History of Nursing in Pacific Canada

The Vancouver Medical Association Bulletin: June, 1936 Vancouver Medical Association Jun 30, 1936

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(With Cascara and Bile Salts)
. . FOR . .
Chronic  Habitual
Western Wholesale Drug
(1928) Limited
(Or at all Vancouver Drug Co. Stores) THE     VANCOUVER     MEDICAL     ASSOCIATION
Tublished \Month\y under the tAuspices of the Vancouver ^Medical dissociation in the
-."dSf*,w'J °f *^e *M-*&ic<d "Profession.
203 Medical Dental Building, Georgia Street, Vancouver, B. C.
Editorial Board:
Dr. J. H. MacDermot
Dr. M. McC. Baird Dr. D. E. H. Cleveland
All communications to be addressed to the Editor at the above address
Vol. XII. JUNE, 1936 No 9
OFFICERS  193 5-1936
Dr. C. H. Vrooman Dr. W. T. Ewing Dr. A. C. Frost
President Vice-President Past President
Dr. G. H. Clement Dr. W. T. Lockhart
Hon. Secretary Hon. Treasurer
Additional Members of Executive—Dr. T. R. B. Nelles, Dr. F. N. Robertson
Dr. W. D. Brydone-Jack Dr. J. A. Gillespie Dr. F. Brodie
Auditors: Messrs. Shaw, Salter & Plommer
Clinical Section
Dr. J. R. Neilson     Chairman
Dr. Roy Huggard — - .—Secretary
Eye, Ear, Nose and Throat
Dr. H. R. Mustard - —-  Chairman
Dr. L. Leeson . — — —Secretary
Pediatric Section
Dr. G. A. Lamont  - - Chairman
Dr. J. R. Davies  Secretary
Cancer Section
Dr. J. W. Thomson    - _ __.— Chairman
Dr. Roy Huggard *  __ Secretary
Library Summer School
Dr. G. E. Kidd Dr. J. W. Arbuckle
Dr. W. K. Burwell Dinner Dr. J. E. Walker
Dr. C. A. Ryan Dr. Lavell Leeson Dr. H. A. DesBrisay
Dr. W. D. Keith Dr. J. E. Harrison Dr. H. R. Mustard
Dr. H. A. Rawlings Dr. A. Lowrie Dr. A. C. Frost
Dr. A. W. Bagnall Dr. J. R. Naden
Publications Credentials
Dr. J. H. MacDermot Dr. H. A. Spohn
Dr. Murray Baird Dr. J. W. Thomson
Dr. D. E. H. Cleveland Dr. W. L. Graham
V. O. iV. Advisory Board
Dr. I. T. Day &eP- to B- C- Mel^'ca^ A*sn-
Dr. W. H. Hatfield Dr. Wallace Wilson
Dr. A. B. Schinbein
Sickness and Benevolent Fund — The President — The Trustees
1 Iffi
1 \\
i i-*
% I
ll -^—
Biological Products
Anti-Anthrax Serum
Anti-Meningococcus Serum
Anti-Pneumococcus Serum (Type I)
Anti-Pneumococcus Serum (Type II)
Diphtheria Antitoxin
Diphtheria Toxin for Schick Test
Diphtheria Toxoid
Perfringens Antitoxin
Scarlet Fever Antitoxin
Scarlet Fever Toxin for Dick Test
Scarlet Fever Toxin
Staphylococcus Antitoxin
Staphylococcus Toxoid
Tetanus Antitoxin
Tetanus Toxoid
Pertussis Vaccine
Rabies Vaccine (Semple Method)
Smallpox Vaccine
Typhoid Vaccine
Typhoid-Paratyphoid Vaccine
Liver Extract for Oral Administration
Liver Extract for Intramuscular Use (l cc.
containing extract from 10 gms. of liver)
The following additional products have been made available recently
by the Connaught Laboratories
Adrenal Cortical Extract
Epinephrine Hydrochloride Solution 1:1000
Epinephrine Hydrochloride Inhalant Solution 1:100
Liver Extract for Intramuscular Use
(1 cc. Containing Extract from 20 gms. of Liver)
Outfit for Rapid Typing of Pneumococcus by Physicians
Depot for British Columbia
Total Population (Estimated)    _  247,558
Japanese Population   (Estimated)   8,05 5
Chinese Population  (Estimated)             7,895
Hindu Population (Estimated)     320
Rate per 1,000
Number Population
Total   deaths         248 12.2
Japanese deaths  _ _._            3 4.J
Chinese  deaths           12 18.5
Deaths—residents only          217 10.7
Birth registrations: Male 175; Female 146       321 15.8
INFANTILE MORTALITY— April, 193 6 April, 193 5
Deaths under one year of age  -       14 4
Death rate—per 1000 births         43.6 13.5
Stillbirths  (not included in above)   7 4
March, 1936
Cases Deaths
Smallpox   0               0
Scarlet   Fever     41             0
Diphtheria    -   5              3
Chicken   Pox      34             0
Measles    L__  46             0
Rubella     1152             0
Mumps  - __ _. 262             0
Whooping Cough   10             0
Typhoid Fever    0             0
Undulant Fever    0             0
Poliomyelitis-   -  0             0
Tuberculosis  43 22
Meningitis   (Epidemic) _ 0             0
Erysipelas       6             0
Encephalitis Lethargica  0             0
Paratyphoid Fever  — 0             0
to 15th
, 1936
High Blood Pressure...
frThe most effective therapy available."
Formula—Each 1 cc. Ampoule contains:
Pancreas    25 grammes of the fresh hypotensive principle
Anterior Lobe Pituitary. 2 grammes of fresh substance
Embryonin  2 grammes of fresh substance
Biological and Research
Ponsbourne Manor, Hertford, England.
Rep., S. N. BAYNE
1432 Medical Dental Building       Phone Sey. 4239       Vancouver, B. C.
References: "Ask the Doctor who has used it."
Page 193 fM,YC)U
Then you know how the average diabetic dreads the
daily hypodermic injection. He will welcome oral medication with Pancrepatine and a moderate restriction of
Pancrepatine contains the hormones of pancreas and
liver, ACTIVE BY MOUTH. These hormones are
fully protected from ferment action in the duodenum
by the special capsule of the globule.
Many physicians attest the efficacy of Pancrepatine as
an effective oral treatment for diabetes mellitus. Especially useful in the mild or average uncomplicated case.
Reduces blood and urinary sugar and spares insulin.:
Controls the annoying symptoms of polyuria and polydipsia. The general condition of the patient is improved.
When treating your next case of diabetes we invite you
to try Pancrepatine. You will be pleased with the results revealed by Benedict's test.
Prescribe 2 to 4 globules t.i.d. after meals in increasing
doses. Bear in mind the appropriate dietary restriction.
Supplied in bottles of 100 hormone-protected globules.
May we send you a liberal complimentary sample?
Write to Anglo-French Drug Co.
354 St. Catherine Street East,
Montreal,    Quebec
cff^Mpe  Oral Tre^me/tl/br Diabetes [We publish herewith the Programme of the Summer School of the Vancouver Meidcal
Association, to be held on dates given below. The) names of the lecturers and their subjects
are a guarantee of an excellent and most profitable session. We will give more details
ool Programme
September 8, 9, 10, 11, 1936
1. Dr. Gordon B. New—Department of Oral and Plastic Surgery, Mayo
Clinic, Rochester, Minn.
1. Malignant diseases of the mouth and accessory structures.
2. Tumours of the neck.
3. Reconstructive surgery of the face.
4. Tumours of the larynx.
2. Dr. W. McK. Marriott—Department of Pediatrics, Washington
University, St. Louis, Mo.
1. Infant nutrition and gastrointestinal disturbances.
2. Ear, nose and throat infections during infancy and childhood.
3. Conditions associated with alterations in the chemical equilibrium of the
4. Diagnosis and treatment of the more important blood disease of infancy.
3. Dr. Evarts A. Graham—Surgeon, University of Washington, St.
Louis, Mo.
1 and 2.    Lectures on thoracic surgery.
3. Certain phases of gallbladder disease.
4. Surgery of the pancreas.
Dr. Graham will also give one clinic.
4. Dr. J. McF. Bergland—Lecturer in Clinical Obstetrics, Baltimore.
1 and 2.    Complications in labor.
3. Relief of pain.
4. Infections in pregnancy.
5. Dr. C. B. Farrar, Psychiatric Hospital, Toronto, Canada.
1. Evolution of a delusion.
2. Psychoses which may simulate organic disease.
3. Subject left to speaker's choice.
Dr. Farrar will also give one clinic.
6. Dr. Rollin T. Woodyatt, Chicago, III.
Subjects for lectures not yet available.
7. Dr. C. E. Dolman—Provincial Health Laboratory, Vancouver, B. C.
Undulant Fever.
The forthcoming meeting of the Canadian Medical Association in the
latter part of this month of June should receive a good deal more from us
than the expression of a pious hope that as many medical men as possible
will see fit to attend it.
"The time has come," the Walrus said. At the risk of identification with
an animal who is hardly ever mentioned except in a rather derogatory way,
we should like to say the same thing. Our profession has much to learn, and
much to unlearn, and one can only hope that opportunity, who has only a
forelock to catch as it fleets by, has not escaped us wholly.
We are, and it is very largely excusable in us, a very incoherent profession. We are isolated units of force to a great extent, and our influence in
the community is very largely personal and not corporate. One sees this in
the common experience that the same man who will accuse the medical
profession of almost all the crimes in the calendar, will loyally, almost
blindly, adhere to his own family doctor, submit himself and his loved ones
willingly, if not altogether cheerfully, to the various forms of torture and
discipline which the said family physician thinks wise to inflict, and will
trust him through it all; so that the relation of a doctor to his patients
carries with it satisfactions and friendships which are perhaps some of the
happiest and deepest of any to be found.
Nothing must impair this relationship. More and more we should try
to see that every family, every individual, shall have his own trusted medical
friend and father confessor and physician. In what we may say of the need
of change, we shall never lose sight of the fact that this to us is a wellnigh
sacred obligation of ours to society. So much so that we agree cordially,
and have always agreed, with the conclusions of the British Medical Association, who lay it down as an axiom in their Report on Proposed Medical
Service for the Nation, that every family, indigent or working, poor or
rich, should have its own family physician. There is something in this relationship that makes for loving service—in the sense that love is sometimes
defined, as the "intense desire to help." Or as St. Paul would say, "Love is
kind." There are kindness and unselfishness and devotion in this relationship—and neither we nor those we try to serve can do without it and fail
to suffer loss.
But there is something more to be said, too. We must not continue to
live in the shadow of an outworn tradition, and one which no longer fits
the needs of either ourselves or society. Today the isolated unit is a very
useless and helpless thing. He is useless to himself or others because he is
helpless, and cannot do what he would, or what he knows he should. The
medical man of today needs badly to learn that his duty to society entails,
as one of its items, that he should be part of a firmly knit organism, which
is efficient because of solidarity and flexibility, which knows its work and
what it should be doing, and is able through unity and a clear knowledge
of itself to impress these things upon society at large.
And it is just this that the Canadian Medical Association is aiming at,
and gradually bringing to pass—and our provincial and local associations
are gradually articulating their energies and powers with those of the larger
body. The programme in Victoria is an amazing one—it is worth a week of
any man's time; one cannot remember any programme as good. Victoria in
June is apt to be a dream of loveliness, and its people are hospitality itself;
Page 195 SBSS
the week can and will be a thing to look back to for years, just for the
pleasure and profit to be gained; but at this present juncture, most important
of all,—and this means important to every man jack of us, not merely this
section or that section—is the opportunity this meeting will give us to link
ourselves together more closely than ever.
This has been said in various forms many, many times. But never has
it been so true as now. Why are we so slow to grasp the truth that "no man
liveth to himself," and only in so far as you and I and the other man does
his or your or my share, can we ever hope for that measure of security and
protection that should be ours and that are so important to the community
at large—for, and we know it, the health and well-being and prosperity of
the community at large will depend mainly, "under the providence of God"
as the Prayer Book says of the British Navy, on the health and well-being
and scientific achievement of the medical profession. There is too much of
a tendency to divide ourselves into compartments—so that the right hand
of therapeusis knows nothing of what the left hand of prevention is doing
—and the leg of the orthopaedist says to the stomach of the abdominal
surgeon, "I have no need of thee." This is all wrong, of course. All our
branches derive from the same tree, and draw their sap and strength from
the same roots, and we forget this continually—so that the "health" department of medicine and the practising physician have not the understanding
of each other's problems, and the consequent sympathy, that they should
have for each other. Medicine, with its broad humanity, its freedom from
international or racial or creedal barriers, should be the most united of all
the professions, for our aims and interests are all one in reality.
So go to Victoria, for five days if you can, or for four or three or two
or one, as you can afford time, and perhaps money, and add your essential
bit to that of others, till in the sum we achieve a new and better order of
The Health Insurance Committee of the College of Physicians and
Sturgeons had a meeting on May 28 th, when they had a talk from Mr. E.
M. Casey, of the Washington State Medical Bureau.
Mr. Casey gave us some very interesting and timely information. The
Bureau was started some three or four years ago as a definite attempt on the
part of the profession in Washington to give to the public a health service.
Today, in King County alone, they have 406 physicians, with some
28,000 beneficiaries, and the scheme is apparently growing.
At present, families are not included, but the wage-earner receives a
large measure of medical service, including doctor, hospital, drugs, consultations, etc. Each patient has free choice of doctor. Payment is by the fee
system for services rendered, and appears to be fairly satisfactory, working
out at from 50% to 60% of the statutory fee list, with prospects of improvement.
We are gathering more data on this through Mr. Casey.
The luncheon of the B. C. Medical Association on Health Insurance
held on May 21st was a great success, and it is hoped to hold others.
Dr. T. R. Whaley has just returned from a trip to Great Britain and
the Eastern States.
196 ■_■■_.
Dr. A. C. Frost's second son, Jack, has just completed his medical course
at McGill. His older son, Gardner, another graduate of McGill, is at present
spending a holiday in Vancouver.
Dr. Herman Robertson of Victoria, president of the Canadian Medical
Association, also has a nephew who has just graduated in medicine at McGill,
with very high honours: Dr. Rocke Robertson, son of Mr. Justice Robertson.
Dr. Howard Spohn has gone to Vienna on a postgraduate trip.
Dr. W. A. Kemp has recently opened an office in Vancouver, specializing in endocrinology.
The Osier Club had their annual blow-out at Vancouver Golf and
Country Club at Burquitlam on May 28th. It had rained heavily all morning, and some of the members shewed a lamentable lack of faith in the
special divinity that looks after Thursday afternoons and golf and the medical profession, in their hesitation about going. But the deity aforesaid was
on the job, and the afternoon was quite fine.
The days of summer holidays are approaching. Perhaps the most ominous
sign is that Dr. "Jimmy" Sutherland has missed several games of golf, in
obedience to what he doubtless thinks is the higher law of family duty. He
was last seen with "a hammer and two of his daughters" (sic!) disappearing
in the direction of his summer cottage on the North Arm.
Ranson, S. W.—Anatomy of the Nervous System. 193 5.
French, H.—Differential Diagnosis.   1936 (donated).
1936 Yearbook of Paediatrics.
1936 Yearbook of Obstetrics and Gyn_cology.
1936 Yearbook of General Therapeutics.
Keys and Cromwell—Management of Fractures.   1934.
Harrison, B. M. J.—Textbook of Roentgenology.   193 J.
White, J. C.—Autonomic Nervous System.   193 J.
Butlin, H.—Diseases of the Tongue.   1931.
Rehfuss, M. Z., and Belson, G. M.—Medical Treatment of Gallbladder Disease. 1936.
Mosenthal, H. O.—Variations in Blood Pressure and Nephritis.   1931.
Boyd, W.—Pathology of Internal Diseases.   1936.
Jennings, H. S.—Genetics.
Hirschfield, M.—Men and Women.
Yearsley, M.— Le roi est mort.
Marette, J. R.—Race, Sex, and Environment.
Hale-White, Sir W.—Great Doctors of the 19th Century.
Ballance, Sir Charles—History of Surgery of the Brain.
MacAlister, E.—Sir Donald MacAlister.
Reid, E. G.—The Great Physician (Sir Wm. Osier).
Williams, L.—Minor Medical Mysteries.
Munthe, A.—Story of San Michele.
Gosse, P.—Go to the Country.
Schleich, C. L.—Those Were Good Days.
At this time, a little more than a month before our annual meeting,
it seems fitting that a review of the happenings in the British Columbia
Medical Association during the past few months be undertaken in order
that the members generally have some understanding of our present position, particularly in regard to such important matters as our relationship
with the Canadian Medicali Association, and with the College of Physicians
and Surgeons of this Province.
You will recall that at our last annual meeting a resolution was passed
authorizing the present Executive of the British Columbia Medical Association so to change our Constitution that we be known as the Canadian
Medical Association, British Columbia Division. Our Constitution and
Bylaws Committee promptly undertook the study of this, conferred with
the Council of the College of Physicians and Surgeons, and secured their
hearty support. The Council in turn referred the whole matter to their
legal advisor for his considered opinion as to how this could best be! accomplished. After careful study on his part, he gave it as his opinion that the
change could not be satisfactorily made without amending the Medical Act.
Accordingly, at the request of your Executive, the Council had the necessary amendments to the Medical Act of British Columbia drafted and ready
for introduction at the last session of the Legislature. As you are aware,
Health Insurance became the dominant issue at that time and the relationship between our profession and the Government became so delicate that
it was deemed inadvisable to attempt to introduce any amendments to the
Medical Act for the time being. Hence, postponement of our becoming a
Division of the Canadian Medical Association became imperative. Your
Executive had hoped to have completed the change at its annual meeting
this coming June, and had not these difficulties arisen would undoubtedly
have done so, but now it will be another year, at least, before anything final
can be accomplished in this regard. In the meantime the Canadian Medical
Association has been kept acquainted with our difficulties and I am sure
it is in full agreement with our action.
Despite some difficulties that occurred during the winter between the
Canadian Medical Association, particularly the Journal, and our own Asso-
^ption, which I feel were very satisfactorily cleared by the excellent gesture
of the Executive of the Canadian Medical Association itself in sending
Doctors Bazin and Routley to the coast to assist us in any way they could,
there still exists the happiest relationship between the Canadian Medical
Association and the profession of British Columbia. The very frank and
open way in which our problems were discussed could only lead to better
understanding and ultimate good, not only to the medical organization in
this Province, but to the profession in Canada as a whole. The Journal
recognized the mistake it had made in publishing at a very inopportune time
an article that was detrimental to our interests, and I feel confident that the
policy of that publication will be altered in such manner as to give some
leadership in solving the economic problems that are facing the profession
today. I earnestly hope that in the near future Canadian Medicine will enjoy
a much better solidarity than at present exists; it appears to me that the
greatest need facing Medicine in Canada is solidarity. In that I include1 all
branches of the profession, public health, hospital authorities, Universities
Page 198 ,   :.
and those engaged in actual practice. We are far too divided at the moment.
Why cannot we all unite under one banner, with one object in view, namely:
collectively and through our own purely Medical organization to put Medicine on the highest plane possible in every particular that affects our relationship with the public we serve? Our primary allegiance should be to our
own medical organization no matter in what department we happen to find
Health Insurance has been of necessity the main concern of the profession this year, and your Executive has given its full support to the Council
of the College of Physicians and Surgeons and the Health Insurance Committee in their struggle with the Government and the Legislature over this
rather miserable legislative experiment. I am satisfied that everything possible was done to protect the public and the profession in combatting the
Health Insurance Bill; the Government was apparently committed to
Health Insurance in some form, no matter what its consequences to the
medical men of the province might be. I feel that to protect the public and
ourselves we would be fully justified in taking a very decided stand against
anything that would tend to lower the standard of medical practice in
British Columbia. The Health Insurance Q>mmittee is still gathering data,
and studying all aspects of medical work here, in order to be ready when the
occasion arises to protect the interests of the profession. It deserves our
heartiest support. Our main efforts must be toward developing strong effective organization, and to that end your Executive, on recommendation from
its Constitution and Bylaws Committee, has decided to incorporate under
the Societies Act of the Province as the Scientific and Educational Section of
the College of Physicians and Surgeons, still retaining its name. This will
clearly define the functions of the two bodies, which have the same membership and the one fee. This should simplify and materially strengthen medical
organization here in British Columbia. It will in no way interfere with our
becoming a Division of the Canadian Medical Association when the time is
The appointment of an Executive Secretary of the two bodies in the
person of Dr. M. W. Thomas, a man who knows first hand actual conditions
of medical practice in B. O, has been a very wise move. A man with his
knowledge and experience of medical life here, and devoting his full time to
the work, should materially help in uniting the profession in B. C. and help
us solve our many problems. This appointment fills a gap that has been
staring at us for a long time. It is for us to give him our hearty support
and the confidence that his position demands if he is to be of most value to
us. He should be a key man with us and it is up to us to make him so.
There are many other activities of your Association during the year
which I could cite, but space does not allow more at this time. These will
be presented at our annual meeting in the form of reports. I sincerely hope
that all who possibly can will be present at our annual meeting on June
23rd, which is held during the Canadian Medical Association Convention
in Victoria.
The C. M. A. Convention has been very carefully arranged and should
be well worth anyone's while attending. Health Insurance will likely
again be a dominant issue at the annual meeting of the College of Physicians
and Surgeons, and that alonef should impel everyone to be present if at all
possible. Kindly make every effort to be present in Victoria, June 22nd
to 26th.
Page 199 I wish to thank the members of the Executive and the various Committees for their hearty co-operation and support during the year.
Thanking you all very sincerely,
H. H. Milburn, President,
B. C. Medical Association.
By C. E. Dolman, M.B., B.S., M.R.C.P., Ph.D.(Lond.), &c.
The following paper, read by Dr. Dolman before the Vancouver Medical
Association on April 7th, 1936, suffers from the unavoidable omission of the
illustrations which added so much to its interest. Dr. Dolman proposes to publish
elsewhere, and at a later date, a more extended version of this paper, and meantime
we appreciate the opportunity to give this to our readers.—Editor.
Definition: Serum. Therapy may be broadly defined as the transference
of a specific humoral antibody from an animal known to have a high concentration of this antibody in its blood, to another animal which it is
desired to endow temporarily with an increased supply of the same antibody.
The advantage of so broad a definition is that while it emphasizes the
basic principle of serum therapy, yet all the proper applications of the term
appear to be covered. Thus the antivenins come within the scope of our
definition; the possible use of a species other than equine as donor, or other
than human as recipient, is not precluded; hyperimmunization of the donor
is not made an essential prerequisite; and recognition is given to both the
prophylactic and the remedial aspects of serum therapy.
Time will not permit any attempt to cover, this evening, the whole
subject of serum therapy as above defined. I must not discuss its past history,
nor speculate as to its possible future. Neither the antivenins, for instance,
nor the applications of serum therapy to veterinary practice, can be considered. I propose to confine attention to the principles and problems involved in the use of certain specific antitoxic and antibacterial substances
(obtained from the blood serum of hyperimmunized horses) for the prophylaxis and treatment of human infections.
Classification: Hyperimmunized horse serums are customarily classified into two main groups, antitoxic and antibacterial.
Antitoxic serums, or antitoxins, are prepared from horses which have
received a series of injections of a bacterial filtrate containing either crude
exotoxin, or formalinized exotoxin (toxoid); and are assayed by determination of their specific neutralizing power for the corresponding toxin. The
laptitoxic serums currently available, with their approximate dates of introduction to the medical profession, will neutralize in vitro the toxins of the
following micro-organisms:
C Diphtheriae (1890) ; Cl. Tetani (1892); Cl. botulinum (1897);
Bact. Shigae (1904); Cl. welchii, Cl. septique, Cl. cedematiens (1918);
Str.   scarlatina;   (1924);   Staphylococcus   (1934);   N.   meningitidis
Antibacterial serums, on the other hand, are prepared from horses which
have received a series of injections of a suspension containing either dead
or living bacteria; and are assayed in terms of either their agglutinating
power against suspensions of the homologous micro-organisms, or—more
satisfactorily—their power to protect a laboratory animal against the lethal
effects of a measured dose of this micro-organism. Serums of this type were
Page 200
S1 M
introduced, at the approximate dates shown, for use against the following
1. B. anthracis (1895); 2. N. meningitidis (1906); 3.   Str. pneumoniae (1910).
Other less well-known anti-bacterial serums have been prepared and
their clinical use reported, against:
Bact.   flexneri   (1902);   H.   influenzae   (1911);   Bact.   typhosum
(1935); Br. abortus (193 5).
I shall first give consideration to certain general principles and difficulties underlying successful application of serum therapy, illustrating my
remarks by reference to some of the foregoing antitoxic and antibacterial
Principles of Serum Therapy: The first principle of serum therapy
is Specificity. That is, the antibodies which the patient receives must be
specific for the toxaemia, or the infection, or both, from which he is suffering, or against which it is desired to protect him. This principle clearly
presupposes correct diagnosis. An acute pharyngitis due to staphylococcus
will not be benefitted by diphtheria antitoxin; nor an acute tuberculous
broncho-pneumonia by anti-pneumococcus serum; nor a streptococcal
osteomyelitis by staphylococcus antitoxin; nor a meningitis due to H. influenzae (Pfeiffer's bacillus) by anti-meningococcus serum. When no laboratory facilities are available for an immediate attempt to identify the casual
micro-organism in severe cases of acute pharyngitis simulating diphtheria,
of pneumonia, of osteomyelitis, or of cerebro-spinal meningitis, it is justifiable to administer, without delay, the serum homologous with the microorganism most commonly responsible for the disease in question. But a
definite proportion of failures of serum therapy will be attributable to this
source of error.
Apart from species specificity, there must be considered type specificity.
Type specificity should be particularly kept in mind in pneumonia. Type 1
anti-pneumococcus serum is of no avail to a patient with pneumonia due to
Type 2 pneumococcus. To take another example, Cl. botulinum occurs as
two types, A and B, which produce antigenically distinct toxins. A case of
botulism, fortunately a rare disease, due to Type A would derive no benefit
from antitoxin prepared from Cl. botulinum Type B. As more is learned of
the relationship of antigenic structure to pathogenic effects, the importance
of type specificity as an important factor in other varieties of serum therapy
may become increasingly recognized.
The second principle of serum therapy is Potency. That is, the desired
antibodies must be present in high concentration in the serum, so that they
may be available to the patient in a minimum bulk of alien protein. Satisfactory observance of this principle depends upon the acceptance of unilS
the imposition of standards, and distribution under licence. International
units of potency have been proposed and accepted for the majority of the
antitoxic and antibacterial serums already listed. It is interesting and gratfSjj
fying to note that the investigation and control of these units has latterly
been conducted under the aegis of the League of Nations (Committee on
Standardization of the Health Organization of the League). Most of these
units involve, officially, determination of the highest dilution of the respective serums which will protect some small laboratory animal (usually
guinea-pig or mouse) against a stated number of minimal lethal doses of
the corresponding toxin or live culture. Various other methods of determining potency are practised.
Page 201
*_w H The production of high potency serum depends upon the operation of
several factors, among which are the following: the selection of suitable
horses; the use of a satisfactory antigen; correct volume, time, and route
of doses; careful checking of the fluctuations in circulating antibody by
frequent trial bleeds of the horse; prompt exsanguination when the trial
bleed shows an appropriately high titre of antibody; efficient methods of concentration and refinement. While the aim of every ethical manufacturer of
serums is to increase the potency of the products, a definite limitation is
set by a regulation which prohibits a content of more than 20% of total
solids in therapeutic serums.
The licensing authorities on the North American continent are the
National Institute of Health, Washington, and the Laboratory of Hygiene,
Ottawa (operating under the Department of Pensions and National
Health). Connaught Laboratories, the only serum institute in Canada
licensed to manufacture biological products by both Washington and
Ottawa, is subject to inspection by their representatives, and must observe
the standards they impose. The United States regulations require the potency
of every serum to be printed on the outside of the package as well as on the
label of the vial. Where no official unit has been accepted, the words "No
U.S. standard of potency" must appear. Substandard serums have undoubtedly been distributed in the past in certain countries, but increasingly
stringent regulations are now being applied.
The third principle of serum therapy is Early Administration. That is,
given a supply of specific, high-potency serum, its efficacy will diminish
EJipidly with delay before administration, till a time is reached in the progress of the disease when no amount of serum, however specific and potent,
will exert any apparent beneficial effect. This principle presupposes a prompt
diagnosis, the knowledge that serum therapy is indicated, and availability
of the requisite serum. To defer the diagnosis of diphtheria, for example,
until a case of presumed broncho-pneumonia has come to autopsy, will not
help anybody; and one has encountered many examples of staphylococcal
septicaemia, particularly in adults, which remained undiagnosed until the
disease had progressed to a hopeless stage. One man, I recall, had an appendectomy performed at a large teaching hospital for staphylococcus septicaemia. Another got infected after a prostatectomy, and ran an intermittent
fever for three weeks before a blood culture was done and a septicaemia
found. Make good use, therefore, of your laboratories.
Then there are many instances of the diagnosis having been made early
enough but serum therapy being delayed until the patient was moribund.
The doctor does not know there is a serum, or else he decides to hope the
patient will get well without it. Moreover, it is regrettable that serums are
not always as readily available as they should be. They are costly, and while
some provincial or municipal governments make provision for the supply
of certain types of serum to those who cannot afford to pay for them, there
is no doubt the expense of serum therapy is often regarded as prohibitive.
But a greater demand for serum would permit a lesser price. When there is
a very rare demand for a serum, the manufacturers will tend to be less
interested in its production than in the improvement of a serum which is
widely used. If you encounter tomorrow a case of botulism, for instance,
you would certainly experience some delay before obtaining a supply of the
appropriate serum.
The importance of this principle of early administration derives from
the fact that the deleterious effects of pathogenic micro-organisms upon the
Page 202 ■%'
animal body are attributable to a process akin, in certain respects, to
chemical union between the animal cells and the toxic substances derived
from the micro-organisms. This chemical union is to some extent irreversible.
The final firmness of the union may vary with the different micro-organisms
concerned, and for every bacterial toxaemia there is possibly a period of
definite duration in which the union between cell and toxin is relatively
loose. The local blanching of the scarlet fever erythema following the early
injection of the specific antitoxin into the skin (Schulz-Charlton reaction)
is possibly an instance of a relatively loose cell-toxin union. In gas gangrene
infections, again, the toxins appear to form a looser type of union with the
body cells than in diphtheria, tetanus, or botulism, where the union appears
to be almost completely irreversible. In these latter diseases, indeed, once
symptoms have appeared, our resort to serum therapy is founded on the
hope that widespread toxin-cell union has not already occurred to an extent
not yet manifest clinically, and on the assumption that all newly-formed
toxin will henceforward be neutralized.
It is interesting to contrast the small amounts of circulating antibody
which suffice to protect from an infection, with the relatively enormous
amounts which may be got into the blood stream in serum therapy, to no
advantage if they get there too late. The presence of %00 unit of diphtheria
per cc. of serum generally suffices to ensure protection against the disease;
yet a patient treated with antitoxin at a late stage may die despite the
presence of 10 units or more of antitoxin. Again, the prophylactic dose of
1500 units of tetanus antitoxin will usually result in a circulating titre of
about % unit of antitoxin a few days later, and this will protect against the
disease. Yet one hundred times this titre of antitoxin acquired through late
serum therapy may prove absolutely useless. Patients who recover from
lobar pneumonia rarely develop a sufficient amount of antibody in their
serum to protect mice against more than 100 lethal doses of homologous
pnemococci per cc. After late administration of anti-pneumococcus serum,
on the other hand, 1 cc of a patient's blood may be able to protect mice
against 1,000,000 lethal doses of homologous culture, and yet the patient
may die. The very small amount of measles antibody which can reach the
blood of a measles contact, following injection of 10 cc of convalescent
serum, is almost always sufficient to prevent the development of the disease
if given during the first five days after exposure, but no amount of convalescent serum has any apparent effect upon the disease once manifest.
Antivaccine virus serum injected intradermally into a rabbit before injection of vaccinia virus into the same site, will prevent the characteristic
reaction. Given one minute after the virus, the serum will have no inhibiting
effect. Anti-Rous sarcoma serum given to a fowl before injection of a sarcoma filtrate will confer temporary immunity; given after the injection will
not prevent development of the tumour. Examples of the operation of this
principle might be multiplied; and I have gone into it at some length
because it is of such fundamental importance, and is on the whole ill-appreciated.
Closely related to the third, are the fourth and fifth principles of serum
therapy, namely, those of optimal route and adequate dosage. Bearing in
mind what has been already stated, it is clearly of paramount importance
that, once the disease is diagnosed, a decision to resort to serum therapy
reached, and a supply of specific serum at hand, our main' object must be
to bring a large quantity of the antibody into as intimate a contact as
possible with those parts of the body where extensive cell-toxin union has
Page 203 occurred, in an attempt to break up this «_ion; with those foci where toxin
is still being produced, in order that neutralization in situ may take place;
and with those tissues which have so far resisted the effects of the toxin, with
a view to protecting them therefrom. In generall all this is best achieved
by the intravenous route of administration. Given by this route, all the
serum injected is at once distributed throughout the body, and the maximum
concentration of circulating antibody will be reached just after completion
of the injection. The delayed absorption of antibody from the muscles is
not sufficiently realized. Following an intramuscular injection of a serum,
e.g., diphtheria, scarlet fever, or staphylococcus antitoxins, from 48 to 72
hours must elapse before the maximum titre of antibody is detected in the
blood stream. Such a delay may be literally fatal in a disease of rapid course,
such as lobar pneumonia; and little or nothing is gained by administering
antipneumococcus serum by any route other than the intravenous. Indeed,
with few exceptions, all serums should, both in theory and in practice, be
given intravenously, although this route undoubtedly entails more trouble
to the doctor, and constitutes a greater reaction hazard to the patient.
Meningitis is one exception to this rule. In the serum therapy of meningitis
—whether meningococcic, influenzal, pneumococcal, streptococcal or
Iffiaphylococcal—the intrathecal route must be adopted, since very little
^ptitoxin permeates from the blood stream, through what Friedemann has
called the "blood-brain barrier," into the cerebrospinal fluid. On the other
hand, intravenous serum should also be given when there is a concomitant
septicaemia. There are occasions when direct application of serum to an
exposed infected surface would seem to be indicated; as, for instance, in a
pneumococcal empyema drainage wound, an osteomyelitis, or a carbuncle.
Again, in the prophylactic use of serums, the intramuscular route, if
resorted to very soon after exposure to infection, usually permits sufficiently
rapid absorption to ensure protection. The same route will serve in the ordinary case of uncomplicated, well-localized carbuncle. But, in general, therapeutic serums should be given intravenously, if possible.
So much for the principle of optimal route. The principle of adequate
dosage is self-explanatory, though in actual practice far too seldom observed.
The general tendency is to give too little serum, and to this fact many of
the failures of serum therapy are undoubtedly due. There is no fixed treatment dose of serum, although direction sheets usually state some figure as a
guide. In prophylaxis, a definite dose may be fairly safely recommended; but
in treatment, each case presents a special problem. The age and general condition of the patient, the type and severity of the infection and toxaemia,
the presence of complications, and especially the duration of the illness, and
the response to the first doses of serum, must all be taken into consideration.
The longer the time since onset, the more serum will be necessary. More
must be given by the intramuscular route than by the intravenous route.
And it is important! to be especially liberal in dosage when there has been a
blood stream infection, with multiple foci, as e.g. in staphylococcal septicaemia. In such conditions, the blood stream may become sterile and the
patient appear much better, so that serum is withheld; the circulating antitoxin is excreted, or at any rate diminishes in titre; and then, a few days
later (this has happened so often) a relapse occurs, and staphylococci reappear in the blood stream. The principle of adequate dosage really involves,
in fact, that a high titre of circulating antibodies should be maintained until
the infection, is well localized, and toxaemia satisfactorily abated.
The sixth and final principle is that of accessory treatment. Serum
Page 204
t» w
therapy is too frequently the last resort of the harassed practitioner. All
else may have been done for the unfortunate patient—quite commonly
under a mistaken diagnosis; and then, with the patient moribund, recourse
is had to serum therapy. I hope from what I have said, and shall say tonight,
to make clear to you that recourse to serum therapy at this stage of a disease
is tantamount to the requisition of a miracle. In other instances, serum may
be given comparatively early in the infection, but is expected to eliminate
the disease without any other treatment except for rest in bed, an attractive
nurse, and a reasonably digestible diet. In the pyogenic infections particularly, pus can be expected to form, and should be considered of favourable
portent, provided it be drained. The letting out and mopping up of pus is,
after all, one of the surgeon's chief functions; but one1.has been continually
surprised to find a reluctance to perform this very important accessory
Difficultees in Serum Therapy. Some of the main difficulties militating against successful serum therapy may be considered under the heading Complications. These complications may occur during the course of
any relatively simple infection, just as a satisfactory outcome appears in
sight. First, one may mention secondary infection. This has occurred several
times in my own experience: e.g., a patient being given staphylococcus antitoxin for severe osteomyelitis and septicaemia, and doing well, takes a grave
turn, and dies of streptococcal pericarditis; another, making a most gratifying recovery with the help of serum therapy from staphylococcal meningitis,
developed a double secondary infection of the meninges with a haemolytic
streptococcus and a diphtheroid bacillus, which proved fatal; yet another,
having turned the corner in a staphylococcal septicaemia, in the course of
which it was necessary to resect a rib to drain an abscess, developed a pneumococcal empyema. Full use should therefore be made of the laboratory at
all stages of severe infections of this type. The reports will not only add
inestimably to the value of case records, but will indicate eventualities of
the foregoing order.
More common types of complication are those attributable to the peculiar habits or habitats of the micro-organisms involved. Abscess formation
may occur, for instance, in remote and vital parts of the body, such as the
brain, kidneys and lungs. Serum has no power to cause absorption of an
abscess any more than the therapeutic serums in common use can act like
an in vitro antiseptic and directly kill their homologous micro-organisms.
Again, infection may settle in certain foci inaccessible to the blood stream
and there prove comparatively unamenable to serum therapy. Hence an
osteomyelitic focus may be expected to discharge pus and micro-organisms
long after the patient is convalescent from septicaemia. An ear may discharge following streptococcal otitis media, for weeks after the patient has
overcome, with the help of scarlet fever antitoxin, a severe attack of scarlatina. Or pneumococcal pus may continue to discharge from an empyema
drainage tube during convalescence from pneumonia successfully treated
with pneumococcus antitoxin. In other words, the value of a high titre of
specific circulating antibody to any one part of the body infected with a
micro-organism, will depend upon the extent to which the blood fluids gain
access to that part.
Reactions constitute another serious difficulty rather frequently encountered in serum therapy. These reactions are of different aetiology and character, and may be considered as of three main types, the Allergic, the Thermal,
and Serum Sickness
Page 20 ■> The allergic reactions arise from parenteral injection of certain substances peculiar to the horse and highly toxic to certain human beings,
which it has not yet proved possible to separate from the desired specific
antibodies. Dyspncea, cyanosis, rapid weak pulse, flushing of face, pain in
abdomen and in lumbar or substernal regions, apprehension, and collapse,
may all be present in varying degree, and their onset is usually within one-
half hour of the first injection of serum. In its most severe manifestation,
this reaction may prove almost immediately fatal; but this acute shock-like
form is fortunately rare. In other less severe types of allergic reaction, the
above syndrome may be complicated by urticaria or an acute asthmatic
attack. The treatment of allergic reaction is by epinephrine, one-half to one
cc. of the 1:1000 solution, given subcutaneously, intramuscularly, or in
severe cases intravenously. Repeated doses may need to be given. While mild
degrees of allergic reaction are no contra-indication to further administration of serum, provided they prove controllable by epinephrine, in the more
severe types of reaction—particularly those accompanied by urticaria or
asthma—no more serum should be given.
Most, though not all, allergic serum reactions may be avoided by doing
eye and skin sensitivity tests on every prospective recipient of horse serum.
In the eye, or ophthalmic, test, a drop or two of normal horse serum, diluted
1 in 10, is placed in the conjunctival sac. A positive reaction is marked by
erythema, lachrymation, and reddening of the eye, within 20 minutes after
instillation of the serum. In the skin, or intradermal test, 0.1 cc. of normal
horse serum, diluted 1 in 10, is injected intradermally into the flexor surface
of the forearm. A positive reaction will be indicated within 5 to 20 minutes
by the formation of an urticarial wheal at the site of injection, surrounded
by a zone of erythema which may show irregular, pseudopodia-like extensions.
Positive sensitivity reactions to horse serum will usually be given by the
following individuals:
1. Those who are spontaneously sensitive to horse dander. A history of
such sensitivity signifies that serum therapy would be very hazardous,
and is best avoided.
2. A certain proportion of persons who are subject to asthma, hay fever,
and similar allergic conditions. Even if the sensitivity tests are negative, it is advisable to precede the injection of serum, in patients of
this type, by an injection of epinephrine; while, if the intravenous
route is to be used, a smaller initial dose than usual is indicated, and
the injection must be given with extreme slowness.
3. Patients who have had an injection of horse serum within a period of
from 7 to 10 days up to a few months previously, or who are still
suffering from serum sickness (videinfra). Sensitivity to horse serum
acquired from previous parenteral administration is not commonly
very acute after a few months have elapsed; but the precautions
stated in the preceding paragraph should be observed.
4. Positive sensitivity tests will be given in some instances where there
is no history of either allergy or a previous injection of serum. The
existence of such individuals alone makes the performance of the
sensitivity tests a desirable routine procedure.
Desensitization may be attempted in individuals who give a positive eye
or skin reaction. No one method is prescribed for this, but in severe cases
of sensitivity, a commencing dose of the serum to be used as small as %o cc->
subcutaneously, is advocated. Successive doses should be given by the same
Page 206
, % route at intervals of 10 to 15 minutes, each dose being double the preceding
dose, provided that no undue reaction has occurred in the meantpie. When
1 to 2 cc is well tolerated by the subcutaneous route, intravenous administration may be commenced. The rate should be very slow. Anti-pneumococcus serum, for instance, which is usually injected from a syringe directly
into the vein, should be given at a rate not faster than 1 cc. per minute;
while other serums are perhaps best given intravenously by a slow continuous drip method, diluted in saline, so that the first 1 cc. may take 1 hour.
While the allergic reaction hazard is greatest when serum is given intravenously, it should be emphasized that severe reactions of this type may
occur following the intramuscular or any other route of administration, if
due precautions be not taken to guard against them.
Thermal or chill reactions are not due to allergic sensitivity, as this is
ordinarily understood, but to some factor peculiar to the serum, to the
patient, to the disease, or to the interaction of these three variables. Between
20 minutes and 1 J_ hours after the first injection of serum, a general rigor
will occur, lasting up to J_ hour, accompanied by cyanosis, dyspncea, rapid
pulse, low blood pressure, and apprehension. The temperature may rise several degrees, and subsequently falls, with profuse sweating. Milder reactions
of this type need give rise to no alarm; but if severe, further serum should
be withheld for a few hours. In pneumonia, or septicaemic conditions where
the temperature is usually already high, alarming degrees of hyperthermia
may result, accompanied by pronounced cyanosis, almost uncountable pulse,
delirium, convulsions and collapse. When this occurs, no further serum
should be given. In the presence of pre-existing obstruction to the pulmonary circulation, severe myocarditis or hyperpyrexia, a fatal issue may
occur in consequence of a superimposed thermal reaction.
Liability to thermal reactions is not indicated by tests for serum sensitivity. Certain batches of serum seem more prone to contain the reaction-
producing factor than others, but in general concentrated and refined
products are less liable than crude serums to produce thermal reactions.
Epinephrine has little or no effect upon this type of reaction, and the
treatment is symptomatic. Precautions to be taken to minimize their incidence include very slow administration of the serum, warming serum to
body temperature prior to administration, and rejection of all serums containing a precipitate.
Serum sickness is a fairly common type of delayed reaction to horse
serum therapy, with onset characteristically on the 7th to 10th day after
the first injection. Urticaria (which may be troublesome for a day or so),
joint pains and swelling, generalized glandular enlargement, cedematous
foci, with mild fever, are the most common features. Epinephrine and
ephedrine may prove useful, but for the most part treatment is symptomatic. The condition is never dangerous and is transitory.
A further difficulty of serum therapy may be defined as that of the
unknown extent of irreparable antecedent damage to vital cells and tissues.
The patient may, in other words, have already suffered fatal, but not clinically apparent, damage before any attempt is made to give specific serum
therapy. Such patients are to all intents already dead. A toxic myocarditis,
metastatic abscesses in the lung, or thrombosis of a cerebral vein, may be
present but undiagnosed at the time the decision is made to give serum.
This difficulty is, in fact, a restatement (from a somewhat different viewpoint) of Principle 3, viz. early administration.
The final difficulty, to which only brief allusion will here be made, arises from the incompleteness of available specific antibodies. This incompleteness derives, in turn, from our comparative ignorance of the parts played by
various bacterial antigens in furthering the progress of any one infection.
Diphtheria, tetanus, and botulism represent true toxaemias; that is, the
respective micro-organisms have no invasive powers, and all the outstanding
signs and symptoms of these diseases are attributable to toxins disseminated
throughout the body from a localized focus of multiplying bacteria. The
situation is very different in many of the other diseases for which serum
therapy is advocated. In streptococcal and staphylococcal septicaemias, for
instance, our problem is not only to neutralize toxins, but also to aid destruction of the infecting micro-organisms.
None of the antitoxic serums at present in use are actively bactericidal,
but certain of them are believed to promote phagocytosis by neutralizing
specific leucocidic substances liberated by the homologous micro-organisms.
One of the outstanding problems in serum therapy is the production of
specific antibodies to combat those factors which bestow the property of
invasiveness upon certain micro-organisms. There has recently been a considerable revival of interest in the analysis of the mechanism of bacterial
invasiveness, and this is yielding promising results.
By H. H. Pitts, M.D.
(Read before the Osier Club, April 22, 1936.)
These tumours are said by same authorities to be relatively rare and by
others to be relatively common, and the fact that I have seen, probably I
should say recognized, only this one case, which serves as the excuse for this
paper, in well over 50,000 surgical specimens of all types examined in the
past fifteen years, would seem to point to their rarity, at least as far as
one's own experience is concerned. These tumours vary greatly in size, many
being extremely minute and others seen only on microscopic examination,
and this fact may account for the relatively small number reported in the
literature until fairly recently, when previous reports have stimulated
interest in them and probably caused observers to be more watchful for
Up to the present time approximately 245 "cases have been reported,
and these have been admirably reviewed by Bland and Goldstein in the
August, 193 5, number of Surgery, Gynecology and Obstetrics. Novak and
Brawner, in the November, 1934, number of the American Journal of
Obstetrics and Gynecology, present an excellent clinical and pathological
study of 36 cases coming under their own observation, and present details
of historical interest, histogenesis, diagnosis and treatment. They begin
their paper with the two following paragraphs:
"A striking illustration of the slowness with which new knowledge
permeates the medical profession is to be seen in the case of the granulosa
cell tumours of the ovary. Within the past few years this group of neoplasms
has been so much discussed by gynaecologic pathologists that one might get
the impression that they constitute a newly described type of growth. As
a matter of fact, the pathologic characteristics of these tumours were fully
described more than twenty years ago, while during many years before and
after this a considerable group of more or less clearly defined instances of
Page 208 I
1 ■.
the lesion had been reported, though often under other names. The present
common designation of these tumours as 'granulosa cell carcinoma' was
applied more than a score of years ago.
"The present-day interest in tumours of this variety is due, first, to a
realization of the fact that they are not nearly as rare as was once believed;
and, second, to the fact that they possess interesting biological properties
not shared by most other ovarian tumours. It is this latter characteristic
especially which, in this day of feverish interest in gynaecological endocrinology, has stimulated the study of granulosa cell tumours of the ovary."
We are indebted chiefly to Robert Meyer and Von Werdt for the present-
day knowledge of these tumours—to Von Werdt for the name and thorough
pathologic study, and to Meyer for the theory of histogenesis; i.e., origin
from granulosa cell rests, which is now generally accepted. Von Kahlden
reported the first case in 1895 under the name of "adenoma of the Graafian
follicle," and soon many other reports followed with, also, the coinage of
many new terms. Meyer's theory is that these tumours arise from granulosa
cell rests remaining f roh the early oophorogenetic phase of ovarian development and he offers as support for this theory! the histological characteristics
of the cells, their frequent arrangement in folliculoid fashion and the effect
on the endometrium. Embryonal cell rests have been found in theovaries
of the newborn and with the findings reported by Te Linde and Geist from
the microscopic study of very early granulosa cell tumours, still further
support is given to the probable origin in embryonic rests of the ovarian
parenchyma in the ovarian medulla.
The tumours vary from millimetre or even microscopic size to 15 or
20 cm. in diameter, but some have occupied almost the entire abdominal
cavity. The shape varies, but, generally speaking, they assume a more or less
ovoid form, frequently somewhat lobulated, usually unilateral but quite
frequently bilateral. On section they present a more or less solid pinkish-
white cut surface but, especially in the larger ones, there may be considerable degeneration or cystic change. They are generally fairly well circumscribed. Histologically, the tumours can be subdivided into three fairly
well defined sub-groups according to the predominating arrangements of
their cells: (1) the folliculoid, in which the cells show a tendency to follicle
reproduction or simple rosette formation; (2) the cylmdromatoid, where
the cells are arranged more in column-like masses or alveolar aggregations
without definite follicle formation. This type is said by some to be the most
common and they are frequently diagnosed, even microscopically, as carcinoma solidum, medullary carcinoma and endothelioma. (3) The diffuse or
sarcomatoid group. Here the epithelial cells assume a much more atypiggij
appearance and both cylindroid and folliculoid characteristics are seen, as
well as diffuse sarcomatous-appearing masses and nests of cells, or the whole
picture may be sarcomatous in appearance.
The clinical aspects of these tumours are even more interesting than
their rather complex and varied histological structure, due to the definitely
established fact of the secretion of ovarian follicular hormone by them
with resultant very remarkable manifestations, more especially during what
might be termed the "latent" period of ovarian activity, i.e., before puberty
and postmenopausal. Children show well marked sexual precocity with
hyperplastic and hypertrophic mammary changes even in 5 and 9-year-old
girls, secretion of colostrum, development of pubic and axillary hair and
vaginal bleeding. In old women, there occurs what might be termed a
rejuvenation manifested by hypertrophy of the breasts, either regular or
Page 209 irregular menstruation, enlargement of the uterus to the size of the normal
uterus of the childbearing years and hyperplastic changes in the endometrium.
A more confusing picture is presented during active sexual life, but
where there is a long history of metrorrhagia not responding to the usual
endocrine therapy, it should suggest the presence of a granulosa cell tumour,
especially so if either unilateral or bilateral ovarian enlargement can be
detected. Then, again, amenorhcea may be the prominent feature, or it may
alternate with profuse and prolonged bleeding, which array of symptoms
in the presence of a unilateral pelvic mass, breast changes, etc., may make
the diagnosis of an ectopic pregnancy a very plausible one. Margaret Schulze
of the University of California Department of Obstetrics and Gynxcology,
in a paper on these tumours, notes the possibility of sterility being dependent
upon endocrine influences of the tumour, one of their patients who had
been sterile for five years having had a child two years after the removal
of one of these tumours and this without any further treatment. In this
same paper Schulze further states, "The tumour may arise at any age, but
is relatively rare before puberty and relatively common in old age. Of 80
cases which Klaften collected, 7, or 8.7%, occurred before or at the beginning of puberty; 34, or 42.5%, after the menopause. Two cases occurred
at 5 years, and 8 between 70 and 80 years."
Pain and evidence of pressure may occur at any time and age. Abdominal
enlargement is not particularly common, as generally speaking the tumours
are small, but occasionally there may be ascites. There may be evidence of
anaemia only, due to continued haemorrhage, but generally their physical
condition is good. Klaften reported that two of his cases had BMR's of plus
18 and plus 24 respectively, which returned to normal following extirpation
of the tumour. Estimations of follicular hormone in urine and stool have
been made and are found to be much increased when the tumours are
present, and gradually diminished after their removal. Besides folliculin,
progestin has also been found to be secreted. The folliculin effect has been
demonstrated by the production of cestrous effects in castrated mice. Novak
and Brawner state as follows, in a recent paper: "It is of interest to note that
the Aschheim-Zondek reaction has been positive in a number of instances,
through this mild response is not, of course, conclusive. In Pahl's case, however, both the second and third degrees of reaction were positive. This is
significant in view of what has been said as to the possibility of lutein-like
changes in the tumour cells. Just how these are to be explained we can only
speculate. The frequent finding of prolan A in the urine of these patients
suggests that there must be some interaction between the ovary and the
anterior lobe, and that the luteinizing factor of the latter brings about the
occasional transformation of granulosal into lutein or lutein-like cells.
After all, the normal lutein cell of the corpus luteum is only a modified
granulosa cell, and for that matter it is possible, as some believe, that progestin is only a modification of folliculin. If this is true, it is not difficult to
understand the occasional transforation occurring in the granulosal tumour,
while the effects of the tumour hormones are in conformity with what we
know of these effects upon the genital mucosa and sex character development generally."
In this same paper these two authors make the following statement,
which might be accepted as a diagnostic criterion for these tumours: "It is
in childhood and in the postmenstrual years that the preoperative diagnosis
of the nature of the tumour can most often be made, at least presumptively.
Page 210 . I
This is because of the physiological and biological effects produced by the
growth, which stand out sharply in patients at these ages, as already emphasized in a previous paragraph. If an ovarian tumour is demonstrable in a
child with precocious menstruation and puberty, it is very likely to be of
the granulosa cell type. Again, if a tumour is found in a patient well beyond
the menopause, associated with periodic and perhaps pseudomenstrual bleeding, it is almost sure to be a granulosa cell cancer. The likelihood is converted
into almost absolute certainty if a diagnostic curettage yields a frankly
hyperplastic endometrium. In both of these groups, hormone studies are of
even greater value that in the case of tumours encountered in patients during
reproductive life."
The following case is reported through the kindness of Drs. J. J. Mason
and J. W. Lang of West Vancouver.
Mrs. N. D. R., age 68 years.
Past history essentially negative except for radical amputation of breast, V. G. H.,
November, 1934. Typhoid fever at age of 40.
Menses began at age of 12, regular 5-6 days every 28 to age 52. Has had 7 full term
pregnancies, no miscarriages. Children all alive and well, the youngest 36 years of age.
Between the ages of 52 and 64 had no menstrual flow either regular or irregular but for
past four years has had regular menstrual flow lasting 10 days every three weeks. Complained of dyspncea during past summer but did not see her doctor. For the past few weeks
has had some pain in right lower quadrant. Bowels regular until she went to bed 10 days
ago. Vomiting past two days. A mass is palpable in lower abdomen to right of uterus and
slightly movable. Has cystocele and rectocele. Catheter urine shows trace of albumen and
moderate number of pus cells. Nocturia 1. Has been gaining weight.
Operation on March 11, 1936, by Dr. J. J. Mason. On opening the abdomen much thin,
bloody fluid was found free in the abdominal cavity. Liver, etc., normal. Left ovary was
occupied by a tumour mass which was to the right of the uterus and attached to right pelvis
by thin adhesions and in one place to the bowel, where capsule of the tumour had split
and a h„matoma the size of a golf ball was present here. Tumour delivered and resected.
Right tube and ovary normal. Uterus well developed, not menopausal type, and was not
removed. No diagnostic curettage was done but probably would have shown a hyperplastic
endometrium. The tumour measured 20x12x10 cm. A diagnosis of possible granulosa cell
carcinoma was made by Dr. Mason.
Pathological Findings
Macroscopic examination.—Specimen consists of a large, roughly ovoid but slightly
lobulated or nodular tumour mass weighing 153 gm., and measuring 20x12x10 cm.,
replacing the left ovary. A Fallopian tube stretched over it shows nothing of particular
note beyond two small parovarian cysts in its mesentery. The surface of the mass is smooth
and dilated blood vessels course over it. On section it presents, generally, the appearance of
a markedly enlarged ovary, the various structures of gigantic proportion. One pole is
replaced by a simple cyst the size of an orange, smooth lined and filled with bloody fluid.
The central portion is extremely h_emorrhagic, containing masses of blood clot arranged
within cystic structures, and here and there small yellowish masses indicate luteal tissue.
The most characteristic feature, however, consists of smaller and larger nodules of greyish,
smooth, brainlike tissue probably arising from the stratum granulosum, as would certainly
be suggested by the history. These bodies, for the most part, appear fairly well circumscribed, but the tissue itself is so cellular as to suggest a malignant process. Numerous other
small simple cysts are encountered throughout the mass, the actual size of which is largely
due to them. They are interspersed throughout, scattered amongst the tumour tissue. The
supporting structure in some fairly large areas, however, has a somewhat cellular appearance.
Microscopic examination.—A great many sections were taken through various portions
of the tumour mass and show a very variable type of structure. For the most part, the cells
are relatively closely packed, rather ovoid or somewhat spindle-shaped, almost of sarcomatous appearance, of fairly large size and showing a moderately large, fairly deeply
staining nucleus. Occasional mitotic figures are seen as well. The cells are supported by a
relatively sparse stroma. Sometimes in these masses of cells there are smaller and larger
spaces that may be immature follicles and very poorly defined as such. In still other areas
there is a somewhat glandular or pseudo-rosette/ type of arrangement, but these are very
scarce, and the whole structure is very well vascularized with some areas of quite extensive
haemorrhagic extravasation and a rather cystic or cedematous degenration. This is, appar-
Page 211 ently, a definite granulosa cell carcinoma of the ovary and evidently of the so-called mixed
Prognosis.—The general consensus of opinion is that these tumours are
less malignant than ovarian carcinoma generally, but they should not be
considered so relatively benign as some writers claim. While those that recur
do so locally or in the peritoneum, a number of cases in which osseous metastases have occurred have been reported. Novak and Brawner in their cases
report a percentage of 28.1 clinical malignancy as against the 5 to 10% rate
as an average or mean in the general literature of reported cases.
Treatment.—This is primarily surgical, and the extent of the surgical
intervention naturally varies according to the operator's idea of the degree
of malignancy of these tumours. Novak and Brawner hold the view that
in the young patient removal of the adnexa on the affected side alone, with
careful, fairly frequent, periodic check-up postoperatively, will be sufficient ; while in the patient who has borne children, or in the postmenopausal
case, it is probably the wiser procedure to do a panhysterectomy. Deep x-ray
therapy is probably a useful adjunct both pre- and postoperatively, especially
in view of the radio-sensitivity of granulosal tissue.
In conclusion, I might make a plea, at least from a pathologist's standpoint, for closer co-operation between surgeon and pathologist in the matter
of history in those cases presenting such symptoms as have been enumerated
in this paper, since this might serve as a lead in establishing more accurate
diagnoses by putting the pathologist on the qui vive for the existence of
these tumours. I feel sure that I have overlooked a goodly number in the
past and so will endeavour to burden the surgeon with a measure of the
blame due for my sins of omission.
R. G. Leland, M.D.
(Bureau of Medical Economics, American Medical Association)
(Concluded from May issue)
There is no question but Sir Henry approves health insurance. No one
disputes that position, but this restatement and emphasis of the official
statement of the British Medical Association to the Royal Commission are
of especial significance to us in the United States. In his opinion, "the organization of a national health insurance scheme is not necessarily, or even
probably, the best means of utilizing limited resources for the promotion of
national health." The United States is just now ready to discuss the question
of "the best means."
In the twenty-one years that the British system has been in operation,
about two billion dollars have been spent under the national health insurance scheme. If we are to enter on the spending of the much larger sum
which would be necessary in this country, is it not well to consider the "other
directions" in which such an "expenditure would produce an even more
satisfactory return." These quotations of Sir Henry's may be interpreted to
mean that however much he may now believe it is necessary to develop and
expand national health insurance as the only line of advance open in England, he would not advise a nation that had not entered upon this plan so to
utilize its "limited resources." This is the important phase of the question
that interests us in the United States.
That the British Medical Association recognizes that in many ways the
Page 212 I; «
existence of a national health insurance system has rendered more difficult
the problem of a proper organization of all medical facilities is shown in the
"Memorandum of Evidence by the Association's Scottish Committee" on
"The Scottish Health Services." This appears as a Supplement to the British
Medical Journal oi July 7, 1934. Paragraph 164, page 15, of this memorandum says:
"With all its imperfections, the present system of national health insurance has become
an accepted and valued part of the national life, and preserves what the Association regards
as essential factors in the relationship between patient and doctor. It would appear, therefore, to be the wiser course to provide a national medical service by the extension of the
present compulsory contributory system rather than to scrap the whole of the existing.
machinery and proceed to build on an entirely new foundation.
In other words, it is evidently still a debatable question whether if it
were possible it would be desirable "to scrap the whole of the existing
machinery and proceed to build on an entirely new foundation." Too much
stress should not be laid on this quotation, which may be to some extent
rhetorical. The previous paragraph indicates that the choice is now between
the extension, development and adjustment of the national insurance system
to meet the larger problems of medical service and "a salaried state service."
Concerning the latter, the report says, "There can be no doubt that the
great majority of the profession is strongly opposed to this." It would seem
to be a fair interpretation of the entire report to say that because the "present
system of National Health Insurance has become an accepted and valued
part of the national life" that now only two alternatives are left for the
British Medical Association to consider. One of these is the salaried state
service and the other an effort to patch up and co-ordinate the present system of national health insurance with other forms of medical service.
Sensing the opportunity to make some changes in the methods of
administering medical care to persons with low incomes, without following
the European pattern of health insurance, several county medical societies
in the United States have placed in operation plans which are worthy of
1.    Williams, J. H. Harley: A Century of Public Health in Britain, 1832-1929, London,
A. & C. Black, Ltd., 1932, pp. 46-54.
A. G. P.: This Panel Business, pp. 125 and 261-264.
Williams, loc. cit., p. 48.
Majority Report, British Medical Association to the Royal Commission on National
Health Insurance, p. 34.
McCleary, G. F.: National Health Insurance, London, H. K. Lewis & Co.,  1932,
pp. 75-80.
Lockhardt, L. P.: Industrialized Man and His Background, Lancet  1:826-828   (April
21)  1934.
Brownlie, J. L.: National Health Policy: A Critical Survey, Brit. M. J. 2:275 (Aug. 12)
1933.   Davies, Walter: Presidential Address on a Coming-of-Age: Promise and Performance, J. Roy. San. Inst. 54:219-222  (Oct.)  1933.
A. G. P.: This Panel Business, pp. 79-8 5.
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Seymour 6606
Announcing ♦ ♦ ♦
WHETHER for a vacation or definite period of
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and lovely rendezvous in Canada. With the extra
attractions of golf, trout fishing, riding, tennis,
bowls, boating and hiking over the beautiful trails,
contentment and good health are more easily and
abundantly attained. FIFTEENTH ANNUAL MEETING
JULY 8, 9, 10, 11, 1936
Chevalier Jackson, D.Sc, M.D.,
Walter J. Meek, A.B., Ph.D.  S
Harry E. Mock, B.S., M.D., Sc.D.
Roy D. McClure, M.D.
Lewis J. Pollock, M.D.
N.B.—Additional speaker in Medicine to be announced later.
This will be one of the finest meetings in the history of the Association.
Flan to attend.
For Memberships Apply to:
Medical-Dental Bldg., 530 Stimson Bldg.,
Portland, Oregon. Seattle, Washington.
DR. C. W. COUNTRYMAN, Secretary-Treasurer,
262 Paulson M. & D. Building, Spokane, Washington.
Ray M. Balyeat, M.A., M.D.
Russell  L. Cecil, A.B., M.D.,
Carl Henry Davis, A.B., M.D.
D. J. Davis, B.S., M.D., Ph.D.
Paul John Hanzlik, Ph.C, A.B.,
A.M., M.D.
Alexis F. Hartmann, B.S., M.S.,
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A recent scientific study has added
important new facts to our knowledge
of bran. The November, 1935, issue
of the Journal of the American Dietetic Association reports a comparative study of bran and egg-yolk, a
known rich source of iron.
The subjects were healthy young
women The conclusions developed by
the experiment were "that the iron of
egg-yolk and of bran can be used with
equal efficiency for the maintenance of
iron equilibrium in the human adult."
This study continues a series of researches, conducted over a period of
five years, in which new contributions
to our information on bran have been
made. Some of these tests have confirmed the value of bran
as a safe laxative food for
normal people. Others have
demonstrated that it does
not lose its effectiveness
with continued use.
Further independent tests on men
have indicated that the "bulk" in bran
is often more effective than that found I
in fruits and vegetables.
Laboratory studies have shown that
Kellogg's All-Bran supplies generous j
"bulk," which absorbs moisture and
gently sponges out the intestinal tract.
This delicious cereal corrects constipation due to insufficient "bulk." It is
usually more satisfactory for this
purpose than the continued use of
All-Bran may be served as a cereal,
with milk or cream, or cooked into
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nut-sweet flavor. Sold by all grocers.
Made by Kellogg in London, Ontario.
The natural food
"/3z4f JQejtet* and *Tutute Teate"
In addition to difficulty in putting away the cares and worries of "dead yesterday"
and "unborn tomorrow" some of your sleepless patients have the additional hurdle
of fear. Fear—engendered by recollection of other sleepless nights—that sleep, so
much needed, will again elude them; fear that continued loss of sleep will break
down health.
Insomnia, whatever its cause, may easily become chronic, and establishment
of normal sleep habits frequently requires temporary use of a hypnotic.
Ortal Sodium is effective—one five-grain capsule will usually induce quiet,
restful sleep (a three-grain capsule is often sufficient). Ortal Sodium is gentle and
its effect is not unduly prolonged; the patient is alert and refreshed the following morning.
Ortal Sodium   (sodium  hexyl-ethyl barbiturate) is supplied in
capsules of 3/4, 3, and 5 grains, in bottles of 25, 100, and 500.
PARKE, DAVIS   &   CO., Walkerville, Out. :i'
Treatment Room, showing the Irrigation Table.
Ty EALIZING the need for a properly equipped centre where those suffering
■*•*■ from constipation, worms, indigestion, etc., could be assured of modern
scientific colonic irrigation and internal medication, Nurse Leonard has fitted
out operating rooms with the most up-to-date scientific equipment. Here the
patient will receive every attention, and proper thorough treatment under the
care of a fully trained nursing staff, at a moderate charge.
Individual   Treatment „_. $ 2.50
Entire Course  10.00
Medication (if necessary)  $1 to $3 extra
There is no better step towards ridding yourself of constipation, indigesti<_j8H
acidity, rheumatism, arthritis, worms, diverticulosis, colitis, acne, and all the
numerous complants which afflict mankind, than to take a colonic irrigation
and internal medication. To ensure comfort, convenience and thoroughness in
this undertaking, call at the colonic irrigation rooms, Suite 631, Birks Building,
phone Seymour 2443. Registered nurses always at your service.
Colonic Irrigation Institute
Superintendent—E. M. LEONARD, B.N., Post Graduate, Mayo Bros.
631 Birks Bldg.     Phone Sey. 2443.     Vancouver, B. C.
506-7 CAMPBELL BLDG. Phone Empire 2721 VICTORIA, B. C.
■i Important Announcements
Emmenin is now available in tablet form.
This convenient method of administering
Emmenin will appeal to many physicians
because of the simplicity and accuracy
of the dosage, each tablet representing
one teaspoonful of Emmenin Liquid.
Consistent with our policy of passing on
to the consumer, savings effected in
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Emmenin Liquid (32 doses) has been substantially reduced. Likewise, the price
of the new Emmenin tablets has been
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Acknowledged throughout the world as standard
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Novarsenobenzol Billon to these days.
Since then, Novarsenobenzol Billon has consistently retained
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is a handy, convenient, clean commodity for the bag or the office.  Supplied
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Breaks the vicious circle of perverted
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Dosage: 1 to 2 capsules
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Ethical protective mark MHS
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Nutritional Anemia iniInfant
Months of Age.
C-l     I _      2'3     3'4    4»5    5'6     6*7 _7-B    8*9    9-H>    10*11   II'-
Hemoglobin level in the blood of infants of various ages. Note fall in hemoglobin, which
is closely parallel to that of diminishing iron reserve in liver of average infant. Chart
adapted from Mackay. It is possible to increase significantly the iron intake of the bottle-fed
from birth by feeding Dextri-Maltose With Vitamin B in the milk formula. After the third
month Pablum offers substantial amounts of iron for both breast- and bottle-fed babies.
Reasons for Early Pablum Feedings
*| The iron stored in the infant's liver at birth is rapidly depleted during the first month:
of life.   (Mackay,1 Elvehjem.2)
O During this period the infant's diet contains very little iron—1.44 mg. per day from
the average bottle formulae of 20 ounces, or possibly 1.7 mg. per day from 28 ouncej
of breast milk.  (Holt. 3)
For these reasons, and also because of the low hemoglobin
values so frequent among pregnant and nursing mothers
(Coons,4 Galloway5), the pediatric trend is constantly toward
the addition of iron-containing foods at an earlier age, as
early as the third or fourth month. (Blatt,6 Glazier,7 Lynch8).
The Choke of the Iron-Containing Food
Many foods reputed to be high in iron actually add very few milligrams to the diet
* because much of the iron is lost in cooking or because the amount fed is necessarily
small or because the food has a high percentage of water.   Strained spinach, for
instance, contains only 1 to 1.4 mg. of iron per 100 gm.   (Bridges.?)
O   To be effective, food iron should be in soluble form.  Some foods fairly high in total
•^ • iron are low in soluble iron.   (Summerfeldt.10)
2    Pablum is high both in total iron (30 mg. per 100 gm.) and soluble iron
***• (7.8 mg. per 100 gm.) and can be fed in significant amounts without digestive]
upsets as early as the third month, before the initial store of iron in the liver
is depleted.   Pablum also forms an iron-valuable addition to the diet of
pregnant and nursing mothers.
Pablum (Mead's Cereal thoroughly cooked and dried) consists of wheatmeal, oatmeal, cornmeal, wheat embryo, brewers' yeast, alfalfa leaf, beef bone, iron salt and sodium chloride.
*"10 Bibliography on request.
MEAD JOHNSON & CO. OF CANADA, LTD., Belleville, Onf.
Please enclose prot
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For the treatment of
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Reference—B. C. Medical Association
For information apply to
Medical Superintendent, New Westminster, B. C.
or 51J Birks Building, Vancouver
Seymour 4183
Westminster 288


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