrenia with
maternal influenza were carried out in annual epidemics flu , there are studies that have investigated the
relationship between flu and schizophrenia in historically pandemics( 1918 , 1957, 1968) and the recent
pandemic of 2009.

Rates impact Historical pandemics Seasonal flu Pandemic –2009

Attack rates* 15– 50 % 1 -10 % 11-14 %

(1918)
Complication rates** 10-15% 3-7 % 5- 8 %
(Mexico )
Fatality rates*** 0,1 - > 2 % 0,01- 0,05% 0,05 %
( 1918) ( severe)
Reproduction case rate 1/3 ( first wave ) 1/2 ( first wave )
****( Ro ) 1/2 ( wave 2 ) 1/2 - 1/1 1/1 (wave 2)
1/1 ( wave 3 )

* Number of symptomatic illness/ population

** Number of complications of symptomatic cases/ population
*** The number of deaths from symptomatic cases/ population
**** The number of secondary cases from an index case

Figure2.

137
 Category Historical Seasonal flu Pandemic - 2009
pandemics

Age groups 15-45 years <5 years->65 years 20-59 years

Pregnant 23-53% 3-5% 5-8 % (USA)

Associated chronic 47% 0.09 % 64% (USA )

diseases 46% (Mexico)

Healthy people 53% 0,001% 54 % (Mexico)

36% (USA)

Figure3.

EVENT NUMBER OF MORBIDITY COMPLICATION MORTALITY

PREGNANT /NUMBER RATES/ NUMBER RATE/
OF CASES OF CASES NUMBER OF
CASES

THE 208.000.000 5% 13,85% 11%

ANNUAL (10.400.000) (2.163.200) (94.545)
EPIDEMIC

PANDEMIC 208.000.000 15% 20% (6.240.000) 10%

(31.200.000) (624.000)

Figure4.

VIII. PREVENTION OF INFLUENZA IN PREGNANT WOMEN AND FETUS

Besides illness , complications and death, abortion , premature birth, birth of stillbirth, newborn with less birth
weight are also registered in pregnant women. Also an increased risk of schizophrenia in children born to
mothers with influenza during pregnancy.
 Influenza vaccination is currently difficult accepted by pregnant women and by some practitioners ,
especially obstetricians, who do not know or have a misperception on the effects of the influenza vaccine
and do not promote immunization .
 Inactive influenza vaccine as well as other inactive vaccines ( tetanus ) have no harmful effects on
pregnancy and in no way affect the product of conception.
 Flu vaccination can be done after the new recommendations from WHO , CDC - Atlanta and ECDC in all
trimesters of pregnancy.
 Influenza vaccination protects both the mother and the fetus from influenza and its complications .
138
REFERENCES:

1. Maternal infection during pregnancy and schizophrenia

Patricia Boksa J Psychiatry Neurosci.v33 (3) 2008 May PMC 2441883
2. Prenatal Infection as a Risk Factor for Schizophrenia
Alan S Brown1,2Oxford Journals > Medicine&Health > Schizophrenia Bulletin Volume 32 , Issue 2> Pp.200-
202
3. Risk of Schizophrenia Rises With Flu Exposure in First Trimester, Study Suggests
Jennifer Warner Schizophrenia Health Center ;WebMD Health News aug ,2,2004
4. Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia
Alan S. Brown, MD; Melissa D. Begg, ScD; Stefan Gravenstein, MD; Catherine A. Schaefer, PhD; Richard J.
Wyatt, MD; Michaeline Bresnahan, PhD; Vicki P. Babulas, MPH; Ezra S. Susser, MD, DrPH ;JAMA Psychiatry
august 1, 2004 Vol61, No8
5. Maternal Influenza Viral Infection Causes Schizophrenia- Like Alterations of 5-HT2A and mGlu2 Receptors
in the Adult Offspring
Jose´ L. Moreno,1 Mitsumasa Kurita,1 Terrell Holloway,1 Javier Lo´pez,1,2 Richard Cadagan,3 Luis Martínez-
Sobrido,3 Adolfo García-Sastre,3,4,6 and Javier Gonza´lez-Maeso1,2,5
Departments of 1Psychiatry, 2Neurology, 3Microbiology, and 4Medicine, 5Friedman Brain Institute, and Global
Health and Emerging Pathogens Institute,
6. Mount Sinai School of Medicine, New York, New York 10029; The Journal of Neuroscience, February 2,
2011 • 31(5):1863–1872 • 1863

139
 ASPECTS IN CONVENTIONAL IMPRESSION FOR CROWN AND BRIDGES

Claudia Florina Andreescu DMD, PhD, Associate Professor, Department of Prosthetics, Faculty of
Dental Medicine, University Titu Maiorescu, Andreea Mariana Bănățeanu DMD, PhD, Assisstant
Professor, Department of, Faculty of Dental Medicine, University Titu Maiorescu, Cristina Hăineală
DMD, PhD, Assisstant Professor, Department of, Faculty of Dental Medicine, University Titu
Maiorescu Eugenia Diana Rădulescu DMD, PhD, Assisstant Professor, Department of, Faculty of
Dental Medicine, University Titu Maiorescu.

Corresponding author: Claudia Florina Andreescu DMD, PhD, Associate Professor, Department
of Prosthetics, Faculty of Dental Medicine, University Titu Maiorescu, Bucharest, Romania,
Bucharest, 67A Gheorghe Petraşcu Street, sector 3, code 031593, telephone/fax: +4021.325.14.16
claudia_andreescu@yahoo.com

Abstract. One of the most challenging procedures in prosthetic still is making of a good impression.
The objective of this study is to evaluate the type of impressions for crowns and bridges send to commercial
laboratories and the type of fixed prosthetic work ordered. According to results of this study, preferred method of
imprisoning for dental practitioners is dual arch (partial or total) without tray or with plastic flexible tray. The
most common type of restorations ordered are porcelain fused to metal and nowadays full cast crowns are less
ordered due to increased aesthetic demands.
Keywords: conventional impression, crown and bridges, commercial laboratories

INTRODUCTION

Well-adapted crowns are needed for longevity of abutment teeth and a correct impression of right tooth
preparation is necessary to perform a well-adapted crown. One of the most challenging procedures in prosthetic
still is making of a good impression [1, 2]. Despite the improvement of digital technology that made a shift in
making dental impression [3], the impression remains a challenging step in making of perfect restoration, and in
many countries, the majority of dentists use conventional impression techniques.
There are several ways that conventional impressions for crowns and bridges are taken: the single-step
technique using only one material (monophase technique), the single-step technique with impression materials of
two different viscosities light body and heavy body (dual-phase one-stage, known as sandwich technique), and
the double-step technique which also includes two materials with different viscosities putty and wash (putty-
wash two-stage technique, known as washing technique).
Depending on the extent of the impression, impressions are classified in full or complete dental impressions
and partial or segmental dental impressions. A wide variety of trays are used for taken dental impression: stock
trays (partial and total), custom trays and dual arch trays (partial and total) with different dental impression
materials: addition cured silicone, condensation cured silicone or polyether.

OBJECTIVE

The objective of this study is to evaluate the type of impressions for crowns and bridges send to commercial
laboratories and the type of fixed prosthetic work ordered.

MATERIAL AND METHODS

Three dental laboratories are visited over one month period. A number of 173 impressions for dental crowns
and bridges were examined. From the study, impressions for veneers, resin bonded bridges and implant-
supported restorations were excluded.
All impressions were evaluated under ambient room light without any additional room light and with 2.5
magnification loupes. All impressions were evaluated after disinfection and before being poured with stone.
For each impression were recorded following criteria: type of tray used, size of tray, type of impression
material, impression material combination, number of units impressed, and type of prosthesis ordered.

RESULTS

173 dental impressions for crowns and bridges sent to commercial laboratories were evaluated. Classification
of dental impressions according to type and size of tray used during impressioning is presented in Figure 1.
Classification of dental impressions according to type dental impression material is shown in Figure 2.

140
 In Figure 3 is presented classification of dental impressions according to impression technique: mono-phase
technique, sandwich technique and washing technique.
The recording of the canine in dual arch impression is evaluated in Figure 4 and classification according to
type of prosthetic work ordered is presented in Figure 5.

Partial dual arch tray Total dual arch tray Single arch tray No tray

Metal Plastic Metal Plastic Metal Plastic -

0/43 43/43 0 14/14 24/62 38/62 -

Total 43/173 Total 14/173 Total 62/173 Total 54/173 (31.21%)

(24.86%) (8.09%) (35.84%)

Figure 1: Classification according to type and size of tray.

Condensation cured silicone Addition cured silicone Polyether

Ex. Zetaplus + Oranwash (Zhermack), Ex. Elite HD (Zhermack), Affinis Ex. Impregum (3M ESPE)
Speedex (Coltene Whaledent) (Coltene Whaledent)

93/173 (53.76%) 71/173 (41.04%) 9/173 (5.20%)

Figure 2: Classification according to type of material.

141
 Dual –phase technique Mono-phase technique

160/173 (92.49%) 13/173 (7.51%)

Figure 3: Classification according to impression technique.

Total dual Single arch

Partial dual arch tray No tray
arch tray tray

2/43 (4.65%) - - 0/54 (0%)

Figure 4: Registration of the canine.

Polymeric veneer
All-ceramic Porcelain fused to metal Full cast crown
crown

33/173 (19.08%) 107/173 (61.85%) 28/173 (16.18%) 5/173 (2.89%)

Figure 5: Type of prosthetic work ordered.

142
DISCUSSION

The most widely used impression is segmental dual arch without tray and with two different consistency
condensation cured silicone impression material. Majority of dentists chose plastic trays when trays are used.
According to results of this study, preferred method of imprisoning for dental practitioners is dual arch
(partial or total) without tray or with plastic flexible tray. The main reason is material economy in comparison
with full arch impression [4]. Dual arch method permits imprisoning of the prepared teeth, the opposing
dentition, and the registration of intercuspal relationship in the same time, saving chair time and money, but
practitioners seem not to be aware of limitations of this technique when used it. Dual arch is recommended for
one or two dental preparation in a quadrant when there are other teeth to occlude with and existing anterior
guidance [5].
A rigorous case selection is mandatory when dual arch impression technique is chosen and includes [6]:
 The technique should be used in cases with class I or class II occlusion, if the occlusal scheme is acceptable.
 Canine guidance is the ideal occlusal scheme. When working with a group function occlusion, supply a
lateral check bite.
 The opposing teeth must have intact occlusal surfaces.
 Adjacent teeth must have acceptable morphology.
 The patient must be able to close into maximum intercuspation with no interference.
 The tray must not impinge on soft tissue.
 The impression must be poured and mounted before separating. Do not pour both sides and then try to
articulate them using the impression.
 Hand articulation creates errors and destroys the occlusal information that is captured with the technique.
Also used of flexible plastic trays is questionable in making of a good dental impression. Successful
impressioning rely on a rigid tray. A study from 1998 [7] concluded that metal and rigid plastic stock trays give
greater accuracy in the putty/wash silicone twin mix impression technique compared with flexible plastic ones
for crown and bridge work. A rigid tray, stock or custom, with elastomeric impression material guarantees
accurate gypsum cast [8] and a tray should be rigid in order to resist distortion during impressioning making
process and after removal from the mouth [9]. However, custom trays offers a more accurate in-mouth
positioning, significant saving of heavy body material, and facilitated fabrication of the master model in the
laboratory [10]. In vivo studies revealed that heavy body light body two-step technique with custom tray
provided the best results in terms of dimensional accuracy [11].
Registration of occlusal relationship is also uncertain when total dual arch impression technique is used for
multiple abutment, but quadrant dual arch technique reproduces more accurate maximal intercuspal relationships
than conventional full arch impressions technique according to Parker et al [12] and is suitable for fabrication of
single crowns [13]. The posterior dual arch tray must be check prior to impressioning to extend distally in order
to avoid interference to maximum intercuspation, while providing sufficient length to record the canine. In this
study quadrant dual arch with tray technique succeed to impressioning the canine, while without tray canine is
missing in some cases.
The most common type of restorations ordered are porcelain fused to metal and nowadays full cast crowns
are less ordered due to increased aesthetic demands.

CONCLUSION

Within the limitations of this study, these data lead to following conclusions: the most commonly used
impression technique for crowns and bridges in private practice is segmental without tray with two different
consistency condensation cured silicone impression material. Simplifying the technique of impression may
results in distortion due to lack rigid support for impression material. The widespread of dual arch impression is
related to low cost of material and armamentarium and perhaps of lack of knowledge about its deficiencies.

REFERENCES

[1] Christensen GJ. Have fixed-prosthodontic impressions become easier? J Am Dent Assoc
2003;134(8):1121-3.
[2] Mechanic E. Making a Great Impression. Dent Today. 2010 Dec;29(12):88;90-1.
[3] Nayar S, Mahadevan R. A review of contemporary impression materials and techniques. Journal of
pharmacy & bio allied sciences 2015 Apr;7(Suppl 1):S213-5.
[4] Lane DA, Randall RC, Lane NS, Wilson NH. A clinical trial to compare double-arch and complete-arch
impression techniques in the provision of indirect restorations. J Prosthet Dent 2003;89(2):141-5.
[5] Small BW. Revisiting impressions using dual-arch trays. Gen Dent 2012;60(5):379-81.

143
[6] Abrams SH. Benefits of the dual-arch impression technique. Accurate impressions and fewer than 1%
remakes. Dent Today. 2002 Jul;21(7):56-9.
[7] Carrotte PV, Johnson A, Winstanley RB. The influence of the impression tray on the accuracy of
impressions for crown and bridge work--an investigation and review. Br Dent J. 1998 Dec 12-
26;185(11-12):580-5.
[8] Rueda LJ, Sy-Munoz JT, Naylor JT, Naylor WP, Ghoodacre CJ, Swartz ML. The effect of using custom
or stock trays on the accuracy of gypsum casts. Int J Prosthodont 1996; 9:367-373.
[9] Hoyos A, Soderholm KJ. Influence of tray rigidity and impression technique on accuracy of polyvinyl
siloxane impressions. Int J Prosthodont. 2011 Jan-Feb;24(1):49-54.
[10] Perakis N, Belser UC, Magne P. Final impressions: a review of material properties and description of a
current technique. Int J Periodontics Restorative Dent. 2004 Apr;24(2):109-17.
[11] Singh K, Sahoo S, Prasad KD, Goel M, Singh A. Effect of different impression techniques on the
dimensional accuracy of impressions using various elastomeric impression materials: an in vitro study. J
Contemp Dent Pract. 2012 Jan 1;13(1):98-106.
[12] Parker MH, Cameron SM, Hughbanks JC, Reid DE. Comparison of occlusal contacts in maximum
intercuspation for two impression techniques. J Prosthet Dent. 1997 Sep;78(3):255-9.
[13] Kaplowitz GJ. Trouble-shooting dual arch impressions II. J Am Dent Assoc. 1997 Sep;128(9):1277-81.

144
 CROWN RESTORATIONS WITH THE AID OF DIFFERENT
INTRARADICULAR DEVICES

Andreea Mariana Bănățeanu,DMD, PhD, Lecturer, Department of Prosthetics, Faculty of Dental

Medicine, UniversityTitu Maiorescu,Claudia Florina Andreescu,DMD, PhD, Associate Professor,
Department of Prosthetics, Faculty of Dental Medicine, University Titu Maiorescu, Mariana Bria,
dentist,Eugenia Diana Rădulescu,DMD, PhD,Lecturer, Faculty ofDentalMedicine,University
TituMaiorescu, Cristina Hăineală DMD, PhD, Lecturer, Faculty of Dental Medicine, University
TituMaiorescu

Abstract
The purpose of the paper is to present therapeutic possibilities of restoring teeth with massive coronary
destructions by using different types of intraradiculardevices.
Material and method. In order to achieve the purposed objective, several studies from the literature were
analyzed and clinical cases were pursued. Presentations of the clinical cases aim at emphasizing the treatment
stages and characteristics of treatment methodby using intraradiculardevices such as glass fiber, quartz fiber,
carbon fiber and metal.
Results. Using fiberglass and quartz fiber pins shortens the duration of treatment and enables superior esthetic
results compared to the use of carbon fiber and metalpins.
Conclusions. Dental restoration using dental intraradiculardevicesprefabricated made of fiberglass, quartz
fiber and carbon fiber constitutes a modern, fast and effective treatment option for coronary destruction with
great loss of tooth substance. Intraradicular metal devices have the advantages of mechanical strength and
durability but in some clinical cases persists the chromatic disadvantage.
Key words: intraradicular devices, crown restorations

Introduction. The direct method of restoring coronary with the aid of prefabricated crown-root devices is
gaining more ground due to biocompatibility, radio opacity, the elasticity similar to that of dentin and the easy
and quick technique of application. Combining these devices with dually polymerizablecomposite materials
allows homogeneous reconstitution both mechanically and physicochemically.
The purpose of the paper is to present therapeutic possibilities of restoring teeth with massive coronary
destructions by using different types of intraradiculardevices.
Material and method. In order to achieve the purposed objective several studies from the literature were
analyzed and clinical cases were pursued.
Crown-root reconstructions are indicated when natural tooth crowns present reductions of volume
determined by: [1,2,4,8,9] deep cavities where healthy tissues remain unsubstantiated (extensive in surface and
depth), crown fractures of the teeth with bulky obturations, partial fractures as a result of trauma and
accompanied by opening the pulp chamber, teeth with abrasion degree III-IV, discoloration, teeth with abnormal
position that cannot be recovered through orthodontic treatment., anomalies of form and volume that cannot be
corrected by crowns, short abutments with endodontic treatment, in movable prosthesis (skeletal) when fixing on
a tooth of a particular special means of support, maintenance and stabilizationis indicated.
Preparation of root canals is common to all crown-root restoration techniques using intraradicular
devices. It is advisable to first perform root canal therapy and then to prepare the root canal in order to
incorporate the device. This will ensure lateral canals closure. [4,]First of all, tooth shall be examined
radiologically. It shall be established the existence of a complete and accurate root obturation, without periapical
damage, the status of the periodontal tissues apical and marginal tissues and if the root is good. On the X-ray, the
form and root volume shall be evaluated in oder to appreciate the distance to which the root canal should be
deobturated if the dentisthas notperformed it and the root canal working length is not known.
In order to be inserte the root canal device a space should be made. The practitioner must meet some
basic preparation principles in order for the root device which he wants to insert to be able to play its role, to
protect the remaining structures and retain coronal portion of the restoration.
Preparations must be 2/3 the length of the root canal length or be at least equal to the height of the
future crown. The canal must remain blocked over a distance of 3-5 mm to the apex. [3,4,8,9]
Thickness of the root device shall not be more than 1/3 of the root transferal diameter of the root. Root
canal for molded devices shall easily be prepared with walls converging towards the apex. Apical convergence
of the canal walls must not be more than 5-6˚in order not to influence the retention. For prefabricated devices as
regards the thickness it should be taken into account the thickness of the root in the area with the smallest
diameter. Dentinal walls of the canal must have a thickness of 1 mm. [3,4,10,11]
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 Prefabricated devices gained ground due to reduced manual labor and time involved. According to the
material these devices are made of metal we know of metal devices (Titanium, Co-Cr alloy, silver, stainless
steel, gold-platinum-palladium, etc.) and non-metallic devices (fiberglass, carbon fiber, zirconium, quartz). [3,16]
According to the attachment within the root canal there are pins that are fixed by friction with the aid of
cement (passive pins) and those fixed by screwing (active pins) [4,6,8].
Regardless of how they are fixed they present themselves in a wide range of shapes and sizes that can
accommodate different clinical situations.
The use of these prefabricated devices presents a series of of advantages. Thus, therapy solution occurs
only in the dental office without the delp of the dental technique laboratory. The application is easier and
workmanship is of short duration. They can be used for all teeth, including the pluriradicular ones. And they can
be easily removed especially the screwed ones.[2,7,9]
But these prefabricated devices are not perfectly adapted to the intraradicular space as the molded ones.
And due to the physical characteristics of the alloys they are made of (elasticity, resistance to torsion and
pressure), their resistance will be diminished. The coronal portion of these devices is shaped to replace coronary
defect.
It shall be always considered that the prefabricated pin adapts asas possible to the canal walls.
Therefore, one does not use prefabricated pins in an oval root canl as contact with the root walls is minimal, and
the remaining space will be filled with cement that in time can lead to loosening the pin. If one opts for a larger
device to have a larger surface contact with the canal walls, the latter preparation will shrink considerably the
risk of puncture or root fracture. [6,7]
When coronary destruction is reduced it is indicated preferentially to use prefabricated devices because
the sacrifice of dental tissues is minimal compared with molded devices.
The role of the root canal device is to ensure coronal retention, but the retention of the root canal device
depends on the contour of the canal, pin size, its shape and surface and the cement used.
The development that has restorative dentistry undergone in recent years opens new horizons to
prosthetic treatments targeting direct restorations, one of the ways being the use of prefabricated pins reinforced
with fiberglass, carbon or quartz. [9,10] These gains more ground due to biocompatibility, the elasticity similar to
that of dentin, the easy and fast application technique (15-20 min), combining them with dual polymerised
composite materials allowing a homogeneous reconstruction both mechanically and physico-chemically.[2,4,9,10]
Being white, the quartz and glass ones successfully meet aesthetic requirements, and allow the
placement on them of full ceramic crowns. [2,6,8,10]
Due to the composition of these pins (60-65% of glass fibers embedded in a matrix of resin), and the
surface prepared by the silane methods, they allow a chemical bond with the adhesive and composite materials
used in theirfixingat the root canal level (1- 1.6 mm diameter) allowing their application inthinner canals
(mandibular incisors, mesial canals of mandibular molars, superior premolars, vestibular canals of upper molars).
Contraindications to the use of these pins are connected to the placement of the crown under the
gingiva, in which case a perfect connection cannot be made between dentine and composite material due to the
presence of gingival fluid, thus it cannot be achieved a proper insulation. In this situation molded pinsare
preferred. [2,4,6,8,10]
The cases selected for presentation required crown-root reconstructions and different techniques were
chosen based on clinical features. The choice of method of treatment took into account the degree of coronary
destruction and reconstitution instructions for each type of crown-root but also the patients’ requests without
making compromises.
CLINICAL CASE I
The patient G.M. aged 28, bartender as profession, presented for consultation and specialized treatment
in order to restore masticatory function.During the oral clinical examination there were revealedsimple and
complicated multiple carious lesions treated. The patient has a Class III mandible edentation according to
Kennedy without prosthesis and the tooth adjacent to this edentulous space (4.7) shows coronal massive
destruction.
The treatment plan proposed was to achieve a tooth fixed prosthesis with pillars 4.7, 4.5 and
intermediate 4.6 followed by the treatment of simple caries.To achieve this level of treatment the patient has had
coronary recovery options (cast pins, prefabricated pins) and the patient requested that treatment be done in a
short time and materials to be aesthetic. With patient’s consent, the reconstitution of 4.7 was chosen by using
fiberglass pins and making metal-fused-to-ceramic dentures.
For starters the proper endodontic treatment was performed on 4.7 (Figure 1). The root canals
preparation was timed for pins because it was realized that extraction of 4.8 has complicated caries and the tooth
could not be recovered.When preparing the space for the pins Beutellrock drillswere used , taking care to remain
at least 5 mm apically of the root canal obturation . In order to restore this tooth three pinswere used, one for
each canal, because the amount of remaining dental hard substance was substantially reduced and the root
canals anatomy allowed the proper fitting of pins.Pins test was performed in the root canals (Fig.2), then etching
with 37% phosphoric acid was performed for 30 seconds, followed by copious irrigation and moderate drying.

146
 Adhesive was applied in successive layers (between applications the air stream was used to remove the
excess), and then adhesivephotopolymerization.The root space is filled with dual composite material and the pins
are inserted into the photopolymerized spaces prepared.(Fig.3). The reconstitution of the coronary portion of
dual composite (Fig.4) and photopolymerization , pins sectioning followed byreconstruction finishing.
By using glass pivots we have complied with the patient’s requirementsregarding the reduced working
time through easy handling and aesthetics. But, from our point of view, these pins has several advantages such as
elasticity similar to dentin, it is biocompatible, has increased strength, they are non-corrosive, minimum
preparation of the root canals, and are easily removed when needed.The treatment was able to maintain the
dental unity which had crown massive destruction and included in a prosthesis the recovery of the masticatory
function which was scarce in this sector.

Fig.1 Endodontic treatment was performed on 4.7

Fig.2 Pins test was performed in the root canals

Fig.3 The root space is filled with dual composite material

Fig.4 The reconstitution of the coronary portion of dual composite

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CLINICAL CASE II
Patient V.I. aged 23, female presented for consultation and specialized treatment.
During the oral clinical examination there were revealedmultiple simple and complicated carious
lesions partially treated and a complex,untreated carious lesion at the level of 1.5 (Fig.5). The latter was also due
to presentation in the dental office, the patient had pain from thermal stimuli to the tooth 1.5.The patient also
hadKennedy Class III edentation without prosthesis.
The endodontic treatmentaws performed correctly and after the removal of the tissues affected by caries
there was evidenced a lack of dental substantial hard tissue requiring thecoronary reconstruction , then a crown
coating in order to prevent fracture of coronary walls. The patient refused a crown prosthesis envelope for
financial reasons. But expressed request as for the crown restorationto be aesthetic.
We opted for a reinforcement of crown restorations using fiber quartz pins. Crown-root reconstruction
by using quartz fiber pin was carried out according to these steps:
 Isolation of the tooth
 Preparation of the radicular lodge by using Beutelrock drill out of the kit from a higher to a
lower diameter
 Cleaning lodge using a syringe with water jet, moderate drying (Fig.6)
 Pin testingwithin the lodge created (Fig.7)
 -Demineralization with 37% phosphoric acid for 30 seconds, copious irrigation, moderate
drying with paper points
 Applying adhesive at the dental tissues level and at the pin level and photopolymerization
 Filling the lodge with dual composite, pivot placing in the lodge and photopolymerization
 Ending the reconstitution of the coronary party made of composite and photopolymerization
 Cutting the pin and finishing reconstitution (Fig.8).
The treatment carried out allowed the reconstruction of morpho-functional unit in a reduced time with
dentalaesthetic materials havinggood physicochemical and mechanical qualities.

Fig.5 Untreated carious lesion at the level of 1.5

Fig.6 Cleaning lodge using a syringe with water jet, moderate drying

Fig.7 Pin testing within the lodge created

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 Fig.8 Final reconstitution

CONCLUSIONS
In the caseof endodontically treated teeth affected by carious processes that are spread both in surface
and depth, in order to restore their integrity and their functionality,retention crown-root devices can be used as
additional means.With the advent of prefabricated non-metallic devices on the market issues raised by the metal
ones have been resolved such as root fracture, colour difference to dental structures and composite materials.
This method is gaining more ground due to other characteristics: biocompatibility, quick and easy technique,
elesticity, non-corrosivematerial, yhey do not stain the dental tissues, they are non-allergenic.

BIBLIOGRAPHY
1. Addy LD, Bartley A, Hayes SJ. Crown and bridge disassembly-when ,why and how. Dent Update 2007
Apr;34(3):140-2; 145-6; 149-50
2. Andreescu, FL., Banateanu,AM, Ghergic DL, Protetica dentara fixa,editura Printech 2015
3. Bratu D, Nussbaum R. Bazele clinice i tehnice ale protezării fixe.Ed.Signata, Timi oara 2001.
4. Bums DR, Beck DA, Nelson SK. A review of selected dental literature on contemporary provisional
fixed prosthodontic treatment report of the Committee on Research in Fixed Prosthodontics on the
Academy of Fixed Prosthodontics. J Prosthet Dent ., 2003 Nov;90(5);474-97.
5. Edelhoff D, Scrensen JA. Tooth structure removal associated with various preparation designs for
anterior teeth. J Prosthet Dent 2002;87; 503-509.
6. Forna N. Protetică dentară. Volumul I . Editura Enciclopedică Bucure ti 2011
7. Forna N, Trăistaru M. Ghid de practică în protetica dentară Editura Enciclopedică 2010.
8. Ghergic DL, Comăneanu RM, Andreescu CF, Banateanu AM, Restaurarea edentației parțiale prin
protezare fixă. Editura Printech Bucure ti 2013, ISMB 978-606-521-961-8
9. Janardanan K, Varkey VK, Lovely M, Anuroopa M. Coronal disassembly systems and techniques.An
Overview. Journal of Interdisciplinary Dentistry / Jan-Apr 2014 / Vol.4/ Issue -1:33-40.
10. Rosenstiel S, Land M, Fujimoto J,.Contemporary Fixed Prosthodontics , 4 th ed. 2006 Mosby Elsevier.
11. Shillingburg HT, Hobo S, Whitsett L, Jacobi R, Brackett SE. Fundamentals of fixed prosthodontics 3rd
ed. Chicago : Quintessenence 1997.
12. Wiskott HW, Nicholls JI, Belser UC. The effect of tooth preparation height and diameter on the
resistance of complete crowns to fatigue loading. Int J Prosthodont 1997;10:207-15.

149
 METAL-POLYMER BRIDGES-A VIABLE WAY OF TREATING
PARTIAL EDENTATION

Andreea Mariana Bănățeanu, DMD, PhD, Lecturer, Department of Prosthetics, Faculty of Dental
Medicine, University Titu Maiorescu, Eugenia Diana Rădulescu, DMD, PhD, Associate Professor,
Department of Prosthetics, Faculty of Dental Medicine, University Titu Maiorescu, Alexandru
Barbu, dentist, CristinaHăineală, DMD, PhD,Lecturer, Faculty of Dental Medicine,University Titu
Maiorescu, Tudor Ionescu, DMD, PhD, Lecturer, Faculty of Dental Medicine, University Titu
Maiorescu

Abstract.
The purpose of this paper is to show that hybridconnective metal polymer dentures constituteeven at present a
viable alternative of treatment in cases where prosthetic conjunct (bridges) metal-ceramic prostheses cannot be
madedue to clinical, technical or socio-economicreasons.

Material and methods. To achieve the purpose of the articlewe studied literature and analyzed in the dental
offices different clinical cases, prostheses restored by using metal acrylic, metal composite and metal ceramic
materials. We observed the peculiarities of reductionl polishing of abutments, impression techniques, materials
used and carrying out technical-clinical stages.

Results.Comparatively the selected clinical cases show a prosthetic restoration by metal ceramic and metal
acrylic restoration bridges. We pursued characteristics of the clinical phases and the peculiarities of the final
results.

Conclusions.Despite failures and complications of the metal polymer systems, at present, due to improved
mechanical properties of materials one can observe a favorable prognosis for these systems which can be used
in varied clinical situations, showing high success rate yielding the desired results. Partial edentulous cases
solved by metal polymer bridges support this type of prosthetic treatment as a viable option.

Key words: metal acrylic bridge, metal ceramic bridge

Development of acrylic resins, improvement of their properties and the lately appearance of
cyanoacrylates and composites (which are also based on acrylate) allowed for fixed dentures, especially semi
physiological ones, at a low price, with satisfactory results not involving an exceptional endowment of the dental
laboratory (ceramic oven).

The purpose of this paper is to show that hybrid connective metal polymer dentures constitute even at present a
viable alternative of treatment in cases where prosthetic conjunct (bridges) metal-ceramic prostheses cannot be
made due to clinical, technical or socio-economic reasons.

Material and methods. To achieve the purpose of the article we analyzed in the dental offices different clinical
cases, prostheses restored by using metal-polymer and metal ceramic materials.

Patients were selected from a batch of patients who came to the dental office for oral rehabilitation.
Criteria were represented by: age over 30 and clinical diagnosis of partial, without prostheses,edentation. Data
were collected from observation charts and tracked along with the development of cases.

Results.Clinical cases selected comparatively show a prosthetic restoration with s metal ceramic and metal
acrylic bridges.

The first case is of a patient aged 56. Her main reason for coming to consultation was given by
masticatory and aesthetic deficiencies (fig.1).

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 The diagnosis was prosthetic jaw: Class III Kennedy edentation with one modification, incorrect
prosthesis and mandible with Class II Kennedy edentation with 3 changes, without prosthesis (fig.2).

The treatment plan required the presentation of several treatment options:

• Fixed prosthesis, semi/total physiognomic of different materials (metal acrylic, metal, composites, metal
ceramic)

• Partial acrylic prosthesis

• Skeletal prosthesis

• Implant variant (implants in the edentulous area)

The variant chosen was a semi/total physiognomic, connective prosthetic bridge made of metal acrylic
material consisting of: elements of aggregation on teeth3.5-3.4-3.3-3.2 and 4.2-4.3-4.5and extension with
physiognomic intermediaries represented by 3.1-4.1-4.4 distally performing extensions for 3.6 and 4.6, the
bridge having tangential contact with the edentulous ridge

Phases of treatment consisted in:

• The patient’s health education

• Preparing of the local pre-prosthetic field
• Polishing
• Impression making
• The laboratory phase
• Post-prosthetic treatment
Preparing of the local pre-prosthetic field: We opted for endodontic treatment in the future prosthetic
abutments, they are going to get an extensive loss of hard tooth substance as a result of polishing phase. Factors
that influenced the selection of extractingdental pulp were degree 1 and 2 mobility of the teeth. (2,8,10)

Polishing: With the aid of a cylindrical-conical diamond drill, achieving orientation grooves on the
vestibular surfaces. We aimed at reducing occlusal and incisal edge surfaces up to the free gingival margin, with
a trench of 1 mm depth. We aimed at ensuring a space of 0.5mm of the metal component and 1.5 mm of the
acrylate one. In the tooth neck area, we aimed to achieve a vestibular shoulder of 0.5 mm, for aesthetic
reasons(2,3,7,8,10).
Impression: We opted for impression in 2 phases by using the “wash” technique (using silicone
condensation of two different consistencies: viscous and fluid) by overall impression, both the jaw and mandible,
and sending them to the laboratory.

After obtaining the prosthesis( fig.3), we carried out provisional cementing of the fixed prosthesis
(fig.4,5);final cementation of fixed prosthesis after 3 months (Fig.6); the patient’s follow-up by continuing health
education on sanitation regarding the conjunct prosthesis as well as of the remaining teeth. It was taken in to
consideration the manufacture of a prosthesis for quadrant II .

Checkup every 3 and 6 months revealed an optimal integration of the dental bridge and significant
improvement in masticatory function.

Fig.1 Initial situation

151
 Fig.2 Edentation without prosthesis

Fig.3 The inferior prosthesis

Fig.4 Provisional cementing of the fixed prosthesis

Fig.5 Provisional cementing -vestibular view

152
 Fig.6 Final cementation after 3 months

The second case selected for presentation is of a patient aged 34 who came to the dental office to restore
masticatory function affected by loss of 1.6 molar.(fig.7). The diagnosis of prosthetic jaw was edentation Class
III Kennedy.
Treatment options were: semi/total physiognomic fixed prosthesis, made of different materials (metal
acrylic, metal composites, metal ceramic) or the implant variant (overdenture implant in the edentulous area).
The prosthetic chosen variant was a fixed, onemade of metal composite consisting in: aggregation
elements on teeth 1.5-1.7 and intermediate semi physiognomic bridge, the bridge having tangential contact with
the edentulous ridge. The chosen variant was determined by socio-economic considerations of the patient.
Phases of treatment consisted in :the patient’s health education, preparing of the local pre-prosthetic
field, polishing, impression making, the laboratory phase and post-prosthetic treatment.
Preparing of the local pre-prosthet: dental pulp and odontal afflictions at the level of 1.5 required its
devitalizationin order to support a crown-root device that will represent the future abutment for the crown
covering. It could not benefit from restoration in the mesial tooth wall composite material, due to the large
coronal destruction.
Polishing: We aimed at ensuring a space of 0.5 mm of the metal component and 1.5 mm of the
composite one. In the tooth neck area we aimed to achieve a stuffy vestibular threshold of 0.5 mm, for aesthetic
reasons.We followed the same steps as in the case of metal-acrylic bridges followed by provisional cementing of
the fixed prosthesis final cementation of the fixed prosthesis after 3 weeks the patient’ follow-up by continuing
health education on sanitation of the conjunct prosthesis as well as the remaining teeth checkup after 6 months
(Fig.10).
Metal-composite bridge shows optimum mechanical resistance and aesthetic restoration seems to be
superior to the metal acrylic bridge due to color the increased chemical resistance of the material as compared to
the acrylic composite material.

Fig.7 Initial situation

153
 Fig.8 Polishing

Fig.9 Prepared teeth

Fig.10 Final cementation of the fixed prosthesis

Conclusions At present, due to the improvement of the mechanical properties of materials, one can
observe a favorable prognosis for metal-polymer bridges as they can be used in various clinical situations with
favorable results.
Out of the solved cases by using metal-acrylic and metal-composite bridges, we reached the conclusion
that they exhibit mechanical and chemical resistance, restore masticatory function optimally and can restore
aesthetics and function satisfactorily.
For patients who cannot afford dentures that impose high costs of materials and technique, dentures can
be made in the clinical and technical modest and with moderate costs, with satisfactory results in the short and
long term, both for temporary bridges as well as for those on the long term. It should be taken into consideration
that the practitioner’s duty remains to restore and bring harmony to the stomatognathic system by all clinical and
technicalmeans.

154
 BIBLIOGRAPHY
1. Addy LD, Bartley A, Hayes SJ. Crown and bridge disassembly-when ,why and how. Dent Update 2007
Apr;34(3):140-2; 145-6; 149-50
2. Andreescu, FL., Banateanu,AM, Ghergic DL, Protetica dentara fixa,editura Printech 2015
3. Bratu D, Nussbaum R. Bazele clinice i tehnice ale protezării fixe.Ed.Signata, Timi oara 2001.
4. Bums DR, Beck DA, Nelson SK. A review of selected dental literature on contemporary provisional fixed
prosthodontic treatment report of the Committee on Research in Fixed Prosthodontics on the Academy of
Fixed Prosthodontics. J Prosthet Dent ., 2003 Nov;90(5);474-97.
5. Edelhoff D, Scrensen JA. Tooth structure removal associated with various preparation designs for
anterior teeth. J Prosthet Dent 2002;87; 503-509.
6. Forna N. Protetică dentară. Volumul I . Editura Enciclopedică Bucure ti 2011
7. Forna N, Trăistaru M. Ghid de practică în protetica dentară Editura Enciclopedică 2010.
8. Ghergic DL, Comăneanu RM, Andreescu CF, Banateanu AM, Restaurarea edentației parțiale prin
protezare fixă. Editura Printech Bucure ti 2013, ISMB 978-606-521-961-8
9. Janardanan K, Varkey VK, Lovely M, Anuroopa M. Coronal disassembly systems and techniques.An
Overview. Journal of Interdisciplinary Dentistry / Jan-Apr 2014 / Vol.4/ Issue -1:33-40.
10. Rosenstiel S, Land M, Fujimoto J,.Contemporary Fixed Prosthodontics , 4 th ed. 2006 Mosby Elsevier.
11. Shillingburg HT, Hobo S, Whitsett L, Jacobi R, Brackett SE. Fundamentals of fixed prosthodontics 3 rd ed.
Chicago : Quintessenence 1997.
12. Wiskott HW, Nicholls JI, Belser UC. The effect of tooth preparation height and diameter on the resistance
of complete crowns to fatigue loading. Int J Prosthodont 1997;10:207-15.

155
 THE ADVANTAGES OF PLATELET RICH FIBRIN IN DIFFICULT
EXTRACTIONS: RADIOGRAPHIC IMAGING OF THREE CASE REPORTS

Edwin Sever BECHIR, Prof. Assist., PhD Stud., University of Medicine and Pharmacy, Tirgu
Mures, Romania
Cherana GIOGA, DMD, Prof. Assist., PhD, Titu Maiorescu University, Bucharest, Romania
Anamaria BECHIR, Prof., DMD, PhD, Titu Maiorescu University, Bucharest, Romania
Mircea Marian BURUIAN, DM, PhD, University of Medicine and Pharmacy, Tirgu Mures,
Romania

Abstract
The practical use of PRF biomaterial in the field of regenerative medicine opened a new perspective of its
application in dental surgery.
The aim of this research is to present the advantages of autologous blood concentrates (PRF = concentrated
platelet rich fibrin) used in tooth extraction surgery, highlighted by radiographic imaging.
PRF biomaterial was used after difficult extractions. The radiographic imaging were performed after the
completion of the healing of the patients included in the research.
The realized radiographic imaging demonstrates the advantages of PRF use in stimulating the alveolar bone
regeneration.
Keywords: difficult extractions, PRF, radiographic imaging of healing

INTRODUCTION

The dental biomaterials used to replace or recover the oro-facial tissues may be natural or synthesized [2].
Dental biomaterials such as bone substitutes and collagen membranes, are used at present in regenerative
dentistry as well as for regeneration of bone and cartilage [1].
The use of biomaterials in dentistry aims to rehabilitate oro-facial system functions, and thus improving the
oral health of the patients.
The autologous blood (PRF = Platelet-Rich Fibrin = fibrin rich in platelets), sometimes referred to as PRP (=
platelet-rich plasma) or PRGF (Platelet-Rich Growth Factor), is an autologous fibrin matrix rich in platelets and
growth factors [7,13].
The use of autologous PRF (concentrated platelet rich fibrin) is a new therapeutic concept of medicine. This
types of dental biomaterial is composed of autologous leukocytes, platelets and proteins located in dense fibrin
matrix [3,5].
The objective of the study was to present the advantages of autologous PRF used in difficult tooth extraction
surgery, advantages highlighted by radiographic imaging.
The radiological images were taken after the completion of the healing of the patients included in the study.

MATERIAL AND METHOD

PRF was obtained, before or during the dental surgery, from the collected blood of the patient, and processed
by specific equipment and techniques (Fig. 1).

156
 Fig. 1. Collection of blood and spin in order to obtain the autologous blood concentrate

At the end of the centrifugation process, we observed inside of the tube three different fractions: the lower
portion containing red blood cells (RBC); the surface portion comprising the platelet-poor plasma (PPP =
platelet-poor plasma) and yellow straw containing cell-free plasma; the intermediate portion, comprising a
platelet-rich fibrin clot (Fig. 2).

157
158
159
 Fig. 2. The aspect of the autologous blood concentrate obtained after centrifugation

After the difficult extractions, the PRF concentrate was inserted directly in the open socket. PRF was as a
stopper. At the end of the intervention, the remaining plasma was used to moisturize the area that has been
operated.

RESULTS AND DISCUSSIONS

Case 1

Patient G. A., 36 years old, came to the dental office complaining of discomfort accompanied with dull ache
in the left lower half dental arch. After the clinical and radiological examination, we observed that the left lower
second molar (3.7) presented a longitudinal crown-root fracture (Fig. 3).

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 Fig. 3. OPG of the patient at the presentation in the dental office (case 1)

The treatment plan included the extraction of 3.7 and 3.8 molars with the piezoelectric device, addition of
PRF in an over-correctional manner, lining the edges pf alveolar bone and suturing the buccal and lingual gum
tissue.
On the performed OPG, realized two years after therapeutic intervention, is visible that the volume of the
bone crest was maintained without loss in height and without atrophy, while was preserved the interdental
septum and the bony labyrinth of vestibular site (Fig. 4).

Fig. 4. OPG performed 2 years after the therapeutic intervention (case 1)

Case 2

Patient B. F., 29 years old, came to the dental office complaining of dull ache in the distal area of both
dental arches, especially in upper dental arch. After the clinical and radiological examination, we observed that
the patient has six third molars, of which four on upper arch and two on lower arch (Fig.5).

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 Fig. 5. OPG radiograph at presentation of patient (case 2)

The treatment plan consisted of piezoelectric extraction of the wisdom teeth from upper and lower dental
arch, including the supernumerary molars, followed by the addition of PRF. The roots in mandibular dental arch
were located at the level of the mandibular nerve canal, for which reason there was necessary to perform the
surgery intervention very carefully, avoiding unexpected maneuvers. So, the risk of paresthesia or permanent
anesthesia induction at the level of inferior alveolar nerve was prevented. Due to the conservative technique in
extraction realization with the ultrasonic piezo-electric device, the bone tissues were gained by adding PRF (Fig.
6).

Fig. 6. Radiographic control: healing of postextractional wound at the level of tooth 3.8 (case 2)

In both cases, PRF acted as an osseo-inductive material and stimulated the angioneogenesis through intake of
nutritional factors and healing factors. Also, the PRF acted in prevention of postoperative infections and
postextractional alveolitis.

Case 3

Patient D.A., 28 years old, requested specialized examination, since accused intermittent pain in the right
distal area of lower dental arch. After performing the clinical and radiological examination, we found that a
included wisdom molar (4.8) pressed on the distal root of the lower right second molar (4.7) (fig. 7).
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 Fig. 7. Preoperatory OPG (case 3)

A CBCT examination was recommended in this case, realized prior and after the extraction of the lower
wisdom molar (4.8).
On the initial CBCT's we noticed that the root portion of wisdom molar is within the reach of the mandibular
canal and the neurovascular package, below the oblique mandibular line (Fig. 8).
The classical method of extraction would present a high risk of injury and bleeding, due to its location in the
proximity of anatomical formations, for which reason this challanging extraction was performed by a
conservative technique, using the ultrasonic Piezo device. PRF was added to stimulate the healing process and to
reduce the risk of postextractional alveolitis, before realizing the suture.

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 Fig. 8. Preoperatory CBCT (case 3)

The postoperatory CBCT of case 3 can be observed in Fig. 9.

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 Fig. 9. Postoperatory CBCT (case 3)

The CBCT performed at 5 months after the surgical intervention (Fig. 10) highlight the existence of a
quantity of newly formed bone, exceeding the previous level of the ridge previous the extraction of the 4.8
molar.

Fig. 10. CBCT performed postoperatory at 5 months (case 3)

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 In all presented cases, the evolution of healing was favorable, without any complications. All postoperative
radiological images show the benefits of using this technology in stimulating bone regeneration and mouth tissue
healing with PRF.
All presented cases demonstrate that the placement of autologous PRF has been beneficial for the induction
of hasten postoperative healing, without the apparition of any complications.

The efficacy of the technology to assist and promote tissue regeneration through PRF is now evidenced in a
number of medical fields [11,12,13,14,16].
Choukroun et al, consider that the applied PRF acts much like a fibrin bandage, serving as a matrix to
accelerate the healing of wound edges [4,5,6]. Dohan et al underline that PRF also provides a significant
postoperative protection of the surgical site [8,9]. After Dohan et al opinion, PRF accelerates the integration and
the remodelling of the grafted biomaterial [10]. According to research of Tatullo and all, the time needed for
healing after performing various surgical maneuvers using PRF is greatly reduced [15].

CONCLUSIONS
According to the results of this study, we found that by applying the PRF, the healing time is greatly reduced.
The use PRF was performed through a simple protocol.
Radiographic imaging is of major importance in complementary examinations for correct diagnosis and for
evaluating the results of the instituted therapy. The most complex and exact evaluation method is the CBCT’s
examinations, but due to its price and due to the high risk of irradiation, this technique is not indicated to be used
for all the patients.
In some extreme circumstances, like the high level of the cholesterol, or the excess fat, does not appear a
proper segregation of factions from PRF biomaterial, and so, these ill patients cannot benefit the advantages of
treatment with PRF.

SELECTIVE REFERENCES

1. Anitua E, Tejero R, Zalduendo MM, Orive G, Plasma Rich in Growth Factors Promotes Bone
Tissue Regeneration by Stimulating Proliferation, Migration, and Autocrine Secretion in Primary
Human Osteoblasts, J Periodontol, August 2013, Volume 84, Number 8, 1180-1190
2. Bechir A, Bechir ES, Biomateriale dentare utilizate în cabinetul stomatologic:, Ed. Printech 2012
3. Borie E, Oliví DG, Orsi IA, Garlet K, Weber B, Beltrán V, Fuentes R, Platelet-rich fibrin
application in dentistry: a literature review, Int J Clin Exp Med. 2015; 8(5): 7922–7929
4. Choukroun J, Adda F, Schoeffler C, Vervelle A. Une opportunité en paro-implantologie: le PRF.
Implantodontie 2001; 42:55-62
5. Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, et al. Platelet-rich fibrin (PRF): a
second-generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 2006; 101:e56-60
6. Choukroun J, Diss A, Simonpieri A, Girard M-O, Shoeffler C, et al. Platelet-rich fibrin (PRF): A
second generation platelet concentrate. Part V: Histologic evaluations of PRF effects on bone
allograft maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2006;101:299-303
7. Civinini R, Macera A, Nistri L, Redl B, Innocenti M, The use of autologous blood-derived growth
factors in bone regeneration, Clin Cases Miner Bone Metab. 2011 Jan-Apr; 8(1): 25–31
8. Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101:e37-44
9. Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101(3):e45-50
10. Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, Gogly B. Platelet-rich fibrin
(PRF): A second generation platelet concentrate. III. Leukocyte activation: A new feature for
platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101:e51- 55
11. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T, Classification of platelet concentrates: from
pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF), Trends in
Biotechnology, Volume 27, Issue 3, March 2009, Pages 158–167

166
12. Muñoz F., Jiménez C., Espinoza D., Vervelle A., Beugnet J., Haidar Z.,Use of leukocyte and
platelet-rich fibrin (L-PRF) in periodontally accelerated osteogenic orthodontics (PAOO): Clinical
effects on edema and pain, Journal of Clinical and Experimental Dentistry, Volume 8, Issue 2, 1
April 2016
13. Neel A, Ali E et al., Tissue engineering in dentistry, Journal of Dentistry, Volume 42 , Issue 8 , 915
- 928
14. Preeja C, Arun S, Platelet-rich fibrin: Its role in periodontal regeneration, The Saudi Journal for
Dental Research, Volume 5, Issue 2, July 2014, Pages 117–122
15. Tatullo M, Marrelli M, Cassetta M, Pacifici A, Stefanelli LV, Scacco S, Dipalma G, Pacifici L,
Inchingolo F. Platelet Rich Fibrin (P.R.F.) in Reconstructive Surgery of Atrophied Maxillary
Bones: Clinical and Histological Evaluations. Int J Med Sci 2012; 9(10):872-880
16. Zhao Q, Ding YJ, Si T. Platelet-rich fibrin in plastic surgery. OA Evidence-Based Medicine 2013
Apr 01;1(1):3

167
GIFTED STUDENTS IDENTIFICATION AND IMPROVING THE EDUCATIONAL -
PROCESS IN THEIR CASE

Ciavoi Gabriela *, Bechir Anamaria **, Bechir Edwin Sever *** , Tig Ioan*, Dalai Camelia
*,Dalai Ciprian *
*Lecturer Ph.D. , Oradea University, Faculty of Medicine and Pharmacy
** Prof. Ph.D. Titu Maiorescu University,Faculty of Dental Medicine
*** Assistant Professor, Targu Mures, University of Medicine and Pharmacy

ABSTRACT
The problem giftedness is addressed more frequently lately in our country.Unfortunately, most of them are not
identified in this case being unable to capitalize their potential.In many countries there is still testing to identify
these children from young ages, kindergarten, primary school .The theme of our work is related to the
identification students with high intellectual potential and recovery in a most efficient manner to this In the first
part we identify the main features of this category of students, and in part second try to draw some of the ways
that we can streamline the education process in their case.
Keywords: gifted students, education, identification

INTRODUCTION
Nowadays, between 3-15% of the population of the students are identified as gifted, the number
differing from country to country.
Identifying gifted children is a national priority in many countries, testing of incepad early age, even in the early
years of life.If the parents are educated and informed so that the first signs that indicate a child with high
intellectual potential addresses specialitaty counselor .In our country in recent decades occurred organizations
that are involved in identifying and advising this group of children and their parents .Even though there is a law
in this regard, Law 17/2007 which is based education Law 84/1995 mode of application, even 2016 is quite
ambiguous and ineffective.
According to the mentioned law, 85/1995 Chapter II, Article 22, should be differentiated training
centers, which deal with the education of these children through specific teaching methods, special personnel
trained in this regard and adequate curriculum.
According to art. 24 of the mentioned law, the objectives of these centers are providing educational
facilities for children with abilities and high performance; ensuring training tailored to the personality profiles of
students, their intellectual ability development and creative expression to their specific needs for social and
professional integration; Ensuring the conditions and procedures for the adoption of personalized training paths,
comprising a flexible own research and a credit transfer system adapted deep specialization in certain areas of
interest to students (Law 84/1995 article 16 par 2.
Article 26 says: "Financing Training Centres differentiation. The state will finance the development of education
excellence for children with special skills, in line with economic development strategies and needs of highly
competent specialists required for implementing this strategy. To achieve a high level competitive framework
enabling the development of quality in education, some of the work of education of gifted and talented children
will be financed in part-private, partly public.
Budgetary funds for education by both public and private sectors will finance the following activities:
-selected children
-selected teacher
-development of educational programs supported by grants
- training and teacher training activities will be subsidized by the state at a rate of 25%, but paid the rest privately
- theoretical and applied research and creativity activities will be subsidized by the state at a rate of 40% the rest
being financed with scholarships / grants from external research collaborations, or other sources of funding.
-activitaty in teaching will fund 25% of the budget to public or private centers that were operating agreement
given by the ESM, and the rest will be financially self sustainable by offering educational privately own and
through tutoring programs, scholarships / grants, sponsorships or other forms of financing. "
Ineffective law enforcement led to the detection of a small percentage of missing children with their
high potential .Due to their families, teachers of socio-economic deficit, etc. that children are often wrongly
labeled as misfits, insolent, negative elements in the collective.
These features apply to both students and students who in many cases are considered disinterested,
perform poorly in exams, do not fit into the social group they belong.

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GENERAL CHARACTERISTICS OF GIFTEDNESS

Definition of giftedness is variable depending on cultural context, social, professional or geographical

environment, depending on the program that is geared toward well-defined goals or desired professional horizon.
For each situation of this type are selected certain types of skills being measured value at different levels.
In general the social referential giftedness common definition includes psycho-physical and intellectual
capabilities geared outstanding scientific, artistic, or leadership to management, to medium, or kinesthetic, etc. It
also includes capacity of independence and creativity, and the third feature included in the definition is based on
academic skills.
Gifted people can be found at all ages, races, genders and do not depend on physical or other handicaps.
Children capable of high performance potential shows skills in one area or in combination in the following areas.
• general intellectual abilities
• specific academic skills
• creative or productive thinking
• Skills in leadership
• Visual arts or shows
• psychomotrical skills
The definition has been improved by including high logic capacity in scientific fields or abstract logic games.
1. Typically they learn to read early and with a better understanding of the nuances of language. More than half
of the children gifted and / or talented learned to read before school. All these children are reading more, faster
and have a richer vocabulary than others.
2. Acquire basic skills better, faster and with less exercise.
3. they are more able to build and use abstractions than their age group.
4. they are more able to observe and interpret nonverbal codes and conclusions that other children should be
taught.
5. They are less willing to accept everything on trust themselves searching questions answered such as: why?
How?
6. Have a better ability to work independently at a younger age and for longer periods of time than other
children.
7. Have concentration for longer periods of sustained attention than others.
8. Often interests both very focused and very broad.
9. They often have so much energy that sometimes are wrongly diagnosed as "hyperactive".
10. Have good relations and dialogue with parents, teachers or other adults. Prefer the company of older children
or adults, the children.

The characteristics of gifted students:

1.Cognitive domain.
Characteristics:
- An impressive amount of information, remember with great ease.
- High level of knowledge of vocabulary, its development very quickly
- Persistent
- Aim to end action
- Capacity amazing information processing and concepts
Problems:
- Boredom in classes because the curriculum does not have the patience to wait for the group
- Perceived by others as being great, conceited
- Is seen as stubborn, uncooperative
- Often, does not like routine and stagnation.
2.Affective domain.
Characteristics:
- Unusual sensitivity about expectations and feelings from others
- Sense of humor, sometimes dark humor
- Very strong emotional depth
- Advanced moral judgment

Problems:
- Vulnerability to strong criticism from others
- Necessity of success and appreciation
- Use humor to attack them critically others, causing ruptures in relationships.
- The unusual vulnerability problems on setting goals at work, sometimes unrealistic
- Intolerance and lack of understanding of ordinary people, resulting in rejection and possible isolation.
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3.Physical domain (sensory).
Characteristics:
- Introduce a large discrepancy between the physical and intellectual development
- Reduced tolerance for physical delay on standard athletic abilities
Problems:
- They become adults with a mind / body dichotomy
- Children express themselves more easily in mental activities, resulting in limited development both physical
and mental
- Refuse to take part in activities where they excel, limiting their physical experiences that could have them be
pleasant and very constructive.
4.Intuitive field.
Characteristics:
- Involvement very early in terms of intuitive knowledge, ideas and metaphysical phenomena surrounding
- Creativity apparent in all areas where laying a effort of understanding.
Problems:
- Ridiculed by peers
- Not considered for the adults
- Considered odd and fanciful
- Seen as deviant, gets tired of mundane tasks
- Can be interpreted as a person causing trouble.
5.Social area.
Characteristics:
- Driven by self and updating of their needs, always in a continuous climb in the hierarchy
- Good leadership
- Introduces solutions in company and environmental problems
Problems:
- Frustrated because it is not caused in competitions
- Unrealized loss of talent
- Lack of opportunity to use their skills constructively, these leadership skills can disappear or can turn into a
negative side (to be the leader of a group, gangs)
- It's lost in society if solutions are not appreciated or accepted for development
One of the problems of gifted children is that they process the information provided otherwise (the
majority - 75% are visual spatial, have divergent thought seeing solutions through a tree thinking but are unable
to explain). have higher processing speed. They have increased capacity in terms of analog processing, global -
through the right hemisphere processes information globally and manages emotions simultaneously. Most often
their teachers do not understand why a child is intelligent officially declared unable to apply the same learning
methods / strategies to solve problems that have proven adequate so many children. Practical solutions they see
visually, mentally, and are unable to explain how they got the result, "just know". In most of these children do
not possess naturally gifted ability to organize their thoughts sequentially and not learning methods.

IMPROVING EDUCATIONAL PROCESS FOR GIFTED STUDENTS

The literature describes several techniques to exploit the potential of these students, we try to select only those m
ethods that we believe can be applied in realistic mode in our country and at levels that are nostrum educational
process.
1.Active implication: It is very important that these students to be involved in the learning process, to be heard,
to ask them more creative tasks.
2Creativity stimulation.The gifted students very creative and involved in the learning process and seminaries
when both courses are presented in a creative manner and when being asked for their direct involvement in the
post-secondary through activities that stimulate creativity.
3.The psychologist implication.They often require the intervention of the specialty that every student allegedly
analizezs as giftedt.All cases of students who at first glance seem disinterested, bored, missing classes and
practical activities, often seem arrogant, insolent, but if you pay more attention to notice that although never
seem to learn not have many acquaintances, make easy connections between notions unexpected events,
etc.Sometime the simply changing the attitude of the teacher can work wonders in these students.
4.Trust granting.These students come, most of the traditional education system, which often were placed little
value, often ridicule, marginalized by colleagues and teachers, often the discrepance between their capabilities
physical and intellectual they come with low self trust .The fact that stimulates trust are given this type of
student.
5.Teachers education The teachers need to be educated to identify gifted students and proper approach to these
cases in order to capitalize their potential native. We have concrete cases in which teachers felt offended when
170
these students have shared their knowledge and have responded in the negative sense, limiting future intervence
in student.
6. Advise in developing these student cariers There are cases in which they choose a career that although they
can learn easily in that area can not practice.In skills is important to identify these cases and counseling by
specialist for choosing a career to capitalize qualities.
7. Involvement in extracurricular activities: exchange student involvement in student organizations,
volunteering in the field, etc.

CONCLUSIONS

Through this study we want to draw attention to the importance identification of gifted students, who
fortunately in our country are not few.Unfortunately, out of every 30 gifted students, only 2 are discovered.If a
student is not identified and stimulated, these studies may be completed without great effort or abandons college
and often radical field changes several times over the years, being wrongly categorized as with a low intellectual
potential, rebel, etc.
Fortunately there are some that are identified either during school or the family encouraged and
supported, so it is in a student can find the resources to evolve even if not necessarily in a particularly stimulated
by the teachers.
Knowing the main features of mental and emotional students with high potential as well as methods to
stimulate the satisfaction they cause spectacular transformation and evolution in terms of professional students.
The teaching methods that are based on creativity must address not only gifted students, they should be
a rule incurrent education. In education currently conditions is an outdated rule: dictate- students write what
teacher says. Modern education requires active involvement of students in the teaching-learning, stimulation and
personal contributions to student assessment, development of extracurricular activities (educational projects,
conferences for students, etc).

REFERENCES

1.Baum, S. M., Renzulli, J. S., & Hébert, T.P. (1999). Reversing underachievement: Creative productivity as a
systematic intervention. Gifted Child Quarterly, 39, 224-235.
2.Miller, A,The Drama of the Gifted Child: The Search for the True Self, Revised Edition Paperback – November
30, 1996
3.Renzulli, J. S., & Park, S. . Gifted dropouts: The who and the why. Gifted ChildQuarterly,200. 44, 261-271.
4.Robinson, A. Cooperative learning and the academically talented students(RBDM 9106). Storrs, CT: The
National Research on the Gifted and Talented, University of Connecticut., 1991
5.Silvermann, L .Counseling the Gifted Children,Publisher: Love Pub Co (June 1993)
6.http://www.giftededu.ro/resources/Beneficiile-educatiei-copiilor-supradotati-Cercetari-internationale.pdf
7.https://www.medlife.ro/en/ce-se-intampla-cu-copiii-supradotati-pe-parcursul-vietii.html
8.http://paracelsus.ablog.ro/2007-01/
9.http://www.supradotati.ro/legea-privind-educatia-tinerilor-supradotati-capabili-de-performanta-inalta.php

171
ANTIBACTERIAL EFFECT OF LASER ASSISTED PERIODONTAL THERAPY – A
CASE REPORT

Alin Alexandru Odor1,2, Deborah Violant3, Edwin Sever Bechir4, Victoria Badea5
1
PhD student - Doctoral School of Medicine, Ovidius University of Constanța, Romania
2
Periodontology resident - Department of Periodontics, Faculty of Dental Medicine, Gr.T.Popa
University of Medicine and Pharmacy Iași, Romania;
3
Associate Professor - Department of Periodontics, Faculty of Dentistry, International University of
Catalunya, Barcelona, Spain;
4
Assisst. Professor - Department of Oral Rehabilitation, Faculty of Dental Medicine, University of
Medicine and Pharmacy of Târgu Mureș
5
Head Professor - Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius
University of Constanța, Romania;

Abstract: Chronic periodontitis with rapid rate progression represents a challenge in the periodontal treatment.
This case report describe the clinical and microbiological efficacy of the laser assisted periodontal treatment. To
evaluate the efficacy of the Er,Cr:YSGG 2780 nm and diode 940 nm lasers in the treatment of chronic
periodontitis, digital radiographies, periodontal charts, PCR assays of 11 periodontalpathogenic bacteria were
taken before and after the laser treatment. The postop PCR analysis shows a complete elimination of the
pathogenic bacteria associated with the red complex of periodontal virulence. Also, at 6 months postop all the
periodontal clinical parameters shows significant improvement, as well as the bone regeneration rate. The
combination of two laser wavelength in the treatment of chronic periodontitis, represents efficient alternative for
minimal-invasive treatments.

Keywords: Laser assisted periodontal treatment; Er,Cr:YSGG, diode laser, chronic periodontitis.

INTRODUCTION

The application of laser in periodontology is widely discussed, especially as several laser systems with their
specific wavelength have a different impact on periodontal tissues. Most diode lasers are associated with soft
tissue lasers especially wavelengths like 810 nm, 940 nm, and 980 nm, due to their high absorption in melanin
and hemoglobin, are suitable for removal of granulation tissue and decontamination. Also, wavelengths like 630,
660 nm and 810 nm diode lasers are frequently used in antimicrobial Photodynamic Therapy (aPDT) [1,2,3].
This procedure procedures uses a specific laser light, a dye (photosensitizer) such as methylene blue, toluidine
blue or indocyanine green, in the presence of oxygen [4,5,6].
On the other hand, Erbium lasers (Er,Cr:YSGG 2780 nm and Er:YAG 2940 nm) are known as “hard and soft
tissue lasers” which can be used for removing the calcified bacterial deposits, bacterial biofilm, the smear layer
from the root surfaces and the granulation tissue.
When it comes to the use of lasers in periodontal treatment, results from the literature are controversial, and it
is indicated to use lasers as an adjunct to scaling and root planning (SRP) [7,8,9].
The aim of this paper is to present innovative opportunities for periodontal treatment.

CASE REPORT

A-37-years old male, systemically healthy, non-smoker patient presented with generalized moderate-severe
chronic periodontitis was treated. The patient did not receive any periodontal treatment or antibiotic
administration previously. The oral examination revealed a poor oral hygiene, gingival inflammation, halitosis
and radiographically vertical – horizontal bone resorption was present (Fig. 1).
Periodontal chart was performed at six sites per tooth: mesio-vestibular (MV), mid-vestibular (V), disto-
vestibular (DV), mesio-lingual (ML), mid-lingual (L) and disto-lingual (DL), and evaluated at baseline and 6
months after the laser treatment. At baseline the mean probing depth (PD) was 3.7 mm, mean clinical attachment
level (CAL) was -5 mm, and mean bleeding on probing (BOP) was 53%.
It order to assess the periodontal bacteria involved within the pockets, 11 periodontalpathogenic species was
investigated by means of real-time PCR assay (qualitatively and quantitatively). It was decided to perform
individual microbiological samples from 4 different sites, respectively: distal aspect of tooth 1.2, distal aspect of
tooth 2.2, mesial aspect of tooth 3.1 and distal aspect of tooth 4.2. The baseline result of microbiological assay is
shown in Fig.2.

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 Fig. 1 – Clinical and radiographic aspect before periodontal laser therapy

Fig. 2 – The microbiological assay revealed the presence of red and orange complexes, associated with
periodontal tissue damage

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Treatment procedure

Laser assisted periodontal treatment using Er,Cr:YSGG 2780 nm and diode 940 nm lasers in adjunct to SRP,
was applied in different sessions as follows:

Pre-surgical phase
First session was represented by the periodontal examination. In the second session, after removing the
supra-gingival calculus with ultrasonic scalers and professional tooth cleaning, patient received an endodontic
treatment on tooth 2.2 that closed the buccal fistula. Patient received oral hygiene instructions (OHI).

Surgical phase
The surgical phase was represented by a half-mouth protocol and divided in two sessions: first session –
Upper and Lower Right (UR/LR); second session: Upper and Lower Left (UL/LL).
This phase proceeds with the following steps:
1. Er,Cr:YSGG laser (WaterLase Iplus, Biolase, USA) was used to remove the inner epithelial lining to
the depth of the pocket and the outer-epithelium to the depth of 5mm at 1.5 W, 30 Hz, 40% Air, 50%
Water, H mode (pulse duration 60 µs) with 14 mm MZ6 tip (600 µm diameter).
2. After creating the access with Er,Cr:YSGG laser, SRP was performed with manual curettes and
piezoelectric ultrasonic scalers (Piezotome 2, Satelec-Acteon).
3. Er,Cr:YSGG laser was used at 1.5 W, 75 Hz, 40% Air, 50% Water, H mode with RFPT5-14 mm (500
µm diameter) to remove smear layer created by scaling, along with any residual calculus, and prepare
the root surface for reattachment. Root preparation was performed with the fiber tip angled 10° – 15°
towards the surface and moved side to side and up and down to ensure complete removal and cleaning.
4. aPDT using Diode 940 nm laser (Epic 10, Biolase, USA) with 300 µm uninitiated fiber tip, 1.1 W,
Continuous Wave (CW) for activation of hydrogen peroxide 3% for 30 seconds. The laser fiber was
applied from the bottom to the free gingival margin of the periodontal pocket in parallel with the root
surface, and side to side movements was performed.
5. Pressure was applied to the surgical site with a moist gauze for 3-5 minutes.

Post-surgical phase
After the surgical phase, biostimulation was performed once per day for 5 consecutive days, in order to
promote periodontal wound healing according to the following settings: diode laser 940 nm, 0.3 W power,
fluency of 3 J/cm2, bleaching hand-piece (3 cm2 spot size - total energy 9 J), CW, exposure time: 30 sec per each
treated site.
At 10 days postoperative periodontal decontamination was repeated in the same pattern as used in the pre-
surgical phase (diode 940 nm laser with 300 µm uninitiated fiber tip, 1.1 W, CW + 3% H2O2).
At 3 days postoperatively, microbiological samples was repeated from the same sites, in order to evaluate the
laser periodontal therapy. Patient was evaluated periodically at 1, 3, and 6 months and at 1 year postoperative.

(a) (b (c) (d (e)

) )
Fig. 3 – Surgical laser sequence: (a) Inner epithelium removal with Er,Cr:YSGG laser, (b) Outer epithelium
removal with Er,Cr:YSGG laser, (c) Access created by Erbium laser for SRP, (d) Manual and ultrasonic SRP, (e)
RFPT15-14mm tip for removing the smear layer created by SRP, residual calculus and conditioning of the root
for reattachment

174
 (a) (b (c) (d (e)
Fig. 4 – Post-surgical laser sequence: )(a) The aspect of the periodontal tissues before) diode laser aPDT, (b)
application of hydrogen peroxide 3% within the periodontal pocket, (c) Photolysis of hydrogen peroxide with
diode 940 nm laser, (d) The aspect of aPDT after 30 sec exposure to diode laser, (e) Immediate aspect after
rinsing

Treatment outcomes

Postoperative healing was uneventful and no signs of complications were observed. At 6 months
postoperatively, mean PD was 2.4 mm, mean CAL was -4.2 mm and mean BOP was 13%.
After the laser procedures, the total number of bacteria decreased considerably all the periodontalpathogenic
bacteria were eliminated entirely, as shown in Fig. 5.

Fig. 5 – Results of microbiological assay after the laser periodontal treatment

Fig. 6 – Clinical and radiographic aspect at 1 year postop

175
DISCUSSIONS

Several studies [10-16] have provided significant evidence that photoactivation of hydrogen peroxide with
diode lasers can eliminate the dental pathogens. These studies used diode lasers with wavelengths ranging from
400 – 635 nm, for elimination of microorganism correlated to endodontic and tooth cavities disease. Results
showed that the most frequently encountered pathogens in oral disease, like E. Faecalis, S. Mutans, S. Aureus
and C. Albicans can be photoeradicated by this potent disinfection system. Nevertheless, in the literature there is
no data that investigated the photoactivated disinfection (PAD) using 940 nm diode laser and 3% hydrogen
peroxide in periodontal treatment.
The aPDT procedures uses commercial photosensitizer that is been activated by specific wavelengths [1-6].
Generally, some dyes may be costly, which will increase the cost of the procedure. The 3% hydrogen peroxide
solution may be a cost efficient solution, which can be photoactivated by a wide range of laser wavelengths
(visible and near infrared light devices).
According to this case report, the photolysis of 3% hydrogen peroxide with the help of 940 nm diode laser
can eliminate the viability of the most anaerobic bacteria that are associated with impairment of periodontal
tissues (red and orange complexes).
From the real-time PCR analysis, emerges that red complex bacteria Porphyromonas gingivalis (Pg.),
Tannerella forsythia (Tf.) and Treponema denticola (Td.), were completely eliminated, although Pg. is resistant
to oxidative stress [17]. Also, orange complex Fusobacterium nucleatum (Fn.), Prevotella intermedia (Pi),
Peptostreptococcus micros (Pm.), showed complete eradication, as well the total count of bacteria per sample
had a significant decrease.
During this case report, we noticed that when using diode laser with more than 1.1W in CW (continuous
wave) with 300 µm uninitiated fiber tip for the 3% hydrogen peroxide photolysis, the fiber tip started to initiate,
which conducted to soft tissue removal. To overcome this inconvenient we decided to use a maximum laser
power of 1.1W.
All the periodontal parameters investigated showed significant improvements after the laser assisted
periodontal treatment, results that was according to a recent study that investigated the use of dual laser
wavelengths (2780 nm and 940 nm) in reduction of periodontal pockets [18].
Gutknecht et al. [19] investigated the efficacy of periodontal bacteria reduction aided by Er,Cr:YSGG laser
in a split mouth study design. The periodontalpathogenic species investigated were represented by
Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema
denticola, Fusobacterium nucleatum, and Prevotella intermedia. Result showed a significant reduction of
pathogenic bacteria when SRP was used in conjunct with laser irradiation at three and six months compared to
SRP alone.
The cumulative effect of SRP, Er,Cr:YSGG, and photolysis of hydrogen peroxide with 940nm diode laser
lead to a highly significant elimination of periodontal bacteria biofilm within the periodontal pockets.

CONCLUSIONS

The rationale for using both Er,Cr:YSGG 2780 nm and diode 940 nm laser in periodontal treatment, is
represented by a minimally invasive procedure that covers a wide range of periodontal procedures for pocket
elimination (necrotic tissue removal, biofilm elimination, debridement, decontamination, biostimulation) without
the use of local or systemically administration of antibiotics. We consider imperative to perform a mechanical
biofilm removal (SRP) prior to PAD of hydrogen peroxide in order to achieve optimum results.

REFERENCES

1. Souza LC, Brito PR, Machado de Oliveira JC, et al. Photodynamic Therapy with Two Different
Photosensitizers as a Supplement to Instrumentation/Irrigation Procedures in Promoting Intracanal
reduction of Enterococcus faecalis J Endod. 2010 Feb;36(2):292-6. doi: 10.1016/j.joen.2009.09.041.
2. Swapnil SB, Bhaskar DJ, Agali CR, et al. Assessment of Photodynamic Therapy (PDT) in Disinfection of
Deeper Dentinal Tubules in a Root Canal System: An In Vitro Study. Journal of Clinical and Diagnostic
Research. 2014 Nov, Vol-8(11): ZC67-ZC71
3. Cruz Andrade PV, Euzebio Alves VT, Carvalho VF et al. Photodynamic therapy decrease immune-
inflammatory mediators levels during periodontal maintenance. Lasers Med Sci (2016).
doi:10.1007/s10103-016-2076-7
4. Monzavi, Abbas et al. Antimicrobial photodynamic therapy using diode laser activated indocyanine green
as an adjunct in the treatment of chronic periodontitis: A randomized clinical trial. Photodiagnosis and
Photodynamic Therapy, Volume 14 , 93 - 97

176
5. Kikuchi T, Mogi M, Okabe I, et al. Adjunctive Application of Antimicrobial Photodynamic Therapy in
Nonsurgical Periodontal Treatment: A Review of Literature. Huang Y, ed. International Journal of
Molecular Sciences. 2015;16(10):24111-24126. doi:10.3390/ijms161024111.
6. De Freitas LM, Calixto GMF, Chorilli M, et al. Polymeric Nanoparticle-Based Photodynamic Therapy for
Chronic Periodontitis in Vivo. Másson M, ed.International Journal of Molecular Sciences. 2016;17(5):769.
doi:10.3390/ijms17050769.
7. Magaz VR, Alemany AS, Alfaro FH, Molina JN. Efficacy of Adjunctive Er, Cr:YSGG Laser Application
Following Scaling and Root Planing in Periodontally Diseased Patients. Int J Periodontics Restorative
Dent. 2016 Sep-Oct;36(5):715-21. doi: 10.11607/prd.2660.
8. Sgolastra F, Petrucci A, Gatto R, Monaco A. Efficacy of Er:YAG laser in the treatment of chronic
periodontitis: systematic review and meta-analysis. Lasers Med Sci. 2012 May;27(3):661-73. doi:
10.1007/s10103-011-0928-8. Epub 2011 May 7.
9. Al-Falaki R, Cronshaw M, Parker S. The Adjunctive Use of the Erbium, Chromium: Yttrium Scandium
Gallium Garnet Laser in Closed Flap Periodontal Therapy. A Retrospective Cohort Study. The Open
Dentistry Journal. 2016;10:298-307. doi:10.2174/1874210601610010298.
10. Stojicic S, Amorim H, Shen Y, Haapasalo M. Ex vivo killing of Enterococcus faecalis and mixed plaque
bacteria in planktonic and biofilm culture by modified photoactivated disinfection. Int Endod J
2013;46:649‑ 59.
11. Stamatacos C and Hottel TL. The Advantages of the Photolysis of Hydrogen Peroxide Utilizing LED Light
as a Hydroxyl Radical-Based Disinfection Methodology for Photoeradication of Dental Plaque Biofilms.
Austin J Dent. 2j014;1(1): 6.
12. Nakamura K, Kanno T, Mokudai T, Iwasawa A, Niwano Y, Kohno M. Microbial resistance in relation to
catalase activity to oxidative stress induced by photolysis of hydrogen peroxide. Microbiol Immunol. 2012;
56: 48-55.
13. Ikai H, Odashima Y, Kanno T, Nakamura K, Shirato M, Sasaki K, et al. In vitro evaluation of the risk of
inducing bacterial resistance to disinfection treatment with photolysis of hydrogen peroxide. PLoS One.
2013; 8: e81316.
14. Feuerstein O. Light therapy: complementary antibacterial treatment of oral biofilm. Adv Dent Res. 2012;
24: 103-107.
15. Shirato M, Ikai H, Nakamura K, Hayashi E, Kanno T, Sasaki K, et al. Synergistic effect of thermal energy
on bactericidal action of photolysis of H2O2 in relation to acceleration of hydroxyl radical generation.
Antimicrob Agents Chemother. 2012; 56: 295-301.
16. Hayashi E, Mokudai T, Yamada Y, Nakamura K, Kanno T, Sasaki K, et al. In vitro and in vivo anti-
Staphylococcus aureus activities of a new disinfection system utilizing photolysis of hydrogen peroxide. J
Biosci Bioeng. 2012; 114: 193-197.
17. Henry LG, McKenzie RM, Robles A, Fletcher HM. Oxidative stress resistance in Porphyromonas
gingivalis. Future Microbiology. 2012;7(4):497-512. doi:10.2217/fmb.12.17.
18. Odor AA; Violant D; Badea V; Gutknecht N. Short-term clinical outcomes of laser supported periodontal
treatment concept using Er,Cr:YSGG (2780nm) and diode (940 nm): a pilot study. Proc. SPIE 9670, Sixth
International Conference on Lasers in Medicine, 96700G (March 22, 2016); doi:10.1117/12.2191634.
19. Gutknecht N, Van Betteray C, Ozturan S, Vanweersch L, Franzen R. Laser Supported Reduction of Specific
Microorganisms in the Periodontal Pocket with the Aid of an Er,Cr:YSGG Laser: A Pilot Study. The
Scientific World Journal. 2015;2015:450258. doi:10.1155/2015/450258.

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 CLINICAL OUTCOMES OF LASER SUPPORTED PERIODONTAL TREATMENT
CONCEPT USING ER,CR:YSGG (2780 nm) AND DIODE (940 nm)

Alin Alexandru Odor1,2, Deborah Violant3, Edwin Sever Bechir4, Ciprian Badea5 ,Victoria
Badea6
1
PhD student - Doctoral School of Medicine, Ovidius University of Constanța, Romania
2
Periodontology resident - Department of Periodontics, Faculty of Dental Medicine, Gr.T.Popa
University of Medicine and Pharmacy Iași, Romania;
3
Associate Professor - Department of Periodontics, Faculty of Dentistry, International University of
Catalunya, Barcelona, Spain;
4
Assisst. Professor - Department of Oral Rehabilitation, Faculty of Dental Medicine, University of
Medicine and Pharmacy of Târgu Mureș
5
Assisst. Prof. - Department of Prosthodontics, Faculty of Dental Medicine, Ovidius
University of Constanța, Romania;
6
Head Professor - Department of Microbiology and Immunology, Faculty of Dental Medicine,
Ovidius University of Constanța, Romania;

Abstract:
Backgrounds: Er,Cr:YSGG (2780nm) and diode (940 nm) lasers can be used adjacent to the conventional
periodontal treatment as minimally invasive non-surgical devices.
Aim: To describe the clinical outcomes by combining Er,Cr:YSGG (2780nm) and diode 940 nm lasers in non-
surgical periodontal treatment.
Materials and methods: A total of 25 patients with periodontal disease (mild, moderate, severe) – 560 teeth and
1789 periodontal pockets ranging from 4 mm to 12 mm – were treated with Er,Cr:YSGG (2780nm) and diode
(940 nm) lasers in adjunct to manual and piezoelectric scaling and root planning (SRP). Periodontal parameters
such as mean probing depth (PD), mean clinical attachment level (CAL) and mean bleeding on probing (BOP)
were evaluated at baseline and 6 months after the laser treatment using an electronic periodontal chart.
Results: At baseline, the mean PD was 4.06 ± 1.06 mm, mean CAL was 4.56 ± 1.43 mm, and mean BOP was
43.8 ± 23.84 %. At 6 months after the laser supported periodontal treatments the mean PD was 2.6 ± 0.58 mm (p
<0.001), mean CAL was 3.36 ± 1.24 mm (p <0.001) and mean BOP was 17 ± 9.34 % (p <0.001).
Conclusion: The combination of two laser wavelengths in adjunct to SRP offers significant improvements of
periodontal clinical parameters such as PD, CAL and BOP.

Keywords: Laser supported periodontal treatment concept, Er,Cr:YSGG and diode 940nm lasers, Scaling and
root planning, Minimally invasive non-surgical device

INTRODUCTION

Periodontitis is one of the most prevalent diseases affecting nearly one third of the adult population.
Periodontitis is characterized by loss of connective tissue attachment to the tooth and pathological migration of
the junctional epithelium apically, which leads to pocket formation, tooth mobility, and finally loss of the tooth.
From the literature it is well known that, the key factor in the treatment of periodontal disease is to
successfully eliminate the bacterial biofilm within the periodontal pockets, and to maintain the roots plaque-free
[1].
Various methods, both chemical and mechanical, has been applied to eliminate periodontal pathogens.
Scaling and root planning represents a minimally invasive procedure that cannot eliminate completely
periodontal pathogens within the periodontal pockets, therefor various combinations of chemical agents were
suggested [2-5].
The disadvantages of conventional techniques in the treatment of periodontal disease (allergic reactions, side
effects, antibiotic resistance, invasive surgical methods, etc.), led to the necessity to approach alternative
methods of treatment. Due to the selective ability, in recent years laser technology has gained considerable
interest in the periodontal treatment as an adjunctive tool.
Laser like CO2 (10600 nm), Nd:YAG (1064 nm), Er:YAG (2940 nm), Er,Cr:YSGG (2780 nm) and diode lasers
(800-980 nm) have been the most widely used in periodontal conservative surgery and management of soft tissues.
These lasers has the ability to ablate soft tissue with effective hemostasis and reduction of periodontal pathologic
bacteria.
The wavelengths of the Er:YAG (2940 nm) and Er,Cr:YSGG (2780 nm) lasers are used successfully to
remove subgingival calculus and to prepare the root surface for epithelial reattachment due to the high

178
absorption by the water molecules that are interspersed among the hydroxyapatite crystals, providing these lasers
with the photomechanical or photothermal ability to remove mineralized tissues without heating the adjacent
tissues.
In contrast with Erbium lasers, diode laser can only be suggested for soft tissues ablation and
decontamination procedures. Techniques such as photodynamic therapy (aPDT – antimicrobial Photodynamic
therapy) have been extensively studied and performed with different laser wavelengths in the presence of various
photosensitive substances [6-9]. But so far there is no evidence in the scientific literature, regarding the
bactericidal effects produced by photolysis of hydrogen peroxide with 940 nm diode laser as a method of
decontamination of periodontal pockets.

MATERIAL & METHOD

Patient selection
From the patients record treated during January 2015 to June 2016, a total of 25 patients (14 males and 11
females) with periodontal disease (mild, moderate, and severe), aged between 27 - 63 years (mean age 45.04 ±
9.57) were included according to the following selection criteria:
 Single or multiple rooted teeth with the presence of periodontal pockets over 4 mm depth
 Patients that received the same treatment protocol
 No periodontal treatment received within the last 12 months
 No use of systemic or local antibiotics within the last 6 months
 No systemic diseases, which could potentially influence the outcome of the therapy (diabetes, immune
deficiencies, cancer, hemorrhagic disorders, epilepsy etc.)
 No pregnancy
From the total of 25 patients, 4 were smokers. No control group was included in this study.
Electronic periodontal charts revealed 560 teeth and 1789 periodontal pockets ranging from 4 mm to 12
mm which were treated with Er,Cr:YSGG (2780nm) and diode (940 nm) lasers after manual and piezoelectric
scaling and root planning (SRP).
Signed informed consent was obtained from all individual participants included in the study and all the
following procedures were approved by the Committee for Ethics of University Ovidius Constanța.

Treatment protocol
All patients received the same laser assisted periodontal treatment using Er,Cr:YSGG 2780 nm and diode 940
nm laser in adjunct to SRP, which was applied in different sessions as follows:

Pre-surgical phase
This phase included two sessions: First session was represented by the periodontal examination. In the
second session the supra-gingival calculus / dental plaque was removed with ultrasonic scalers and professional
tooth cleaning, Every patient received oral hygiene instructions (OHI) that included mouth rinse, without
chlorhexidine gluconate, twice a day after tooth brushing.

Surgical phase
The surgical phase was represented by a half-mouth protocol and divided in two sessions: first session –
Upper and Lower Right (UR/LR); second session: Upper and Lower Left (UL/LL).
This phase proceeds with the following steps:
6. Er,Cr:YSGG laser (WaterLase Iplus, Biolase, USA) was used to remove the inner epithelial lining to
the depth of the pocket and the outer-epithelium to the depth of 5mm at 1.5 W, 30 Hz, 40% Air, 50%
Water, H mode (pulse duration 60 µs) with 14 mm MZ6 tip (600 µm diameter).
7. After creating the access with Er,Cr:YSGG laser, SRP was performed with manual curettes and
piezoelectric ultrasonic scalers (Piezotome 2, Satelec-Acteon).
8. Er,Cr:YSGG laser was used at 1.5 W, 75 Hz, 40% Air, 50% Water, H mode with RFPT5-14 mm (500
µm diameter) to remove smear layer created by scaling, along with any residual calculus, and prepare
the root surface for reattachment. Root preparation was performed with the fiber tip angled 10° – 15°
towards the surface and moved side to side and up and down to ensure complete removal and cleaning.
9. aPDT using Diode 940 nm laser (Epic 10, Biolase, USA) with 300 µm uninitiated fiber tip, 1.1 W,
Continuous Wave (CW) for activation of hydrogen peroxide 3% for 30 seconds. The laser fiber was
applied from the bottom to the free gingival margin of the periodontal pocket in parallel with the root
surface, and side to side movements was performed.
10. Pressure was applied to the surgical site with a moist gauze for 3-5 minutes.

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 Post-surgical phase
After the surgical phase, biostimulation was performed once per day for 5 consecutive days, in order to
promote periodontal wound healing according to the following settings: diode laser 940 nm, 0.3 W power,
fluency of 3 J/cm2, bleaching hand-piece (3 cm2 spot size - total energy 9 J), CW, exposure time: 30 sec per each
treated site.
At 10 days postoperative periodontal decontamination was repeated in the same pattern as used in the pre-
surgical phase (diode 940 nm laser with 300 µm uninitiated fiber tip, 1.1 W, CW + 3% H2O2).
No open flap was raised during these procedures, and first probing was performed at the 6 months recall.

Clinical measurements and data collection:

The data and clinical measurements included in this study was as follows: gender, age, medical history, intra-
oral photographs, panoramic and periapical radiographs, and periodontal parameters such as mean probing depth
(PD), mean clinical attachment level (CAL) and mean bleeding on probing (BOP). The clinical measurements
were performed at six sites per tooth: mesio-vestibular (MV), mid-vestibular (V), disto-vestibular (DV), mesio-
lingual (ML), mid-lingual (L) and disto-lingual (DL), and evaluated at baseline and 6 months after the laser
treatment.
Statistical analysis
The statistical analysis was performed using a paired t-Test for mean scores of PD, CAL and BOP at baseline
and at 6 months after the periodontal laser treatment. The significance level was set at p ≤ 0.05.

RESULTS

In the present study, the laser assisted periodontal therapy was well tolerated by the patients and no treatment
complications were observed. All investigated periodontal parameters from baseline and 6 months postoperative
are presented in Table 1.

PD (mean ± SD) CAL (mean ± SD) BOP (mean ± SD)

Baseline 3.97 ± 0.86 mm 4.96 ± 1.16 mm 47.4 ± 20.08 %
After 6 months 2.44 ± 0.7 mm 3.68 ± 1.34 mm 14.72 ± 8.82 %
Improvement (p value) 1.53 mm (0.001)* 1.28 mm (0.001)* 37.3% (0.001)*
Table 1. Mean PD, CAL and BOP at baseline and 6 months after Er,Cr:YSGG (2780 nm) and diode (940
nm) lasers treatment

At baseline, the mean PD was 3.97 ± 0.86 mm (mean ± SD). Six months after laser treatment, the mean PD
was 2.44 (± 0.7) mm, with an improvement of 1.53 mm (p <0.001). A reduction of 1.28 mm (p <0.001) in mean
CAL from 4.96 (± 1.16) mm (at baseline) 3.68 (± 1.34) mm (after 6 months) was observed. At baseline, 47.4 (±
20.08) % of the periodontal pockets presented bleeding on probing (BOP). At 6 months after the laser supported
periodontal treatments the mean BOP was 14 (± 8.82) %, with an improvement of 37.3% (p <0.001). Figure 1, 2
and 3 shows the significant reduction of PD, CAL and BOP of the laser treated periodontal pockets.

Fig. 1 – Mean Probing Depth (in mm) before and after laser supported periodontal treatment

180
Fig. 2 – Mean Clinical Attachment Level expressed in mm before and after laser supported periodontal treatment

Fig. 3 – Mean Bleeding on Probing (in %) before and after laser supported periodontal treatment

DISCUSSIONS

It is widely accepted that periodontal pathogens cannot be completely eliminated by conventional scaling and
root planning, especially in deeper pockets when hand-held instruments are used for removal of subgingival
biofilm and calculus [10].
Even with an adequate oral hygiene and constant follow-ups, the colonization of the tooth surface, internal
and external periodontal epithelium by bacterial biofilms occurs. The risk factor for initiation of periodontal
disease emerges when bacterial disequilibrium is in favor of anaerobic bacteria species like Aggregatibacter
actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium
nucleatum, and Prevotella intermedia [11].
Several researchers studied the effect of adjuvant therapy of diode laser with SRP, in which results was found
to be controversial [12-19]. Some results suggested the beneficial effect of diode laser in combination with SRP
[12,17], whereas others studies have not showed a greater reduction of periodontal pathogenic bacteria in
comparison with conventional mechanical therapy [13,19].
In our study, all 1758 periodontal pockets treated showed an improvement in terms of healing, with good
attached gingiva and keratinized tissue. Although, some of periodontal pockets, especially those that exceeded 9
mm, showed a slower rate of regeneration, but with uneventful healing.
During this study, in the surgical phase of treatment, we noticed that when using the diode laser with more
than 1.1W in CW (continuous wave) with 300 µm uninitiated fiber tip for the 3% hydrogen peroxide photolysis,
the fiber tip started to initiate, which conducted to soft tissue removal. This phenomenon is attributed to further
bleeding during the surgical phase of treatment caused by the potential disruption of the inflamed tissue
conducted by the movements of the laser fiber tip within the periodontal pocket. To overcome this inconvenient,
we decided to use a maximum laser power of 1.1W, which proved to be safer for periodontal tissues. At 10 days
postoperative, we noticed that the initiation of the fiber tips occurred in very few cases in comparison to the
surgical phase, due to the less inflamed periodontal tissues.
Results from present study was according to our previous pilot study with a small patients group [17], which
investigated the same periodontal parameters. In addition to the previous study treatment protocol, the

181
photoactivation of 3% hydrogen peroxide was used in order to amplify the bactericidal effect of laser
decontamination.
The photoactivation of hydrogen peroxide with diode lasers was reported in some studies that were focused
on the bactericidal effect of endodontic and caries treatments. In a new study, Nakamura K. et al. [18]
investigated the bactericidal effect of photolysis of 3% H2O2 with 365nm LED (Light Emitting Diode) on
Streptococcus mutans biofilm. The biofilm was irradiated with 365nm LED for 1 min. Hydroxyl radicals
generated by photolysis of 3% H2O2 effectively killed S. mutans with a 5 log reduction. They concluded that this
technique represent “potentially powerful adjunctive antimicrobial chemotherapy for caries treatment”.
Hmud et al. [19] demonstrated that the 940nm and 980nm diode laser in presence of hydrogen peroxide can
achieve cavitation that are safe in terms of thermal effect against the root structures and surrounding periodontal
tissues. Also the authors, suggested that in the presence of 940nm or 980nm diode lasers, the 3% hydrogen
peroxide exercised greater cavitation than using plain water.
Several studies showed the ability of Er:YAG (2940 nm) and Er,Cr:YSGG (2790 nm) lasers to exhibit high
bactericidal effect, as well to remove calculus and superficial layers of contaminated cementum. Also, reports
showed a minimal thermal damage into deeper tissue, due to the shallow penetration depth of Er,Cr:YSGG
[20,21].
According to a study [22], Er,Cr:YSGG and Er:YAG lasers produced rougher root surfaces without smear
layer in comparison with manual curettes instrumentation, promoting blood elements to adhere to the
conditioned root surfaces. This effect could serve as a potential explanation for greater periodontal re-
attachment.

CONCLUSIONS

This study offers interesting preliminary results in terms of periodontal parameters (PD, CAL, BOP)
improvements. Since dental lasers are known as a versatile tools, this suggested laser periodontal protocol
provides various advantages like bactericidal and detoxifying effects over the periodontal tissues, hemostatic
effect, superior access to difficult anatomical areas, comfortable treatment for patients by avoiding surgery, if
periodontal pockets exceeding 6 mm depth, the absence of administrating antibiotics and periodontal tissue
biostimulation (regenerative effect).

REFERENCES:

1. Archana V. Calculus detection technologies: where do we stand now? Journal of Medicine and Life.
2014;7(Spec Iss 2):18-23.
2. Colombo APV, Boches SK, Cotton SL, et al. Comparisons of Subgingival Microbial Profiles of
Refractory Periodontitis, Severe Periodontitis and Periodontal Health using the Human Oral Microbe
Identification Microarray (HOMIM). Journal of periodontology. 2009;80(9):1421-1432.
doi:10.1902/jop.2009.090185.
3. Teles R, Teles F, Frias-Lopez J, Paster B, Haffajee A. Lessons learned and unlearned in periodontal
microbiology. Periodontology 2000. 2013;62(1):95-162. doi:10.1111/prd.12010.
4. Cugini MA, Haffajee AD, Smith C, Kent RL, Jr, Socransky SS. The effect of scaling and root planing on
the clinical and microbiological parameters of periodontal diseases: 12-month results. J Clin
Periodontol.2000;27:30–36.
5. Valenza G, Veihelmann S, Peplies J, Tichy D, Roldan-Pareja Mdel C, Schlagenhauf U, et al. Microbial
changes in periodontitis successfully treated by mechanical plaque removal and systemic amoxicillin
and metronidazole. Int J Med Microbiol. 2009;299:427–438.
6. Souza LC, Brito PR, Machado de Oliveira JC, et al. Photodynamic Therapy with Two Different
Photosensitizers as a Supplement to Instrumentation/Irrigation Procedures in Promoting Intracanal
reduction of Enterococcus faecalis J Endod. 2010 Feb;36(2):292-6. doi: 10.1016/j.joen.2009.09.041.
7. Swapnil SB, Bhaskar DJ, Agali CR, et al. Assessment of Photodynamic Therapy (PDT) in Disinfection
of Deeper Dentinal Tubules in a Root Canal System: An In Vitro Study. Journal of Clinical and
Diagnostic Research. 2014 Nov, Vol-8(11): ZC67-ZC71
8. Cruz Andrade PV, Euzebio Alves VT, Carvalho VF et al. Photodynamic therapy decrease immune-
inflammatory mediators levels during periodontal maintenance. Lasers Med Sci (2016).
doi:10.1007/s10103-016-2076-7
9. Monzavi, Abbas et al. Antimicrobial photodynamic therapy using diode laser activated indocyanine
green as an adjunct in the treatment of chronic periodontitis: A randomized clinical trial.
Photodiagnosis and Photodynamic Therapy, Volume 14 , 93 – 97
10. Izumi Y, Hiwatashi-Horinouchi, K, Furuichi Y, Sueda T. Influence of different curette insertion depths
on the outcome of non-surgical periodontal treatment. J Clin Periodontol. 1999; 26: 716-722.

182
11. Zijnge V, Ammann T, Thurnheer T, et al. Subgingival biofilm structure. Front Oral Biol 2012; 15: 1–
16.
12. Kamma JJ, Vasdekis VG, Romanos GE. The effect of diode laser (980 nm) treatment on aggressive
periodontitis: evaluation of microbial and clinical parameters. Photomed Laser Surg 2009; 27:11–19.
13. De Micheli G, Andrade AK, Alves VTE, et al. Efficacy of high intensity diode laser as an adjunct to
non-surgical periodontal treatment:a randomized controlled trial. Lasers Med Sci 2011; 26: 43–48.
14. Euzébio Alves VT, de Andrade AK, Toaliar JM, et al. Clinical and microbiological evaluation of high
intensity diode laser adjutant to non-surgical periodontal treatment: a 6-month clinical trial. Clin Oral
Investig 2013; 17(1): 87–95.
15. Giannelli M, Bani D, Viti C, et al. Comparative evaluation of the effects of different photoablative laser
irradiation protocols on the gingiva of periodontopathic patients. Photomed Laser Surg 2012; 30:222–
230.
16. Caruso U, Nastri L, Piccolomini R, et al. Use of diode laser 980 nm as adjunctive therapy in the
treatment of chronic periodontitis. A randomized controlled clinical trial. New Microbiol 2008; 31:
513–518.
17. Odor AA; Violant D; Badea V; Gutknecht N. Short-term clinical outcomes of laser supported
periodontal treatment concept using Er,Cr:YSGG (2780nm) and diode (940 nm): a pilot study. Proc.
SPIE 9670, Sixth International Conference on Lasers in Medicine, 96700G (March 22, 2016);
doi:10.1117/12.2191634
18. Nakamura K, Shirato M, Kanno T, Örtengren U, Lingström P, Niwano Y. Antimicrobial activity of
hydroxyl radicals generated by HYDROGEN PEROXIDE PHOTOLYSIS against Streptococcus mutans
biofilm. Int J Antimicrob Agents. 2016 Oct;48(4):373-80. doi: 10.1016/j.ijantimicag.2016.06.007. Epub
2016 Jul 15.
19. Raghad Hmud, William A Kahler, Laurence J Walsh Temperature Changes Accompanying Near
Infrared Diode Laser Endodontic Treatment of Wet Canals. J Endod 2010 May 7;36(5):908-11. Epub
2010 Dec 7.
20. Convissar RA., [Principles and Practice of Laser Dentistry] 2 nd edition, Mosby Elsevier International,
69-82 (2015).
21. Mishra MK, Prakash S. “A comparative scanning electron microscopy study between hand instrument,
ultrasonic scaling and erbium doped:Yttirum aluminum garnet laser on root surface: A morphological
and thermal analysis” Contemporary Clinical Dentistry 4(2), 198-205 (2013).
22. Mishra MK, Prakash S. “A comparative scanning electron microscopy study between hand instrument,
ultrasonic scaling and erbium doped:Yttirum aluminum garnet laser on root surface: A morphological
and thermal analysis” Contemporary Clinical Dentistry 4(2), 198-205 (2013).

183
 COLOR PERCEPTION – AN UTTERLY IMPORTANT COMPONENT OF
ESTHETIC CERAMIC RESTORATIONS

Rădulescu Eugenia-Diana¹, Bănăţeanu Andreea Mariana¹, Andreescu Claudia Florina²,

Lăzărescu Grigore³
1 – Lector, Faculty of Dental Medicine, Titu Maiorescu University, Bucharest
2-Associate Professor- Faculty of Dental Medicine, Titu Maiorescu University, Bucharest
3– Dentist DMD, PhD, Bucharest

Summary:

The purpose of the study was chosen mainly due to technological developments in dental practice.
Lately, through their tireless efforts, ceramics manufacturers have managed to improve the colors and shades
used for restoration.
Each case of physiognomic dental restoration is important as it creates beauty through facial
expression and a beautiful smile always brings joy.
Our goal here is to highlight the importance of color perception in esthetic ceramic restorations that
should be similar to those of natural structure.

Key words: esthetic restorations, color, ceramics.

Introduction:

The purpose of the study was chosen mainly due to technological developments in dental practice.
Lately, through their tireless efforts, ceramics manufacturers have managed to improve the colors and shades
used for restoration.
While traditional dentistry focuses on diagnosing, preventing and solving dental problems, cosmetic
restorative dentistry focuses on improving and even radically change the smile. One could say that cosmetic
dentistry is general dentistry combined with art. A beautiful smile has a miraculous effect on confidence and
self-esteem, because the way we smile influences our look.

Material and method:

Ceramic material provides the ability to restore the natural appearance of our teeth while having the
highest level of biocompatibility, representing mechanical, physical and chemical properties.
Among their mechanical properties are hardness, similar to the one of the tooth enamel, and
compressive strength.
Enamel is the outermost structure of a tooth’s crown. It is the hardest tissue in the human body. It’s
mainly composed of inorganic matter (95% by weight) that is primarily a crystalline lattice of hydroxyapatite.
The hydroxyapatite is the building block for enamel rods that are packed tightly and oriented in different
directions depending on their position in the tooth crown.
Dentin is the tissue underlying enamel; it forms the bulk of the tooth. It is the second hardest tissue in
the body. It is composed of channels called dentinal tubules, which enclose odontoblasts and their processes.
Dentin has more organic components than enamel. The main organic component is collagen arranged densely as
fibers and soluble proteins. The inorganic component is 75% by weight, which is formed by less organized
hydroxyapatite crystals. The formation of dentin continues throughout life in response to different stimulus or as
part of the natural aging process.
Chemical properties can include the fact that there are no changes among the materials in the case of
large oral pH variation and they are not attacked by acids present in the oral cavity.
As physical properties should be noted: high melting point (it is a refractive material), lower density,
thus less weight than metalwork, translucency, which increases the more we have more glassy phase so the best
possible optical properties will be found in glassy ceramics (the feldspathic ones).
Illumination it is possible to observe a tooth trough direct light exposition. This is the common way we
see a tooth and the image deriving from the incident light is defined as "reflected light". In order to correctly
observe the multiple color details, the light source should contain all wavelengths and correct temperature, i.e.
5.500° Kelvin.

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 Tooth color is a complex phenomenon. It results from a combination of several optical properties of
multiple structures. Multiple factors, as will be described, affect the perceived tooth color.
Color is the visual perception generated by the nerve signals that retina photoreceptors send to the brain
when they absorb electromagnetic radiation of specific wavelengths in the so-called visible spectrum or light
(fig.1).

Fig. 1 Visible spectrum is very limited among all other wavelengths

The visible spectrum corresponds to a narrow segment between the 400 and 800 nm. Short wavelength
correspond to violet, long wavelength to red.
When white light illuminates an object, the color we see is the one that has not been absorbed and that
is reflected to our eyes. So this fact tells us that the quality of light plays an important role in perception of color
of an object.
Color, in facts, is a more a function of light than of the object. Should we have a light source of red
wavelengths, all the objects would look red. In order to have an object showing its true color, it should be
illuminated by all the wavelengths of the visible spectrum, i.e. the light source should have high color rendering
index (CRI).
Human teeth are characterized by varying degrees of translucency, which can be defined as the slope
between transparent and opaque. In general, increasing the translucency of a crown lowers its value because less
light returns to the eye.
Opacity: most of the light rays are reflected due to the presence of dense particulate matter within the
object. E.g. a brick is opaque.
Transparency: most of the light rays are transmitted due to the object being mainly devoid of particulate
matter. E.g. glass is transparent.
Translucency: light rays are both transmitted and reflected due to the presence of discrete minute
particles in the object. A translucent material, by definition, must have particulate matter embedded which when
struck by light reflects and scatters the rays. E.g. porcelain is translucent.
Natural teeth have the ability to fluoresce under ultraviolet radiation. This is particularly noticeable in
nightclubs, where there are lamps that emit the blue end of the spectrum in addition to some ultraviolet radiation
("black light") (fig.2).

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 Fig. 2 Natural dentition has fluorescence

This property makes teeth look whiter and brighter in the daylight. Fluorescence, making light coming
from inside, gives natural teeth their living aspect.
Opalescence is the term given to substances that exhibit properties similar to those of opal stone when
subjected to transmitted and reflected light. In reflected light, an opal has a blue appearance, because most of the
short wavelength is reflected back.
The incisal edge of a natural tooth develops a blue translucency (even though it is colorless) when
viewed under reflected light. Under transmitted light, the overall shade changes to reddish and orange (fig.3).

Fig. 3 The incisal tooth edge shows blue shadows under reflected ligh, orange under transmitted light

This optical effect is a result of the scattering of light by the hydroxyapatite crystals, which are smaller
than the wave- length of the visible ray .
As the light hits the tooth, some part of it is reflected on the enamel surface and produces the perception
of luster and buccal anatomy (vertical white stripes). Most of the light passes the enamel surface and hits the
dentinal opaque particles. This produces light diffusion and scattering. Part of the light spreading in the dentin
bounces towards the observer's eye, giving the perception of the tooth color appearance(fig. 4).

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 Fig. 4 Aspect of a tooth under illumination

The tooth is therefore semi-translucent and dentin is the primary source of color. The enamel, from an
optical stand point, works as a translucent filter on top of the more opaque and colored dentin.
In the tooth cervical third, enamel layer is thinner, thus the filter effect is less. That is why the dentinal
hue is more evident.
Different kind of all-ceramic crowns have been used over the last four decades as an alternative for
PFM crowns to overcome their esthetic limitations due to the presence of metal shielding light from passing
through.
Newer metal-free crowns are increasingly being used in dental practice; these crowns are made from
different ceramic materials such as lithium disilicate and zirconia that nowadays are the most commonly used.

Fig. 5: With an all-ceramic restoration, light transmission can duplicate the one of a natural tooth

One of the biggest limitation of metal free restorations lies on their minor mechanical performances.
Every time an all-ceramic bridge is planned (especially on a long span), the risk of fracture has not been
overcome yet.
Nevertheless, increased light transmission and diffusion can be achieved, resulting in translucency
similar to a natural tooth.

Discussion and conclusions:

Along with form and shade, translucency is one of the most important contributing factors of a natural
tooth. When the surface of a natural tooth is exposed to light, part of it is specularly reflected. Light reflection
from the surface is strictly related to the grade of gloss and texture. Part of the internal light scatters in random
directions as a result of the prismatic effect of the enamel rods and dentinal tubules. In addition, this scattered
light reflects toward the labial surface, contributing to the brightness of the tooth and gingiva.
Along with form and shade, translucency is one of the most important contributing factors of a natural
tooth. When the surface of a natural tooth is exposed to light, part of it is specularly reflected.

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 Light reflection from the surface is strictly related to the grade of gloss and texture. A part of the internal
light scatters in random directions as a result of the prismatic effect of the enamel rods and dentinal tubules. In
addition, this scattered light reflects toward the labial surface, contributing to the brightness of the tooth and
gingiva.
Matching a natural tooth with an artificial restoration will always remain an artistic challenge and, still,
is basically impossible under different light sources.

References:
1.Chiche G.J, Pinault A.- “Esthetics of anterior fixed prosthodontics”, Quintessence, Chicago, 1994.
2.Freedman G, Contemporany Esthetic Dentistry.Mosby Elsevier, St. Louis, 2012, ISBN: 978-0-323-06895-
6.
3.Heymann H.O, Swift E.J, Ritter A.V, Sturdevant C.M.- “Sturdevant's art and science of operative
dentistry”, Elsevier/ Mosby, 2012.
4. Hugo B., Esthetics with Resin Composite: Basics and Techniques. Quintessence, London, Berlin,
Chicago, 2009, ISBN:978-1-85097-183-2.
5.Paravina R. D, Powers J.M. –“Esthetic color training in dentistry”, Elsevier /Mosby, 2004.
6.Powers J.M, Sakaguchi R.L, Craig's Restorative Dental Materials, 12th Edition. Mosby Elsevier, St.Louis,
2006, ISBN:978-0-323-03606-1.
7.Rădulescu E.D, Lăzărescu G, Bănăţeanu A.M– „Estetica ȋn zona frontală din zirconiu prin restaurări
protetice fixe”, Conferinţa Naţională cu participare Internaţională- „Viziunea Interdisciplinară ȋn
Medicina Dentară”, Bucureşti, 2014.
8.Lăzărescu G,Ghergic D.L, Andreescu C, Rădulescu E.D- „Tehnica reabilitării orale”- manual de lucrări
practice pentru tehnicieni dentari, Ed. Printech, Bucureşti, 2013.
9.Summit J.B, Robbins J.W, Hilton T.J, Schwartz R.S.,Fundamentals of Operative Dentistry. A
contemporary Approach, 3rd Edition, Quintessence, Chicago, Berlin, London, 2006, ISBN: 978-
0867154528.
10.Winter R. -"Visualizing the natural dentition" ,J Esthet Dent 5(3): 102-117, 1993 .

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 HEALING IN ENDODONTICS – A SERIES OF CASE REPORTS

Oana Roșu, Assistant, Department of Prosthodontics,

“Titu Maiorescu” University, School of Dental Medicine Bucharest, Romania

Anna-Maria Pangică, Associate Professor, Department of Endodontics,

“Titu Maiorescu” University, School of Dental Medicine Bucharest, Romania

Dana Cosac, Lecturer, Department of Endodontics,

“Titu Maiorescu” University, School of Dental Medicine Bucharest, Romania

Manea Stefan, Assistant, Department of Endodontics,

“Titu Maiorescu” University, School of Dental Medicine Bucharest, Romania

Aim: To explain and present the modern approach of acute and/or chronical apical periodontitis.
Materials and methods: Nowadays endodontics is considered to be the “neurosurgery” of dental medicine.
More and more dentist and patients understand the importance of “saving and keeping” their own teeth,
although implants seem to be very reliable. Teeth with big periapical lesions (even interradicular radiolucency),
can be successfully treated and kept for a long time.
In the following article 2 clinical cases with big periapical and also interradicular lesions (one of them) and the
chosen protocol for treating these cases will be presented.
Results: The radiographic investigations taken after 6 months in one case and one year a half in the other case
show very good healing results. Both patients were happy and very satisfyed with the results.
Conclusions: Modern endodontical procedures and protocols alow us to prolong the life of many teeth which
were extracted 10 or 20 years ago. Therefore, before recomending an extraction of an „infected” tooth we
should think first about the possibility of treating and healing it, the only barrier being the physical support.

Key words: periapical lesion, granuloma, healing, endodontic protocol.

INTRODUCTION

Periapical lesions can appear due to a pulpal disease - most common cases -, but also due to a
periodontal one, or a combination of these factors.
The periradicular area being closely related with the pulpal tissue inside the tooth, results that any
pulpal disease (inflammation or infection), will lead most of the cases without proper treatment, to a
periradicular one. Therefore the periapical lesion can appear even before all the pulp disappears. When the
defense of the pulp is overtaken, and the pulpal tissue is dissolved, all the inflammatory agents, bacteria and their
products and also any other cells which appeared after pulp degeneration migrate into the periradicular area
through different portal of exits (POE) – apex, lateral canals, etc. From this moment, until the clinical and/or
paraclinical symptomatology appears is just a matter of each patient’s immune system and its defense capacity.
In a healthy, mature-young organism it might take years before the periradicular infection becomes known, while
in an old, dragged organism or in an underdeveloped one, is possible that the infection of the periradicular area
should appear very quickly after the pulpal infection and to develop worst symptoms.

Classification of periapical lessions of endodontic origin

Clinically, lesions of endodontic origin can be as follows:

 Acute apical periodontitis
 Acute alveolar abscess
 Chronic apical periodontitis
 Reactivation of chronic apical periodontitis

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 Among these, the most frequent ones are the chronic apical periodontitis, also known as granuloma or,
sometimes cyst. The distinction between the granuloma and cyst can be done only histologycally, not
radiografically.
Treatment protocols are, however, mostly the same for all categories listed above, having very little
discrepancies.

CASE REPORT

Case 1

Patient B.C.M, female, 19 years old, presents herself in the dental office at the recommendation of a
colleague (fig 1). The patient presents a big radiolucency in the right of tooth 12 (fig 1).

Fig.1.

Clinical examination revealed that the patient has been treated for this tooth for almost 2 months with
repetead calcium hydroxide sessions every 2 or 3 weeks.
Due to the fact that the canal was clean, did not have any secretions and was properly shaped, it was
decided that single visit endodontics will be applied for this case.
The preparation was finished in an ISO 50 file, having a lenght of 21.5 mm, ultrasonic activation of
irigation solutions was perfomed using U files at the DTE scaler.
Irigation protocol consisted of :
 5% sodium hypocholrite after every single file during shaping and finishing
 4 series of ultrasonic activation of sodium hypochlorite after finishing the mechanical
treatment, each for 40-50’
 1 serie of ultrasonic activation of Endo Solution from Cerkamed ( containing 17% EDTA ).
 Atfer a 5-7 minutes pause while the EDTA 17% incorporated in the Endo Solution product
was left in the canal, another irigation with 10 ml of sodium hypochlorite.

The root filling technique chosen for obturation of the canal was Continous Wave Condensation (CWC)
using B&L system, followed in the same session by the long term crown restoration using G bond and Gradia
A02 from GC. An immediate in office X –Ray was taken for control (fig. 2).

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 Fig.2.

At the end of the treatement, the patient was kindly asked to call after 6 months to do a recall or for any
other issues regarding this tooth meanwhile.
The recall X-Ray was taken after 7 months and showed a good healing of the periapical lesion (fig 3).

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 Fig. 3

Case 2.

Patient V.G, male, 30 years old presented himself into the dental office referred from another colleague
with a fistula and a temporary cement on tooth 36. The initial X-Ray showed a big radiolucency starting from the
periapical region of the mesial root and stretching into the interradicular area and also a smaller one on the distal
periapical region. The X Ray also revealed a great difficulty of the canals, especially the distal one and a
fractured instrument on one of the mesial canals ( fig 4 ).

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 Fig. 4

During the first session it was discovered that the fractured instrument was situated on the mesio-buccal
canal. 3 endodontic sessions were performed in order to by - pass the fractured instrument and to clean and shape
all the other canals. Every session was completed by abundant irrigation with sodium hypochlorite 5% for
disinfection followed by ultrasonic 30 - 40’ activation on each canal and EDTA solution 17% for chelating and
permeation.
After these 3 sessions during 3 weeks the fistula was still present. Therefore, in the 4th session another
irrigant was used – Chlorhexidine 2 %, followed also by ultrasonic activation.
At the 5th session (7 weeks from the beginning of the treatment) the fistula was still present, but the
control X-Ray showed a reduction of the periapical lesions (fig 5).
Between every session calcium hydroxide was placed on the canals.

Fig. 5
After talking to the patient an antibiotic treatment was recommended, using Augumentin Cp 1000 mg
every 12 hours and Metronidazol, cp, 500 mg, every 12 h, for 7 days and also some medicine for the immune
system for 1 month. Also a periodontist was consulted in order to eliminate an associate periodontal lesion.

193
 After 2 weeks and a half, when the patient came in the office for treatment, the fistula was closed.
Another 2 sessions with the same irrigation protocol as the one from Case 1, were perfomed and, in the
3rd one, the tooth was oburated using CWC technique for the root canal obturation and GlassIonomer Cement (
Kavitan Cem from Spofa Dental) for the crown reconstitution. All the canal entrances were additional sealed
with Flowable Composite for protection (fig 6). The whole treatment stretched over a period of 2 months and a
half.

Fig. 6

The control X- Ray taken after 5 months after the treatment revealed a considerable reduction of the periapical
and interradicular lesion (fig 7).

Fig. 7
CONCLUSIONS

In an “implants dominated world”, the modern endodontic protocol has a success rate of 92% - 93%.
This percent applies even in difficult cases, with large lesions. More and more teeth should, therefore, be treated
and “saved”, most of the patients having a better experience with their own tooth than with an implant placed in
the same position.

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 The location of the lesion is not important, since the treatment protocols work in any of the mouth’s
and/ or tooth’s regions.
Also, if the lesion is of endodontic origin, the histopathology is not important, since the treatment
protocols are exactly the same and with the same benefits. But, however, a proper diagnosis concerning the
lesions’ origin should be made.

REFERENCES:

1. Baet,Sfe,Nef- Endo Practice Today, Volume 7, Issue 2, Quintessence Publishing Co.

Inc, Summer 2013.
2. Bratu D. – Dental materials in the dental practice,2 nd edition, Editura Helicon,
Timişoara, 1998.
3. Arnaldo Castellucci –Endodontics, Volume 1, Trident Publishing, Firenze, 2007.
4. Cohen, S.: Diagnostic procedures. In Cohen S. and Burns R.C. eds., Pathways of the
pulp, 4th ed., The C.V. Mosby Company, St. Louis, 1987
5. Grossman, L.I., Oliet, S., Del Rio, C.E.: Endodontic practice. 11th ed. Lea & Febiger,
Philadelphia, 1988.
6. A. O. Rosu, R. M. Comăneanu, O. Smătrea, D. L. Ghergic, “Metode de soluţionare a
iatrogeniilor în endodonţie", lecture at Congresul Comun de Stomatologie SRS-GAO-
UTM, and the summary published in Revista Română de Stomatologie, Vol LX, No. 3,
Year 2014, pg. 196
7. Roşu A.O., Pangică AM, Ghergic DL, Iatrogenia în endodonţie şi soluţionarea ei,
Viziunea Interdisciplinară în medicina dentară, Ed. Univ. Titu Maiorescu din
Bucureşti, ISBN 978-606-8002-92-7, 2014, pg. 19-21.

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 EVOLUTION OF MANDIBULAR BODY FRACTURES ACCORDING TO THE
THERAPEUTIC APPROACH AND MATERIALS USED IN THEIR TREATMENT -
RETROSPECTIVE CLINICAL STUDY OVER A PERIOD OF 10 YEARS

ȚENȚ PAUL ANDREI1, MAGHIAR TEODOR TRAIAN1, BODOG FLORIAN1*, MEȘTER

LIANA2, JUNCAR MIHAI1
1
Faculty of Medicine and Pharmacy, University of Oradea, Romania Str. Piața 1 Decembrie,
nr.10
2
Department of International Business, Faculty of Economic Sciences, University of Oradea,
Universitatii 1, 410087 Oradea, Romania
Autor correspondent:Bodog Florian Faculty of Medicine and Pharmacy, University of
Oradea, RomaniaStr. Piața 1 Decembrie, nr.10.Email: fbodog@gmail.com.

ABSTRACT
The mandible is the only mobile bone of the facial skeleton. Its anatomic form and position makes it the
most frequently fractured bone of the cephalic extremity. Choosing the optimal treatment and the most adequate
materials for the mandible fractures is of high importance both for the doctor and especially for the patient. The
following study represents a retrospective evaluation on a significant number of patients regarding the post-
surgical evolution of mandibular body fractures in terms of the type of treatment applied and the type of
materials used. In order to perform the study, 615 cases of mandibular body fractures have been analyzed. Their
treatment was performed through an orthopedic procedure on 75.79% of the cases, followed by the orthopedic
combined with the surgical treatment. 1442 of Erich archbars and 542 titanium miniplates were used. Post-
surgical evolution was favorable in 95.26% of the cases. The titanium miniplates used for surgical treatment
presented the least post-surgical complications.
Keywords: trauma, mandible body, mandible, fracture, treatment.

INTRODUCTION
The incidence of the maxillofacial trauma has been constantly growing in the past years causing
continuous problems in selecting its optimal management [14,20] Among the bones of the maxillofacial
complex, the mandible is the most fractured bone due to its prominence in the viscerocranium, therefore being
the most exposed to trauma [17].
Anatomically, the mandible is divided into two major segments : the body and the ascending ramus [1].
The traumatic pathology of the mandibular body has its own characteristics regarding etiopathology, clinical
manifestations and treatment [10].
The sites of mandibular body fractures are symphysis, parasymphysis, lateral body and the mandibular
angle [13]. The commonest fracture site differs from study to study [18]. Some authors claim that the most
frequent fracture site is the lateral body [5,8], while other authors consider the mandibular angle to be the most
fractured region [22]. Ogundare et al. [21] in his study mentions the parasymphysis region to be the most
affected.
The displacement of the mandibular body fractures is influenced by many factors such as: the location
of the fracture line, the muscle insertions present in each region, the degree of bone involvement [3]. Choosing
the correct type of treatment for each type of fracture focus ensures a favorable evolution reducing the post-
surgical complications to a minimum[11].
The treatment of mandible fractures may be orthopedic, surgical or combined orthopedico-surgical.
Specialized studies have evaluated the different treatment methods and criteria[18,24]. Unfortunately, the
observed data appears to be conflicting and does not take into consideration the type of materials used in the
treatment of this type of fracture. The present study evaluates the post-surgical evolution of mandible body
fractures according to the treatment of choice and materials used based on a retrospective evaluation on a period
of 10 years.

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 MATERIALS AND METHODS

In order to perform the present study the patients treated within the Maxillofacial Clinic I of Cluj-
Napoca between 1st of January 2002 and 31st of December 2011 were analyzed.
The data for each patient was acquired from the clinical consultation sheets. The following variables
were analyzed for each case: the fracture site, the degree of bone involvement, the degree of displacement of the
fractured fragments, the type of treatment performed, post-surgical evolution and the type of complications
occurred.
The inclusion criteria was : patients over 18 years old, the presence of a mandible fracture discovered at
the level of the mandible body, the existence in the medical record of an acute trauma episode, the presence of
imaging investigations which confirm the presence and the features of the fracture lines, performing the
treatment within the clinic of the study, complete documentation, patients to be monitored at least six weeks after
surgery regarding their healing evolution and the occurrence of possible complications.
The criteria for elimination from the study: patients treated within other departments, patients with an
associate pathology which interferes with fracture healing (chemotherapy treatment, bisphosphonate treatment
etc.), pathological bone fractures, patients that were not post-surgically monitored.
The variables followed: fracture site (symphysis, parasymphysis, lateral body and the mandibular angle
), the degree of displacement (with displacement, without displacement), the degree of bone involvement
(incomplete, complete), the type of treatment (orthopedic, surgical, orthopedico-surgical and mandibular
cerclage), post-surgical evolution (favorable, not favorable) and the occurrence of complications.
The data summary was performed using Microsoft Excel. The descriptive statistics of the evaluated
cases was performed with a percentage precision of two decimals.
The orthopedic treatment implied the rigid maxillomandibular fixation and was performed using Erich
archbars manufactured from stainless steel, circumdental wires from wipla 0.4 mm thick in order to hold the
Erich archbar at the tooth cervix and a wipla wire 0.6 mm thick to perform the rigid MMF . The surgical
treatment implied open reduction and ostheosyntesis with : 2.0 mm miniplates, two for each fracture site and 1.7
mm diameter and 5 mm long monocortical screws. The length of the titanium miniplates varied according to the
characteristics of each fracture site. In order to perform mandibular cerclage on edentulous patients without
osteosynthesis indications, occlusion braces have been manufactured and attached to the mandible with stainless
steel circummandibular wires.

RESULTS
On a batch of 709 patients with mandible fractures 1099 fracture sites have been discovered. Among them,
615 patients (86.74%) presented mandibular body fractures and only 94 (13.26%) presented ramus fractures.
Most patients presented double mandible fracture followed by patients with unique fracture (Fig. 1).

Fig. 1 Distribution of the lines of fracture

Topographically, the most frequent fracture site was the mandibular angle 317 (38.56%), followed by the
lateral body 267 (32.48%), parasymphysis 191 (23.24%), symphysis 35 (4.26%) and alveolar process with only
12 discoveries (1.46%). Regarding the degree of bone involvement, most patients presented complete fractures;
incomplete fractures were in minority (Fig. 2).

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 Fig. 2 – Distribution of patients according to the degree of bone involvement
Most mandibular fractures presented preoperative bone displacement: 728 (88.56%), only 94 were
without displacement (11.44%). In most cases, orthopedic treatment was preferred; the compound treatment was
secondary followed by osteosynthesis and circummandibular cerclage (Fig. 3).

Fig. 3 – Distribution of mandibular fractures according to the treatment of choice

1442 Erich archbars made of stainless steel were used in order to perform the orthopedic treatment and
the orthopedic-surgical combined treatment and 524 titanium 2.0mm miniplates, along with 2096 1.7 mm/5 mm
titanium screws. Evolution was favorable in 783 (95.26%) of the cases, whereas 39 (4.74%) presented
complications.The septic complications represented by osteitis were the most frequent, followed by vicious
consolidation and non-union (fig. 4).

Fig. 4 – Distribution of fracture sites according to the post-surgical complications occured

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 Post-surgical evolution has been correlated with the type of treatment applied for each fracture focus.
Treating fractures through circummandibular cerclage is proven to be the method most frequently followed by
the occurrence of complications in fracture focuses (table 1).
TREATMENT COMPLICATIONS
Total
osteitis vicious consolidation non-union complications

orthopedic 6 3 3 12
Surgical 2 0 0 2
Cerclage 15 2 5 22
Combined 2 0 0 2

Table 1 – Distribution of post-surgical complications according to the treatment of choice.

DISCUSSIONS
The purpose of this study was reached and therefore we can identify the most frequently used therapy
method for treatment of mandible body fractures and also their future evolution. The etiopathogenesis of
mandible body fractures and their treatment are various in literature. This fact prevented establishing standard
norms in choosing the optimal treatment for each mandibular region affected.
In our research, the incidence of mandibular body fractures is net increased, compared to the
mandibular ramus. This result is similar to the results of Ellis et al. [8] and Shah et al. [5] , and in contrast with
the studies of Passeri and Brasiliero et al . [6] and Ahmed et al [16] who report the mandibular ramus as the most
affected by fractures. We found the mandibular angle being the most affected by fractures,such as in the studies
of Ogundare et al. [21] and Dongas and Hall et al.[22], but in contrast with Ellis et al. [8] and Shah et al. [5] who
discover the lateral region of the mandibular body to be the most fractured. It seems that these differences
depend mostly on the geographical and cultural features of the habitat in which the studies were performed.
These contradictory data found in specialized studies underline the fact that a more in-depth analysis of clinical
features of mandible fractures is necessary for each geographical area.
We found that most of the fracture sites presented bone displacement, result which is similar to the one
acquired by other authors [8,5,21,24]. This is due to the fact that secondary displacement is present in the
mandibular body fracture sites.This occures right after a low kinetic energy trauma and under the strongly
antagonist action of the perimandibular muscles [10,13,22].
The type of treatment applied to mandibular body fractures was mostly orthopedic. Similar results have
been acquired by other authors such as Ramli R. et al. [23](66,3%) and Anyanechi et al. [4](81%), but in contrast
with authors like Ellis et al. [9], de Matos et al.[7] and Alkan et al.[2] who treat all the mandibular body fracture
sites solely by osteosynthesis using the intermaxillary fixation only for the reestablishment of habitual occlusion.
Surgical treatment through exclusive osteosynthesis is found in our study, but in small percentage. This is also
possible due to the high cost of the treatment and the fact that it was not available financially speaking at the
time of the study. Another factor which probably influences the type of treatment applied to mandibular body
fractures is the tradition of each medical school and the experience of each clinician. The retrospective feature of
this study does not allow an objective evaluation from this point of view. The combined treatment of mandible
fractures appears in a smaller percentage in this study, being also rarely encountered in literature as a main
treatment [12,26] The lower incidence of this type of treatment is owed to the fact that it is applied only in the
cases where osteosynthesis or orthopedical treatment are insufficient, fact rarely encountered in our current
activity.
Regarding the materials used: in 10 years there have been used 524 titanium 2.0mm miniplates, along
with 2096 1.7 mm/5 mm titanium screws. This data is similar to the one presented by van den Bergh B. Et al.
[26] who used in 10 years 442 2.0mm miniplates and 1965 tianium screws and Vajgel A. Et al. [25].There were
no situations of complication occurance secondary to a particular material used in this study. Post-surgical
evolution of most patients was favorable where titanium miniplates have been used. The few situations with
post-surgical complications occurred due to the region and septic contamination of the fracture site from the oral
environment and not due to the surgical procedure or the type of material used.
In most cases, post-surgical evolution was favorable, regardless of the therapeutic method applied.
However, certain therapy options are followed by a smaller rate of complications. Therefore, orthopedic
treatment with Erich archbars and surgical treatment implying osteosinthesys with titanium miniplates had the
smallest percentage of post-surgical complication occurence. The most frequently encountered complication was
osteitis similar to the data provided by other authors [2,7,9,25,26]. The only author who presents different data is

199
Yamamoto MK. [27] who discovered non-union as the most frequent complication. If we take in consideration
the high septicity of the oral cavity, is easy to identify the cause for which osteitis is one of the most frequent
complications of mandible body fractures.
Among the patients where circummandibular cerclage was performed we found the highest rate of post-
surgical complications. The data is also similar to the one from van den Bergh B. Et al. [26]. and it is probably
due to the general state of the patients. Cerclage with circummandibular wires is generally performed in
edentulous patients who are generally elders suffering of associated diseases in which rigid intermaxillary
fixation or general anesthesia are not recommended.
The least post-surgical complications were encountered in patients treated through osteosynthesis only
2 people, similar with most authors [2,7,9,12,25,26]. This was either due to the perfect open reduction and
superior fixation in the fracture or due to the relatively small number of such treated cases.
Despite the fact that most of the cited authors treated their cases by osteosinthesys, in our study, where
orthopedic treatment is dominant, the evolution is also favorable 95.26%. This underlines the fact that a well-
managed orthopedic treatment with a correct closed reduction and immobilization of the bone fragments is
followed by a high percentage of healing.
Our study still has its limitations as any retrospective study; the data were collected from the
consultation sheets and some data might have been incomplete. In order to exceed this lack, only complete
consultation sheets were selected and therefore a series of cases from the statistical data base were lost.

CONCLUSION

The surgical treatment which implied open reduction and osteosynthesis with titanium miniplates and
monocortical titanium screws proved to be the most efficient method. However, the orthopedic treatment has
also been proven to be efficient especially if we take in consideration its frequency of use .

References :
1.ALBU I., GEORGIA R.: Anatomie Topografică, Ediţia II, Editura ALL, Bucureşti 1998.
2.ALKAN A, CELEBI N, OZDEN B, BAS B, INAL S: Biomechanical comparison of different plating techniques
in repair of mandibular angle fractures. Oral Surg Oral Med Oral Pathol Oral Radiol Endod (6): p 752-
756, 2007
3.A. M. NAHUM, “The biomechanics of maxillofacial trauma,” Clinics in Plastic Surgery, vol. 2, no. 1, pp. 59–
64, 1975.
4.ANYANECHI CE1, SAHEEB BD., Mandibular sites prone to fracture: analysis of 174 cases in a Nigerian
tertiary hospital. Ghana Med J. 2011 Sep;45(3):p.111-4.
5.A. SHAH, A. S. ALI, AND S. ABDUS, “Pattern and management of mandibular fractures: a study conducted
on 264 patients,”Pakistan Oral & Dental Journal, vol. 27, no. 1, pp. 103–106, 2007.
6. B. F. BRASILEIRO AND L. A. PASSERI, “Epidemiological analysis of maxillofacial fractures in Brazil: a 5-
year prospective study,”Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology,
vol. 102, no. 1, pp. 28–34, 2006.
7.DE MATOS FP, ARNEZ MF, SVERZUT CE, TRIVELLATO AE: A retrospective study of mandibular fracture
in a 40-month period. Int J Oral Maxillofac Surg (1): p.10-15,2010
8.E. ELLIS, K. F. MOOS, AND A. EL ATTAR, “Ten years of mandibular fractures: an analysis of 2,137 cases,”
Oral Surgery Oral Medicine and Oral Pathology, vol. 59, no. 2, pp. 120–129, 1985.
9.ELLIS III E: Treatment methods for fractures of the mandibular angle. Int J Oral Maxillofac Surg (4):
243e252, 1999.
10.FONSECA RJ., WALKER RV. (EDS.) : Oral and maxillofacial trauma.Volume 1. 2nd edition.WB Saunder ,
Philadelphia 1997
11.FREINBERG SE, STEINBERG B. , HELMAN JI. , Healing of traumatic injuries In: Fonseca RJ, Walker RV,
editor. Oral and Maxillofacial Trauma. Vol. 1. Philadelphia: Saunders; 1997. pp. 13–57.
12.GANDHI S1, RANGANATHAN LK, SOLANKI M, MATHEW GC, SINGH I, BITHER S , Pattern of
maxillofacial fractures at a tertiary hospital in northern India: a 4-year retrospective study of 718 patients.
Dent Traumatol. 2011 Aug;27(4):p. 257-62.
13.G. O. KRUGER, Textbook of Oral and Maxillofacial Surgery, Jaypee Brothers, 6th edition, 1990.
14.GASSNER R, TULI T, HÄCHL O, RUDISCH A, ULMER H. Cranio-maxillofacial trauma: a 10 year review
of 9,543 cases with 21,067 injuries. J Craniomaxillofac Surg 2003;p 31:51–61
15.HÄRLE F, CHAMPY M, TERRY B. Atlas of craniomaxillofacial osteosynthesis.Stuttgart, New York: Theime,
2009.
16.H. E. A. AHMED, M. A. JABER, S. H. ABU FANAS, AND M. KARAS,“The pattern of maxillofacial fractures
in Sharjah, United Arab Emirates: a review of 230 cases,” Oral Surgery, Oral Medicine,Oral Pathology,
Oral Radiology and Endodontology, vol. 98, no.2, pp. 166–170, 2004.

200
17.J. A. HALAZONETIS, “The “weak” regions of the mandible,” British Journal of Oral Surgery, vol. 6, no. 1,
pp. 37–48, 1968.
18. KING RE, SCIANNA JM, PETRUZZELLI GJ (2004) Mandible fracture patterns: a suburban trauma center
experience. Am J Otolaryngol 25(5):p:301–307
19. KYRGIDIS A, KOLOUTSOS G, KOMMATA A, LAZARIDES N, ANTONIADES K. , Incidence, aetiology,
treatment outcome and complications of maxillofacial fractures. A retrospective study from Northern
Greece. J Craniomaxillofac Surg. 2013 Oct;41(7): p .637-43.
20. MOCK C, QUANSAH R, KRISHNAN R, ARREOLA-RISA C, RIVARA F. Strengthening the prevention and
care of injuries worldwide. Lancet 2004; 363:p 2172–2179
21. OGUNDARE BO, BONNICK A, BAYLEY N (2003) Pattern of mandibular fractures in an urban major
trauma center. J Oral Maxillofac Surg 61(6):p:713–718
22. P. DONGAS AND G. M. HALL, “Mandibular fracture patterns in Tasmania, Australia,” Australian Dental
Journal, vol. 47, no. 2, pp. 131–137, 2002.
23. RAMLI R, RAHMAN NA, RAHMAN RA, HUSSAINI HM, HAMID AL., A retrospective study of oral and
maxillofacial injuries in Seremban Hospital, Malaysia., Dent Traumatol. 2011 Apr;27(2):p. 122-6.
24. S. LAVERICK A,B,∗, P. SIDDAPPA B, H. WONGC, P. PATEL B, D.C. JONES B , Intraoral external
oblique ridge compared with transbuccal lateral cortical plate fixation for the treatment of fractures of the
mandibular angle: prospective randomised trial, British Journal of Oral and Maxillofacial Surgery 50
(2012) p. 344–349.
25. VAJGEL A, CAMARGO IB, WILLMERSDORF RB, DE MELO TM, LAUREANO FILHO JR,
VASCONCELLOS RJ., Comparative finite element analysis of the biomechanical stability of 2.0 fixation
plates in atrophic mandibular fractures. J Oral Maxillofac Surg. 2013 Feb;71(2):p. 335-42.
26. VAN DEN BERGH B, HEYMANS MW, DUVEKOT F, FOROUZANFAR T., Treatment and complications of
mandibular fractures: a 10-year analysis. J Craniomaxillofac Surg. 2012 Jun;40(4):p. 108-11.
27. YAMAMOTO MK1, D'AVILA RP, LUZ JG., Evaluation of surgical retreatment of mandibular fractures. J
Craniomaxillofac Surg. 2013 Jan;41(1):p. 42-6. ,201013.

201
 EVALUATION OF METHODS AND MATERIALS USED FOR THE TREATMENT
OF FRACTURES OF THE ASCENDING RAMUS OF THE MANDIBLE – A
CLINICAL STUDY OVER A 10 YEAR PERIOD

ȚENȚ PAUL ANDREI1, MAGHIAR TEODOR TRAIAN1, JUNCAR RALUCA-IULIA2*,

MEȘTER LIANA3, JUNCAR MIHAI1
1
Faculty of Medicine and Pharmacy, University of Oradea, Romania Str. Piața 1 Decembrie,
nr.10
2
Department of Prosthodontics, University Hospital Cluj Napoca, Clinicilor 32, 400006 Cluj-
Napoca, Romania, E-mail: ralucajuncar@gmail.com
3
Department of International Business, Faculty of Economic Sciences, University of Oradea,
Universitatii 1, 410087 Oradea, Romania
Autor corespondent: Juncar Raluca-Iulia Department of Prosthodontics, University Hospital
Cluj Napoca, Clinicilor 32, 400006 Cluj-Napoca, Romania, E-mail: ralucajuncar@gmail.com
ABSTRACT
The mandible is the facial bone that is the most affected by cervicofacial trauma. Although fractures of
the ascending ramus of the mandible have a relatively low incidence, their treatment possess a number of
technical and evolution problems. This study assesses the therapeutic methods for fractures of the ascending
ramus of the mandible, as well as the materials used for their treatment. The study was performed in 94 patients
with a total number of 277 fracture lines. Orthopedic, surgical methods, mandibular cerclage, and combined
methods were used for their treatment. Vestibular Erich splints represented 74.29% of the materials used for the
treatment of fractures, followed by titanium osteosynthesis plates (21.71%). Of all patients included in the study,
97.47% had a favorable postoperative evolution. The data of this study show that both types of materials as well
as the procedures used have an increased therapeutic efficiency, without significant postoperative
complications.

Keywords : trauma, ascending ramus, mandible, fracture, treatment.

INTRODUCTION

Due to the high incidence of facial trauma cases worldwide, traumatology has become a medical field of
maximum importance [6,27]. The mandible is the facial bone that is the most frequently affected by fractures
[18].The segments of the mandible are differently affected by fractures; thus, the body of the mandible is more
frequently fractured compared to the ascending ramus of the mandible [19]. However, an injuring agent acting
directly on the body of the mandible can indirectly induce a secondary fracture in a region of the vertical ramus
[3,31].The fractures of the vertical ramus of the mandible have particular characteristics from an etiopathogenic,
clinical and therapeutic point of view [12,15].
Depending on the topographic location of fracture lines present in the vertical ramus of the mandible, its
fractures are classified as follows: fractures of the ramus, condylar fractures and fractures of the coronoid
process [21]. In the literature, the most frequent fracture of the vertical ramus is condylar fracture with its
subcondylar subdivision [2,10,24,25]. Some authors present in their studies subcondylar fracture as the most
frequent mandibular fracture, which is however contradicted by other authors [7,17,34].When it comes to the
clinical features of these fractures, the literature data become even more contradictory[3,13]. This discrepancy
between different clinical studies implicitly leads to a discrepancy regarding the treatment of these fractures,
which creates confusion among clinicians when an optimal therapeutic decision is to be
made[2,12,16].Differences related to orthopedic, surgical or associated treatment of vertical ramus fractures are
significant, and the choice of the optimal type of treatment as well as of the materials used for their treatment is
particularly important for obtaining optimal healing with minimal sequelae[1,8].
The aim of this study is to objectively assess the methods by which the fractures of the ascending ramus
of the mandible were treated and the efficiency of the materials used during treatment.

202
 MATERIALS AND METHODS

For the current study, the clinical observation charts of patients treated in the Clinic of Oral and
Maxillofacial Surgery I Cluj-Napoca in the period 1 January 2002 – 31 December 2011 were available.
The study inclusion criteria were: adult patient, presence of a fracture line located in the vertical ramus of
the mandible, a history of an episode of acute trauma, presence of imaging investigations confirming the
presence and characteristics of fracture lines, the entire treatment performed in the clinic hosting the study,
complete documentation, patient followed up for at least 6 weeks postoperatively.
The study exclusion criteria were: treatment performed in a different service than that of the host
institution, patients with general pathology interfering with the bone consolidation process (osteoporosis,
cytostatic treatment, bisphosphonate treatment), pathological bone fracture, incomplete data of the clinical
observation charts.
The clinical observation charts were retrospectively assessed for the following variables: location of the
fracture line (vertical ramus of the mandible, subcondylar, intracapsularintracondylar, coronoid process), degree
of bone involvement (partial, complete), displacement of fractured bone fragments (with displacement, without
displacement), type of chosen treatment (orthopedic, surgical, orthopedic-surgical and mandibular cerclage),
type of materials used for the treatment of the mandibular fracture, postoperative evolution, complications.
For each therapeutic method, the materials used were analyzed as follows: for orthopedic treatment, the
types of vestibular splints, for surgical treatment, the types of osteosynthesis plates and screws, and for cerclage,
the type of wire used.
The centralization of data in electronic format and statistical interpretation were performed using the
Microsoft Excel software.The descriptive statistics of the assessed cases was calculated with a percent accuracy
of two decimals.

RESULTS
In 709 patients, 1099 fracture lines were evidenced in the mandible. Of all patients, 94 (13.26%) met the
study inclusion criteria. A total number of 277 fracture lines were identified in the ascending ramus of the
mandible.
Regarding the location of the fracture lines, the subcondylar region was the most frequently affected,
followed by the vertical ramus (Fig. 1).

Fig. 1 – Distribution of fracture lines depending on location

Complete fractures with the involvement of both cortical bones represented the majority, being found in a
proportion of 97.83% (271 fracture lines), while incomplete fractures represented only 2.17% (6 fracture lines).
The main option in the choice of treatment was orthopedic treatment, followed by combined orthopedic-
surgical treatment (Fig. 2).

203
 Fig. 2 – Distribution of patients in the studied group depending on the type of treatment
Through orthopedic treatment, the fractures were reduced and immobilized in maxillomandibular fixation
with stainless steel vestibular Erich splints, 0.4 mm thickcircumdentalWipla wire ligatures applied to the tooth
necks for splint fixation, and a 0.6 mm Wipla wire for rigid intermaxillary blockage. For surgical treatment, 2
mm thick titanium miniplates with 4 holes, 2 for each fracture line were used, as well as monocortical screws
with a diameter of 1.7 mm and a length of 7 mm. The shape and size of osteosynthesis plates were selected
depending on the characteristics and the location of the fracture focus. For mandibular cerclage, in edentulous
patients without an indication of osteosynthesis, self-curing acrylic trays were used, which were fixed with
stainless steel circummandibularwire. The most frequently used materials in the treatment of fractures of the
ascending ramus of the mandible were Erich splints, followed by osteosynthesis plates (Fig. 3).

Fig.3 –Distribution of the type of materials used in the treatment of fractures of the ascending ramus of
the mandible

Postoperative evolution was favorable in a proportion of 97.47% (270 fracture foci); 2.53% (7 fracture
foci) presented postoperative complications. Among complications, infectious complications represented by
osteitis in the fracture focus were predominant, followed by vicious consolidation and delayed consolidation
(Fig. 4).

204
 Fig. 4 – Distribution of patients depending on the presence of posttherapeutic complications
After performing the correlation between the type of treatment applied, the materials used and the
presence of postoperative complications, it was observed that strictly orthopedic treatment and
circummandibular cerclage generated the most frequent postoperative complications (Table 1).

Treatment/material
used
Orthopedic/Erich
splints
Combined/Erich splints
& titanium plates
Strictlysurgical/titanium
plates
Cerclage/acrylic trays
Table 1 - Distribution of postoperative complications depending on the type of treatment
Complications
Osteitis Vicious consolidation Delayed consolidation Total
1 1 1 3
0 0 0 0
1 0 0 1
1 1 1 3

DISCUSSIONS

The aim of this study was attained; the most frequently used therapeutic methods for the treatment of
fractures of the ascending ramus of the mandible were identified and their efficiency and the materials used for
treatment were correlated with the postoperative evolution of the fractures.
The fractures of the vertical ramus of the mandible require particular attention. Undiagnosed at the
appropriate time or treated incorrectly, they can generate a number of severe occlusal, functional, articular and
cosmetic complications.
In our study, the incidence of fractures of the vertical ramus of the mandible was low compared to those
of the body of the mandible. This is also found in the results of Ellis et al. [10], Dongas and Hall et al. [2]and
Shah et al.[25], but is not found in the results of Ahmed et al. [17] and those of Motamedi et al.[23], who identify
an increased incidence of vertical ramus fractures compared to fractures of the body of the mandible.By
analyzing the previously mentioned studies, we did not identify the causes that justify these contradictory data,
except for age, children being more frequently affected by fractures of the condylar process caused by accidental
falls on the chin. The most frequent location in the vertical ramus of the mandible was subcondylar, which is
confirmed by other authors [7,23,29,34]. Locations in the ramus and the coronoid process were rare, similarly to
the results provided by Kale TP et al. [20], who report a 3.3% incidence of ramus fractures and a 3.85%
incidence of coronoid process fractures. The high incidence of subcondylar fractures is due on the one hand to
the production mechanism, and on the other hand to local anatomy. These fractures are most frequently caused
by an indirect mechanism; thus, a trauma in the more exposed mandibular areas such as the mental symphysis is
transmitted to the condylar level. From an anatomical point of view, the condylar neck has a reduced thickness

205
and implicitly, a lower mechanical resistance. Unlike subcondylar fractures, intracapsular condylar fractures
were absent in the current study. The explanation of this absence results from the mechanism of production of
these fractures. Intracapsular fractures are induced by a compression mechanism along the long axis of the
vertical ramus, the traumatic agent acting from downward to upward at the inferior margin of the mandibular
gonion, which is less exposed to trauma from an anatomical point of view[1,3,8,16,18,19,31].
In the current study, complete fractures with the displacement of the fractured fragments were
predominant, a result obtained by other authors[10,7,29,34]. Contrary to the results obtained in this study,
Laverick et al. [28] evidence the absence of displacement in the majority of vertical ramus fractures. Vertical
ramus fractures that generally undergo no displacement of the bone fragments are those situated in the muscle
mass,where displacement secondary to the action of perimandibular muscles is minimal [1,8,16] unfortunately,
these are quite rare. In the current study, most of the fractures were located at subcondylar level, where muscles
act in antagonistic directions on the bone fragments, which explains the great number of reported fractures with
displacement.
The majority of the fractures in this study were treated orthopedically, similarly to the reports of some
literature studies that consider orthopedic treatment as the treatment of choice for fractures of the ascending
ramus of the mandible [23,26,29,32]. In contrast, other authors report reduction and immobilization using
osteosynthesis with plates and screws as an exclusive treatment method for fractures of the ascending ramus
[2,9,11]. Both surgical treatment by osteosynthesis alone and combined treatment were used in a low proportion
in the current study. This can be explained by several reasons. A first reason is related to closed reduction. The
orthopedic reduction and immobilization of bone fragments, followed by functional therapy represents a
relatively riskless procedure without major complications, with optimal results most of the times. On the other
hand, the surgical approach clearly involves a number of disadvantages resulting from the presence of an
operative wound, the appearance of large deperiosted areas where mandibular vascularization is deficient, but
also a major advantage represented by the optimal reduction of fragments with marked
displacement[1,3,8,16,18,19,31].The data of this study suggest that in general, a treatment allowing maximum
benefits with minimal intraoperative and particularly postoperative risks was chosen.
To perform orthopedic and combined treatment, 520 stainless steel Erich splints were used, as well as 76
titanium miniplates 2.0 mm thick with 304 titanium screws having a diameter of 1.7 mm and a length of 7 mm,
similarly to materials reported by other authors [2,5,14,22,28].The fact that the same types of materials have
been reported by other authors confirms the international standardization of the type of materials used for
treating fractures of the ascending ramus of the mandible. In this way, the results obtained by different clinical
studies can be compared in order to have an as objective as possible view of the interaction between the
alloplastic material and human tissue.
The postoperative evolution of the patients included in this study was mostly favorable, without
significant differences being evidenced between the evolution of cases treated orthopedically and that of cases
treated by the surgical or the combined method, a result similar to those of the literature data[23,26,28,39,32]. It
can be concluded that the type of material used in the treatment of fractures of the vertical ramus of the mandible
does not significantly influence their postoperative evolution. This result is surprising taking into consideration
the great differences between the various types of materials used. The absence of significant differences between
the two main categories of materials can be explained by the degree of their contact with human tissues.
Vestibular splints are in contact only with the oral mucosa without reaching inside tissues, while osteosynthesis
plates are placed subperiosteally, supracortically. This allows vestibular splints to be tolerated similarly to
titanium osteosynthesis plates. The only authors obtaining different results are Kale TP et al. [20], who report a
higher rate of complications after orthopedic treatment. The difference in this study is given by the effectiveness
of medical therapy, not by the type of material used. Obviously, in all these retrospective studies there are
limitations regarding the accuracy of data recorded for each case, as well as regarding follow-up. No patient
presented for follow-up for more than 6 weeks after the initiation of treatment to allow a long-term monitoring of
the cases.

CONCLUSIONS

For the treatment of fractures of the vertical ramus of the mandible, surgical and orthopedic methods
proved to be equally effective. Mandibular cerclage treatment was the method with the worst therapeutic results
and implicitly, with the greatest number of complications.
The materials used for surgical and orthopedic treatment proved to be well tolerated by human tissues,
without inducing complications in the fracture foci or at regional level.

206
 REFERENCES :

1. ALEXANDRU BUCUR, CARLOS NAVARRO VILA, JOHN LOWRY, JULIO ACERO. - Bucureşti: Compendiu
de chirurgie oro-maxilo-facială Vol I şi II . Q. Med Publishing, 2009 2 voi.
2. ALKAN A, CELEBI N, OZDEN B, BAS B, INAL S: Biomechanical comparison of different plating techniques
in repair of mandibular angle fractures. Oral Surg Oral Med Oral Pathol Oral Radiol Endod (6): p.752-
756, 2007.
3. A. M. NAHUM, “The biomechanics of maxillofacial trauma,”Clinics in Plastic Surgery, vol. 2, no. 1, pp. 59–
64, 1975.
4. A. SHAH, A. S. ALI, AND S. ABDUS, “Pattern and management of mandibular fractures: a study conducted
on 264 patients,”Pakistan Oral & Dental Journal, vol. 27, no. 1, pp. 103–106, 2007.
5. BAURMASH H, FARR D, BAURMASH M (1988) Direct bonding of Arch bars in the management of
maxillo mandibular injuries. J Oral Maxillofac Surg 46:p.813–815
6. BANKS P, BROWN A. Fractures of the facial skeleton. 2nd ed. Oxford, Woburn: Butterworth-Heinemann;
2001. PP 171-185.
7. B. F. BRASILEIRO AND L. A. PASSERI, “Epidemiological analysis of maxillofacial fractures in Brazil: a 5-
year prospective study,”Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology,
vol. 102, no. 1, pp. 28–34, 2006.
8.BURLIBAŞA C., CHIRILĂ I., GĂNUŢĂ N., GOGĂLNICEANU D., HERESCU C., LUNG T., MAFTEI I.,
PRICOP M., ROTARU AL., SURPĂŢEANU M., URTILĂ E.: Chirurgie Orală şi Maxilofacială, Ediţia a II-
a, Editura Medicală, Bucureşti, 2005
9. DE MATOS FP, ARNEZ MF, SVERZUT CE, TRIVELLATO AE: A retrospective study of mandibular fracture
in a 40-month period. Int J Oral Maxillofac Surg (1): p.10-15,2010
10.E. ELLIS, K. F. MOOS, AND A. EL ATTAR, “Ten years of mandibular fractures: an analysis of 2,137 cases,”
Oral Surgery Oral Medicine and Oral Pathology, vol. 59, no. 2, pp. 120–129, 1985.
11.ELLIS III E: Treatment methods for fractures of the mandibular angle. Int J Oral Maxillofac Surg (4): p.243-
252, 1999.
12.FONSECA RJ., WALKER RV. (eds.) : Oral and maxillofacial trauma.Volume 1. 2nd edition.WB Saunder ,
Philadelphia 1997.
13.FREINBERG SE, STEINBERG B. , HELMAN JI. , Healing of traumatic injuries In: Fonseca RJ, Walker RV,
editor. Oral and Maxillofacial Trauma. Vol. 1. Philadelphia: Saunders; 1997. pp. 13–57.
14. GANDHI S1, RANGANATHAN LK, SOLANKI M, MATHEW GC, SINGH I, BITHER S , Pattern of
maxillofacial fractures at a tertiary hospital in northern India: a 4-year retrospective study of 718 patients.
Dent Traumatol. 2011 Aug;27(4):p.257-62.
15. G. O. KRUGER, Textbook of Oral and Maxillofacial Surgery, Jaypee Brothers, 6th edition, 1990
16.HÄRLE F, CHAMPY M, TERRY B. Atlas of craniomaxillofacial osteosynthesis.Stuttgart, New York: Theime,
2009.
17. H. E. A. AHMED, M. A. JABER, S. H. ABU FANAS, AND M. KARAS, “The pattern of maxillofacial
fractures in Sharjah, United Arab Emirates: a review of 230 cases,”Oral Surgery, Oral Medicine,Oral
Pathology, Oral Radiology and Endodontology, vol. 98, no.2, pp. 166–170, 2004.
18. J. A. HALAZONETIS, “The “weak” regions of the mandible,” British Journal of Oral Surgery, vol. 6, no. 1,
pp. 37–48, 1968
19.J. J. SWEARINGEN, Tolerance of the Human Face to Crash Impact, Office of Aviation Medicine, Federal
Aviation Agency, Stillwater, Okla, USA, 1965.
20.KALE TP, KOTRASHETTI SM, LOUIS A, LINGARAJ JB, SARVESH BU. Mandibular Ramus Fractures: A
Rarity. J Contemp Dent Pract 2013;14(1):p39-42.
21.KING RE, SCIANNA JM, PETRUZZELLI GJ (2004) Mandible fracture patterns: a suburban trauma center
experience. Am J Otolaryngol 25(5):p301–307
22. LELLO JL, LELLO GE (1988) The effect of interdental continuous loop wire splinting and
intermaxillary fixation on the marginal gingiva. Int J Oral Maxillofacial Surg 17(4):p.249–252.
23.M. H. K.MOTAMEDI, “An assessment ofmaxillofacial fractures:a 5-year study of 237 patients,” Journal of
Oral and Maxillofacial Surgery, vol. 61, no. 1, pp. 61–64, 2003.
24.OGUNDARE BO, BONNICK A, BAYLEY N (2003) Pattern of mandibular fractures in an urban major
trauma center. J Oral Maxillofac Surg 61(6):p713–718
25.P. DONGAS AND G. M. HALL, “Mandibular fracture patterns in Tasmania, Australia,” Australian Dental
Journal, vol. 47, no. 2, pp. 131–137, 2002.
26.RAMLI R, RAHMAN NA, RAHMAN RA, HUSSAINI HM, HAMID AL., A retrospective study of oral and
maxillofacial injuries in Seremban Hospital, Malaysia., Dent Traumatol. 2011 Apr;27(2):p.122-6.
27.ROWE NL, WILLIAM J. Maxillofacial injuries. 2nd ed. Edinburgh: Churchill Livingstone; 1994.PP216.

207
28.S. LAVERICK A,B,∗, P. SIDDAPPA B, H. WONGC, P. PATEL B, D.C. JONES B , Intraoral external oblique
ridge compared with transbuccal lateral cortical plate fixation for the treatment of fractures of the
mandibular angle: prospective randomised trial, British Journal of Oral and Maxillofacial Surgery 50
(2012) p.344–349.
29.VAN BEEK GJ, MERKX CA (1999) Changes in the pattern of fractures of the maxillofacial skeleton. Int J
Oral Maxillofac Surg 28(6):p.424–428.
30.VAN DEN BERGH B, HEYMANS MW, DUVEKOT F, FOROUZANFAR T., Treatment and complications of
mandibular fractures: a 10-year analysis. J Craniomaxillofac Surg. 2012 Jun;40(4):p 108-110.
31.V. R. HODGSON, “Tolerance of the facial bones to impact,”American Journal of Anatomy, vol. 120, pp.
113–122, 1967..
32.YAMAMOTO MK1, D'AVILA RP, LUZ JG., Evaluation of surgical retreatment of mandibular fractures. J
Craniomaxillofac Surg. 2013 Jan;41(1):p.42-6.
33.ZACHARIADES N, MEZITIS M, MOUROUZIS C, PAPADAKIS D, SPANOU A: Fractures of the mandibular
condyle: a review of 466 cases. Literature review, reflections on treatment and proposals. J
Craniomaxillofac Surg (7): p.421-432, 2006.
34.ZIX JUERGEN ANDREASA, SCHALLER BENOITA, LIEGER OLIVIERB, SAULACIC NIKOLAA, THORÉN
HANNAA, IIZUKA TATEYUKIA, Incidence, aetiology and pattern of mandibular fractures in central
Switzerland, Swiss Med Wkly. 2011;p.141.

208
 THE BENEFITS OF USING ELECTROMAGNETIC FIELD THERAPY WITH
ELECTRONIC DOCTOR STEM GENERATOR: CASE PRESENTATIONS

Bogdan VLADILĂ, DMD, PhD, Electronic Doctor SRL Nice, 5A Jean Monnet str., Bucharest,
Romania
Anamaria BECHIR*, DMD Ph.D., Professor, Titu Maiorescu University of Bucharest, Dental
Medicine Faculty, Romania
Cristian PETRESCU, DMD, Electronic Doctor SRL Nice, 5A Jean Monnet str., Bucharest,
Romania
Alexandru BURCEA, DDS, PhD, Lecturer, Titu Maiorescu University of Bucharest, Dental
Medicine Faculty, Romania
Edwin Sever BECHIR, DMD, PhD stud., Assist Prof., Medicine and Pharmacy University of
Tirgu Mures, Dental Medicine Faculty, Romania

*Correspondent author: Anamaria Bechir, mail: anamaria.bechir@gmail.com

Abstract
The purpose of this research was to use a conservative adjuvant therapy in the treatment of periodontal diseases,
so that the patients, diagnosed with this condition, to maintain their natural dentition as long as possible.
An innovative medical device, “Electronic Doctor Stem Generator” device, homologated with CE mark, in 2a
class, was used in our study. The study was performed by using a standard protocol of 30 exposures of 2 hours
each, on the upper or lower dental arch. Subjects were both male and female, aged between 30-50 years, in
healthy state and having a good oral hygiene status. Before and after 2 months from the start of treatment,
radiological examinations were effectuated, for evaluating the obtained results.
After the assessment of clinical and radiological results, we ascertained a good bone densification in the
exposed regions of alveolar bone.
The conclusions of this study recommend the treatment with the "Electronic Doctor Stem Generator" device, that
is an minimally invasive and nontraumatic innovative therapy, for bone regeneration.
Keywords: innovative medical device, implantology, bone densification

INTRODUCTION

Many researches were conducted in tissue regeneration, for restoring the alveolar support of the teeth.
Regenerative medicine is a distinct major advancement in medical treatment which is based on the principles
of stem cell technology and tissue engineering in order to replace or regenerate human tissues and organs and
restore their functions [6].
A regenerative medicine model of care entail production and standardized application of bio therapies,
supported by acomprehensive integrated sourcing of manufacturing and health care [8].
The objective of regenerative medical therapy is to induce the regeneration and repair of defective tissues
based on the natural healing potential of patients themselves [7].
The purpose of this research was to use a conservative adjuvant therapy, represented by “Electronic Doctor
Stem Generator" device, in the treatment of periodontal diseases.

MATERIAL AND METHOD

“Electronic Doctor Stem Generator” medical devices consist of a power generator and a bobbins system, and
generate an electromagnetic field. The duration of emission and the electromagnetic characteristics of this device
are controlled by personalized software, incorporated into the extraoral component of Electronic Doctor device.
The power supply is represented by the rechargeable batteries.
The intraoral thermoforming ethylene acetate base mouthguard (the intraoral part) is shaped like the letter
"U" and include the electromagnetic applicator for the treated area that need regeneration, between the two poles.
The distance between the poles is variable and is chosen according to the thickness of the dental arch in the area
of application, ranging between 15 and 21 mm. The electromagnetic field (EMF) is acting towards the maximum
21 mm. The applicator is coated with a biocompatible silicone film, which is customized for each patient in part
and will act strictly to the indicated area (mandible or maxillary dental arch and alveolar bone).
The extraoral apparatus is homologated with CE mark in class 2a (fig. 1).

209
 Fig. 1. The aspect of Electronic Doctor Stem Generator device

This research studied the results of the use of this device in the therapy of periodontal affections.
Clinical trials were conducted in private clinics.
The selected subjects were both male and female, aged between 30-50 years, in healthy state, not diagnosed
with metabolic or systemic diseases with resounding in orofacial area, and having a good oral hygiene status.
All patients were adequately informed about the procedures, first verbally and then in a written form, for the
informed consent. Before the treatments, the professional oral hygiene was realized in all patients, by meticulous
supra- and subgingival scaling.
After the recording of dental and periodontal status, respectively the establishing the dental plaque index, an
initial panoramic radiograph was indicated.
The treatment was performed by using a standard protocol of 30 exposures of 2 hours each, on the selected
area for treatment.

Case 1
Patient G.P. came to the dental office complaining about pain, during chewing, in the left side of the lower
jaw. The intra-oral examination at presentation in the dental clinic and the first panoramic radiograph of the
patient F.P., revealed that the second left mandibular premolar (3.5) presented third class dental mobility, with a
deep periodontal pocket (fig. 2).
After explaining in detail all adequate information regarding the procedures, the patient signed the written
consent, and then was accomplished the super- and subgingival scaling of the patient's teeth.
The therapy in electromagnetic field with “Electronic Doctor Stem Generator” devices was conducted for 30
days, with lasting two hours daily session.

210
 Fig. 2. OPG of the patient F.P., realized before the beginning of treatments

The monitoring of patient was conducted weekly, for one month.

Two months after the surgery intervention, the second panoramic radiograph was realized (fig. 4).

Fig. 3. OPG of the patient F.P., realized 30 days after completion of the treatment

Case 2

Patient V.M. came to the dental clinic complaining about pain during chewing in the right side of the upper
half dental arch. After the intraoral and radiological examination, it has been found at the level of the teeth 1.6
and 1.7 the existence of periodontal pocket (fig. 4).

Fig. 4. OPG radiograph of the patient V.M., realized before the beginning of treatments

211
 The procedures have been explained, the patient signed the written consent and then was accomplished the
super- and subgingival scaling with curettage of the patient's teeth. Second day after scaling, the treatment
sessions with EMF therapy was realized for 30 days, two hours daily/session.

Fig. 5. The panoramic radiograph of the patient V.M., realized 30 days after completion of the treatment

One month after completion of the treatment with EMF, so after two months after the beginning of treatment
sessions with Electronic Doctor Stem Generator device, the second panoramic radiograph was performed (fig. 5).

Case 3

Patient E.A. came to the clinic accusing pain in chewing, halitosis, tooth mobility and bleeding of gum. On
clinical examination was found the existence of supra- and subgingival calculus, OHI index=3, the existence of
pain in the cross percussion. Were observed horizontal and vertical migration of teeth. Pathological tooth
mobility was between with first and second degree. Occlusal interference was too observed.

Fig. 6. Initial OPG radiograph of patient E.A.

As a treatment plan, was accomplished the super- and subgingival scaling of the patient's teeth, it was
recommended rigorous personal dental hygiene and exposure to EMF, for 30 sessions.
After the EMF treatment, on OPG radiographs (fig. 7) can be noticed the densification of alveolar bone. The
clinical examination, performed after completion of therapy EMF, revealed significant reduction of the degree of
gingival bleeding and of tooth mobility.

212
 Fig. 7. OPG radiograph of patient E.A., after 30 sessions in EMF

RESULTS AND DISSCUTIONS

This study was performed by using a standard protocol of 30 exposures of 2 hours each, on the selected area
for treatment.
After 2 months from the start of treatment, the results were recorded by intraoral and radiological
examinations, by comparing the radiographs effectuated before and after the treatment.
The results were assessed and proved decreased mobility of the implants, in all axes of teeth; reduction of the
periodontal pockets depth; increased bone densification in the exposed regions to EMF, in all patients, noticeably
by comparing the initial and at the end radiographs.
After Kohara et al [4] and Lee et al [5], it is indispensable to provide cells with a local environment, which
enables them to proliferate and differentiate efficiently, resulting in cell-induced tissue regeneration for good
tissue regeneration.
In conformity with the researches of Albulescu and al [1], the application of low intensity and low frequency
electromagnetic fields on the proliferation of stem cells and on the differentiation into adipocytic and osteocytic
phenotypes, had a benefic effect, with potential use in regenerative medicine.
Over the past 30 years, the beneficial therapeutic effects of selected low energy, time varying
electromagnetic fields (EMF) have been documented with increasing frequency to treat therapeutically resistant
problems of the musculoskeletal system [4].
Duan et al [3] have reported that electromagnetic field may produce genotoxicity at relative high intensities.

CONCLUSIONS

Treatment with the device “Doctor Stem Electronic Generator” is minimally invasive and nontraumatic
innovative therapy that causes dental bone regeneration.
Clinical signs of dental mobility test shows that the degree of mobility and decreased in all clinical cases of
periodontitis affections.
Radiographs made before and after the therapy demonstrates EMC beneficity of this type of innovative
minimally invasive and non traumatic treatment which causes bone regeneration in dental tissues.

SELECTIVE REFERENCES
1. Albulescu R, Codrici E, Mihai S, Enciu AM, Vladila B, Neagoe S, Albulescu A, Tanase C, Effects of low
intensity/very low frequency electromagnetic fields on stem cells proliferation and differentiation, FEBS
Journal. Special Issue: FEBS EMBO 2014 Conference, Paris, France, 30 August-4 September 2014. Volume
281, Issue Supplement s1, pages 785–808
2. Chen F.M., Jin Y., Periodontal tissue engineering and regeneration: current approaches and expanding
opportunities, Tissue Eng Part B Rev. 2010 Apr;16(2):219-5
3. Duan W, Liu C, Zhang L, He M, Xu S, Chen C, Pi H, Gao P, Zhang Y, Zhong M, Yu Z, Zhou Z. Comparison
of the genotoxic effects induced by 50 Hz extremely low-frequency electromagnetic fields and 1800 MHz
radiofrequency electromagnetic fields in GC-2 cells.Radiat Res. 2015 Mar;183(3):305-14
4. Kohara H, Tabata Y, Review: Tissue Engineering Technology to Enhance Cell Recruitment for Regeneration
Therapy, Journal of Medical and Biological Engineering, 30(5): 267-276

213
5. Lee K, Silva EA, Mooney DJ, Growth factor delivery-based tissue engineering: general approaches and a
review of recent developments, J. R. Soc. Interface 2011 8 153-170; DOI: 10.1098/rsif.2010.0223. Published
23 December 2010
6. Sampogna G, Guraya SY, Forgion A, Regenerative medicine: Historical roots and potential strategies in
modern medicine, Journal of Microscopy and Ultrastructure, Volume 3, Issue 3, September 2015, Pages
101–107
7. Tabata Y, Current status of regenerative medical therapy based on drug delivery technology, Reproductive
BioMedicine Online, Volume 16, Issue 1, 2008, Pages 70-80
8. Terzic A, Pfenning MA, Gores GJ, Harper CM Jr., Regenerative Medicine Build-Out, Stem Cells Trans Med,
December 2015 vol. 4 no. 12, 1373-137

214
 AUGMENTING THE BONE DEFECT RESULTING FROM THE EXTRACTION OF
SEMIINCLUDED WISDOM TEETH – CASE PRESENTATION

Silviu STANESCU, Dana COSAC, Anna-Maria PANGICĂ

Faculty of Dental medicine
Titu Maiorescu University

Abstract: We present a case of a patient with a semiincluded wisdom tooth which resulted in resorption
of mesial septum of alveolar bone. To save molar 3.7 we have successfully applied local therapies for tissue
regeneration.
Keywords: wisdom tooth, bone regeneration, periodontal pocket.
Introduction:
Careful evaluation of remaining bone defects after odontectomy impacted third molars is made
regarding the stability on the arch and the risk of damage and vitality of the molar 3.7. The bone
augmentation involves three different mechanisms: osteogenesis (bone formation and development),
osteoinduction (stimulating bone formation) and osteoconduction (mechanism which provides a
matrix for new bone formation). The mechanism by which bone augmentation materials used are
working is different depending on the properties and composition.
The bone augmentation techniques are frequently using resorbable or non resorbable membranes that
protects the grafted bone from the mucoperiostal flap.
Depending on the material they are made, the membranes can be divided into (1, 2, 3, 4):
- non resorbable membranes, which must be removed after a period of time,
- resorbable membranes, which can be synthetic or natural, and did not need a new intervention for
removal.
Straumann Pref Gel is a pH neutral, 24% EDTA root surface conditioner intended for topical
application onto exposed root surfaces during periodontal surgery. The gel offers an effective, yet
gentle removal of the "smear layer" during periodontal surgical procedures. Mechanical debridement
of a root surface inevitably produces a smear layer, which in turn may prevent or retard periodontal
healing.
Emdogain is an easy-to-apply, protein-based gel that is designed to promote predictable regeneration
of lost periodontal hard and soft tissues caused by periodontitis, helping to save and preserve the
tooth.Easy to apply with prefilled syringes, it is convenient to use and easily integrated into
periodontal surgery.
In more than 60 clinical trials involving over 2,000 intraosseous periodontal defects, Emdogain has
been proven to be effective in stimulating the formation of new periodontal attachment in:
- Soft tissue - measured as a gain of clinical attachment level and reduce periodontal pocket
probing depth
-Bone tissue - evidence of new alveolar bone.
Clinical studies have shown, 1 year after treatment with Emdogain, an average of 60-70%
filling of a bone defect, evaluated with a gain of radiographic bone.

215
 Case presentation:
Patient A S., aged 35, was presented in our clinic with periodic pain episodes at level 3.8. On
examination I found the presence of 3.8 semiincluded. At probing with the periodontal probe, I
detected the presence of periodontal pocket with a depth of 10 mm measured disto-lingual and disto-
vestibular of 3.7.
Complementary imaging examination shows the presence of significant bone resorbtion in the area
and the horizontal position of 3.7, targeted to 3.8 crown.

Fig. 1 – Initial clinical and radiological situation

Proposed treatment plan accepted by the patient consists in extraction of 3.8, which position
favored the formation of periodontal pocket, and bone regeneration techniques performed for the
recovery of 3.7 distal alveolar wall. Surgical steps were peripheral truncal anesthesia, incision, muco-
periosteal flap, removing the 3.8 crown with diamond bur and removing the roots with an elevator.
When examining the distal alveolar wall of 3.7, I found the lack of bone on more than half of the root
length. To help bone regeneration I have prepared the exposed surface of the root with Pref Gel
Straumann, I washed with saline solution then applied topically Emdogain.

Fig. 2 – Incision and exposure of 3.8

Fig. 3 – Evaluation of the loss of alveolar bone in the distal wall of 3.7
216
Fig. 4 – Augmenting the remaining bone defect with bone mixture of bovine and human bone

Fig 5 – Pericardium membrane protecting bone graft

Fig. 6 –Postoperative clinical aspect

217
 Fig. 7 – Radiological postoperative aspect

Fig. 8 – Radiological aspect after15 months

I filled the defect with a mixture of 0.5-1 mm Granules Cerabone bovine bone and human
bone Maxgraft Corticocancellous Granules <2 mm. I protected the grafted bone with a pericardium
membrane ZIMMER 15/20 mm and I closed the wound with a simple suture in three points.
The purpose of applying bone regeneration technique is to save the tooth 3.7 that otherwise would
have the distal root exposed to the oral environment and could suffer various impairments from
sensibility to dental caries susceptibility.

Conclusion: Imaging Control at one year and three months shows recovery of bone volume absent at
the time of extraction of 3.8.

Bibliography:

1. Peterson J.L. : Oral and Maxillofacial Surgery. Mosby Company, 1998.

2 Mihai, A.: Implante Endoosoase Osteointegrate in Stomatologie. Editura Sylvi – 1995 Bucuresti
3. Zarb, A.G., Bolender, C.L.: Prosthodontic Treatment for Edentulous Patients. Complete Dentures
and Implant-Supported Prostheses. Mosby-Elsevier, 2004.
4 Sato, N., DDS: Chirurgie Parodontala. Atlas Clinic. Quintessence Publishing, 2009.

218
THE PREVALENCE IN THE USE OF FOUR MINIMALLY INVASIVE THERAPIES
IN ROMANIAN DENTISTS: a preliminary study

Edwin Sever BECHIR1, Anamaria BECHIR2, Gabriela CIAVOI2, Carmen BIRIȘ*1, Ilinca
SUCIU1, Alexandru BURCEA2, Roxana MANU2, Marius MARIȘ2, Horia Mihail BARBU2
1
University of Medicine and Pharmacy Târgu-Mureș, Faculty of Dental Medicine, 38 Gh. Marinescu
str., 540139 Târgu-Mureș, Romania
2
Titu Maiorescu University of Bucharest, Dental Medicine Faculty, 67A Gheorghe Petrașcu Str.,
031593 Bucharest, Romania
3
University of Oradea, Faculty of Medicine and Pharmacy, Department Dental Medicine, 10, 1
Decembrie Sq., 410073 Oradea, Romania

Abstract
Currently, holistic dentistry includes minimally and non-invasive therapies. Piezo-
surgery is a promising technical modality for bone surgery. Platelet Rich Fibrin is a patient`s
blood-derived and autogenous living biomaterial, used as an adjunctive autologous
biomaterial to promote bone and soft tissue healing and regeneration. ”Electronic Doctor” is
a new medical device used in the treatment of chronic pathosis, based on a low frequency
magnetic fluctuation. The hyperbaric oxygen therapy is realised in hyperbaric chambers with
special technology.
This research studied the prevalence in the use of four minim-invasive therapies by the
Romanian dentists. A questionnaire was distributed to the dentists of three Romanian areas.
The number of participants to this preliminary study was 125.
82 dentists of those who completed the questionnaire had information about these
minimally invasive therapies, compared with 43 dentists who did not know about any of these
four therapies. From 82 of those who had information about these therapies, the reason for
not were used was that are considered time-consuming procedures (100%) and expensive
(100%), respectively cause patient discomfort (64.4%).
The perception on minimally invasive therapies will be improved through continuous medical
education.
Keywords: minimally invasive therapies, questionnaire, prevalence in the use in
Romanian dentists

INTRODUCTION

Currently, holistic dentistry includes minimally and non-invasive therapies. The dental
biomaterials used to replace or recover the oro-facial tissues may be natural or synthesized
[4].
Regenerative medicine is a distinct major advancement in medical treatment which is
based on the principles of stem cell technology and tissue engineering in order to replace or
regenerate human tissues and organs and restore their functions [17].
Piezo-surgery is a true revolution in bone surgery as it fulfils both biological and technical
criteria. This minimally invasive therapy uses a low frequency modulated ultrasonic insert
which produces microvibrations in the range of 60-200micro meter/sec and leads to safe and
precise bony incision without damaging underlying vital structures like nerves, mucosa and
vessels [1].

219
 Piezo-surgery is a new and modern technique of bone surgery in implantology. Selective
cutting is possible for different ultrasonic frequencies acting only on hard tissues
(mineralized), saving vital anatomical structures. With the piezoelectric osteotomy technique,
the receptor site preparation for implants, autogenous bone graft acquisition (particles and
blocks), osteotomy for alveolar bone crest expansion, maxillary sinus lifting, and dental
implant removal can be performed accurately and safely, providing excellent clinical and
biological results, especially for osteocyte viability [16].
After the conclusions of Pavlíková et al [15], piezo-surgery is a promising technical
modality for different aspects of bone surgery with a rapidly increasing number of indications
throughout the whole field of surgery.
Dental biomaterials such as bone substitutes and collagen membranes, are currently used in
regenerative dentistry as well as for the regeneration of bone and cartilage [3].
The prospect of having new therapies, biomaterials and bioactive surgical additives
available that will improve success and predictability of patient outcomes on soft and bone
tissue healing and regeneration are key treatment objectives in dental implantology,
periodontology and oral surgery [11].
Platelet Rich Fibrin (PRF), a patient`s blood-derived and autogenous living biomaterial,
is increasingly being investigated and used worldwide by clinicians as an adjunctive
autologous biomaterial to promote bone and soft tissue healing and regeneration. The gold
standard for in vivo tissue healing and regeneration requires the mutual interaction between a
scaffold (fibrin matrix), platelets, growth factors, leukocytes, and stem cells [13].
These key elements are all active components of PRF, and when combined and prepared
properly are involved in the key processes of tissue healing and regeneration, including cell
proliferation and differentiation, extracellular matrix synthesis, chemotaxis and angiogenesis
(neo-vascularization) [9,12].
An improved understanding of the development, biological and physiological properties
and characteristics of PRF in tissue healing and regeneration over the last two decades, has
led to more successful therapeutic applications, especially in the fields of dental implantology,
periodontology and oral surgery [11].
In conformity with the researches of Albulescu and al [], the application of low intensity
and low frequency electromagnetic fields on the proliferation of stem cells and on the
differentiation into adipocytic and osteocytic phenotypes, had a benefit effect, with potential
use in regenerative medicine [2].
Over the past 30 years, the beneficial therapeutic effects of selected low energy, time
varying electromagnetic fields (EMF) have been documented with increasing frequency to
treat therapeutically resistant problems of the musculoskeletal system [14].
Duan et al [10] have reported that electromagnetic field may produce genotoxicity at
relative high intensities.
„Electronic Doctor” is a medical device used in the treatment of chronic pathosis, based
on a low frequency magnetic fluctuation created by an inductor placed in a personalized
dental tray for a minimum of 15 sessions. The treatment with „Electronic Doctor” is an
unpainful treatment, which is also a stem cell stimulator, for dental prevention and bone and
gingival regeneration. This procedure is indicated in the treatment of bone resorption and
periodontal affections, including the increasing of bone densifications. The therapy with
„Electronic Doctor” is not indicated for patients that present premalignant and malignant
lesions discovered during the preventive oncological examination, nor for patients with
atypical gingival epithelial proliferation or patients with benign tumours. „Electronic Doctor”
is absolutely unindicted for patients with previous oncological lesions or oncological
surgery’s [19].

220
 The use of the „Electronic Doctor” medical device as a minimally invasive and atraumatic
innovative periodontal therapy is recommended for a better healing compared with the classic
treatment techniques [6,18].
The hyperbaric oxygen therapy (HBOT) is a topic with more than 50 years of
experimental and clinical study, HBOT is realised in hyperbaric chambers with a special
technology. The pressure increase must be systemic and the treatment is carried out in one of
two ways, in mono-place chambers (acrylic single person chambers pressurized with O2), or
multi-place chambers of steel, designed to hold two or more people pressurized with air [5].
In theory, HBOT stimulates cellular processes involved in wound healing, directly impairs
the growth of anaerobic pathogens, and enhances the potency of the oxygen-dependent
antimicrobial mechanisms [7].
HBOT acts as a bactericidal/bacteriostatic agent against anaerobic bacteria by increasing
the formation of free oxygen radicals. HBOT restores the bacterial-killing capacity of
leukocytes in hypoxic wounds by increasing tissue oxygen tensions, increases the amount of
oxygen in the blood and can temporarily restore normal levels of blood gases and tissue
function. These promote healing and the ability of the tissues to fight infection. In addition,
HBOT acts synergistically with a number of antibiotics [8].

MATERIAL AND METHOD

This research studied the prevalence in the use of four minim-invasive therapies by
Romanian dentists.
A questionnaire with 8 questions was distributed to some medical members of the Titu
Maiorescu University of Bucharest, UMF Târgu-Mure , and University of Oradea,
respectively to practitioners that practice dentistry on the territories of these areas
The number of participants to this preliminary study was 125.
The questionnaire is presented in fig. 1.
The completed questionnaires were collected and grouped. Grouping questionnaires was
carried out according to gender, i.e. according to the professional status of doctors in the
study:
- Specialists in periodontology - specialization and / or dental alveolar surgery,
- Specialist physicians in other specialties,
- General dentists with under 5 years of experience
- General dentists with experience between 5-10 years
- General dentists with over 10 years’ experience.

221
 Fig. 1. Questionnaire on the use of minimally invasive techniques by dentists

The graphs were made in Microsoft Excel.

RESULTS

Of the 125 dentists participating in the study, 44 physicians were specialists [24 in
periodontics (P), 12 in dento-alveolar surgery (DAS) and 8 specialists in other specialties
(OS)], and 81 general dentists [35 general dentists with less than 5 years of experience
(GDL5Y), 24 general dentists with experience ranging 5-10 years (GD5-10Y), and 22 general
dentists with more than 10 years’ experience (GDM10Y)], all operating in Romania, in
Bucharest, Târgu-Mure and Oradea areas (fig. 2).

222
 35

35

30

24 24
25 22

20

15 12

8
10

P DAS OS GDL5Y GD5-10Y GDM10Y

Fig. 2. The distributions of the participants to the study

82 dentists (65,6%) of those who completed the questionnaire had information about these
non and minimally invasive therapies included in the study (21 dentists about one therapy, 14
about two of the four therapies, 12 on three of the four therapies, and 7 on all four therapies)
compared with those 43 dentists (34,4%), who did not know about any of these four therapies
(fig. 3).

223
 43

no one
7 therapy
3 therapies

2 therapies
12

1 therapy

14

21

0 10 20 30 40 50

Fig. 3. The distributions of the dentists according to the information about the four
studied minimally invasive therapies

From 82 of those who had information about these minimally invasive therapies, the
reasons for not used these four therapies is that they are considered time-consuming
procedures (100%), expensive (100%), respectively cause patient discomfort (64.4%).
99% of dentists who completed the questionnaire, wish to acquire new expertise on the use
of the therapies studied.

CONCLUSIONS

In the Bucharest, Târgu-Mure and Oradea areas, dentists still show many reservations on
the introduction of the practice of the studied minimally invasive therapies.
The reduced percentage in use these therapies is due by the specific investments in the
equipment’s (piezo-surgery device, centrifuge to obtain PRF), and the relatively high cost for
the patient of the electromagnetic field therapy with „Electronic Doctor” device and HBOT.
The application of these therapies requires the clarification of the problems of
quality/safety assistance, including forensic issues for both dentist and patient.
The perception of dentists on minimally invasive therapies has improved through
continuous medical education, which since its debut during college, aims to increase the level
of inter- and multidisciplinary knowledge.

224
 The mentality of the patients on the acceptance these minimally invasive therapies should
be amended by presenting their advantages and by persuasiveness, and in both aspects the
responsibility is of the medical team.

REFERENCES

1. Agarwal E, Masamatti SS, Kumar A. Escalating Role of Piezosurgery in Dental Therapeutics. Journal of
Clinical and Diagnostic Research : JCDR. 2014;8(10):ZE08-ZE11
2. Albulescu R, Codrici E, Mihai S, Enciu AM, Vladila B, Neagoe S, Albulescu A, Tanase C, Effects of low
intensity/very low frequency electromagnetic fields on stem cells proliferation and differentiation, FEBS
Journal. Special Issue: FEBS EMBO 2014 Conference, Paris, France, 30 August-4 September 2014. Volume
281, Issue Supplement s1, pages 785–808
3. Anitua E, Tejero R, Zalduendo MM, Orive G, Plasma Rich in Growth Factors Promotes Bone Tissue
Regeneration by Stimulating Proliferation, Migration, and Autocrine Secretion in Primary Human
Osteoblasts, J Periodontol, August 2013, Volume 84, Number 8, 1180-1190
4. Bechir A, Bechir ES, Biomateriale dentare utilizate în cabinetul stomatologic:, Ed. Printech 2012
5. Bechir ES, Ion BC, Bechir A, Buruian MM, The possibilities of use the hyperbaric oxygen therapy in
dentistry, Österreichische Nationalbibliothek Wienm The International Conference Education and Creativity
for a Knowledge – based Society – MEDICINE, DENTAL MEDICINE AND PHARMACY, Vienna,
Osterreichish Rumanischer Akademischer Verein, 2014 ISBN 978-3-9503145-7-1
6. Bowler P.G., Duerden B.I., Armstrong D.G.: Wound Microbiology and Associated Approaches to Wound
Management, Clin. Microbiol. Rev. April 2001 vol. 14 no. 2 244-269
7. Çimşit M., Uzun G., Yıldız Ş.: Hyperbaric oxygen therapy as an anti-infective agent, Expert Review of Anti-
Infective Therapy, October 2009, vol. 7, no. 8, pp. 1015-1026(12)
8. Dohan Ehrenfest DM, Bielecki T, Mishra A, Borzini P, Inchingolo F, Sammartino G, Rasmusson L, Evert PA.
In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich
plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes. Curr Pharm Biotechnol.
2012; 13(7): 1131–1137
9. Duan W, Liu C, Zhang L, He M, Xu S, Chen C, Pi H, Gao P, Zhang Y, Zhong M, Yu Z, Zhou Z. Comparison
of the genotoxic effects induced by 50 Hz extremely low-frequency electromagnetic fields and 1800 MHz
radiofrequency electromagnetic fields in GC-2 cells.Radiat Res. 2015 Mar;183(3):305-14
10. Hartshorne J, Gluckman H, A comprehensive clinical review of Platelet Rich Fibrin (PRF) and its role in
promoting tissue healing and regeneration in dentistry. Part 1: Definition, development, biological
characteristics and function, International Dentistry – African Edition, 2015, 6, 5: 14-24
11. Jenne CN, Urrutia R, Kubes P, Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab
Hematol. 2013; 35: 254– 261
12. Kawase T. Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative
medicine: basic principles and concepts underlying recent advances. Odontology 2015; 103: 126-135
13. Kohara H, Tabata Y, Review: Tissue Engineering Technology to Enhance Cell Recruitment for Regeneration
Therapy, Journal of Medical and Biological Engineering, 30(5): 267-276
14. Pavlíková G, Foltán R, Horká M, Hanzelka T, Borunská H, Sedý J, Piezosurgery in oral and maxillofacial
surgery, Int J Oral Maxillofac Surg. 2011 May; 40(5):451-7
15. Pereira CC, Gealh WC, Meorin-Nogueira L, Garcia-Júnior IR, Okamoto, Piezosurgery applied to implant
dentistry: clinical and biological aspects, R. J Oral Implantol. 2014 Jul; 40 Spec No:401-8
16. Sampogna G, Guraya SY, Forgion A, Regenerative medicine: Historical roots and potential strategies in
modern medicine, Journal of Microscopy and Ultrastructure, Volume 3, Issue 3, September 2015, Pages
101–107
17. Vlădilă B, Bechir ES, Use of thermoforming ethylene acetate for an innovative device, Rev Mat Plastice, Vol.
52, No. 1, 2015, pp 87-89
18. Vlădilă B, Răescu M, Savuica V, Manu R, „Electronic Doctor”- Apical granuloma treatment Clinical case,
Österreichische Nationalbibliothek Wienm The International Conference Education and Creativity for a
Knowledge – based Society – MEDICINE, DENTAL MEDICINE AND PHARMACY, Vienna, Osterreichish
Rumanischer Akademischer Verein, 2015 ISBN 978-3-9503145-7-1.

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 PROPOLIS-ACTIVE SUBSTANCE IN PHYTHOAPITHERPY RAISING SOME
TYPES OF DISEASES

Daniel CORD1; Mariana POPESCU1 Anca Daniela RAICIU1

¹Facultuy of Pharmacy "Titu Maiorescu", Gh. Şincai Street, no.16, district 4, cod. 040 313,
Bucharest
Pharmacognosy, phythochimie, phythotherapy discipline
*Correspondent author: daniela_raiciu@yahoo.com

INTRODUCTION
From ancient times, many quacks used honey, pollen, propolis and royal jelly,beeswax and
venom to treat some disease.
In the modern epoch, and now, studies on natural resources capable of ensuring human body
nutritional balance and normal operation, have highlighted nutritional and therapeutic value of these
products of the beehive.
Propolis is as old as honey, and it has been used by man for ages. There are records
suggesting the use of it by ancient Egyptians, Persians, and Romans. [1].The fact that propolis was
known by the ancient Greeks is called "propolis" derived from two Greek words "pro" (meaning
"forward" or "front") and "polis" (meaning "fortress" or "community"), the Greek philosopher
Aristotle considered it as a product engaged in the defense of "community or hive. Ancient Greeks
used propolis as the main ingredient in "„polzanthus”" perfume with propolis and various herbs. There
are some data about propolis being rediscovered much later in the works by Claudius Galen of
Pergamum (physician of antiquity) and his Varrone (Marcus Terentius Varro). At the same time in his
"Canon of medical science" paper well known Abu Ali Ibn Sina's (Avicenna) - a scientist of the
Muslim world, speaks of two types of wax: pure wax and black wax.
Knowledge and use propolis, according to popular medicine, has been enriched gradually
replaced by scientific studies depth confirming the complexity of its chemical composition and special
effects offered by this natural product in the prevention and treatment of some degenerative diseases,
infectious diseases, viral diseases.

MATERIALS AND METHODS

Propolis is constituted by a variety of chemical compounds, including the derivatives of
cinnamic acid, such as p-coumaric acid and Artepillin C, substituted benzoic acids, phenolic acids,
flavonoids and aminoacids. Different studies have already proved that the chemical composition of the
propolis, and consequently its biological effects, depends on various factors such as the geographic
origin, types of vegetable sources, time of collection and season of the year [1]. Among the types of
chemical substances found in propolis are waxes, resins,balsams, aromatic and ethereal oils, pollen
and other organic matter, the proportion of these types of substances varies and depends on the place
and time of collection.The smell, color, constitution, and composition of propolis greatly vary as a
function of the different botanical sources available around the hive and the geographical and climatic
conditions but also depend on the method of harvest [9].
Flavonoids and phenolic acids or their esters often form up to 50% of all propolis
constituents [9]. Several biological activities, such as antibacterial, antiviral, antioxidant, anti-
inflammatory anticancer, and antifungal properties, have been reported for propolis and as a result this
resin is a highly valued bee product. In propolis has demonstrated a large number of chemical
compounds active and in terms of quantity, it presents different concentrations of the major groups of
substances identified through laboratory test: - 55% resins and balsams (softeners being defined as
natural substances, liquid or semi-liquid generally obtained by special methods in the bark of trees [9];
7,5 to 35% waxes of plant origin with different solubilities and beeswax (always present in the
composition of propolis), 10% volatile oil (essential) compounds characterized by the presence of
flavors; 5% pollen; 5% of fatty acids; 4,40 to 19% impurities; terpenes, vitamins A, B, E, PP;
oligoelements: aluminum, silver, chromium, cobalt, iron, magnesium, amino acids: proline and
arginine; tannin substances, which results salivary gland secretions from bees; accidentally in propolis
are different components such as woodchips bee body fragments. [6].

226
 For separating and analysis of this complex mixture of propolis conditioner are need
performance methods. For this purpose, using gas chromatography coupled with mass spectrometry
(GC-MS) in order to highlight the presence of flavonoids in the chemical composition.The chemical
composition of propolis is variable (depending on the geographical location, the variety of trees and
other plant species used by bees to collect), yet there is a certain group of substances (flavonoids,
phenols and terpenes), permanently present in its structure, substance its physico-chemical conditions
and particularly pharmacodynamics. Among these chrizina, vanillin, isovanillin, caffeic acid,
quercetin, rutin, pinocembrina, galangin, ferulic acid, 5-oxy-dimetoxiflavone etc. (Also known as
having antibacterial and antiviral activity), together with resins and oils, oligoelements such as Fe, Zn,
Cu, Co, Mo, Mn, Li, Mg, and other substances such as flavonoids gives propolis complexes biological
properties : anti-bacterial antiviral ,antioxidant,anti-inflammatory and immunomodulatory.
Tabel no.1-Important flavonoids from propolis
Flavonoids Important flavonoids from propolis
Flavones chrisine, tectochirosine, luteoline, apigenine, acacetine, pectolinarigenine
Flavonols galangin-3-metyl eter, quercetine, quercetin-3,3-dimetyleter, rutine, kaempferol,
isalpinine, kaempferid, rhamnetine, isorhamnetine
Flavanones pinocembine, pinostrobine, naringenine, herpesitine,
Flavononols pinobanksine
Flavonoids are the most important pharmacologically active constituents from propolis can
be found in different fractions soluble in organic solvents, such as ethyl alcohol is the main solvent
used to obtain the pharmaceutical extract and water-soluble fractions. Flavonoids from propolis are
well represented quantitatively (in proportions of 15-20%), therefore, can be considered major
components with outstanding pharmacodynamic properties.
The interest of researchers in connection with the biological properties of flavonoids, the
active compounds present in the chemical composition of plants is motivated by the fact that many
products of natural extracted from plants or bee products that are already in the therapeutic arsenal,
containing the bioactive complex mixtures of polyphenols such as flavonoids.
Table no. 2 Anti-microbial activities of Flavonoids [2].
No Properties Microrganism Flavonoid
1 Anti-fungal property Candida albicans Chrysoerol, Quercetin
Candida tropicalis Chlroflavonin, Epicatechin
Fusarium solani Echinacin, Rutin, Apigenin,
Botrytis cinerea Phaseolinisoflavan
2 Anti-bacterial activity Staphylococcus aureus Quercetin,Fisetin, Baicalin,
Staphylococcus albus Hesperitin,Apigenin, Rutin,
Escherichia coli Chrysin,Datisetin, Naringin
Bacillus subtilis
Proteus vulgaris
Bacillus anthracis
3 Antiviral property Candida albicans Quercetin, Rutin, morin, naringin
Candida tropicalis
Fusarium solani
Botrytis cinerea
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 Experimental tests in vitro and in vivo studies have revealed antiviral, antibacterial,
fungicidal, anesthetic, mitogenic, trophic, anti-inflammatory, anticarcinogenic and immunoregulatory
activities of propolis extracts or components thereof.
The main properties of biologically active propolis based preparations are mainly attributed
to flavonoids, natural compounds widely in the plant kingdom and complex biological effects exerted
by interacting with a broad spectrum of cellular enzymes and metabolic chains [8].
Table no. 3- Summary of the effect of flavonoids on various diseases [2].
No. Type of disease Flavonoids Action mechanism
1. Thrombosis Quercetin, rutin, sinesetin, Erythrocyte aggregation, vascular
catechol, hesperidin. permeability.

2. Atherosclerosis Quercetin Decrease in LDL oxidation,

inhibition of leucocyte adhesion
3. Rheumatoid arithritis Rutin, apigenin Inflammation decreased by acting on
COX
4. Hepatoprotective Luteolin, quercetin, hirustrin Binds to RNA polymerse I in the
liver
From the graphs shown below HPLC Components may be identified the type of flavonoid
although propolis comes from different areas Geography; bioactive substances contained in propolis,
regardless of origin, are found in various concentrations, forming a complex mixture of flavonoids.

Figure no. 2- Chromatogram type of flavonoids components

Figure no.3- Chromatogram type of flavonoids components

228
 Figure no.4- Chromatogram type of flavonoids components

A specific mechanism of pharmacodynamic activity can not be attributed entirely to only one
of these components of propolis, but only together with other compounds with similar bioactivity and
intermediaries metabolic results.

RESULTS AND DISCUSSIONS

Flavonoids are complex chemical molecules once they are in the body-releasing a number of
active compounds with therapeutic effects important for maintaining health. Regarding their
pharmacological activity was found, firstly, absence of toxicity for humans and animals, which is
consistent with the distribution of these substances in food of plant origin or feed [5].
-Antiviral activity:
Natural compounds are considered an important source for new antiviral drugs because their
bioavailability and reduced side effects. Were tested in cell culture (in vitro) specific antiviral effects
of five flavonoid present in propolis: chrisine, kaempferol, acacetine, galangine and quercetin. They
determined the antiviral activity of flavonoids - chrisine and kaempferol, following replication of
strains of herpes virus, adenovirus, coronavirus and rotavirus. The results showed that the flavonoids
both show a dose-dependent inhibitory activity on the replication of the viral used intracellular viral
strains tested, but without affecting their infectivity.Also, these flavonoids have been shown to be
highly active to inhibit the replication of the two types of herpes (HSV type-1 and type-2) and
particular HSV-1 (0.5 mg / ml and 2 mg / ml ) and HSV-2 (0.2 mg / ml and 0.1 mg / ml). Thus, at a
concentration of 10 mg / ml of a mixture of chrisine and kaempferol was shown to reduce the
replication of viruses in 45%.
-Antitumour activity:
Highlighted the presence in propolis three compounds with antitumor activity, including:
quercetin, phenethyl ester caffeic acid (CAPE) and a new compound - clerodan-diterpenoidului taken
into consideration, as demonstrated arresting the development of tumor cells in the S phase and It
showed a massive degradation of the tumor cells (HuH13) in the culture media less than 3 days. On
the other hand, it has been observed that it produces a weak cytotoxic effect on rabbit kidney cells are
in early stage, as well as the absence of changes on human diploid cells. It showed that the new
compound shows antibacterial activity liver and can kill tumor cells without being harmed normal
cells [7]. From Brasilian propolis was able to identify and isolate, Artepillin C, a compound with a
compound with a strong antitumor activity in concentrations of approx. 5%. Many researchers have
concluded that some antitumor properties of propolis is due primarily to the presence of the chemical
structure of phenolic esters of caffeic acid.

Figure no. 5. The chemical structure of caffeic acid phenethyl ester (CAPE) [39]

Caffeic acid and its phenolic acid CAPE (relevant concentrations in propolis) imprints
anticarcinogenic properties of this natural product, antimitogenice and immunomodulators, but also
play an important role in antibacterial and antiviral activity. European propolis contains bioactive
component CAPE has the following properties: anti-inflammatory, antioxidant, inducing apoptotic
process. It has been found that propolis effectively exhibit anti-inflammatory properties similar to the
synthetic anti-inflammatory drugs, used as controls, positive controls. In addition, flavonoids

229
(hesperidin) of European propolis have shown similar effects in indomethacin- in a case of induced
edema in mice with carrageenin [3]
Studies on prevention and strategy for HIV infection, have highlighted that caffeic acid
phenethyl ester can inhibit the integrase enzyme activity - specific HIV-1, with an important role in the
proliferation of transformed unit cell. As a result, the CAPE can induce apoptosis in transformed
fibroblasts and interfere with intracellular signal transduction in the cell lines and EGF affect enzyme
protein kinase C activity and ornithine decarboxylase, necessary for replication of the virus. [4].

CONCLUSIONS
The main bioactive properties of propolis-based products are mainly attributed to the
polyphenolic compounds such as flavonoids (natural compounds widespread in the plant kingdom)
whose effects exerted at the cellular level through interaction with a broad spectrum of cellular
enzymes and metabolic chains.
Propolis has immunomodulatory action to stimulate and strengthen immunity.
Caffeic acid, phenolic acid and its the CAPE (in significant concentrations in propolis)
anticarcinogenic properties of propolis imprints, antimitogenice and immunomodulators, plays an
important role in antibacterial and antiviral activity.

References
1.Alves de Castro P. Savoldi,M. Bonatto D., Barros M. H., Goldman M. H. S., Berretta A.,
Goldman G. H; Molecular Characterization of Propolis Induced Cell Death in Saccharomyces
cerevisiae;2010
2.Durga M., Nathiya S., Devasena T.; Multivarious actions of dietary flavonoids –
implications in cancer and cataract; Int. J. Pharm. Bio. Sci.; 5(2): pp.404-416;2014
3.Emim J.A., Oliveira A.B., Lapa A.J.; Pharmacological evaluation of the anti-inflammatory
activity of a citrus bioflavonoid, hesperidin and the isoflavonoids, duartin and claussequinone, in rats
and mice.; J. Pharm. Pharmacol., 46:118-122;1994
4.Fesen M.R., Pommier Y., Leteurtre F., Hiroguchi S., Yung J., Kohn K.W.; Inhibition of
HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds; Biochem.
Pharmacol., 48, pp.595-608;1994
5.Kumar S., Pandey A.K.; Chemistry and biological activities of flavonoids: an overview;
The Scientific World Journal, Hindawi Publishing Corporation;2013
6.Mateescu C., Dumitru I.F.; Propolis and Propolis Extracts in: News in Biotechnology, Ilex
publishing house, Bucharest, Romania, 64-117;2001
7. Matsuno T.; Anti-tumoral effect of 3 substances isolated from propolis (quercetin, caffeic
acid phenetylester and a diterpenoid of clerodane; The 50-th annual Reunion of the Cancer Japanese
Society;1991
8.Olinescu R., Gîdoiu T., Safta T., Popescu E.; Biochemical mechanism involved in the
pharmacodynamic effect of propolis; Stud. Cercet. Biochem., 25, pp.258-264;1982
9.Papotti G, Bertelli D, Bortolotti L, Plessi M.J.;Chemical and functional characterization of
Italian propolis obtained by different harvesting methods;Agric Food Chem.; 60(11):2852-62; Mar
21;2012.

230
 STUDY OF GENETIC AND VIRAL MARKERS ASSOCIATED WITH NON-
RESPONSE TO TRIPLE THERAPY FOR PATIENTS WITH GENOTYPE 1
CHRONIC HEPATITIS C

Gabriela Oprisan, Associate Professor, Faculty of Pharmacy, Titu Maiorescu University, Bucharest
and Scientific researcher I, Cantacuzino National Institute of Research, Bucharest
Sorin Dinu, PhD, Scientific researcher, Cantacuzino National Institute of Research, Bucharest,
Romania
Laurentiu Micu, Doctor at Fundeni Clinical Institute
Georgiana Micu, Doctor at Fundeni Clinical Institute
Monica Ecobici, Doctor at Fundeni Clinical Institute
Sonia Spandole, PhD Scientific researcher, Personal Genetics SRL
Georgeta Cardos, Scientific Manager at Personal Genetics SRL
Mihai Voiculescu, Professor at Fundeni Clinical Institute

ABSTRACT
Background
In 2011, the Food and Drug Administration (USA) approved the use of two new "direct acting
antivirals' (DAAs). The two compounds, telaprevir and boceprevir, act directly on viral protease NS3-NS4A
complex binding to the active catalytic center. The compounds may be used alone or in combination with
interferon alpha and ribavirin. This is justified by the rapid emergence of new chemotherapeutic resistance
mutations. Using triple therapy with interferon, ribavirin and telaprevir or boceprevir, the response rate of
genotype 1b could be increased from 50% to approximately 70%. Unfortunately, telaprevir and boceprevir
induce selection and rapid expansion of minor viral populations showing resistance to these antivirals. There
have been described a number of mutations to protease inhibitors, located in the coding region of NS3 which
gives different degrees of resistance, both in vivo and in vitro: V36, T54, T55, R155, A156, V170. Amino acid
substitutions at positions 70 and 91 of the HCV core region have been reported to be associated with response to
Pegylated interferon /Ribavirin therapy. Among the host markers, the IL28B gene region has been reported as a
major predictor of HCV treatment response and of viral kinetics during HCV therapy.
Objective
Therapy with first generation of protease inhibitors has been introduced in Romania only in some
clinical trials. There is no information about the pattern of resistance to these protease inhibitors in HCV strains
circulating in Romanian patients. The aim of this study was to investigate whether amino acid substitutions in
the core and NS3 regions among patients with HCV genotype 1b and the IL28B gene polymorphism could be
correlated with the treatment response.
Methods
Sequence analysis of the HCV core and NS3 regions as well as the IL28B genotyping were conducted in
non-responders to Boceprevir or Telaprevir-based triple therapy combined with pegylated interferon and
ribavirin compared with patients treated with the interferon/ribavirin only.
Results
The less favorable IL28B CT is the predominant genotype in the population analyzed. The core R70Q mutation
is present in more than half of the treated patients while the core L91M was present in almost all the patients.
Both boceprevir resistance mutations: 54S, 156S and telaprevir resistance mutations: 54S, 132V, 156S were
found in 4 relapse cases treated with boceprevir-based tri-therapy. Telaprevir 132V mutation was detected in
relapse or non-responders to the boceprevir or telaprevir therapy. Only one patient was found to have no
resistance mutations in the NS3 viral protease. Ten out of 14 naïve patients for protease inhibitors treated with
pegylated interferon and ribavirin presented the telaprevir 132V mutation with low fold change (1.8).
Conclusion
The treatment failure to the boceprevir or telaprevir-based tritherapy seems to be correlated to the
patient interferon-sensitivity and the preexisting resistant variants.

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INTRODUCTION
The HCV prevalence in Romanian population is estimated to be around 3.5%, higher than in other
European countries [1]. The hepatitis C virus is a major cause of chronic liver disease
Worldwide with risk to be associated with liver cirrhosis and hepatocellular carcinoma (HCC) in more than 20%
of patients [2]. Hepatitis C virus is prone to develop resistance to antiviral drugs due to a high mutagenic
capacity [3]. Triple therapy with Interferon (IF) with or without Ribavirin (Rv) and first generation protease
inhibitors, Boceprevir and Telaprevir have been raised the sustained viral response (SVR) to 70-80% [4].
However, a high relapse rate has been noticed for both regimens (dual therapy and triple therapy with first
generation protease inhibitors), due to the development of clones resistant to Boceprevir and Telaprevir.
Boceprevir and Telaprevir are peptidomimetic compounds which inhibit NS3-NS4A serine protease complex.
The problem of development of resistance to direct-acting antivirals (DAAs) with first generation protease
inhibitors is extremely important, taking into account the fact that the risk of developing resistance also exists for
new DAA molecules, even if the 5A/5B polymerase seems to be more stable and less vulnerable than the 3/4
protease [5]. Amino-acid substitution at positions 70 and 91 of the hepatitis C virus 1b core region were
described as predictors for IF/Rv treatment response and HCC evolution [6; 7]. On the other side, a human
genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 is associated with response to
standard therapy with IF and Rv [8].

OBJECTIVE
The objective of this study was to investigate whether amino acid substitutions in the core and NS3 regions
among patients with HCV genotype 1b and the IL28B gene polymorphism could be correlated with the treatment
response.

MATERIALS AND METHODS

Two categories of patients were studied:
- patients with previous therapeutic failure to dual therapy (Interferon and Ribavirin), represented by relapsers
and non-responders
- patients with previous therapeutic failure to dual therapy (Interferon and Ribavirin) and subsequent therapeutic
failure to triple therapy (Interferon, Ribavirin and Boceprevir or Telaprevir) (breakthrough, relapsers, non-
responders).
To achieve the aims of this study, we tested the frequency of viral mutations in the two cohorts. The
viral RNA was extracted from sera using QIAamp Viral RNA Minikit (Qiagen, Hilden Germany) according to
the instructions provided by the manufacturer. The core and NS3 viral genes were analysed by PCR and
sequencing as previously described [9;10]. Resistance mutations in NS3 were identified with the Geno2Pheno
program [11]. We have also analyzed clinical, biological and imagistic parameters, in order to establish variable
correlations. Statistical analysis was performed using SPSS, with the calculation of mean frequencies and
correlation indexes.

RESULTS AND DISCUSSION

The control group of patients treated with only Interferon and Ribavirin, included 15 patients (8 men
and 7 women), with a mean age of 54.9 years. Ten out of 15 patients were non-responders and 5 patients were
relapsers. The study group included 14 patients with therapeutic failure to bi-therapy and to the subsequent triple
therapy, 8 men and 6 women, with a mean age of 51.6 years. Eleven patients were treated with Boceprevir, while
3 received Telaprevir. Concerning the response to triple therapy, 6 patients presented breakthrough, 3 were
relapsers and 5 were nonresponders. There were no significant differences between the two groups in terms of
clinical, biological or imagistic parameters.
Resistance mutations to both boceprevir (54S, 156S) and telaprevir (54S, 132V, 156S) were found in 4
patients with relapse, treated with triple therapy (boceprevir/IF/Rv). Two mutations are being common to both
protease inhibitors: 54S and 156S.
In 4 relapsers of the triple therapy group, treated with boceprevir, we identified resistace mutations to
both boceprevir: 54S, 156S and telaprevir. With the exception of two patients, mutation 132V to telaprevir was
detected in all cases of nonresponders and relapsers to boceprevir or telaprevir. This mutation was also present in
10 out of 14 protease inhibitor-naïve patients. The pre-existence of mutations to protease inhibitors were already
observed in Romanian patients unexposed to the triple therapy [11] but the clinical relevance is not yet well
understood. Only one patient did not present any resistance mutations in the NS3 viral protease.
The IL28B CT genotype, which is also the less favorable genotype, prevails in the analyzed population.
The core R70Q mutation is present in over half of the treated patients, while the core L91M mutation was
present in almost all patients from the study group..

232
 Therapeutic failure in patients treated with boceprevir or telaprevir from the study group seems to
correlate with sensitivity to interferon (predominance of the unfavorable genotype TT or CT and the prezence of
HCV core mutations) and with the pre-existing protease inhibitor resistant variants. Both mutations to boceprevir
and telaprevir appeared in patients who received triple therapy, regardless of the protease inhibitor which was
used. Resistance mutations pre-exist in the NS3 gene of the virus in the group of patients naive to triple therapy
(I132V mutation in 71.4% of cases). As reported in literature, preexistence of resistance mutations and interferon
sensitivity might affect clinical outcome in patients treated with telaprevir and boceprevir [12]. Moreover, the
two mutations of the viral gene core, R70Q and L91M, are present in a higher percentage to patients who
experienced treatment failure with IF/Rv and were retreated with triple therapy than to the control group. The
core genomic mutations and the presence of TT or CT IL28B genotypes as negative predictors for evolution of
hepatitis C in Caucasian patients treated with Interferon and Ribavirin were confirmed in our previous studies
[9].

CONCLUSION
In conclusion, the resistance to direct-acting antivirals (DAAs) with the first generation protease
inhibitors seems to be correlated to patient interferon-sensitivity and to viral mutations in core and NS3 genes.
Viral and host markers should be taken into account when analyzing the treatment failure to the first generation
and the new DAA molecules.

BIBLIOGRAPHY
1. Gheorghe L, Iacob S, Csiki IE. Prevalence of hepatitis C in Romania: different from European rates?
Replay. J Hepatol. 2008 Oct; 49(4):661-2.
2. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and
hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006. 45: 529-
38.
3. Bukh J, Miller RH, Purcell RH. Genetic heterogeneity of Hepatitis C Virus: quasispecies and
genotypes. Semin Liver Dis 1995, 15:41–63
4. Esteban R, Buti M. Triple therapy with boceprevir or telaprevir for treatment naïve HCV patients. Best
Pract Res Clin Gastroenterol. 2012 Aug;26(4):445-53.
5. Carter W, Connelly S, Struble K. Reinventing HCV treatment: Past and Future Perspectives. J Clin
Pharmacol. 2016 Sep 22
6. Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, SuzukiY, Hosaka T, Kobayashi M, Kobayashi M,
Arase Y, Ikeda K, Kumada H. Predictive factors of early and sustained responses to peginterferon plus
ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino
acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol 2007; 46:
403-410
7. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi
M, Saitoh S, Arase Y, Ikeda K, Kumada H. Amino acid substitutions in hepatitis C virus core region
predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. J Med Virol.
2011 Jun;83(6):1016-22.
8. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH,
Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C
treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401
9. Sultana C, Oprişan G, Teleman MD, Dinu S, HepGen 88/2012 Project Team, Oprea C, Voiculescu M,
Ruta S. Impact of hepatitis C virus core mutations on the response to interferon-based treatment in
chronic hepatitis C. World J Gastroenterol. 2016 Oct 7;22(37):8406-8413
10. Dinu S, Calistru PI, Ceauşu E, Ţârdei G, Oprişan G. Screening of protease inhibitors resistance
mutations in hepatitis C virus isolates infecting Romanian patients unexposed to triple therapy. Roum
Arch Microbiol Immunol. 2015 74(1-2): 18-25.
11. Kalaghatgi P, Sikorski AM, Knops E, Rupp D, Sierra S, Heger E, Neumann-Fraune M, Beggel B,
Walker A, Timm J, Walter H, Obermeier M, Kaiser R, Bartenschlager R, Lengauer T.
Geno2pheno[HCV] - A Web-based Interpretation System to Support Hepatitis C Treatment Decisions
in the Era of Direct-Acting Antiviral Agents. PLoS One. 2016 May 19;11(5):e0155869. doi:
10.1371/journal.pone.0155869. eCollection 2016
12. Wyles DL. Beyond telaprevir and boceprevir: resistance and new agents for hepatitis C virus infection.
Top Antivir Med. 2012 Oct-Nov;20(4):139-45.

233
 PERSONALISED ANTI-INFECTIVE PHARMACOGENOMICS AND THERAPY

Prof. PhD.Viorel Ordeanu1, Stud. Mirela Claudia Rimbu2, Lector PhD. Roxana Colette Sandulovici1

(1University “Titu Maiorescu” , Faculty of Pharmachy, Bucharest,2Faculty of Medicine, UMF

Carol Davila, Bucharest)

Abstract:
The pathogenic mechanisms of microorganisms are coded in the genome, formed by the DNA or RNA
macromolecule in viruses, the sole chromosome in the nucleoid and the plasmids in bacteria, or the pairs of
chromosomes found in the nucleus of more evolved microorganisms: protists, fungi, plants, animals. The
bacterial resistance to antibodies is also coded in their genome (because of a better research on them we shall
use them as an example).
The spectrum of microbial sensitivity (the resistance pattern) and the dynamic evolution in time of the
resistance to antimicrobial chemotherapy have been studied and we reached the now usual testings based on
antibiotic diffusion, antifungal testing etc. to orientate the anti-infective therapy. These tests have entered in the
current medical practice.
In the last two years genotyping of bacteria has also become possible, both for species diagnosis and
pathogenicity characters, and for antibiotic resistance: PCR Techniques (Polymerase Chain Reaction), RT PCR,
Real-Time PCR, Multiplex PCR, Nested PCR, Quantitative PCR, Nucleic Acid Sequencing etc. The bacterial
genome is rather simple, containing only 4-5 million base pairs, from which some distinctive genes have been
identified, either of pathogenicity or resistance.
The pharmacogenomic particularity of infectious diseases lies in the necessity to decipher: both the
genome of the pathogenic microorganism involved (for its resistance pattern), nowadays obtainable, and the
genome of the patient (to avoid any unwanted side effects of the antibiogram), that will be obtainable in the
future.
The recent progresses in pharmacogenomics make us optimistic about individualized therapy, including
anti-infective therapy by genotyping in the near / distant future.

Key words: pharmacogenomics, anti-infective therapy, infectious diseases, genetics, personalized therapy

Introduction:

Genomics, the study that uses methods and techniques of molecular biology on the genome, including
the human one, has enabled the knowledge of genetic traits in species as well as the particularities of each
individual. The individual, familial, racial etc. genetic particularities explain many different behaviors regarding
the illness and the treatment. Hippocrates, the father of medicine, said that “There are no illnesses, just ills”.
And here it is, after 25 centuries, we have scientific proof of this truth that guided over a thousand generations of
doctors. Now we can explain why some patients react well and some don’t to the same medication, we can find
the responsible gene and individualize the treatment, not just by age, sex, weight, history or preferences, but also
according to the genetic “heritage” of that particular patient.
Scientific research in pharmacogenomics have made specific methods and techniques available to
medical laboratories, that allows us, with the proper equipment, to personalize therapy and practice a medicine
based on proofs.

Pharmacogenomics

Therapy: a way to treat an illness through drugs, physical agents etc,; it includes both treatment and prophylaxis
Infection: pathologic process caused by a pathogenic agent that entered the body (not contamination!)
Genotype: the entirety of hereditary features of an organism
Genome: the entirety of hereditary information present in the cell, as DNA /RNA molecules (“the helix of life”
Watson and Crick)
Until the near end of the 20th century, contagious-infectious diseases were the main cause of mortality
for the human race. As a result, they also represent the first group in the International Classification of Diseases
(WHO). Medical tradition also suggests that there are no illnesses but ills, and anecdotic history also tries to
raise awareness in this direction.

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 Pharmacogenomics is so new that it lacks an actual history, but surely has a future, with practicability in
different medical specialties, especially antimicrobial treatment: antibacterial, antiviral, antifungal and
antiparasitic.
To complicate furthermore the anti-infective therapy, in the second half of the 20 th century it was
discovered that some bacteria develop resistance to antibiotics, widely known afterwards as “microbial
resistance to anti-microbial substances” that we also encounter at other beings in regard to xenobiotics: viruses,
fungi, parasites, insects, rodents etc. Of course, the therapeutic arsenal must be constantly updated.
Moreover, a new entity has appeared and is spreading: Nosocomial Infection (Hospital-Acquired
Infection or HAI) as a complication or superinfection of the treated patients (iatrogenic disease) whose etiology
is related to the hospital’s multidrug-resistant flora, as a result of the selection caused by the anti-microbial
drugs used in the medical practice; the etiology of HAI is very complex.

The Microbial Genome

The pathogenic mechanisms of microorganisms are coded in the genome, formed by the DNA or RNA
macromolecule in viruses, the sole chromosome in the nucleoid and the plasmids in bacteria, or the pairs of
chromosomes found in the nucleus of more evolved microorganisms: protists, fungi, plants, animals. The
resistance of bacteria to antibiotics is also coded in their genome, which is better studied and is presented as a
study example.
Bacteria that have a natural resistance for one or more antibiotics (AB) transmit it conservatively to the
next generations, by direct division of the cell and implicitly the chromosome (species resistance). Bacteria that
have acquired resistance through contact with an AB can conservatively or semi-conservatively transmit the
resistance to the following generations through R plasmids (Resistance factor), but not in a permanent manner
(just as long as it is necessary).
Bacteria, especially GNB ones, can transfer genetic informations through R plasmids to other bacteria
from the same species or related: the cell emits a “sexual bridge” from the membrane that connects to the cell
membrane of the other bacterium (like a small trunk), to whom it injects R plasmids, and so a bacterium that has
“learned” to defend itself from an antibiotic can “teach” others, transmitting any mechanisms of resistance
mentioned previously, via genetic material transfer.
The spectrum of microbial sensitivity (the resistance pattern) and the dynamic evolution in time of the
resistance to antimicrobial chemotherapy have been studied and we reached the now usual testings based on
antibiotic diffusion, antifungal testing etc. to orientate the anti-infective therapy. These tests have entered in the
current medical practice.
In the last two years genotyping of bacteria has also become possible, both for species diagnosis and
pathogenicity characters, and for antibiotic resistance: PCR Techniques (Polymerase Chain Reaction), RT PCR,
Real-Time PCR, Multiplex PCR, Nested PCR, Quantitative PCR, Nucleic Acid Sequencing etc. The bacterial
genome is rather simple, containing only 4-5 million base pairs, from which some distinctive genes have been
identified, either of pathogenicity or resistance.
The bacterial specific chromosomal structure is an DNA formed of 4 amino acids (A, T, C, G) placed in
a double helix, like a spiral staircase that is turned, twisted and overtwisted and the folded, so that it can take up
a volume of 0,1 μmc at a length of over 1 mm ( so it is compacted nearly 10.000 times, like a clew). At the
moment it is possible to do a microbiological diagnosis using genotyping; let’s also not forget that this huge
quantity of genetic information is still the most primitive and simple chromosome. In this immensity of genetic
information we can identify a series of characteristic structures, some of which can be useful for diagnosis and
treatment in the near future. Currently we are genotyping the resistance genes, in order to establish rapidly and
precisely the sensibility of the phyla isolated from the patient, and implement an effective treatment. Studying
the sensibility / resistance of bacteria to antibiotics is also based on these techniques, necessary to predict the
dynamics of the phenomenon. For resistance patterns there are databases, for example The National Database
(INC Cantacuzino / The National Centre of Reference for Nosocomial Infections and Bacterial Resistance) is
affiliated to ECDC and WHO.
The MarMutans identification (multiple chromosomal resistances to antibodies) for clinical bacterial
isolates was first studied at Enterobacteriaceae: for Escherichia coli there have been identified loci for
resistance to tetracycline: marRAB, marO, marC, marR, marA etc.; for Salmonella spp.: acr-AB-TolC, acrF,
acrB, acrD, gyrA etc. for the multidrug efflux pumps (poli xenobiotics); for Klebsiella spp. there are ompF for
permeability, marRAB, soxRS etc. and for Enterobacter spp. there are marA, marB, marA-Ea, marA-Kp,
marRAB etc. And even for Mycobacterium spp. marA and others are still being researched.
Bacterial ecology uses genotyping to establish the filiations of some bacteria of interest: pathogenic for
humans, animals or plants, useful for biotechnology, including pharmaceutical biotechnologies, for the transfer
of some resistance genes either intra or interspecific and others.

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 Genotyping the patient

From the early ages of humankind it has been noticed that some people get sick from an infectious-
contagious disease and some don’t, some have severe forms or mortal ones while others have mild or invisible
ones, so “There are no illnesses, just ills”. For example: the resistance to leprosy in 95% of people, the resistance
to plague in the majority of Europeans, the frequent resistance to specific regional-related diseases and the lack
of resistance to “import diseases” (e.g. the Asian flu), the increased resistance to tuberculosis of townspeople and
Jews ( the oldest urban population) and others.
The human genome is extremely complex, incomparable with the primitive genome of bacteria, being
also the most evolved (but not the biggest). Shortly after decoding the human genome (the Nobel Prize) in 2009
the 3D structure has also been deciphered. For the time being we don’t know with precision every gene’s role,
and from what is known some data are secret for security or competitiveness reasons.
Every human cell has around 3 billion pairs of DNA, that unfolded would be over 2 meters long. This is
contained in structures with a diameter of few μm, thanks to the specific layout. All the billions of cells that
make an individual have identical DNA (with the extremely rare case of mutations) but there are no two
individuals with an identical DNA, just similar.
The human genome is organized in two compartments: the dense storage compartment containing
separate and accessible genes in which the DNA is not used, from which the chromosomes enter and exit to the
second compartment that has DNA that is alternatively active or inactive. So there are structural and functional
reserves, as the case with tissues and organs.
At a smaller scale, the genome adopts an unusual structure, like a mobile kaleidoscope, named by the
mathematicians as “fractal”. Geneticists name this specific architecture “the fractal globe” that explains the
stunning density of information in the nucleus, thousand of billion times greater that a computer chip.
The cell has the capacity to read its own genome, because the DNA can be read and reread extremely
fast during the gene’s activation, repression or cellular replication. Nature has found (in billions of years) an
elegant solution for storing information, with a super-dense structure and no knots (Lauder, 3/2009). This layout
allows reading and/or copying the DNA with an extraordinary speed.
Deciphering the 3D structure of the human genome was made possible by developing the new Hi-C
technology that allows the analysis of the whole genome by fixing with formaldehyde and performant ADN
sequencing.
Unfortunately we are not yet capable of diagnosing the human genes to assess the specific or
unspecific immunity, neither in systemic infections nor in organ or tissue infections, but with the current
immunology techniques we can do phenotypic highlight for some of them.
Already there are some practical results to genomic research: traceable nanotransporters for the
application of gene therapy, protein expression recombination systems, applications for the new generation of
DNA sequencing to accelerate the quantification and for data libraries (banks), drugs to prevent non-sense
mutations in the cell, biofunctional molecular triggers for the protective immune response (molecular recruiting
antibodies) and others.
The latest genomic technology for 3D research of the whole human genome map (Genome Institute of
Singapore, 2009) is ChIA-PET (Chromatin Interaction Analysis using Paired End Tag sequencing) introduces
the results in the Encyclopedia of DNA Elements, USA. To be noted that such advanced techniques of
individualizing the therapy using genotyping could be useful not only in beneficial purposes, but also as biologic
weapons (Japan may already have the 21th century biological weapons).

Genomics and Pharmacology

The genomic analysis system facilitates: the research of new drugs through softs with advanced
methods to access the data, nominalization (standardization), pattern detection, treatment comparison, functional
analysis for the genomic expression etc. In Romania also there are efforts to do pharmacogenomic research
(despite chronic under financing for scientific research) and some projects in this domain are unfolding, with
practicability in infectious, cardio-vascular, neuropsychological diseases etc.
The pharmacogenomic particularity of infectious diseases rests in the necessity to decipher both the
microorganism’s genome involved in the pathogenic process (for its resistance patterns), already realizable, as
well as the patient’s genome (to avoid unwanted side effects of anti-biotherapy), realizable in the future.

Comment
We can anticipate that Genetics and its connected sciences will change the world, including medicine
and pharmacology, in ways we now don’t even fully understand. Probably the humans will “play God” and will
create Heaven and Hell, here, at our reach.

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 Conclusions
The recent progresses in pharmacogenomics make us optimistic about individualized therapy, including
anti-infective therapy by genotyping in the near / distant future, but it is important to have access to equipment
and reagents, but also to the adequate medications for therapy.

Bibliography
1. Ordeanu V. “Farmacogenomica antiinfectioasa” conferinta medicala EMC, Predeal 2013
2. Ordeanu V. “Terapia antiinfectioasa si farmacogenomica” prelegere Cerc de microbiologie
farmaceutica, Universitatea de Medicina si Farmacie, Facxultatea de Farmacie, 2015

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 DUAL BIOTECHNOLOGYS

Prof. PhD.Viorel Ordeanu1, Stud. Mirela Claudia Rimbu2, Lector PhD. Roxana Colette Sandulovici1

(1University “Titu Maiorescu” , Faculty of Pharmachy, Bucharest,2Faculty of Medicine, UMF

Carol Davila, Bucharest)

Abstract:
Security experts are preoccupied and worried especially for the diversity of the arsenal and the
possibility of it being purchased by terrorist groups. The concern becomes dramatic when it comes to CBRN
mass destruction weapons (chemical, biological, radioactive and nuclear), some of them being purchasable on
the black market or handcrafted. Biological agents (microbes) can be illegally acquired from hospitals,
laboratories and biotechnological industry.
The terms of double-usage products (civil and military), and dual technology, or in our case dual
biotechnologies have recently been introduced. This means that a technology or a (pharmaceutical) product
obtained through biotechnology can also be used for military, terrorist or criminal purposes.
In the terrorism context out of all mass destruction weapons, the biological ones are the most
important, being considered “the poor’s atomic bomb”. Pathogenic biological agents (bacteria, viruses, fungi,
parasites and microbial toxins are very dangerous. They are easily obtainable, multipliable and spreadable, can
contaminate the population, animals, plants and environment and create long distance secondary outbreaks.
Locally, nationally or regionally there forms a virtual network of Consequence Management after a
Biological Attack, in which the first step, and also the most important for public health, is that primary care
providers (general practitioners for families, institutes and military units, pharmacists, veterinarians), the first
ones that come in contact with the sick, apply the first medical measures and alert the responsible authorities.

Key words: dual biotechnologies, bioterrorism, medical protection, CBRN attack

Introduction
Everybody speaks about terrorism and terrorists, especially after 9/11, when Western Civilization was
hit by the biggest terrorist attack. Antiterrorist coalitions have been made, population surveillance measures have
been intensified to the limit of ignoring democratic norms, funds, forces and means assigned by the governments
to structures that prevent and combat terrorism have been increased.
Terrorist attacks, especially Al-Qaeda and ISIS, have multiplied and extended through Europe, USA,
Middle East, Russia and mostly in occupied countries (Afghanistan, Iraq, Syria) and have become an
international phenomena. Military analysts from USA, NATO and EU consider that the destructive potential of
international terrorism is immense (see the CIA reports on the internet).
Security experts are especially preoccupied and worried about the arsenal’s diversity and the possibility
of acquirement by the terrorist groups. The concern develops dramatic proportions when CRBN weapons are at
stake, some of them being available on the black market or hand-made. Biologic agents (microbes) can be
illegally acquired from hospitals, laboratories or the biotechnology industry.
Terminology:
 Biological crisis: major epidemiological emergency of infectious etiology, that by the severity or large
number of sickenings to humans / animals / plants leads to the disruption of the social and economical
life of a community.
 Biological weapon: nonconventional weapon system of mass destruction in which the ammunition
transports biological agents and contaminates the enemy with the purpose of sickening him.
 Biological agent: microorganisms and/or microbial, animal or vegetal toxins, used as specific
ammunition for biological weapons, or used by terrorist in bio-chem attacks.

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 DUAL BIOTECHNOLOGYES
The term of double-use products (for civilian and military purposes), as in dual technologies or in our case
dual biotechnologies is quite recent. This means a technology or a (pharmaceutical) product obtained by
biotechnology might also be used by militaries, terrorists or criminals. Recently the United States Air Force
(USAF) has bombed a pharmaceutical factory in Sudan for this reason.
Examples of dual biotechnologies:
 Continuous and submerged culture biotechnology used for obtaining of alive bacteria meds (Bacillus
subtilis, Lactobacili etc.) could be used for obtaining biological agents (Bacillus anthracis, Brucella
etc.) as ammunition for biological weapons;
 Botox contains Botulinum toxin, which is neurotoxin extracted from Clostridium botulinum, and is the
most toxic substance known;
 Castor oil contains Ricin toxin, which has been used in biological attacks;
 Insect growth for biomedical research can be used as microbe vectors etc.

CONSEQUENCES
There has been created an International consortium for the study of possible implications of dual
biotechnologies in bioterrorism RECOPST (coordinated by Dr. Vari Sandor, USA), also attended by the
University of Medicine and Pharmacy “Carol Davila” Bucharest through the Faculty of Pharmacy (official Conf.
Dr. Lacrimioara Popa). In Romania, the Military Medical Scientific Research Center has the objective of main
protection against CBRN.
From a military point of view the sanitary losses are known / estimated in case of a CBRN attack,
militaries are instructed and armed and medical doctors know what to do in this kind of situations. But in case of
attack on civilians the follow-ups can be unpredictable, even catastrophic! Gabriel Liiceanu said: “The hate
bomb, the bomb created from human ardor and equipped with ideology is perhaps the only global weapon, the
only one by which the human race will succeed in destroying itself” (Despre ura, ed. Humanitas 2007).

BIOTERRORISM
Out of all the weapons of mass destruction, in the context of terrorism, biological weapons are the most
important, being considered the “atomic bomb for the poor”; pathogenic biological agents (bacteria, viruses,
fungi, parasites or microbial toxins) are very dangerous, easily acquirable, multipliable and spreadable, they can
contaminate the population, animals, plants and the environment and create secondary distanced outbreaks.
Defining bioterrorism = using alive biological pathogenic agents (bacteria, viruses, fungi, parasites
etc.) or toxins to sicken the people, animals or plants. The definition for bioterrorism cannot be found in
dictionaries, which does not mean it does not exist, but solely reflects the insufficient awareness there is.
Goals: Infliction of lethal or incapacitating diseases, creating panic that leads to social disorders,
forcing huge financial and material costs for public health, creating food crisis etc. to gain in the end politically,
military, religious, economic, pecuniary concessions or just antisocial psychopathy.
The press draws attention over this potential danger, always current – bioterrorism. Specialized press
offers informations on the effective clinical conduct in case of deliberately induced infections (for example the
article “Bioterrorist infections. Diagnostic and management” Medical UPDATE magazine, march 2008, p. 70-
73). Official statements: on 03.28.2016 CSAT has raised the level of terrorist alert for Bucharest from “cautious”
(blue) to “moderate” (yellow) in context with NATO’s Summit etc.

RISKS
Biological weapons can give a large number of illnesses, almost simultaneously (after an incubation
period of several hours, days or weeks, depending of the microbial specie) and the diagnosis, prophylaxis and
treatment are according to the doctors and pharmacists competences. Because of the large number of patients
that will be either ill, suspected, contacted or contaminated, the health care services will be overwhelmed and
will lack workforce and equipment and there is necessary a cooperation of all National Systems: health, defense,
security, public order, NGO’s, local communities etc.

Classification of biological agents according to the Biological and Toxin Weapons Convention
(BTWC 1972):

 living agents capable of self-reproduction: bacteria and fungi

 living agents capable only of in host cell – reproduction: viruses and parasitical intracellular bacteria
 not alive agents incapable of reproduction, obtained through chemical synthesis, but with an identical
or very similar structure to the natural ones
The lists of biologic battle agents are known, but the bioterrorism agents are extremely diverse, practically
any pathogenic agent.
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 A list of illnesses caused by biologic weapons (examples):
 Biologic battle agents* (A/CDC group)
o pulmonary, gastro-intestinally or cutaneous anthrax = Bacillus anthracis
o smallpox = Variola virus (eradicated)
o pulmonary, bubonic plague = Yersinia pestis
o tularemia = Francisella tularensis
o brucellosis = Brucella spp
o botulism = Clostridium botulinum neurotoxin
o viral hemorrhagic fevers (Ebola, Lassa, Marburg, Crimea-Congo, Machupo etc.) = namesake
viruses and others.

BIOCHEMICAL CONTAMINATION
Any pathogenic microbes, obtained from anywhere, conditioned under any form, disseminated in any
way:
 contaminated water (Bucharest 1989)
 contaminated food (EU, China, USA, Romania)
 A/C (USA, EU 2002)
 contaminated mail (USA, EU)
 contaminated drugs (USA)
 live vectors carriers of biologic agents
 any contaminated objects, natural or artificial

PLANNING THE COUNTERMEASURES

Different authors present measures of preplanning and planning to combat bioterrorism, to manage a
biological crisis and for the liquidation of the aftermath of a biologic attack (inclusively on the internet). These
complete the Standard Operating Procedures for predictable situations, but up to date and individualized plans
for sanitary institutes are confidential, for obvious reasons; what must be known are the principles and ways of
specific actions.
Prediagnosis Illnesses caused by biologic agents (biologic weapons or bioterrorism) are diagnosed as a
speculative diagnosis by the general practitioner / family doctor that establishes the first medical measures, sends
the patient to a specialist and alerts competent authorities. They can send teams of epidemiologists and
microbiologists on the field for at-source intervention, preferable with mobile laboratories, with the purpose to
limit the number of cases and coordinate treatment and of-sight prophylaxis.
Non-medical prophylaxis Biologic agents can be detected and identified long time ahead by the secret
services, allowing time for military, police and medical preventive measures; a recent example: the Las Vegas
police arrested a bioterrorist that stocked up on ricin, a toxic dust, in the kitchen of a rented apartment.
Microbiology and biotechnology laboratories are, or should be, supervised by authorities, including the cops, just
like gun stores.

The battle against biologic war

The prevention of biologic war is realized by implementing the BTWC (Geneva, 1972) to which over 150
countries have acceded, including Romania and by international control over biological weapons and agents.
Military use of bioweapons may be considered tactically and operationally inefficient and strategically risky.
Recent events show that the risk of bioterrorist attacks committed by civilians is greater than ever.

The battle against biologic terrorism

 The fight against bioterrorist attacks includes the National Health System, National Defense System,
local communities, Nongovernmental Organizations etc.
 The liquidation following a bioterrorist attack is also controlled by Prefectures (with the subsequent
county authorities: Territorial Civil Protection, Health Departments and Units, laboratories etc.),
Nongovernmental Organizations (for example: The Red Cross) and local communities.
 The prevention of bioterrorist attacks is mainly a political and social problem, realized firstly with the
intervention of secret services, police and justice.

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 MANAGING THE CONSEQUENCES OF A BIOLOGICAL ATACK
The biologic attack with live agents, whatever the magnitude (war act, bioterrorism, criminal or biologic
accident) can spread by auto-multiplication on extensive areas and even at distance, getting out of control and
potentially becoming a global danger, even for the ones that started it: the international sign for biological danger
is suggestive in this matter.
Managing the biological crisis
Locally, nationally or regionally there forms a virtual network of Consequence Management after a
Biological Attack, in which the first step, and also the most important for public health, is that primary care
providers (general practitioners for families, institutes and military units, pharmacists, veterinarians), the first
ones that come in contact with the sick, apply the first medical measures and alert the responsible authorities.
The biologic crisis can have consequences that are so extensive and severe that the health system does
not have the workforce and means for medical countermeasures. CIMIC (Civil-military co-operation) is imposed
in an integrated interdepartmental system. The main institute specialized in elaborating methods and means of
protection against CBRN agents is the Military Medical Scientific Research Center, including against
bioterrorism.

Conclusions
Bioterrorism is a real threat of contemporary society. Dual Biotechnology, with civil and military usage,
can be used by occult forces for the production of weapons / biological agents for bioterrorist attacks. Medical
protection against biological agents can be realized with the cooperation to scientific research projects of
defensive microbiology and anti-infectious pharmacology.

Bibliography
1. Ordeanu V. BIOTEHNOLOGIILE DUALE SI PROTECTIA CONTRA BIOTERORISMULUI
Workshop (3) “Biotehnologii duale” Universitatea de Medicina si Farmacie “Carol Davila” Bucuresti,
Facultatea de Farmacie 2011.

241
 NEW MICROSCOPY TECHNIQUE FOR 3D STRUCTURAL BIOLOGY:
FEI CRYO-TEM WORKFLSOLUTIONSOW

PROF. UNIV. DR. VIOREL ORDEANU, CS I*/**, ASIST.UNIV. DR.FARM. IULIAN

SARBU*/***, ASIST.UNIV. DR.ALICE PIPEREA*
*Universitatea “Titu Maiorescu” Bucuresti, **Centrul de Cercetari Stiintifice Medico-Militare,
***SC Laropharm S.R.L
Abstract
CRYO-TEM: A new area for 3D structural biology. Only 1% of structures in the Protein Data Bank that have
been solved by XRD are complex structures of larger than 4 chains. Most proteins act in complexes (>10
chains), are asymmetric, and are large. NMR - existing methods are generally limited to small protein
complexes. Researchers often cut up proteins to study them with NMR. Scientists want to be able to study larger
complexes in their native states.

Cryo EM fills the gaps generated by the fact that XRD limits what kinds of samples can be studied and the
fact that NMR focuses on protein fragments.Cryo-TEM visualizes biologically important proteins in their larger,
native context.
Complementarity of XRD/NMR and Cryo-TEM: 2 – 20 Angström information required to understand
function of dynamic biological complexes. Hybrid methodology using NMR, XRD and Cryo-TEM are often
required to answer biological questions and for Imaging, characterization, analysis and modification in 3
dimensions, down to the sub-Ångström level.
FEI Life Sciences CRYO-TEM
FEI Life Sciences goal is to be the global leader in providing complete microscopy solutions for life
scientists focused on important nanoscale biological knowledge which fundamentally impacts world health and
well being.
FEI Life Sciences Mission is to provide complete microscopy workflows which include hardware, software
and wetware which are easy to use and to adopt. FEI solutions will enable life scientists to develop critically
important knowledge.

Fig 1. Life Sciences - Segmentation and Expansion From fundamental research to applied medicine. From bio-
imaging to quantitative biology. From bio-imaging to quantitative biology

242
 The ultimate goal is to study single proteins that perform key roles in diseases in their native context in
the cell at (near)-atomic resolution. Understanding their specific function on a molecular level will ultimately
help to uncover critical molecular processes to design “better” drugs and improve the quality of life.
Protein interaction network: Human proteins act in complexes so structural biology is neded.The
important needs and aplications: Increased Need for 3D imaging of Protein complexes. Understanding the
fundamentals of Life in vivo. Unique for cryo-TEM – optimal structural preservation.SPA and Tomography are
leading applications.
Researchers are targeting for: Improved time to quality data, reduced cost per structure, more
publications and increased funding opportunities
Imaging of protein complexes/organelles that play crucial role in main cellular pathways protein
synthesis, enzymatic activities(ribosomes, proteosomes).
Quality control on production of novel medications.Imaging membrane protein complexes their role as
receptor/donor for drugs/drug carriers.
Molecules: Deliver Structure-Functions Relationship.

From Structure To Function - From Basic Research To Applied Science.

There are over 1000 structural biology labs world widew. Cryo-TEM is the next logical step to deliver
THE important yet missing level of information. Today's structural biologists need to get to 3D structural
information of small and large protein complexes in order to link structure to function and to be able to answer
real biological questions.
Scientific: XRD - many macromolecular complexes of biomedical interest cannot be crystallized.
Only 1% of structures in the Protein Data Bank that have been solved by XRD are complex structures
of larger than 4 chains. Most proteins act in complexes (>10 chains), are asymmetric, and are large. NMR -
existing methods are generally limited to small protein complexes. Researchers often cut up proteins to study
them with NMR. Scientists want to be able to study larger complexes in their native states.
Cryo EM fills the gaps generated by the fact that XRD limits what kinds of samples can be studied and
the fact that NMR focuses on protein fragments.Cryo-TEM visualizes biologically important proteins in their
larger, native context.
Complementarity of XRD/NMR and Cryo-TEM: 2 – 20 Angström information required to understand
function of dynamic biological complexes. Hybrid methodology using NMR, XRD and Cryo-TEM are often
required to answer biological questions
Towards an integrative structural biology approach usage of Cryo-TEM Visualizing Pore Formation for
Membrane Insertion of Aerolysin ryo-TEM single particle analysis reveals various conformational states of
areolysin pore formation.

Fig 2 Prepore state. Degiacomi et al. 2013 Nat Chem Biol. 9(1): 623-629. Molecular assembly of the aerolysin
pore reveals a swirling membrane-insertion mechanism

243
Fig.3 Areolysin pore.Degiacomi et al. 2013 Nat Chem Biol. 9(1): 623-629.Molecular assembly of the aerolysin
pore reveals a swirling membrane-insertion mechanism

Increasing binding efficiency of Mab fragments

The binding footprint of Mab is determined through fitting the cryo-TEM reconstruction with a
homology model following sequencing of the variable AAV-2 domains, and provides a structural basis for
integrating epitope mappings. The Cryo-TEM reconstruction showed superior definition of side chains and
flexible loops compared to the x-ray crystal structure of AAV and provided more critical information.{Dustin
M.McCraw, JasonK.O’Donnel, Kenneth A.Taylor, Scott M.Stagg, MichaelS.Chapman, 2012 Virology431(1-2)
40–49.
Seeing more with Cryo-TEMDirect and fast epitope Mapping for Localizing Fab binding sites
Unlike X-ray crystallography , cryo-TEM can visually distinguish viruses and VLP’s with and without
Fab’s bound. Cryo-TEM has a single molecule resolving power.
CryoEM images and 3D reconstruction of HPV VLP without (left) and with (right) Fab binding. 3D
Difference mapping allows localization of the Fab binding sites
Throughput illustration. Conway et al collected >3000 Falcon II images per day, to the point where in 3-4 days.
They have more particle images that tey can gainfully use, i.e., the image count is no longer the resolution
limiting factor.

Fig.4 Associate Professor James Conway, Univ. of Pittsburgh, D3 phage of Pseudomonas aeroginosa (resolution
< 4 Å after analysis of only 1387 images ~ 30k particles).

244
Conclusions:

Structural Biology workflow solutions provide answers to the real biological questions.Workflow
solution is focused on increasing data throughput, data quality and reduced cost per structure.3D images of
protein complex mechanistics (exclusive cryo-TEM domain).Shifting the boundary: Towards smaller proteins
and improved resolutions
Cryo-TEM provides complementary information to NMR and XRD

Acknewledgement for:1. Diane van Rossum, Marc Storms, Jeff Langyel, Thomas Wohlfarth “FEI Cryo-TEM
workflow solutions: A new area for 3D structural biology” Conference UPB 20152. Ordeanu V. et all. “Cercetari
de morfologie comparata intre Stafilococul auriu si MRSA prin tehnica Cryo-TEM” (nepublicat)3. ***
Societatea de Microscopie Electronica din Romania4. *** Laboratorul de polimeri, ICECHIM Bucuresti

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 MINT ESSENTIAL OIL - PHARMACEUTICAL AND USE ISSUES

Monica GAGIU (Student year IV Pharmaceutical University, University „Titu Maiorescu” Bucharest)

Coordinator: ANCA DANIELA RAICIU Conf. Univ. University „Titu Maiorescu”, Pharmaceutical
University, Doctor in Pharmaceutical Science, Vice-President of Romanian Chemists Cosmetology,
Vice-President of OIPMA, Marketing Director of Hofigal S.A.

Abstract

Volatile oils are complex mixtures of aliphatic, aromatic hydro aromatic, aldehydes,
alcohols, and other constituents. The compound class that prevails is the terpenoids. From the physical
point of view, the volatile oils are liquids with characteristic aroma, pleasant, drivable by water vapor.
Romanian Pharmacopoeia edition X explains that volatile oils are mixtures of volatile and lipophilic
substances, with aromatic smell, which belong to different classes of organic compounds, particularly
terpenes and oxygenated derivatives. The principle of use of essential oils is the same as for drugs,
"prima non nocere" - first of all do no harm.

Peppermint (Mentha, from Greek: míntha) is a genus of 25-30 species of plants (aromatic
and medicinal ) of the family Lamiaceae, worldwide seen, seven in Australia, one in North America
and the other in Europe and Asia ; There are hybrids too. It is part of an extended family, along with
other herbs like thyme, marjoram, sage and lavender. Volatile mint oil is obtained by steam coaching
the fresh flowering tops of the leaves or Mentha x piperita L. which contains at least 50% of the total
alcohol expressed as menthol and at least 4%, expressed as acetate esters.

The therapeutic properties of peppermint oil are: weak analgesic (intestinal), anesthetic,
general antiseptic (especially intestinal), anti-inflammatory, antispasmodic, astringent, antilactosis,
carminative, emmenagogue, cephalic, cordial, decongestant, expectorant, febrifuge, hepatic, nervous
system stimulant, stomachic, stimulant, stomach, sudorific, vasoconstrictor, vermifuge.

In conclusion peppermint essential oil can be used both internally and externally. It is used
in asthma, bronchitis, migraine headaches, dental neuralgia, sinusitis, influenza states, emesis and
many other diseases.

Keywords: oil, mint, chemical composition, menthol, uses

1. Peppermint essential oil

The volatile oil of peppermint, known in Romanian Pharmacopeia tenth edition as Menthae
aetheroleum and European Pharmacopoeia sixth edition as Menthae piperitae aetheroleum, is the
volatile oil resulting from steam distillation with water of the upper leaves or flowering tops, freshly
picked of Mentha x piperita L., of the family Lamiaceae. They must contain the following titrimetric
dosage by at least 50% in menthol of the total alcohols and esters expressed at least 4% in ethyl
acetate.

In terms of chemistry, peppermint essential oil is a colorless or slightly colored yellow to

yellow-green liquid, with odor, characteristic, menthol and burning taste in the beginning and then
cooler and then burner. It is miscible with fatty oils and apolar solvents and alcohol 70 °. This helps to
dilute the essential oil. Volatile oils with a high concentration in components are required to be
diluted. Generally dilution is made with sunflower oil or other inert oil. Never apply essential oil
directly on the skin without being diluted before. By cooling to a temperature of -10 ° C the menthol in
the composition is crystallized.

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 2. Chemical Composition

Minth volatile oil is rich in free menthol about rate of 30-50%. This, however, is not alone, but
together with other similar compounds as neomenthol, isomenthol, neoizomenthol and piperitol.
Besides menthol, the oil contains ketones monoterpens represented menthone and piperitone in 65%,
monoterpenes esters as acetate, neomentil and neoizomentil and valerate methyl hydrocarbon
monoterpene and sesquiterpene form of α and β-pinene, limonene, β caryophyllene, coumarin
derivatives, predominantly esculetin and monoterpen oxides as 1-8 cineol, metofuran and
piperitonoxid.

3. Therapeutic action and Indications

The therapeutic action of essential oils is given in general by its components. Peppermint oil
can be used both internally and externally. It has actions such as: tonic, anti-infective, analgesic,
anesthetic, strong local anticataral, antiinflammatory, bactericidal, mucolytic, expectorant,
decongestant, cholagogue, antiparasitic, antifungal, antitumoral healing and more. It is a weak
analgesic and antiseptic, in particular intestinal. It has a good carminative and a good-sickness.
Romanian Pharmacopoeia ninth edition provides water mint use as a stomach anesthetic and for
preventing vomiting.

For internal use, is used in disorders such as flatulence, asthma, chronic bronchitis,
indigestion, bloating, diarrhea, liver disease, the strong dose prevents sleep, parasites, stimulant of the
central nervous system, cholera, gastralgia, poisoning gastrointestinal impotence, palpitations,
dizziness, migraine, menstruation insufficient or painful neuralgia dental, general fatigue, tuberculosis,
sinusitis, gastric spasms and cramps, vomiting nervous asthenia, headache, ENT diseases, viral
diseases, hypotension, congestive respiratory, faintness and more.

For external use is used as a repellent against mosquitoes, in scabies, sinusitis, decongestion
and others.

4. Contraindications

Oral administration or as local applications on the temporal and frontal lobes of the ears
preparations based on peppermint and menthol in children aged 30 months may induce vasospasm
tightness. This risk can occur in children up to 7 years, but much less frequently. Due ketones
contained, apears the abortion risk for pregnant women. Gelatin capsules should not be used in
irritable bowel fermentation colitis, constipation or diarrhea.

5. Interaction

Do not use with antacids gelatin capsules because they increase the pH of the stomach,
which favors the intergastric solubilisation of the capsule.

6. Pharmaceutical preparations containing peppermint oil

The known drugs peppermint essential oil containing as the main component are: Colebil
tablets (SC Biofarm S.A.) containing bovine bile powder, methenamine, sodium salicylate, Oleum
Menthae and excipients; Herbaflu inhalant (SC Biofarm S.A.) containing tree oil: peppermint,
eucalyptus, lavender and alcohol; Administration doze recommended 1-2 drops mixed in a teaspoon of
honey after meals; Carmol Flu (SC Biofarm S.A.) Voseptol V (Plantavorel); Ben gay greaseless
(PFIZER CONSUMER HEALTHCARE); Saliform forte cream (ANTIBIOTICE S.A.).

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 7. Conclusions

Volatile oils are spread everywhere in nature. The volatile oil of peppermint has many uses,
it is used to prevent vomiting. It is a gastric mucosal anesthetic, decongestant, anti-inflammatory and
anti-infective mainly. Bear in mind that essential oils can not be administered directly to the skin
because can cause burns. They should be used diluted because of the high concentrations compounds.
Do not use in children under 7 years because may cause asphyxia. Due the big number of uses, they
can replace many medicines, but not recommended withdrawal of treatment with antineoplasics or
anti-hypertensive medication and replacement with peppermint essential oil in all cases. Always ask
your doctor or pharmacist before using any essential oil in combination with other drugs.

BIBLIOGRAPHY

1. Romanian Pharmacopoeia ninth edition, 1976, and supplements

2. Romanian Pharmacopoeia X edition, Publishing House Medical Bucuresti 1993 and supplements
3. www.wikipedia.ro/uleiuri
4. www.uleiurivolatile.ro/uleimentă
5. Cornelia Bejenaru, Honorius Popescu, Dan George Mogosanu, Pharmacognosy - phytotherapy Vol.
1, Ed sietch 2015
6. Viorica Istudor, Pharmacognosy, Phytochemistry, Phytotherapy, vol 3 Medical Publishing House
2005
7. Gârd C. E., Lecture of Pharmacognosy, Phytochemistry, Phytotherapy, Printech Press, Bucharest,
2013, vol. I, II edition, 431 pages, ISBN 978-606-23-0130-9.

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