132 CALIFORNIA S'T'ATE JOURNAL OF MEDICINE
4
frequently in the male sex, the ratio, as given by a
number of writers, being six to one. In the Agnew
State Hospital during the last seven and a half
years there have been sixty-seven men and six
women die of this disease, making a ratio of over
eleven to one. The whole number of deaths during
this same period was six hundred and fifty-five,
which shows a fraction over eleven per cent of all
our deaths due to this disease alone. The class of
persons affected by this disease are the more intelli-
gent, better educated and hard brain workers, who
live rapidly and dissipate along the usual lines of
high life; however, they are seldom failures until
the disease undermines their reason and their judg-
ment is destroyed. They are a companionable class,
and although frequently selfish, are sought after in
society, and when admitted into a hospital for insane
are in the earlier stages of the disease a very inter-
esting class. Later they become very demented,
are filthy in their habits, and are exceedingly trouble-
some to the attendants who care for them. When
first committed to a hospital, those of the maniacal
form are excited and violent, will resort to any
means to gain their liberty; this failing, will become
filthy, smearing their person and room with fecal
matter, but after a short time will become more
quiet and cleanly, resume many of the habits of
polite society and endeavor to make themselves com-
fortable in their present surroundings, and as before
stated, become companionable patients and so re-
main until the dementia advances so far that the
mind becomes nearly a blank.
The exciting cause of general paresis is allowed by
all to be in a majority of cases syphillis; a few go
so far as to claim that all cases are due to this
poison. Among the contributing causes alcohol
leads, to be followed by sexual excesses (debarring
masturbation), metallic and vegetable poisons and
mental strain.
The early recognition of this disease is very im-
portant, for, as mentioned before, it usually attacks
the people who are successful, and a well-to-do
business man becomes exceedingly venturesome, and
before the real condition is realized he has involved
his property so deeply that his family is left desti-
tute. Symptoms in the early stages resemble
neurasthenia, and as time passes lapses of memory
shown by the dropping of a letter from a word or a
word from a sentence while writing or in speaking,
a slight hesitancy or a mispronounced word is no-
ticed. Sleep is irregular. The proprieties of life
are not so closely observed; they become careless in
dress, show extravagance in the use of money, use
alcoholic beverages more freely, indulge in sexual
excesses and show a condition a little below par men-
tally, morally and physically. In the beginning the
patient realizes that something is amiss, but as the
disease advances they lose the sense of being ill and
take no further notice of their irregular actions.
When the time arrives that it is advisable to commit
these persons to a hospital, the delusions of grandeur
are especiallv manifested by the belief that they
possess untold wealth.
To illustrate this: When F was received at
Vol. VI, No.
the hospital he claimed to be worth a thousand bil-
lions. He was going to start on a trip around the
world the next day in his airship and engaged me
to accompany the party as surgeon at a salary of
ten millions a day. At the same time he gave the
correct amount of a debt of less than one hundred
dollars which he wished to pay.
One of our cases of general paresis eluded his
attendant one day and climbed to the top of a four-
story building. When he was at last rescued he was
making his way to the edge of the roof with the in-
tention of flying to his hotel and if he had not been
intercepted would have deliberately jumped off and
probably been killed. He was safely lowered by
means of a rope. He died eight months later.
To commence again the delusions of grandeur,
stammering speech, trembling tongue, changes in the
pupil and patellar reflex and general inco-ordina-
tion of movement give so vivid a picture that diag-
nosis is quickly made. Convulsions are another
prominent symptom of general paresis, and closely
resemble epileptic or apoplectic seizures, and are
frequently followed by partial paralysis, which
usually improves rapidly but leaves the patient on a
lower plain than before.
In conclusion, a few words in regard to prognosis.
and treatment. Prognosis is always bad; the aver-
age length of life is three years. Some cases go
very quickly to a termination, while others improve
for- a time to such an extent that they are able to
resume their work for an indefinite time, and some
intercurrent disease may cause death; if this does not-
occur the active symptoms become more pronounced
again and the decline continues until they die of
exhaustion. I have tried a number of different
lines of treatment, but the only drug that has ap-
peared to have any beneficial effects has been small
doses of iodid given three times a day for months at
a time. All the cases that have improved enough to
leave the hospital for a time during my service have
received this treatment, and, contrary to the usual
teachings, it has not interfered with digestion, and
the patients have usually gained in strength and
weight.
My usual prescription is:
R Iodide of Potash - z v
Bichloride of Mercury gr. t
Water - - z v iii
of which zi is given in water three times a day
after meals.
The absence of stomach irritation may be due to
the small doses of mercury, which in itself is a
tonic.
SOME NOTES ON POSOLOGY.*
By GEO. F. HANSON, M. D., San Francisco.
A well-known medical author prefaces his re-
marks upon posology by the statement that the dos-
age of medicines is the weakest part of the thera-
peutic armamentarium, and says that "if the ac-
cumulated rubbish of ages, which has been called
therapeutic knowledge, is ever to be given scientific-
*Read before the cooper College Science Club.
APR., I90o8. CALIFORNIA STATE JOURNAL OF MEDICINE
shape, the question of dosage must form one of the
principal cornerstones in the foundation." May it
not be that this matter of dosage is largely re-
sponsible for much of the so-called therapeutic
nihilism existing at present even among our promi-
nent men?
As a matter of course it is essential that our
text books should furnish a list of doses as a guide
in the writing of prescriptions, but it is only in the
latest (8th) edition of the U. S. Pharmacopeia
that the Committee of Revision has ventured to
suggest average doses for adults. During the
previous three quarters of a century, comprising the
life of the seven previous revisions, no doses were
even suggested, and it was not intended that the
present average doses should be by any means con-
sidered arbitrary.
The pharmacopeias of some other leading na-
tions, such as of Great Britain and Germany, also
disclaim any intention of attempting to fix un-
changeable standards of dosage. Committees of
revision generally recognize the well nigh insur-
mountable difficulty of reconciling the widely vary-
ing elements of sex, strength, habits, individuality,
idiosyncrasy, etc. The numerous factors qualifying
the amount to be administered at one time have, in
the case of a large number of agents, been care-
fully worked into equations, such as the relative ab-
sorbability per orem, per rectum and hypodermical-
ly, or during varying states of the circulation, etc.
How often if we adhere to the average dosage out-
lined, do we either fail of getting any results or
only feeble or disappointing ones. Too often these
results are modified materially by the administra-
tion of other remedies given simultaneously, or in
too frequent alternation. Poly-pharmacy and poly-
prescribing for symptoms are twin evils that beset
the pathway of the beginner. His anxiety to al-
leviate each new ache as it arises leads him to mul-
tiply bottles upon the bedside stand of his patient
until it soon puzzles the attendant to keep their
rotation accurately timed. Again, results may be
nil because of inert preparations, or because the
fear of overdosing by a shotgun prescription may
impel to the giving of such small amounts of each
remedy that the combined effect is only a disordered
stomach.
The usual state of health of individual patients
must necessarily have considerable weight, as a high
average of vitality would be likely to render cell re-
sistance to drugs greater, just as to other poisons.
Some chronically ailing, feeble little middle-aged
women are affected proportionately as compared
with a big, robust young athlete, about in the ratio
of their physical strength and weight to his. The
difference is practically as great as between a child
of two or three years and an adult. If an epi-
demic of disease were crossing the pathway of both
we would expect the little woman to be attacked
although the young man might escape. And this
means that while the average pharmacopeial dose
of a remedial agent might be followed by its full
physiological effect upon the little woman, no ef-
I33
fects would follow a like dose administered to the
man. In the latter case we are prone to resort to
a change of remedies, perhaps with no better result,
and after shifting about from one remedy to another
for a time we may eventually come to the conclusion
that drug giving is a failure. The method to be
pursued is obvious. If the physiological action of a
certain drug is required or worth having, it is worth
having at once. We are justified in increasing the
dose or shortening the intervals between doses until
we get its action. It can then usually be main-
tained without difficulty by smaller doses, less fre-
quently administered. In the case of the two
classes of drugs requiring the greatest caution, the
narcotics and depressants, of the latter the oft quoted
coal-tar derivatives and allies being most frequently
followed by untoward or alarming effects, the
damage is rarely from a large initial dose, but from
frequency of repetition beyond the safety line.
When, during the administration of the average
line of medicine, such as the salicylates or the
iodides for instance, we appear, day after day, to be
getting little or no benefit from our treatment, is it
not commonly the fault of our doses?
Often we may determine the question as to
whether our remedies are being fairly well absorbed
or assimilated by some simple test, as for example,
when we are endeavoring to maintain alkalinity of
the urine, or vice versa, or when we are administer-
ing salol or other phenol or salicylic acid compounds.
Negative results from a drug do not necessarily
mean its abandonment. If we are sure of our diag-
nosis and are reasonably certain that no impedi-
ment exists to the absorption of the medicinal
agent, that agent should be promptly pushed until
we do get results. The only exception to such a
course is in cases where cumulative overdoses might
do serious injury to some of the tissues of the body.
The old familiar example of digitalis might here
be cited. The average dose of the tincture men-
tioned, I5 m., is supposed to represent the whole
activity of i 2 grains of the leaf. Three drachms
of the infusion contains twice as much of the leaf
and is usually repeated with the same frequency.
Is it any wonder that many physicians have become
so skeptical regarding the tincture? And that it
has become the habit of many practitioners to speci-
fy individual "makes" of the tincture because the
drug is known to be assayed and because experience
has justified the choice?
Digitalin, in the form of the i-iooth gr. hypo
tablets so abundant in the market, was another of
the disappointing preparations. More recently
considerable use has been made by preference of the
German digitalin (dose i/io-Y2 gr. t.i.d.) this be-
ing a mixture of Kilianis digitalin with digitoxin,
digitalein, and some inert matter. Reports of its
efficacy are, I believe, generally favorable.
Another example is the spiritus glycyrilis nitra-
tis, with its specified average dose of i m. How
often do we get any noticeably beneficial result from
that dosage? So small an amount of a i % alcoholic
solution of nitro-glycerin may be tried as a "feeler,"
134 CALIFORNIA STATE JOURNAL OF MEDICINE
but if we get the anticipated results from it those
very effects are fairly positive evidence that we
were not really dealing with a case of high arterial
tension.
An instance by way of illustration of the faulty
administration of a nitrite is shown when death
impends during chloroform anesthesia. A nitrite is
frequently employed even when the arterial tension
may be nil. Should the patient not take his de-
parture for the happy hunting grounds under such
circumstances it is certainly not our fault.
The pharmacopeial dose of fldext, cannabis indica
is given as i m. I believe that only in rare in-
stances does any appreciable effect follow that dos-
age, and have known a young man to take 6o m.
without other results than a prolonged sleep; little
or no dreaming and no hallucinations. Twenty-four
hours' continuous sleep.
Still another example of conservative dosage is
that of the various fluid extracts of rhamnus pur-
shiana, I5 m. How often is three or four times that
amount lost in the devious pathway of the ali-
mentary canal?
From the instances cited one might gain the im-
pression that much larger doses are sought to be
recommended as a general procedure; this is certain-
ly not the writer's intention. ,In the majority of
instances the dosage would appear to be satisfactory,
particularly in those cases where a long continued
impression upon the system is to be made rather than
a prompt and a fleeting one. It is rather the aim
of the paper to impress the necessity for sufficient-
ly large doses to secure the physiological action of
the remedy administered. Repeating the average
stated dose day after day in the hope that we will
soon get results, is at least disappointing, and as
already suggested tenders to foster therapeutic
nihilism. In those rather numerous cases where
large doses of a given drug are commonly followed
by physiological effects notably different from small
ones, the action desired has, of course, always to be
borne in mind. Of this feature the pharmacopeial
average dosage takes no cognizance, the dose being
fixed with few exceptions in reference to the most
generally sought or most pronounced effect of a
given remedy. (Exception, e. g. Ipicacuanha.)
After all, so many factors have to be taken into
consideration when attempting to fix doses, that
although we may administer only assayed drugs, in
order to get uniform results we would have to have
our patients assayed as well.
Fortunately much has been accomplished and is
still being accomplished by earnest investigators into
the pharmacological action of remedial agents.
Laboratory research and control experimentation are
gradually clearing up much that has been simply
empirical. Through the knowledge thus gained may
we not hope to be enabled to more accurately gauge
amount and frequency of dosage for the attainment
*of certain results under known, even though variable
conditions ?
Apropos of the tolerance to increased dosage of
drugs acquired by individuals and by considerable
Vol. VI, No. 4
proportions of tribes or peoples, as so familiarly in-
stanced in the hasheesh eaters of India, the arsenic
takers of Styria, the opium smokers of China and
the highball colonels of Kentucky, a rather unique
instance is mentioned in a September, I906, number
of the London Lancet, of a man aged forty-three
who took 576 grains of morphin in two doses an
hour apart. He was a habitual user of the drug
and had reached a daily consumption of about one
drachm. On this occasion he swallowed pills to the
amount of 288 grains, possibly with suicidal intent,
and shortly after repeated his pharmacological ex-
periment. It is perhaps superfluous to add that his
age limit was forty-three.
INDICATIONS FOR OPERATIONS ON
THE STOMACH.*
By WALLACE I. TERRY, M. D., San Francisco.
Within the past few years many articles have
appeared in the literature on the surgery of the
stomach, but the subject is such an important one
that I felt it might not be amiss to consider a few
phases of it and more particularly the indications
for operative measures.
The disease which is responsible for most of the
serious stomach disorders is gastric ulcer. Its inci-
dence has in the past been underestimated and its
numerous sequelae were not fully appreciated until
stomach surgery was put on a firm basis, and living
instead of dead pathology studied. Gastric ulcer
occurs in various forms, from the mere insidious
erosion of the superficial cells of the mucous mem-
brane to the acute perforating ulcer of the entire
stomach wall, and its sequelae vary from an insig-
nificant little scar to extensive contractures, even
almost complete obliteration of the stomach lumen.
Taken in time and under proper dietary and
medicinal treatment the majority of ulcers will heal
without leading to unfortunate after results, but
in a considerable number of cases the depth of the
ulcer and its anatomical position are such that per-
manent and serious damage to the stomach is the
inevitable result.
That the diagnosis is often overlooked can
scarcely be gainsaid, the term "gastric dyspepsia" is
applied so frequently and covers a multitude of
pathological conditions, but it seems to me that our
knowledge of gastric diseases is now in a similar
transitional stage to that of lesions of the ap-
pendix in the early nineties. Then a diagnosis of
appendicitis was obscured under the term "in-
flammation of the bowels," but today the symptoma-
tology and pathology of appendicitis are so well
understood that the proper diagnosis is usually made
and I am fully convinced that in the near future
the diagnosis of gastric diseases will be as well un-
derstood.
About the most important indication for surgical
intervention in acute ulcer of the stomach is hemor-
rhage. The quantity of blood lost and the persist-
ency are the factors which should determine the
* Read before the Santa Clara County Medical Society,
March 18, 1908.