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OF THE CANDIDATE AND ADDRESS DR. GAURAV SHIREESH BABAR, P.G IN (M.D) GENERAL MEDICINE, DEPT.OF MEDICINE A.I.M.S., B.G.NAGARA., MANDYA DISTRICT-57 !!" ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G.NAGARA. M.D. IN GENERAL MEDICINE $
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COURSE OF STUDY AND SUBJECT DATE OF ADMISSION TO THE COURSE TITLE OF THE TOPIC BRIEF RESUME OF INTENDED +ORK *. NEED FOR THE STUDY *.# REVIE+ OF LITERATURE *.$ OBJECTIVES OF THE STUDY *.! INCLUSION AND EXCLUSION CRITERIA
MAY #''7
(A STUDY OF C-REACTIVE PROTEIN IN ACUTE ISCHEMIC STROKE) APPENDIXAPPENDIX- A APPENDIX- B APPENDIX- C APPENDIX- D APPENDIX-II APPENDIX-IIA APPENDIX-IIB
MATERIALS AND METHODS 7. SOURCE OF DATA 7.# METHOD OF COLLECTION OF DATA (INCLUDING SAMPLING PROCEDURES ANY)
7.$ DOES STUDY RE,UIRED ANY INVESTIGATIONS OR INVESTIGATIONS TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY 7.! HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.$ " PROFORMA AND LIST OF REFERENCES SIGNATURE OF THE CANDIDATE ' REMARKS OF THE GUIDE
THIS STUDY IS TO KNO+ THE ASSOCIATION BET+EEN CRP LEVEL IN ISCHEMIC STROKE AND THIS IF FOR+ARDED TO RGUHS DR. CHETAN KUMAR J G PROFESSOR DEPT. OF GENERAL MEDICINE A.I.M.S., B.G. NAGARA.
.# SIGNATURE OF THE GUIDE .$ CO-GUIDE .! SIGNATURE OF CO-GUIDE ------------.5 HEAD OF THE DEPARTMENT DR. PADMANABHA M C PROFESSOR . HOD DEPT.OF GENERAL MEDICINE A.I.M.S., B.G.NAGARA. --------------
#.# SIGNATURE
APPENDIX *. BRIEF RESUME OF THE INTENDED +ORK APPENDIX A *. . NEED FOR THE STUDY
Ischemic stroke is a common problem faced day to day . The burden of stroke on the community is best reflected by the incidence. There is increasing mortality and morbidity with stroke. It has been found convincingly that in ischemic stroke, there will be rise in acute phase reactants like C- Reactive protein
1!, "!, #!
and $%R.
&therosclerosis is recogni'ed as an inflammatory process rather than a mere obstructive one. Increased CR( production is a feature of noninfective as well as infective disease and CR( binds to a wide range of autogenous products. )ipids and phospholipids, polycations and polyanions all of which are constituents of cells and likely to be abnormally e*posed in or released from damaged tissues. In +ivo binding of CR( to necrotic cells has been described and contribute to resolution and repair. ,owever, the main role of CR(, for which it evolved and has been conserved is to recogni'e in the plasma the potentially to*ic autogenous materials released from damaged tissues to bind them and thereby to deto*ify them and -or facilitate their clearance .!, /!, 0!.
APPENDIX-IB
sensitivity CR(; to add prognostic information to the 9ramingham Risk %core but also linking hs CR( to metabolic syndrome and the development of incident type " diabetes. In addition, the 9ramingham ,eart study itself has provided evidence that hsCR( independently predicts thrombotic events in the cerebral circulation. 9inally within the 9ramingham ,eart study, data have also been presented that demonstrate the ability of hsCR( to predict stroke risk independently of the 9ramingham covariates. &fter ad<ustment for age, smoking, blood pressure, diabetes and total and ,8), )8) cholesterol, the risk of future stroke in the 9ramingham ,eart study increased "/= in men p>?.?#0! and "@=in women p>?.??4! for each increasing 1uartile of hsCR( 1?!. Thus, measures of inflammation such as hsCR( seem to provide independent and complementary information on risk beyond that achievable by direct measures of atherosclerotic burden.
EXCLUSION CRITERIA
&cute infectious disease
o &ll patients of stable or unstable angina, acute myocardial infarction. o Immunological disorders. o Bnown or suspected neoplastic disorders o Recent:less than # months;ma<or trauma, surgery, burns 7steoarthrosis, costochondritis, rheumatoid arthritis, ankylosing spondylitis
PROTOCOL OF THE STUDY0 9or every case and control selected, clinical data and results of routine investigations will be prospectively recorded. In both cases and controls, blood for CR( and $%R will be taken by performing venipuncture and estimation will be done in Clinical 6icrobiology )aboratory, & I 6 % F.E Dagar.
P178379:40 The CR( is a rapid slide agglutination procedure for the direct detection and semi1uantitation of C-reactive protein. The reagent, a late* particle suspension coated with specific antihuman C- reactive protein antibodies, agglutinates in the presence of CR( in patients serum.
P12345614 ,6;:7&;&7<4 T4%&0 &ll the reagents as well as samples brought to room temperature.
1. 7ne drop of serum placed in circled area of slide with the help of disposable serum dropper. ". 7ne drop of CR( late* antigen added to above drop and mi*ed well with disposable applicator stick. #. 7bserved for agglutination by rocking the slide gently back and forth upto to "min using a bright source of light. S4=7>6;8&;&7<4 T4%&0 To find out the titre of positive sample, it is feasible by the serial dilution method to carry out semi1uantitative titration.
1.
/? micro liter diluted glycine saline buffer placed onto each of si* circles of slide.
".
Csing a /? microliter pipette, /? microliter of serum sample added to drop of glycine saline buffer in 1 st circle.
#.
Csing the same microlitre pipette the sample is mi*ed by saline by aspirating back and forth "-# times, /? microliter from first circle aspirated and transferred to second circle to repeat the same operation up to 0 th circle, /? microliter from 0 th circle aspirated and discarded.
Third GGGGGGGGGGGGGG. 1H4 9ourth GGGGGGGGGGGGGG 1H10 9ifth GGGGGGGGGGGGGGG 1H#" %i*th GGGGGGGGGGGGGGG 1H0.
C;:36:;&7280 Concentration of CR( in serum can be calculated. CR( I ?.0 * highest dilution of serum showing agglutination %ensitivity > ?.0 mg-d).
The detection limit of this test is ?-0 mg-dl. therefore, values of less than ?.0 mg-d) will be taken as normal concentration of CR(. +alues of more than ?.0 mg-d) will be taken as elevated CR(. ESR LEVEL ESTIMATION 5 11 6$T,785 The International Committee for %tandardi'ation in ,ematology IC%,! recommends the use of the Jestergren method. $thylenediaminetetraacetic acid $8T&! anticoagulated blood sample is preferably diluted in a large bore tube before using the Jestergren tube. Jith this modified JestergrenKs method, there is an e*cellent correlation with the IC%, reference. Flood samples can be stored for up to ". hours at .LC, but not at room temperature, without affecting the Jestergren level. FACTORS AFFECTING THE TEST@
#, $
$rythrocyte aggregation is affected by two ma<or factorsH red cell surface charges and
frictional forces around the red cell. The erythrocytes normally have net negative charges and, therefore, repel each other. ,igh molecular weight proteins, especially when positively charged, increase viscosity and favor rouleau* formation and thus would raise the $%R. 9ibrinogen, the most abundant acute phase reactant, has the greatest effect on the elevation of $%R when compared with other acute phase proteins. 7n the other hand, a change in the frictional forces around the red blood cell can affect the $%R. & drop in the red cell number, as in anemia, slightly elevates the $%R since this also physically interferes with rouleau* formation. 6acrocytosis with a small surface-tovolume ratio have charge relative to their mass and thus sediment more rapidly. Dormal values are 1/ mm-hr or less for men and "? mm-hr or less for women.
PROFORMA
S&65A 2B S416= C28348&1;&728 2B C-14;3&7<4 912&478 78 I%3C;4=73 %&12D4 %l.Do DameH &geH %e*H &ddressH C28%48& IMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMM, unreservedly and in my full sense give my consent to take part in this study, the risks and benefits of which have been e*plained to me in my vernacular language. %ignature (atient-Relative! I(.Do. 8ate of &dmissionH 8ate of dischargeH 7ccupationH
P14%48&78E C2=9:;78&%0 1. Jeakness of H Right upper limb - Right lower limb - )eft upper limb - )eft lower limb. %ince MMMMMMMM ". 8eviation of mouthH (resent - &bsent5 to left - right, since MMMMMMMMM #. <ered level of consciousness5 (resent - &bsent5 sinceMMMMMMMMMMM H7%&21A 2B 914%48&78E 32=9:;78&%0 1. Jeakness of right upper limb - right lower limb - left upper limb - left lower limb5 (resent - &bsent 7nset H sudden - gradual I 7ver minutes - ,ours - 8ays 8uring activity - at rest - while asleep ". Inability to speak - altered speech H (resent - &bsent #. ,istory of altered level of consciousnessH (resent - &bsent .. ,istory of ,eadache H (resent - absent /. ,istory of vomiting H (resent - absent 0. ,istory of convulsionsH (resent - absent A. ,istory of sensory disturbancesH (resent - absent 4. ,istory of bowel bladder - disturbance H (resent - absent @. ,istory of swaying H (resent - absent 1?. ,istory of loss of vision - diplopia - change in voice - nasal regurgitation P;%& H7%&21A0 8iabetes mellitus - Ischemic heart disease - Claudication - ,ypertension 6igraine - R,8 - Trauma to head and spine stroke - Transient Ischemic &ttack - R& - &% - 7%
P41%28;: H7%&21A0 8iet I +eg - 6i*ed &ppetite I Eood - (oor %leep I %ound - 8isturbed 6artial status I married - unmarried Fowel I regular - altered Fladder I regular - altered ,abits I %moker - alcoholic - tobacco chewer 7bstetric and menstrual history in females!H &ge of menarche Cycles I regular - irregular &ge of menopause I
PCA%73;: EF;=78;&7280 1. 8ecubitus ". Fuilt H Jell built - moderately built - poorly built #. %tate of Dutrition H over weight - normal - under weight .. ,ydration status H Jell hydrated - 8ehydrated /. $yes H (losis - leterus - (allor - &rcus senilis - B9 ring - cataract
0. $ars A. 7ral cavity 4. )ymphadencopathy I (resent - &bsent (edal $dema @. $*amination of peripheral vessels and neck vessels
SA%&4=;&73 EF;=78;&7280 1. Dervous system e*aminationH a. ,anded ness I right -left b. 6ental status e*amination i. 6emory H Intact - lost If alertH ii. iii. 6emory H Intact - lost 7rientation H (resent - &bsent5 if present to time -
c. Cranial nerves e*amination i. 1st cranial nerve I sense of smell H (reserve - altered - lost ii. "nd cranial nerve I acuty of vision I normal - reduced
9ield of vision I normal - reduced Colour vision I normal - altered 7ptic fundus e*amination H Dormal - abnormal iii. #rd, .th and 0th Cranial nervesH 1. 7cular movements I full range - restricted ". %1uint I present - absent #. Dystagmus I present -absent .. (tosis I (resent - &bsent /. (upils si'e I Right )eft )ight Refle* I Right5 )eft &ccommodation refle* I Right )eft
iv. / th cranial nerve nerveH 1. 6otor ". %ensory #. %ecretory function .. Refle*es a. corneal I (resent -absent b. Con<uctival I present -absent c. Naw <erk I present -absent v. Ath Cranial nerveH
1. 6otor ". %ensory #. %ecretory vi. 4th cranial nerves 1. RinneKs test ". JeberKs test vii. @th and 1? th cranial nerves 1. (alatal refle* I Cvula central - deviates to leftH right side ". Eag refle* I (resent -absent-e*aggerated viii. 11th cranial nerve
i*.
d. 6otor system e*aminationH Right C) a. Dutrition b. Tone c. (ower d. Coordination e. Involuntary movementsH (resent - absent f. Refle*esH Right )eft )) C) )eft ))
a. %uperficial i. &bdominal ii. iii. b. 8eep i. Ficeps ii. iii. iv. v. Triceps %upinator Bnee &nkle Cremastric (lantar
c. (rimitive refle* I (resent - &bsent d. %ensory system e*aminationH Right Touch (ain Temperature +ibration Noint sense Cortical sensation e. Cerebrallar system e*aminationH Right 9inger Dose test Bnee ,eel test )eft )eft
8ysdiadokinesia
g. E&ITH h. %igns of &utonomic 8isturbances I (resent-&bsent i. %igns of 6eningeal iriitation Deck Rigidity-Bernings sign-Frud'enski sign <. $*amination of skull and spine I 8eformity (resent -&bsent ". Cardiovascular %ystemH 7n InspectionH 7n (alpationH 7n (ercussionH 7n &uscultationH #. Respiratory %ystemH 7n InspectionH 7n (alpationH 7n (ercussionH 7n &uscultationH .. (er &bdomen $*aminationH 7n InspectionH 7n (alpationH 7n (ercussionH 7n &uscultationH
I8<4%&7E;&728%0 1. Flood ,b= TC 8C $%R RF% F.urea %.Creatinine ". Crine&lbumin %ugar 6icroscopy #. $CE.. Chest O-ray /. CT %can Frain 0. %erum CR( )evels A. 7ther, if any-
S7E8;&614 2B G6754
APPENDIX-IIC 7.$ DOES THE STUDY RE,UIRE ANY INVESTIGATIONS OR INTERVENTION TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS, IF SO PLEASE DISCRIBE BRIEFLY YES
CT %can ,ead plain of the patient C-Reactive protein CR(! of patient and age and se* matched healthy controls $%R of patient and age and se* matched healthy controls
APPENDIX-IID 7.! HAS THE ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.$G YES
1. 8i Dapoli 6, (apa 9, Focola +. 2(rognostic Influence of increased CR( and fibrinogen levels in ischemic stroke3. %troke "??15#"H1##-1#4. ". Nialal I, 8evara< %. 2Inflammation and atherosclerosis5 the value of the high sensitivity c-reactive protein assay as a risk marker3. &m N. Clin (athol. "??1H8ecH110H %upplH%1?4-1/ #. &garwal 6(, %ingh DR, Baur IR. 2C-Reactive (rotein in acute cerebral infarction3. N&(I. +ol/158ec "??# .. Beith J. 6uir, 68, 6RC(5 Christopher N. Jeir, F%C5 Jafa &lwan, 6RC (ath5 et al. 2C-Reactive protein and outcome after ischemic stroke3. %troke 1@@@5#?H@41-@4/. /. 8hami<a RB, Eaba (, Nais 6, Bumar 6, %herwal F) PK& %tudy of C-Reactive (rotein levels in patients of &cute Ischemic %troke and its correlation with lipidsKK N&(I.+ol/1,8ec"??#. 0. 8i Dapoli 6, (apa 9. 2&ssociation between blood pressure and c-reactive protein levels in acute ischemic stroke3. ,ypertnsion 8ec "??#5." 0!H111A-"#. A. (aniker ND, Thomas 6, (avithran B, Dair 8, %arma (%. 26orbidity predictors in ischemic stroke3. Deurol IndiaH"??#H6arH/1 1!H.@-/1 4. )ofstrom E, 2Comparison between the reactions of acute phase serum with pneumococus C-polysaccharide and with pneumococcus type -"A3, Fr. N. $*p. (athol 1@..5"/5"1-"0. @. +an 8er 6eer I6, 8e maat 6(, ,ak &$,et al 2C I reactive protein predicts progression of atherosclerosis measured at various sites in the arterial treeH the Rotterdam %tudyH%troke "??" 8eecH## 1"!H"A/?-/
1?.
Datalia % .Roast, (hilip & Jolf, Carlos %, Base et al,KK(lasma concentration and risk of ischemic stroke and trancient ischemic
of C- reactive protein
attackKK. The 9ramingham %tudy. %troke Dov "??15#"5"/A/-"/A@. 11. International Council for %tandardi'ation in ,aematology $*pert (anel on Flood Rheology!H IC%, recommendations for measurement of erythrocyte sedimentation rate. N Clin (athol 1@@#5 .0H1@4-"?4 1". Thomas R8, Jestengard NC, ,ay B), et alH Calibration and validation for erythrocyte sedimentation tests. &rch (athol )ab 6ed 1@@#5 11AHA1@-A"# 1#. %mith $6, %amadian %H Cse of the erythrocyte sedimentation rate in the elderly. Fr N ,osp 6ed 1@@.5 /1H#@.-#@A
APPENDIX-IID
(A STUDY OF C-REACTIVE PROTEIN IN ACUTE ISCHEMIC STROKE) DR. GAURAV SHIREESH BABAR P.G (M.D) GENERAL MEDICINE A.I.M.S. B.G.NAGARA. DR. CHETAN KUMAR J G PROFESSOR DEPT. OF MEDICINE A.I.M.S., B.G.NAGARA NA
B.
P178379;: 78<4%&7E;&21
C. C2-78<4%&7E;&21 GUIDE D. N;=4 2B &C4 32::;H21;&21 D49;1&=48& I 78%&7&6&4 E. +C4&C41 941=7%%728 C;% H448 2H&;7845 B12= &C4 C4;5 2B &C4 32::;H21;&78E 549;1&=48& ;85 78%&7&6&728 SECTION-B
NA
APPENDIX-II S6==;1A 2B &C4 912J43& SECTION-C APPENDIX-IC OHJ43&7<4 2B &C4 %&65A SECTION KD APPENDIX-IIB M4&C252:2EA A. +C414 &C4 91292%45 %&65A L7:: H4 AH . RC, B.G.NAGARA. B. U8541&;D48 D61;&728 2B &C4 912J43& " MONTHS
C. N;&614 2B &C4 %6HJ43& 0 D24% &C4 %&65A 78<2:<4 ;56:& 9;&748&%G D24% &C4 %&65A 78<2:<4 3C7:5148G D24% &C4 %&65A 78<2:<4 821=;: <2:68&441%G YES NO YES
D24% &C4 %&65A 78<2:<4% 9%A3C7;&173 9;&748&%G D24% &C4 %&65A 78<2:<4 914E8;8& L2=48G D. IB &C4 %&65A 78<2:<4% C4;:&CA <2:68&441% . L7:: &C4A H4 78%&7&6&4 %&6548&%G #. L7:: &C4A H4 78%&7&6&4 4=9:2A44%G $. L7:: &C4A H4 9;75G !. 7B &C4A ;14 &2 H4 9;75, C2L =63C 941 941%28G E. F. I% &C4 %&65A =6:&7 348&1;: &17;:G IB A4%, LC2 7% &C4 3221578;&21G (8;=4 ;85 54%7E8;&728) H;% &C4 &17;: H448 ;9912<45 HA &C4 4&C73;: 32==7&&44 2B 2&C41 348&41%G IB &C4 %&65A 78<2:<4% &C4 6%;E4 2B 516E%0 P:4;%4 78573;&4 LC4&C41, . &C4 516E 7% =;1D4&45 78 I857; B21 &C4 78573;&728 78 LC73C 7& L7:: H4 6%45 78 &C4 %&65A. #. &C4 516E 7% =;1D4&45 78 I857; H6& 82& B21 &C4 78573;&728 78 LC73C 7& L7:: H4 6%45 78 &C4 %&65A. $. &C4 516E 7% 28:A 6%45 B21 4F9417=48&;: 6%4 78 C6=;8%. !.3:4;1;834 2B &C4 516E 328&12::41 2B I857; C;% H448 2H&;7845 B21 0 -U%4 2B &C4 516E 78 &C4 C4;:&CA <2:68&441% -U%4 2B 516E 78-9;&748&% B21 ; 84L 78573;&728.
NO NO
NO NO NA NA NO NA NA
NA
NA NA
NA NA
-9C;%4 284 ;85 &L2 3:7873;: &17;:%. -4F9417=48&;: 6%4 78-9;&748&% ;85 C4;:&CA <2:68&441%. G. H2L 52 A26 91292%4 &2 2H&;78 &C4 516E &2 H4 6%45 78 &C4 %&65AG -G7B& B12= ; 516E 32=9;8A -C2%97&;: %699:74% -9;&748&% L7:: H4 ;%D45 &2 9613C;%4 -2&C41 %26134% (EF9:;78) H. F68578E (7B ;8A) B21 &C4 912J43&. P:4;%4 %&;&4. -N284 -A=268& -S26134 -T2 LC2= 9;A;H:4 I. D24% ;8A ;E483A C;<4 ; <4%&45 78&414%& 78
NA NA
NA NA NA NA NA NONE
NO &C4 26&32=4 2B &C4 912J43&G J. +7:: 5;&; 14:;&78E &2 %6HJ43&%I328&12:% H4 NO %&2145 78 ; 32=96&41G K. +7:: &C4 5;&; ;8;:A%7% H4 5284 HA YES -TC4 14%4;13C41G -TC4 B68578E ;E483A NO
L.
+7:: &43C873;: I 861%78E C4:9 H4 14>67145 B21 &C4 %&;BB 2B C2%97&;:, 7B A4%, L7:: 7& 78&41B414 L7&C &C471 56&74% G L7:: A26 143167& 2&C41 %&;BB B21 &C4 561;&728 2B &C4 %&65AG IB A4% E7<4 54&;7:% 2B I D4%7E8;&728 II ,6;:7B73;&728 III N6=H41 IV D61;&728 2B 4=9:2A=48& NA NA NA NA YES NO NO
M.
+7:: 78B21=45 328%48& H4 &;D48G IB A4%, +7:: 7& H4 L17&&48 78B21=45 328%48&G +7:: 7& H4 21;: 328%48&G +7:: 7& H4 &;D48 B12= &C4 %6HJ43&% &C4=%4:<4%G +7:: 7& H4 B12= &C4 :4E;: E6;157;8G IB 82, E7<4 14;%280
YES NO YES NA
N.
E&C73;: 3:4;1;834 C;% H448 ;3321545. D;&40 P:;340 CC;71=;8 PG T1;7878E-36= 14%4;13C 32==7&&44 A.I.M.S., B.G.N;E;1