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The Journal
of the
Michigan State Medical Society
Published under the Direction of The Council
Publication Committee G. B. Saltonstall, M.D., Chairman William Bromme, M.D.
B. M. Harris, M.D.
O. B. McGillicuddy, M.D.
W. S. Stinson, M.D.
T. P. Wickliffe, M.D.
Wilfrid Haughey, B.A., M.A., M.D. Editor
L. Fernald Foster, M.D., Secretary and Business Manager Wm. J. Burns, LL.B., Executive Director
VOLUME 56 19 5 7
Copyright 1957 by Michigan State Medical Society
Printed in U.S.A.
THE JOURNAL
of the Michigan State Medical Society
►LUME 56 JANUARY, 1957 NUMBER I
Contributors to This Issue Table of Contents
V. Hoobler, M.D.
C. G. Johnston
R. C. Moehlig, M.D.
J. Starkman, M.D.
Clinical Evaluation of Sintrom (G-23350), a New
Oral Anticoagulant
J. A. Polhemus, M.D. , W. S. Wilson, M.D., P. W. Willis III, M.D., J. R. Gamble, M.D. , D. R. Griffin, M.D., P. E. Hodgson, M.D., and I. F.
Duff, M.D 49
Diuretics in the Treatment of Congestive Heart Failure
Toshikazu Morita, M.D 52
Interatrial Septal Defect
James B. Blodgett, M.D 57
Familial Heights as a Useful Guide in the Diagnosis of Genitourinary Anomalies
Robert C. Moehlig, M.D 61
Paroxysmal Tachycardia in Infants
Irving F. Burton, M.D. , and Morris Starkman, M.D 64
Modern Techniques for the Diagnosis of Pheochro- mocytoma
5. W. Hoobler, M.D., Robert D. Johnson, M.D.,
and Ray Warzynski, M.D
Cerebral Angiography
H. Harvey Gass, M.D
Anomalous Left Coronary Artery and Endocardial Fibroelastosis
John F. Sander, M.D., and Ronald C. Peets, M.D
67
72
80
Diagnosis of the Operable Arterial Lesion
Herbert J. Robb, M.D., and Charles G. J ohnston, M.D .84
Detecting Glycosuria
Joseph D. Mann, M.D
89
President’s Message: I Challenge You...
91
Editorial :
Congress and Medical Legislation 92
Jenkins-Keogh 92
Health Reinsurance 93
Medical Education 93
Medical Draft 93
Government Employes’ Insurance 93
Michigan Legislation 94
The Year 1956: Medicare 94
Michigan Clinical Institute:
Heart Association Program 95
Color Television Program 96
Michigan’s Department of Health 98
In Memoriam 100
News Medical 102
Legal Opinions 118
Correspondence 122
The Doctor’s Library 124
You and Your Business 14
Michigan Medical Service 18
Heart Beats 28
Foundation for Eye Care 34
Prevention of Rheumatic Fever 38
PR Report 40
Blue Shield is for Everybody 42
© 1957 by Michigan State Medical Society
ilIARY, 1957
3
THE JOURNAL
of the Michigan State Medical Society
=VOLUME 56 JANUARY, 1957 NUMBER 1 =
PUBLICATION COMMITTEE
G. B. SALTONSTALL, M.D., Chairman Charlevoix
WILLIAM BROMME, M.D Detroit
B. M. HARRIS, M.D Ypsilanti
O. B. McGILLICUDDY, M.D Lansing
W. S. STINSON, M.D Bay City
T. P. WICKLIFFE, M.D Calumet
Office of Publication 2642 University Avenue Saint Paul 14, Minnesota
Editor
WILFRID HAUGHEY, M.D.
610 Post Bldg., Battle Creek, Michigan
Secretary and Business Manager of THE JOURNAL
L. FERNALD FOSTER, M.D.
Thome Bldg., 919 Washington Ave.
Bay City, Michigan
Executive Director
WM. J. BURNS, LL.B.
606 Townsend Street, Lansing 15, Michigan
All communications relative to exchanges, books for review, manu- scripts, should be addressed to Wilfrid Haughey, M.D., 610 Post Bldg,, Battle Creek, Michigan.
All communications regarding advertising and subscription should be addressed to Wm. J. Burns, 2642 University Avenue, Saint Paul 14, Minnesota, or 606 Townsend Street, Lansing 15, Michigan. Telephone Ivanhoe 57125.
© 1957, by Michigan State Medical Society.
Published monthly by the Michigan State Medical Society as its official journal at 2642 University Avenue, Saint Paul 14, Minnesota.
Entered at the post office at Saint Paul, Minnesota, as second class matter, May 7, 1930, under the Act of March 3, 1879.
Acceptance for mailing at special rate of postage provided for in Section 1103 Act of October 3, 1917, authorized August 7, 1918.
Yearly subscription rate, $6.00; single copies, 60 cents. Additional postage; Canada, $1.00 per year; Pan-American Union, $2.50 per year; Foreign, $2.50 per year.
PRINTED IN U.S.A.
OFFICERS OF THE SOCIETY
1956-1957
President ARCH WALLS, M.D ..Detroit
President-Elect G. W. SLAGLE M.D Battle Creek
Secretary L. FERNALD FOSTER, M.D Bay CiW
Treasurer „..W. A. HYLAND, M.D Grand Rapids
Speaker K. H. JOHNSON, M.D Lansing
Vice Speaker J. J. LIGHTBODY, M.D... - Detroit
Editor. WILFRID HAUGHEY, M.D Battle Creek
THE COUNCIL
D. BRUCE WILEY, M.D., Chairman, Utica W. B. HARM, M.D., Vice Chairman, Detroit L. FERNALD FOSTER, M.D., Secretary, Bay City
Term
District Expires
A. E. SCHILLER, M.D 1st Detroit 1961
0. B. McGILLICUDDY, M.D 2nd Lansing 1960
H. J. MEIER, M.D 3rd Coldwater 1960
RALPH W. SHOOK, M.D 4th Kalamazoo 1961
C. ALLEN PAYNE, M.D 5th Grand Rapids 1961
H. H. HISCOCK, M.D 6th Flint 1961
H. B. ZEMMER. M.D 7th Lapeer 1957
L. C. HARVIE, M.D 8th Saginaw 1957
G. B. SALTONSTALL, M.D 9th Charlevoix 1957
W. S. STINSON, M.D 10th Bay City 1957
W. M. LeFEVRE. M.D Uth Muskegon 1958
B. T. MONTGOMERY, M.D 12th Sault Ste. Marie.. .1958
T. P. WICKLIFFE, M.D 13th Calumet 1959
B. M. HARRIS, M.D Uth Ypsilanti 1959
D. BRUCE WILEY, M.D 15th Utica 1960
G. THOMAS McKEAN. M.D 16th Detroit 1960
W. B. HARM, M.D Uth Detroit 1958
WILLIAM BROMME, M.D 18th Detroit 1959
ARCH WALLS, M.D President Detroit
G. W. SLAGLE, M.D President-Elect Battle Creek
K. H. JOHNSON, M.D Speaker Lansing
J. J. LIGHTBODY, M.D Vice Speaker Detroit
L. FERNALD FOSTER, M.D Secretary Bay City
W. A. HYLAND, M.D Treasurer Grand Rapids
W. S. JONES, M.D Past President Menominee
EXECUTIVE COMMITTEE OF THE COUNCIL
D. BRUCE WILEY, M.D Chairman
W. B. HARM, M.D Vice Chairman
W. M. LeFEVRE, M.D Chairman, County Societies Committee
G. B. SALTONSTALL, M.D Chairman, Publication Committee
RALPH W. SHOOK, M.D Chairman, Finance Committee
K. H. JOHNSON, M.D Speaker, House of Delegates
J. J. LIGHTBODY, M.D Vice Speaker, House of Delegates
4RCH WALLS, M.D President
G. W. SLAGLE, M.D President-Elect
L. FERNALD FOSTER, M.D Secretary
W. A. HYLAND. M.D Treasurer
SECTION OFFICERS
Dermatology and Syphilology
Wm. T. Kruse, M.D Grand Rapids
Chairman
Coleman Mopper, M.D Detroit
Secretary
Gastroenterology and Proctology
N. D. Nigro, M.D Detroit 1
Chairman
E. J. Tallant, M.D Detroit
Secretary
General Practice
F. P. Rhoades, M.D Detroit 2
Chairman
F. C. Brace, M.D Grand Rapids
Secretary
Gynecology and Obstetrics
J. H. Beaton, M.D. Grand Rapids
Chairman
R. W. McClure, M.D Detroit 26
Secretary
Medicine
J. M. Kaufman, M.D Detroit 26
Chairman
J. W. Hall, M.D Traverse City
Secretary
Nervous and Mental Diseases
W. R. Slenger, M.D Ann Arbor
Chairman
S. C. Mason, M.D Ann Arbor
Secretary
Occupational Health
O. J. Johnson, M.D Bay City
Chairman
P. B. Rastello, M.D. Detroit 9
Secretary
Ophthalmology and Otolaryngology
B. C. Wildgen, M.D Muskegon
Chairman (Ophth.)
W. K. Locklin, M.D Kalamazoo
Co-Chairman (Oto.)
H. A. Dunlap, M.D Detroit 14
Secretary (Ophth.)
H. L. LeVett, M.D Lansing
Co-Secretary (Oto.)
Pediatrics
C. E. Booher, M.D Grand Rapids
Chairman
A. M. Hill, M.D Grand Rapids
Secretary
Public Health and Preventive Medicine
J. D. Monroe, M.D Pontiac
Chairman
J. K. Altland, M.D Lansing 4
Secretary
Radiology, Pathology, Anesthesiology
R. B. Sweet. M.D Ann Arbor
Chairman (Anes.)
E. R. Jennings, M.D Detroit
Vice-Chairman (Path.)
E. O. Pearson, M.D Kalamazoo
Secretary (Rad.)
Surgery
E. T. Thieme, M.D Ann Arbor
Chairman
H. M. Bishop, M.D Saginaw
Secretary
Urology
R. P. Lytle, M.D Detroit 1
Chairman
J. F. Harrold, M.D Lansing
Secretary
Delegates DELEGATES
W. A. Hyland, M.D., Grand Rapids, Chairman 1957
J. S. DeTar, M.D., Milan 1957
C. I. Owen, M.D., Detroit 1957
W. D. Barrett, M.D., Detroit 1958
W. H. Huron, M.D., Iron Mountain 1958
R. L. Novy, M.D., Detroit 1958
TO A. M. A. Alternates
W. W. Babcock, M.D.. Detroit 1957
E. F. Sladek, M.D., Traverse City 1957
O. J. Johnson, M.D., Bay City 1957
William Bromme, M.D.. Detroit 1958
J. R. Rodger, M.D., Bellaire 1958
G. W. Slagle, M.D., Battle Creek 1958
Section Delegate
G. C. Penberthy, M.D. (Surgical Section) Detroit
4
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You and Your Business
1957 MCI, MARCH 13-14-15 and Blue Shield plans for diagnostic out-patient
“HIGHLIGHTS AND KNOW HOW! services.
That’s the modern theme of the 1957 Michigan Clinical Institute — the best regional “refresher course” in the country. Each of the 29 speakers will bring to the Institute an important segment of NEW clinical information evolved in the past 365 days! Famous teachers will speak only of the LATEST in medical knowledge and techniques.
“Highlights” will draw a record attendance of M.D.’s to the 1957 MCI from Michigan, Ohio, Indiana, Ontario, and Wisconsin.
POPULAR BLOCK-TYPE PROGRAM
The successful “block-system” presentation of eight important sections of medicine — so attrac- tive at last year’s Institute — will be featured in 1957 as a novel time-saver for the busy Doctors of Medicine:
New “Block” 3/13/57 A.M. Surgery P.M.
3/14/57 A.M.
P.M.
3/15/57 A.M.
P.M.
Program
Trauma
Heart and Rheumatic Fever Internal Medicine Obstetrics-Gynecology-Pediatrics General Medicine
CLOSED CIRCUIT COLOR TV
An outstanding color television program will be beamed to the Grand Ballroom of the Sheraton Cadillac Hotel, Detroit, through the co-operation of The Grace Hospital Staff and Smith, Kline & French Laboratories of Philadelphia.
(See pages 96-97.)
IMPORTANT HOUSE OF DELEGATES ACTIONS— 1956
The MSMS legislative body, meeting in De- troit, September 24-25, 1956, adopted resolutions (a) urging establishment of departments of gen- eral practice in medical schools’ curricula; (b) instructing that a committee be appointed to study the use of the word “clinic”; (c) instruct- ing that a permanent advisory committee on fees be appointed; (d) objecting to Michigan’s At- torney General’s Opinion that the practice of psychotherapy is the practice of medicine; (e) urging expansion of medical school facilities at Wayne State University; (f) urging adequate funds to carry out civil defense; (g) directing The Council to build a new MSMS headquarters; (h) instructing that a committee be appointed to study excess beds in tuberculosis sanitoria; (i) urging total participation of Michigan M.D.’s in Michigan Medical Service; (j) urging more com- prehensive prepaid medical care insurance plans
Resolutions re Michigan Medical Service
The more important resolutions concerning Michigan’s Blue Shield were the following: Resolution Urging Total Participation of M.D.’s in Michigan Medical Service
( Substitute resolution approved by 1956 MSMS House of Delegates)
Whereas, there is an apparent lack of full under- standing and appreciation of the basic principles and philosophy of Michigan Medical Service, and
Whereas, the survival of the voluntary system of prepayment medical care depends on unity within this State Medical Society; therefore be it
RESOLVED, That the House of Delegates recom- j mend to each county medical society that it include in its indoctrination of new members a thorough explana- tion of the principles, practices and objectives of Michi- gan Medical Service; and be it further
RESOLVED. That this State Medical Society, its members and officers, assist each county medical society in its campaign to see that Michigan Medical Service continues as the most successful medically-sponsored pre- payment plan.
* * *
Resolution re Comprehensive Prepaid Medical Care Insurance Plan
(Substitute resolution approved by 1956 MSMS House of Delegates)
Whereas, it is the proper role of medicine to assume leadership in determining the type and form of pre- paid medical care plans, and
Whereas, a prepaid medical care plan ideally should embody within it a sense of mutual responsibility on the part of the physician and on the part of the | patient, and
Whereas, a medical care plan should preserve the traditional right of the patient to select the physician of his own choosing; therefore be it
RESOLVED, That the Michigan State Medical So- s ciety approve exploration with Michigan Medical Serv- I ice of a comprehensive prepaid deductible and/or co- insurance contract and also the possibility of extension of the present contract; and be it further
RESOLVED, That the Speaker of this House of ! Delegates be authorized to appoint forthwith a special j committee to accomplish the following:
A — Meet with the representatives of Michigan Medi- cal Service to study and develop details and mechanisms.
B — Initiate, as a joint endeavor and in co-operation I with Michigan Medical Service, necessary studies to ascertain what would best serve the public.
C — Prepare a complete report for presentation to the House of Delegates at its meeting in 1957 with the proviso that copies of this report shall be sent to each member of the House of Delegates by August 15, 1957.
* * *
Resolution re Michigan Medical Service Annual Report to MSMS House of Delegates
(Substitute resolution approved by 1956 MSMS House of Delegates)
Whereas, the Michigan State Medical Society estab- lished Michigan Medical Service with the intention of providing medical services on a voluntary basis through a prepayment plan, and
Whereas, the expansion of Michigan Medical Service
( Continued on Page 16)
14
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(Continued from Page 14)
has become a significant factor in the practice of medicine in the State of Michigan, and
Whereas, the members of the House of Delegates of the Michigan State Medical Society usually function as the legally qualified members of the corporation of Michigan Medical Service on the second day of their annual meeting and do not have a report submitted along with the reports of other Society activities as published in the Delegates’ Handbook; therefore be it
RESOLVED, That the annual report of Michigan Medical Service be included in the Handbook for Delegates for informative purposes.
Dues Increase Eliminates Assessment
Two actions of the House of Delegates in- creased the dues by $10.00, at the same time abolishing the $10.00 assessment of 1956. The first was a resolution setting aside $5.00 annual dues to build and equip a new MSMS head- quarters building; the second was approval of the report of the Committee on Study of MSMS Financial Structure which included a $5.00 dues increase to permit the continuation of the modern MSMS program at its current level:
Resolution re New MSMS Headquarters
(Approved by 1956 MSMS House of Delegates)
Whereas, increasing demands for service are being made upon the MSMS by the medical profession and the public, and
Whereas, such demands must be met by well-planned and effectively executed programs, and
Whereas, the administration of such programs must of necessity center in the Executive Office of MSMS, and
Whereas, present Lansing facilities for the Executive Office are already strained to the utmost and unless expanded shortly will hamper the efficient execution of MSMS programs, and
Whereas, it is reliably estimated that a proper head- quarters can be built and equipped for an amount approximating $300,000, therefore be it
RESOLVED, That a new MSMS headquarters be built and equipped in Lansing, Michigan; and be it further
RESOLVED, That for the building of this new headquarters the sum of $300,000 be raised by:
1. The sale (at the proper time) of our present headquarters.
2. By the use of present building reserves.
3. By the increasing of dues in the amount of $5 per year, beginning in the 1957 fiscal year, said in- crease in dues to be used only for the purpose of de- fraying the cost of building and equipping a new MSMS headquarters.
* * *
Conclusions of Committee on Study of MSMS Financial Structure
(Approved by 1956 MSMS House of Delegates)
1. The officers and professional staff of the MSMS are to be commended for their leadership in a pro- gram which is sound and well administered.
2. The part-time officers and full-time key profes- sional staff are under- rather than over-paid. The AMA delegates and alternates as well as members of The Council, committees and others active in the Society make a very valuable contribution to the public and Society welfare at a significant personal sacrifice in most instances.
3. Evidence was not produced to justify a reserve equal to two years of Society operation.
16
4. The current $45 dues and $10 assessment has placed the Society in good condition financially, with a reserve anticipated for December of 1956, of ap- proximately $275,000 to $300,000. During times of stress, such as tbe last depression or last war, this will permit Society operation at the current level for at least three to four years with a curtailment of 25 per cent of income. With a reasonable curtailment of expenditures, one year’s operation without any income whatever is possible. By the same token, a reasonable increase in program is possible with this reserve to meet any possible emergency in the interval between meet- ings of the House of Delegates.
5. The $10 assessment levied in 1956 should not be renewed.
_6. A dues increase of $5 is recommended to protect this reserve, offset higher costs, to permit a continuation of program at its current level, and to adequately re- imburse part-time officers, key full-time staff and others.
HIGHLIGHTS OF THE EXECUTIVE COMMITTEE OF THE COUNCIL Meeting of November 14, 1956
Eighty-nine items were presented to the Execu- tive Committee of The Council at its November 14 meeting in Detroit. Those of chief importance were:
»
• Discussion of matters referred to The Council by the 1956 House of Delegates, including 22 resolutions, the reference committee’s report on the Annual Reports of The Council, and the reference committee’s report on the recommen- dations of the Committee to Study MSMS Financial Structure.
• Medicare Program. A report on the Washing- ton, D. C., negotiation conference of October 24-25, was presented by Council Chairman Wiley and by Jay C. Ketchum, Executive Vice President of Michigan Medical Service. The Medical Advisory Committee of Michigan Medical Service was designated, as per the re- quest of the Armed Services, to review specific cases (in the nature of a medical advisory committee) ; Michigan Medical Service was ap- pointed as agent of MSMS for fiscal arrange- ments under the Medicare Program and the MSMS President was authorized to sign the medicare contract on behalf of the State So- ciety; a letter explaining the Medicare Pro- gram, to be signed by President Walls, was authorized to be sent to all MSMS members, to be followed by additional detailed informa- tion.
• President Walls stated he attended a meeting of the Governor’s Study Commission on Public Health in Lansing on October 26 (W. S. Jones, M.D., of Menominee is a member of this Com- mission) and presented a comprehensive report on health problems from the viewpoint of the Michigan State Medical Society.
• Speaker K. H. Johnson, M.D., Lansing, re- ported on a session of the Steering Committee to set up a meeting of the Citizen’s Public
(Continued on Page 26)
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Michigan Medical Service
One of the most important phases of Michigan Medical Service operations — vital to Michigan doctors and MMS subscribers — is the work of the Wayne County Medical Advisory Board to Michigan Medical Society.
The board, representative of nearly every field of medicine, has for many years contributed in- valuable service to members of the medical pro- fession of Michigan and to MMS. In fact, its labors provide assurance to Michigan doctors that unusual and complicated medical and surgical cases receive careful professional consideration where precedent has not been established in the MMS payment schedule.
Just how the Advisory Board functions for MMS is important to all MMS participating doc- tors in the state. It is important to know what steps are taken before MMS makes payment to the doctor for any complex medical or surgical case requiring more than the usual amount of professional care or skill.
All cases reported on the Doctors Service Re- port forms, of course, go through the examina- tion department of Michigan Medical Service. If, during this study, a doctor’s service report shows any unusual type of work, it is referred to the MMS Medical Director, Dr. Dewey Moll. After close scrutiny by Dr. Moll and his staff, the cases requiring consideration by the Advisory Board are then presented by Dr. Moll to the Board for prompt atention. Cases are presented anonymously to the Board, with identity of the patient and the doctor undisclosed. Only if further information is needed on the case is the doctor’s identity made known. The determination of fees by this Board must be in relation to the income limits of the contract carried by the subscriber and must be consistent with the other fee allow- ances in the $2,500 or $5,000 contracts.
“Fairness to the doctor and the patient is the paramount aim of the Board,” Dr. I. S. Schem- beck, Chairman, says. “It is our job to recommend to the MMS Board equitable payment of fees for specific cases. These recommendations for pay- ment are reached only after thorough study by the Advisory Board of all the facts involved in each case presented — the extent of the surgery, length of time required to perform necessary pro- cedures and any accompanying complications.”
Dr. Schembeck points out that such recom- mendations for fees can be reached only if the doctor has submitted a complete report to MMS of the case in question. He emphasized that much time and expense can be saved by doctors and MMS if the doctors make every effort to submit reports to MMS describing in detail every aspect of their cases. To go a step further, it is
even recommended that for unusual cases the doctor send in a copy of his operative notes.
Completeness of reports, Dr. Schembeck ex- plains, automatically expedites handling of com- plex cases — thereby hastening payment of the MMS fee to the doctor.
“We must know just what work the doctor has done for his patient before we can know whether payment for such procedure has been established in the MMS Schedule of Fees, or whether or not the doctor is entitled to further payment,” Dr. Schembeck says. He explains that when the Board receives a report, incomplete in details, MMS must then write the doctor for further information, adding up to considerable delay before a decision can be reached. At times it has been necessary for MMS field representa- tives to make personal calls on the doctor to clear up facts in cases when reports were inconclusive.
However, a recommendation by the Advisory Board on a specific payment does not have to be final until the doctor indicates his approval. Should the participating doctor feel at any time that the payment recommended by this Advisory Board for his work is not satisfactory, it is his privilege to ask for a re-review of the case. The Advisory Board is always willing to reconsider any case, according to Dr. Schembeck — in fact, will consult with the doctor in person at a meet- ing of the Board if the doctor so desires. Also, cases which have been paid routinely without the aid of the Advisory Board will be reviewed by that Board if the doctor reporting so desires.
The Advisory Board, originally formed more than fifteen years ago to establish precedent fees, is still concerned with reviewing cases which are different from previous claims and are classified as out of the ordinary procedures.
The Advisory Board has no authority to set fees, policies or practices of MMS, it can only recommend certain action. For instance, if an established fee for a particular procedure ap- pears to be inequitable as part of the set Schedule of Fees, the Advisory Board may recommend to the MMS Board of Directors that such a fee should be reconsidered and changed as being too large or too small a payment for such services. The same action or recommendation may be made for new procedures as they appear. Actually, each individual doctor has this same right if he chooses to have a certain procedure reviewed for modifica- tion in the fee allowance.
A hard-working group, the Advisory Board meets two days each month, handling approxi- mately 2,000 cases each year. Service by the Board members has always been without remuner- ( Continued on Page 32 )
18
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11. Mildly laxative.
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18. Valuable in many allergy diets.
19. Belongs among foods useful in certain acute intestinal infections.
20. A protein sparer.
21. Favorably influences mineral balance.
22. Useful in the management of ulcer diets.
23. One of the easiest foods to eat or prepare.
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:
January, 1957
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YOU AND YOUR BUSINESS
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HIGHLIGHTS OF THE COUNCIL
(Continued from Page 16)
Health Advisory Committee for December 5. Tuberculosis, mental health, local public health units, and urbanization were to be discussed at this citizen’s meeting.
• William Bromme, M.D., Detroit, was appointed as MSMS representative to the Second Nation- al Conference on Veterans Affairs, January, 1957, Chicago.
• 1957 Michigan Clinical Institute Press Rela- tions Committee: A. B. Gwinn, M.D., Hastings, Chairman, H. F. Dibble, M.D., Detroit; L. R. Leader, M.D., Detroit; J. J. Lightbody, M.D., Detroit; Ralph W. Shook, M.D., Kala- mazoo; and C. L. Weston, M.D., Owosso.
• Edward M. Vardon, M.D., Detroit, presented a Verifax (photographic reproducing machine) to the Michigan State Medical Society, which was accepted with high thanks.
• B. L. Masters, M.D., Fremont, presented re- port on Study Conference for Chairman of State Rural Health Committees, held at Purdue University October 19-20; the report was re- ceived with high thanks.
• F. E. Ludwig, M.D., Port Huron, and H. A. Towsley, M.D., Ann Arbor, were appointed as members of MSMS Liaison Committee with University of Michigan.
• Legal Counsel Lester P. Dodd presented opin- ions on ten questions of legal import.
• Report of Rheumatic Fever Co-ordinator Leon DeVel, M.D., Grand Rapids, was approved with thanks.
• Public Relations Counsel presented a report on the Gold Medal Award judging committee; Good Citizenship Get-Out-the-Vote Campaign; Professional Day of the 1957 Michigan Rural Health Conference; Hospital-Community Re- search Project of Michigan State University; the MSMS public relations library; copies of “Medicine and the Law” film series (AMA) ; and on the new M.D. placement pamphlet.
• Committee Reports. The following committee
reports were presented: (a) Formation of
American Association of Medical Assistants; (b) Committee on Arbitration, meeting of September 8; (c) Permanent Conference Com- mittee, October 24; (d) Healing Arts Study Committee, October 25; (e) Geriatrics Com- mittee, November 1; (f) Committee to Select Field Secretary, November 7 ; and (g) Commit- tee Organization Meeting (for Chairmen), November 13.
26
JMSMS
One donnagesic Extentab gives 10 to 12 hours of steady, high-level codeine analgesia. Rebuilding of effective analgesia with repeated doses is avoided. Patient comfort is continuous.
There is more pain relief in DONNAGESIC Extentabs than in codeine alone — codeine analgesia is potentiated by the phenobarbital present. In addition, phenobarbital diminishes anxiety, lowering patient’s reactivity to pain.
DONNAGESIC is safer, too, for codeine side effects are minimized by the peripheral action of the belladonna alkaloids.
extended action — The intensity of effects smoothly sustained all-day or all-night by each donnagesic Extentab is equivalent to, or greater than, the maximum which would be provided by q. 4h. administration of one- third the active ingredients.
Donnagesic
xtentabs*
extended action tablets of CODEINE with DONNATAL ®
once every 10-12 hours and
for all codeine uses
DONNAGESIC No. 1 (pink)
DONNAGESIC No. 2 (red)
CODEINE Phosphate 48.6 mg.(%gr.) 97.2 mg. (IV2 gr.)
Hyoscyamine Sulfate 0.3111 mg 0.3111 mg.
Atropine Sulfate 0.0582 mg 0.0582 mg.
Hyoscine Hydrobromide 0.0195 mg 0.0195 mg.
Phenobarbital 48.6 mg. (3/4 gr.) 48.6 mg. (% gr.)
A. H. ROBINS CO., INC., RICHMOND, VIRGINIA Ethical Pharmaceuticals of Merit Since 1878
*Reg. U. S. Pat. Off., Pat. applied for.
January, 1957
Say you saw it in the Journal of the Michigan State Medical Society
27
Heart Beats
THE MICHIGAN HEART ASSOCIATION SERVES THE PHYSICIAN
One of the major activities of the Michigan Heart Association is the support of cardiovascular research. The Association has awarded grants to- talling $164,000.00 to 27 scientific investigators in Michigan to carry out research studies into the baffling problems of diseases of the heart and blood vessels. The research work is being conducted in 8 medical institutions during the twelve month period ending June 30. 1957.
In addition to its own research program, E. A. Irvin, M.D., Dearborn, President of the Michigan Heart Association, points out that the MHA con- tributes to the national research support program of the American Heart Association. The national organization has allocated nearly $1,873,000.00 for 311 grants-in-aid and fellowship awards during the same period.
$80,686.00 of the research funds allocated by the Michigan Heart Association have been awarded from the Association’s Memorial Fund. This fund was established at the request of many persons who have wanted an opportunity to provide a “living memorial” to the memory of a friend, relative or associate who has been afflicted with heart disease. Memorial contributions are used exclusively for heart research studies. The bal- ance has been allocated from funds contributed to the Association by the people of Michigan through “United” fund raising campaigns in many Michigan communities.
The research investigators receiving funds from the Michigan Heart Association during the cur- rent year are as follows :
Dean’s Fund Wayne University
To enable part-time research investigators of proven ability to devote full-time to cardiovascular research.
Dean’s Fund University of Michigan
To enable part-time research investigators of proven ability to devote full-time to cardiovascular research.
W. T. Beher, M.D Edsel Ford Institute
Study of Cholesterol Metabolism.
J. B. Blodgett, M.D Grace Hospital
The Fundamental Problem of Exploring Satisfactory Means of Entrance and Exit through Walls of the Great Vessels and Heart Itself and Problems of Mitral Valve Regurgitation.
D. F. Bohr, M.D University of Michigan
A Comparison of Some Basic Characteristics of the Circulatory System in Response to Renal Ischemic, Renoprival and Hormonal (DOCA) Hypertensions.
A. J. Boyle, M.D Wayne University
Plasma Colloid Stability in Normal and Atheroscler- otic Subjects.
T. M. Brody, M.D University of Michigan
Mechanisms of Experimental Heart Failure.
N. E. Clarke, M.D Providence Hospital
The Chemotherapy of Rheumatic Fever.
F. D. Dodrill, M.D Harper Hospital
Mechanical Heart.
I. F. Duff, M.D University of Michigan
Investigation of the Mechanism of Blood Coagulation with Special Reference to the Problem of Thrombo- embolic Disease.
J. D. Fryfogle, M.D Mt. Carmel Mercy Hospital
Arterialization of the Coronary Sinus by Communica- tion to the Left Ventricular Cavity.
F. E. Greifenstein, M.D Wayne University
Study of the Contractile Force of the Heart.
Cameron Haight, M.D University of Michigan
Temporary Occlusion of a Pulmonary Artery as Means of
(A) Evaluation of the Anticipated Cardiovascular Responses to Pneumonectomy.
(B) A Study of the Pulmonary Vascular Tree by In- jection of Contrast Material Beyond the Point of Occlusion.
H. K. Hellems, M.D Wayne University
The Investigation of the Effects of Exercise and Commonly Used Cardiovascular Drugs on Myocar- dial Blood Flow and Metabolism in the Human Sub- ject.
T. B. Hill, M.D Kent County Health Department
Incidence of Streptococcal Infections in a Rural School with Study of the Carrier State.
S. W. Hoobler, M.D University of Michigan
Atherosclerotic Vascular Disease.
J. J. Jasper, M.D Wayne University
The Study of Serum Surface Tension in Atherosclero- sis.
C. G. Johnston, M.D Wayne University
Prosthetic Replacement or Correction of Valvular Lesions.
J. A. Johnston, M.D Ford Hospital
Studies in Rheumatic Fever.
C. R. Lam, M.D Henry Ford Hospital
Experimental Cardiovascular Surgery.
B. M. Lewis, M.D Wayne University
Diffusion and Distribution Characteristics of the Lung in Heart Failure.
Y. Morita, M.D. and L. T. Iseri, M.D. ..Wayne University Metabolic Aspects of Cardiorenal Diseases.
Jan Nyboer, D.Sc., M.D Harper Hospital
The Evaluation of Electrical Impedance Plethysmog- raphy and Displacement Ballistocardiography.
Prof. F. L. Rights Wayne University
Etiology of Acute and Chronic Pericarditis and Myo- carditis.
Walter Seegers, M.D Wayne University
Blood Coagulation: Purification of Inhibitors and
Mechanism of Their Action.
D. E. Szilagyi, M.D Henry Ford Hospital
An Investigation of the Use of Plastic Vascular Prostheses in the Replacement of Long and Narrow Arterial Segments.
J. L. Wilson, M.D University of Michigan
Investigation of the Effects of Cyanotic Heart Dis- sease and Its Relief on Cerebral Function.
( Continued on Page 32)
28
JMSMS
In one investigation, 75 adult patients with bacterial pneumonia were treated with erythromycin. In his summary, the clinician re- ported: “It is concluded that erythromycin is highly effective in the treatment of pneumonia due to gram-positive bacteria.”2
This, of course, is only one of many reports showing the effective- ness of Erythrocin against coccic infections. You’ll get the same good results (nearly 100% in common, bacterial res- [) n ,, piratory infections) when you prescribe Erythrocin. VAijuXMX
Erythrocin
(Erythromycin, Abbott)
STEARATE
*AJo S>iAMncd Su£c Ooc«aaju£S'
After a study of 171 patients treated with erythromycin, the investi- gator wrote: “No serious side effects occurred with prolonged therapy or with doses up to 8 Gm. per day in the severe infections.”1
Actually, Erythrocin stands on a remarkable record of safety. After four years, there’s not a single report of a severe or fatal reac- tion attributable to erythromycin. In addition, you’ll find allergic manifestations rarely occur. Filmtab Erythrocin n nn Stearate (100 and 250 mg.), in bottles of 25 and 100. LIJMStMX
® Filmtab — Film-Sealed tablets, Abbott; pat. applied for.
1. Romansky, M.J., et al., Antibiotics Annual 1955-1956, p. 48,
2. Waddington, W. S., Maple, F. C., and Kirby, W. M. M., A.M.A. Archives of Internal Medicine, 1954, p. 556.
701051
HEART BEATS
THE MICHIGAN HEART ASSOCIATION SERVES THE PHYSICIAN
( Continued from Page 28)
Through MHA and AHA research projects, new findings in the cardiovascular field are made known immediately to the physicians of the state so that they may better serve their patients and their communities.
Professional education is also an important Heart Association objective and a large selection of professional education and information mate- rials are available to the physician with an interest in cardiovascular disease. Through these mate- rials, the Michigan Heart Association endeavors to aid the physician in continuing his self-educa- tion in the field of cardiovascular disease, and to assist him in the care of the patient with cardio- vascular disease.
These professional materials include films, slides, heart models, three-dimensional cardio- views, phonograph records, clinical charts, pam- phlets and books.
The literature runs the gamut from the tech- nical “Nomenclature for Diagnosis of Peripheral Vascular Disease” to a well-written, easily read booklet which the physician can give to his pa- tients, entitled “Have Fun — Get Well.”
Some of the film and slide titles include: “Con- genital Malformations of the Heart,” “Surgical Correction of Mitral Stenosis” and “Roentgeno- grams of the Heart and Great Vessels.”
Another valuable item available to the physi- cian is a set of three Cardiac Kits. These kits consist of slides and phonograph records which ex- plain the slides. A printed explanation is included for more detailed reference, or in case a phono- graph is not available. The three subjects covered in the kits are: “The Role of the P-A Film of
the Chest in Cardiology” by William R. Christen- sen, M.D., Professor of Radiology, University of Utah; “The Prevention of Rheumatic Fever” by Gene H. Stollerman, M.D., Assistant Professor of Medicine, Northwestern University; “Functional Pathology of Occlusive Coronary Disease,” by Jesse E. Edwards, M.D., Professor of Pathologic Anatomy, Mayo Clinic and Mayo Foundation.
Various publications about cardiovascular di- sease are regularly available to physicians. They include: “Modern Concepts of Cardiovascular
Diseases,” “Heart Research Newsletter” and “The American Heart.” These publications are sent to all physicians who are members of the Michigan Heart Association as part of their membership. Professional journals available are Circulation and Circulation Research.
A new two- volume Electracardiographic Test Book, containing photographs of electrocardio- grams and questions of electrocardiographic in- terpretation, is now available. The electrocardio- grams from the book are available also on slides.
In addition to all of these professional mate- rials, a vast amount of literature, films and exhibits are available to the physician for his use with patients or the lay public in general. A free booklet on all professional education and informa- tion aids available may be secured by writing to the Michigan Heart Association, Doctors’ Building, 3919 John R, Detroit 1, Michigan.
REFRESHER COURSE
Plans for a refresher course in “Cardiology for the Family Physician” have been completed by the Michigan Heart Association, in co-operation with Wayne State University and the Michigan Academy of General Practice. The course will consist of five full-day sessions (8:30 a.m. to 5:15 p.m.) from April 22 through April 26, 1957, incorporating both bedside rounds and lectures.
A registration fee of $25.00 will be charged, and the course has been approved for twenty-five hours credit in Category I. For full details, con- tact either the Michigan Heart Association at the address listed above or Dean, College of Medi- cine, Wayne State University, 1401 Rivard Street, Detroit.
MICHIGAN MEDICAL SERVICE
(Continued from Page 18)
ation. The President of the Wayne County Medi- cal Society appoints the Board each year. Every effort is made to see that nearly all fields of medicine are represented in the group. Also, should a specific case require medical knowledge beyond the scope of the Board members, advisory consultants are called upon for assistance.
Currently, plans are being considered for de- veloping other Advisory Boards in metropolitan areas across the State through which MMS hopes to gain closer contact with and better under- standing by the local medical groups. Kent County Medical Society has appointed an Ad- visory Board to function as does the Wayne Coun- ty Board but with attention to cases stemming from Kent and other nearby counties. If work of the Kent County group becomes successful in this effort, it .is hoped that other County Medical Societies will establish similar Advisory Boards to Michigan Medical Society.
BIRTH RECORDS
The first year when 100,000 births were reported in Michigan was 1941. Present indications are that the year 1 956 will see more than 200,000. The maternal death rate has gone down one half during the same period — 63 to 34 — a great tribute to the efforts of ma- ternal health committees and concentrated efforts of health agencies.
32
JMSMS
for the average patient in everyday practice
# well suited for prolonged therapy
O well tolerated, nonaddictive, essentially nontoxic # no blood dyscrasias, liver toxicity, Parkinson-like syndrome or nasal stuffiness
# chemically unrelated to chlorpromazine or reserpine # does not produce significant depression # orally effective within 30 minutes for a period of 6 hours
Indications : anxiety and tension states, muscle spasm.
Tranquilizer with muscle-relaxant action
DISCOVERED AND INTRODUCED
BY » WALLACE LABORATORIES, New Brunswick. N.J.
2-melhyl-2-n-propyUl, 3-propanediol dicarbamate — l J.S. Patent 2,721,720 SUPPLIED: iOO mg. scored tablets. Usual dose: 1 or 2 tablets t.i.d.
Literature and Samples Available on Request
CM-3706-R2
THE MILTOWN MOLECULE
, 1957
Say you saw it in the Journal of the Michigan State Medical Society
Foundation for Eye Care
Announcement was made November 15, 1956, of the establishment of the National Medical Foundation for Eye Care, a non-profit scientific and educational institution, incorporated in New Jersey. The Foundation has been organized by ophthalmologists of the country to provide Ameri- can ophthalmology with an agency to present to the public generally and to fellow physicians per- tinent information on the care and treatment of the eyes.
Ralph O. Rychener, M.D., Memphis, Tennes- see, is president of the Foundation; Edwin Forbes Tait, M.D., Norristown, Pennsylvania, vice presi- dent, and Charles E. Jaeckle, M.D., East Orange, New Jersey, secretary-treasurer.
Members of the Board of Trustees, in addition to the above named, are: Alson E. Braley, M.D., Iowa City, Iowa; Frederick C. Cordes, M.D., San Francisco, California; Paul Chandler, M.D., Boston, Massachusetts, J. Spencer Dryden, M.D., Washington, D. C.; Harold F. Falls, M.D. Ann Arbor; Everett L. Goer, M.D., Houston, Texas; Erling W. Hansen, M.D., Minneapolis, Minne- sota; A. I). Ruedemann, M.D., Detroit; Barnet R. Sakler, M.D., of Cincinnati, Ohio, and Derrick Vail, M.D., Chicago, Illinois.
In a special statement announcing the Founda- tion’s establishment, Dr. Rychener declared:
“American ophthalmologists have long recognized an urgent need for an organization whose principal func- tion will be to interpret the basic professional and scientific standards of good eye care for the American people, both to our fellow physicians and to the people whom we serve.
“The National Medical Foundation for Eye Care will seek to serve the public interest by helping the people to understand the educational qualifications and the professional functions of physicians specializing in ophthalmology, and the functions of related technical and ancillary personnel who assist them. The Founda- tion will also endeavor to keep our colleagues in the medical profession informed concerning the problems confronting ophthalmology in its efforts to fulfill its
mission as a member of the team of recognized medical specialties serving the American people.”
Dr. Rychener revealed that the Foundation is now enrolling its charter membership, and he invited all ophthalmologists and other physicians interested in eye care to become charter members of the Foundation.
Applications are available through Dr. Charles E. Jaeckle, secretary-treasurer, at 136 Evergreen Place, East Orange, New Jersey. The Founda- tion is establishing an administrative office in New York City, and will make available an Af- filiate Membership for persons other than doctors of medicine who are interested in aiding the pur- poses of the Foundation.
The object and purpose of the Foundation is to advance the public welfare by:
1. Gathering receiving, assembling and study- ing information relative to eye care.
2. Fostering and/or engaging in investigations and research in all aspects of eye care.
3. Sponsoring studies of educational, socio- economic and scientific factors affecting eye care.
4. Issuing reports and otherwise disseminating information relative to eye care to the general public and to members of the medical profession and ancillary workers.
5. Promoting the conservation of vision and the prevention of blindness through the wider dissemination of knowledge of the eye, its de- fects, disfunctions and other diseases and their re- lation to general health.
6. Promoting a more effective utilization of the scientific knowledge of ophthalmology and the other related branches of medicine.
7. Generally performing any act, related to the foregoing, designed to present to the public generally and the medical profession, all pertinent information on the care and treatment of the eyes.
"WHY TAKE CHANCES"
No practice is too small — no group too large to benefit from PM's management experience
WRITE OR CALL FOR INFORMATION
•PROF E S S I 0 11 A L
* in a n a g e m e n t
Security Bank Building — Battle Creek SAGINAW — GRAND RAPIDS — DETROIT
A com PL PTE BUSINESS SERVICE FOR THE 111 E D I CAL PR0FESSI0I1
Affiliated Offices in Other Cities
34
Say you saw it in the Journal of the Michigan State Medical Society
TMSMS
a new maximum in
now available with new mint -flavored
SUSPENSION
A savory mint flavor; that adds the fur- ther certainty of acceptability to anti- biotic therapy, particularly for that 90 % of the patient population treated in the home or office where sensitivity testing may not be feasible, and where pleasant flavor can make the difference betv/een prescription adherence and laxity.
Sigmamycin for Oral Suspension
is available in 2 oz. bottles containing 1.5 Gm. of Sigmamycin (oleandomycin 500 mg., tetracy- cline 1 Gm.). When reconstituted each 5 cc. tea- spoonful contains 125 mg. of Sigmamycin (42 mg. of oleandomycin as the phosphate salt with tetracycline amphoteric equivalent to 83 mg. of tetracycline hydrochloride).
PFIZER LABORATORIES, Brooklyn 6, N.Y Division, Chas. Pfizer & Co., Inc.
PREVENTION OF RHEUMATIC FEVER
the new
B I RTCH E R
cervix
conization
electrodes
shown actual size
HAWKINS* technic
Built by Birtcher of the finest materials to ex- actly meet the requirements of the technic of M. C. Hawkins, Jr., M.D., of Searcy, Arkansas, described in his paper "Re-Evaluation of Coniza- tion of the Cervix," published in Southern Medi- cal Journal.
* Described in his paper which will be sent on request
NOBLE-BLACKMER, INC.
267 W. Michigan 28148
Jackson, Michigan
Thirty- three persons died in Michigan in 1955 from rheumatic fever and 849 from chronic rheumatic heart disease, according to informa- tion from the Vital Statistics Division, Michigan Department of Health. This is a rate of 122 per million per year, out of a total death rate of approximately 7,000 per million — one death in sixty.
A report of two years’ experience with a five- year study of 400 children receiving prophylaxis at Irvington House, which was made to the Amer- ican Heart Association in Cincinnati on October 29, 1956, would indicate that prophylaxis still leaves much to be desired. Ninety-five strepto- coccal infections were discovered by throat cul- ture in eighty-seven of the patients, the rate of incidence being one in six patient years. Thirteen recurrences of acute rheumatic fever, representing 15 per cent of those who had one or more strep- tococcal infections, occurred in spite of prophy- laxis, and the recurrence rate for the entire group was one per forty-four patient years.
By method of prophylaxis, there were thirty- six streptococcal infections and nine rheumaitc fever recurrences among children who had re- ceived 200,000 units of penicillin orally one-half hour before breakfast, forty-four streptococcal in- fections and four rheumatic fever recurrences among the group receiving sulfadiazine, 1.0 grams daily in a single dose, and fifteen streptococcal infections and no rheumatic fever recurrences in the group receiving 1.2 million units of benzathine penicillin G intramuscularly at monthly intervals.
The Rheumatic Fever Control Committee, Michigan State Medical Society, recommends prophylaxis of one of the above types for dura- tion of life or until newer knowledge makes the method obsolete. The Michigan Department of Health provides benzathine penicillin G for any- one upon requisition, and the Michigan Crippled Children Commisison provides payment of a fee from trust funds for its administration to children who have been the subject of a court order under the Crippled or Afflicted Children’s Acts, upon the request of their family doctor of medicine.
Robert E. Fisher, M.D. Medical Co-ordinator Rheumatic Fever Program
38
Of the total AMA budget, not more than 2.5 per cent is spent on legislative efforts. The breakdown on spend- ing: 3 per cent to reserves, 9 per cent to supply mem-
bers with information, 19 per cent for public information, 6 per cent for socioeconomic activities, 60 per cent for publication of journals and other scientific activities, leaving only 3 per cent for Washington Office, Law' Department, and legislative activities combined.
TMSMS
Say you saw it in the Journal of the Michigan State Medical Society
...and when Spasmolysis is essential
LOCALIZED MUCOSAL ANALGESIA
Phenylazo-diamino-pyridine HCI — acts solely on the urogenital mucosa; provides prompt relief from burning, pain and frequency.
LOCALIZED ANTIBACTERIAL ACTIVITY
Sulfacetamide— eliminates mixed infections rapidly because of its unusual solubility in acid urine common to bacterial invasion of the urinary tract. No renal damage, concretions or anuria.
RINARY COMPLAINTS
*)f Sterilizes urine in 1 to 3 days *)f Relieves burning in minutes vf Effective in 93-98% of cases
sjimUTAcI.
The original Azo-Sulfa Formula* Antibacterial • Analgesic
Antibacterial • Analgesic • Antispasmodic
—the dual activity of SULFID with the well-known antispasmodic
effect of natural belladonna alkaloids.
FORMULAE:
SULFID— Each coated tablet contains: Phenylazo-diamino- pyridine HCI, 50 mg. and Sulfa- cetamide, 250 mg., in bottles of 100 tablets.
SULFID B-A — Each coated tablet contains the SULFID formula with natural belladonna alkaloids, 0.065 mg., in bottles of 100 tablets.
COMPANY — Columbus 16, Ohio
•Introduced— July, 1954
January, 1957
Say you saw it in the Journal of the Michigan State Medical Society
39
PR REPORT
THE 1957 LEGISLATURE AND HEALTH
As forecast in the December issue of The Jour- nal MSMS, the Legislature came to Lansing on January 9, appointed officers, organized commit- tees and settled down for what appears to be a six-month session. If recent pronouncements from the Governor and key legislative leaders are borne out, medical care, public health and general wel- fare will be foremost on the lawmakers’ agenda.
The 1956 House of Delegates, recognizing that a changing world needs new and amended laws, recommended action by the Legislature relating to psychotherapy, Wayne State LTniversity Col- lege of Medicine (expanded teaching facilities), regulation of ambulance operation, and more civil defense funds.
The MSMS Legislative Committee (L. A. Dro- lett, M.D., Chairman) met in Lansing, January 10, to finalize these recommendations into its 1956 program and to review legislation anticipated from other sources, some of it perennial, some new.
Of the hundreds of newspaper clippings that monthly come into the PR department from all parts of the state, two recent ones bear re- porting here. In a November editorial, the De- troit News states, “We hope that next year’s Leg- islature will give Michigan children the protection of a compulsory immunization law.”
This attitude was prompted by the recent dis- closure that 1 7,000,000 perishable doses of Salk vaccine were going begging and by the November diphtheria outbreak in Detroit. While the edi- torial deals primarily with polio and diphtheria, the tenor of the article indicates that all immuni- zations are desired on a compulsory basis. A fac- tor not discussed was whether this all-inclusive program would be paid for by the state, the fed- eral government or by the individual family head who today voluntarily protects his own children from the uninoculated carrier.
In the same week, the Battle Creek Enquirer and News editorially takes cognizance of findings and recommendations of the Governor’s Study Commission for the Aged and a Legislative Ad- visory Council on Problems of the Aging. Here is what the editorial said :
“The legislative group, in a public hearing in Lan- sing, took note of demands for state aid in the fields of housing and employment. The Governor’s Commis- sion recommended that state aid be given the aged for medical care, including glasses, hearing aids and den- tures.
“How much dependence and separate maintenance should government provide ? How much even of se- curity? In our free enterprise system, the more free enterprise and private initiative the better.
“Study sponsored by government? Excellent. Care for needy cases by government? Of course. But tak- ing over the lives of the elderly with public housing projects, state medical care and government-made em- ployment? Certainly not.
“The Legislature can help make older lives more meaningful. It also has an obligation to do so in a practical manner.”
NEW FIELD SECRETARY APPOINTED
John K. Pardee, East Lan- sing, has been named to the public relations staff of MS- MS, replacing Warren F. Try- loff in the Detroit office, who was transferred to the execu- tive office in Lansing in De- cember. As Field Secretary, he will co-ordinate liaison be- tween the State Society and the county medical societies in southeastern Michigan and the “thumb” area and will schedule the radio and tel- evision public service activities for MSMS in that part of the state.
Mr. Pardee, a political science graduate of Michigan State University, comes to the State Society with a wide experience in the health, in- surance and public relations fields. “Jack” now lives in East Lansing with his wife (an MSU die- titian) and their two children and is a member of Peoples Church there.
His fraternal associations include the Masons, Lions, Sigma Chi, Alpha Phi Sigma and the American Legion.
Mr. Tryloff is being promoted after two and a half years in Detroit to become Associate Pub- lic Relations Counsel, succeeding A. DeWitt Brewer who resigned in August to become a Vice President with the Mt. Clemens Federal Savings and Loan.
ANOTHER OFFICE OF MEDICAL EXAMINER ESTABLISHED
Members of the Dickinson County Medical Society and county morticians worked together in successful support of the November 6 referendum in that county which abolished the office of county coroner and created the office of county medical examiner. The measure was adopted by a three- to-one margin.
The question was placed on the ballot by ac- tion of the County Board of Supervisors at the request of morticians, who later sought and gained medical society support.
Until 1953, only Oakland, Genessee and Kent
( Continued on Page 42 )
4-0
JMSMS
Tastiest way to dissolve sore throat symptoms
TROCHES
HYDROZETC
(HYDROCORT1SONE-BACITRACIN-TYROTHRIC1N- NEOMYCIN-BENZOCAINE TROCHES)
Adult or juvenile, your patients with sore throats will welcome a course of HYDROZETS. These newest Merck Sharp & Dohme troches offer anti- inflammatory, anti-infective and analgesic proper- ties that promptly alleviate distressing mouth or throat irritation whether caused by infection, mechanical injury or allergic reaction. And HYDROZETS taste so good, it’s hard to believe they're medicine.
Formula: Each HYDROZETS Troche contains — 2.5 mg. ‘H YDROCORTONE’ to reduce pain, heat and swelling; 50 units Zinc Bacitracin, 1 mg. Tyrothricin and 5 mg. Neomycin Sulfate to com- bat gram-positive and gram-negative bacteria; and 5 mg. Benzocaine for rapid soothing analgesia. Other indications: As adjunct therapy in aphthous ulcers, acute and chronic gingivitis and Vincent’s infection.
Supplied: Vials of 12 troches.
MERCK SHARP & DOHME
DIVISION OF MERCK & CO . INC.. PHILADELPHIA 1. PA.
January, 1957
Say you saw it in the Journal of the Michigan State Medical Society
41
ACETYLCARBROMAL tablets
• Proved safe and effective by 6 years’ clinical use.
• Soothes the central nervous system, produces calmness without hypnosis.
• Non-toxic, non-cumulative, non-addict- ing, no known contraindications.
• Does not impair mental or physical function.
• Orally effective within 30 minutes for sustained action up to 6 hours.
• Economical.
BLUE SHIELD IS FOR EVERYBODY
In creating and sponsoring Blue Shield, the doctor has triggered a popular movement that won’t be stopped until every last potential mem- ber is enrolled in a pre-payment plan. For your Blue Shield Plan has not only sold itself — it has sold the American people on the idea of security against the economic consequences of unpredic- table medical needs.
In ten brief years, Blue Shield enrollment has burgeoned from less than 2 million to more than 37 million people, and about 45 million more have bought some form of cash indemnity cover- age for medical-surgical expense through private insurance companies.
While the job of providing voluntary medical care protection to the entire American people is about half done, the demand for this protection is practically universal.
Studies have shown that people in the lowest income brackets are not enrolled in as large proportions as those in the medium income groups. Enrollment among the aged, the self-employed and the rural population is also under par.
Blue Shield’s purpose is to help the profession meet its responsibility to the entire community, and the Plans are now giving particular attention to these segments of the population whose poten- tialities for profitable underwriting do not gen- erally appeal to insurance companies operated for private profit.
It’s no longer a question whether people are going to have voluntary prepayment for medical care. The real question, today, is whether Blue Shield can do the job satisfactorily and in good time.
And the answer lies with the doctor. American medicine has accomplished a modern miracle in the achievements of Blue Shield to date. The job that remains to be done will require as much imagination, as much bold action and devotion to the task as was needed to get Blue Shield off the ground ten years ago. To do this job. Blue Shield needs the help and guidance of every American physician.
Indications: Tension, nervousness, anxiety and muscular spasm.
Supplied: White round tablets Acetylcarbromal 5 gr. in bottles of 100, 1000.
Write for samples and literature
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MALLARD, inc
3021 WABASH, DETROIT 16, MICHIGAN
ANOTHER OFFICE OF MEDICAL EXAMINER ESTABLISHED
( Continued from Page 40 )
Counties, under a special law, had been permitted to establish a county medical examiner system. After passage of the State Medical Examiner Law that year, at the urging of MSMS, it became pos- sible for other counties to adopt this system if voters approved the local change.
Since January 1, 1954, when the law took effect, Wayne, St. Joseph, Allegan, Wexford, Ottawa, Hillsdale, Van Buren and Marquette Counties have adopted the new system.
42
Say you saw it in the Journal of the Michigan State Medical Society
TMSMS
nv JOUR N A L
of the Michigan State Medical Society
Issued Monthly Under the Direction of The Council VOLUME 56 JANUARY, 1957 NUMBER 1
Clinical Evaluation of Sintrom (G-23350), ^ New Oral Anticoagulant
A LTHOUGH anticoagulants are of definite therapeutic value in a variety of conditions, re ideal agent has yet to be found. Wright7 has efined the ideal anticoagulant as having the allowing properties:
1. Therapeutically active orally or parenterally with- out untoward reactions.
2. Rapid action.
3. Predictable response to a given dosage in a patient and between different patients.
4. Prompt termination of its action after discontinu- ance of the drug or after the administration of a nontoxic antagonist.
5. The activity of the drug can be determined by a simple test.
The purpose of this report is to present our icperience with Sintrom (G-23350), an oral anti- Dagulant, and to compare it with the ideal anti- aagulant and with anticoagulants which have een in use for some time.
Sintrom, nitrophenyl acetyl-ethyl-4-oxycumarin Fig. 1) is a member of the cumarin series.
From the Departments of Internal Medicine and urgery of the University of Michigan Medical School, his study was assisted by grants-in-aid from the Michi- in Heart Association and the H. R. Rackham School : Graduate Studies of the University of Michigan, inancial support and Sintrom were also generously sup- lied by Geigy Pharmaceuticals. Supplies of Mephyton ere made available through the courtesy of Merck & o., Inc.
Presented on Heart Day, Michigan Clinical Institute, etroit, March 8, 1956. Heart Day was supported by le Michigan Heart Association.
anuary, 1957
By J. A. Polhemus, M.D., W. S. Wilson, M.D., P. W. Willis III, M.D., J. R. Gamble, M.D., D. R. Griffin, M.D., P. E. Hodgson, M.D., and
I. F. Duff, M.D. Ann Arbor, Michigan
It is a stable compound supplied in 4 mg. scored tablets which are odorless and tasteless and which are administered without difficulty.
0
SINTROM, NITROPHENYL ACETYL- ETHYL-4-0XYC0UMARIN
Fig. 1.
Extensive animal experimentation2 has shown Sintrom to be effective in lowering the prothrom- bin level and to be free of toxicity even after continuous administration for two to three months. Reports from European clinics3 indicate that this drug is effective in man and is free of unto- ward reactions.
Sintrom was given to seventy patients, fifty-two of whom had a normal pretreatment prothrombin concentration (80 per cent or above — Quick method) and are therefore suitable for purposes of comparison with results obtained in other pa- tients treated with indandione derivatives as Di- paxin, Hedulin or Indon (PID) and cumarin derivatives as Dicumarol and Tromexan.
Diagnoses of the patients receiving Sintrom are listed in Table I.
49
CLINICAL EVALUATION OF SINTROM (G-23350)— POLHEMUS ET AL
TABLE I.
DIAGNOSES OF PATIENTS TREATED WITH SINTROM
|
Diagnosis |
Number of Patients |
|
Thrombophlebitis — without emboli |
|
|
Spontaneous |
16 |
|
Postoperative |
5 |
|
Carcinoma |
4 |
|
Pulmonary emboli |
|
|
Associated with thrombophlebitis |
5 |
|
Without apparent thrombophlebitis |
2 |
|
Myocardial infarction |
13 |
|
Basilar artery thrombosis |
1 |
|
Congestive heart failure (prophylactic) |
6 |
|
Total |
52 |
dose or the total amount of Sintrom required to reduce the prothrombin concentration to the therapeutic levels (less than 30 per cent) regard- less of time was 58 mg. The average patient reached therapeutic levels in two and one-third days. Maintenance dosage, usually started on the third or fourth day of treatment, ranged between 6 to 16 mg. with an average of 11 mg. daily. The maintenance dose was found to vary greatly from patient to patient and in the same patient from day to day.
TABLE II. COMPARISON OF THE RESULTS OBTAINED WITH SINTROM, DIPAXIN, PID, DICUMAROL AND TROMEXAN
|
Sintrom |
Dipaxin |
PID |
Dicumarol |
Tromexan |
|
|
Patients treated (normal initial prothrombin) |
52 |
64 |
133 |
122 |
50 |
|
Mean effective dose |
58 mg. |
G3 mg. |
685 mg. |
646 mg. |
3120 mg. |
|
Therapeutic effect achieved: Within 24 hours |
2% |
5% |
18% |
14% |
12% 82% |
|
Within 48 hours |
60% |
67% |
95% |
55 % |
|
|
Average (days) |
2.3 |
2.3 |
1.3 |
2.3 |
2.1 |
|
Average days to recover to 40% or above |
1.5 |
4.1 |
1.5 |
5.0 |
2.5 |
|
Incidence of prothrombin: Escape above 30% |
81% |
38% |
17% |
37% |
90% |
|
Fall below 10% |
27% |
10% |
10% |
15% |
20% |
|
Incidence of bleeding |
17% |
11% |
6.5% |
11% |
9% |
|
Total patients treated |
70 |
104 |
200 |
303 |
100 |
All patients were evaluated before anticoagu- lant therapy by members of the anticoagulant team who then followed the patients daily and determined the amount of the drug to be given. A base line prothrombin concentration was ob- tained prior to instituting therapy and daily prothrombin determinations (Quick method) were made while the patient continued to receive Sintrom and following its discontinuance until the prothrombin concentration had risen above 40 per cent. The aim of therapy was to maintain the prothrombin concentration between 20 per cent (33 seconds) and 30 per cent (22 seconds) of normal. A single daily dose was usually em- ployed, as no difference was noted when the drug was given twice daily. When the clinical condi- tion warranted an immediate effect on the blood- clotting mechanism, intravenous and/or subcu- taneous Heparin was given.
The results obtained with Sintrom and the previously evaluated anticoagulants are recorded in Table II.
The usual initial dose of Sintrom was 28 to 32 mg. followed by 16 to 24 mg. on the second day. The larger doses were usually given to patients of greater weight, but no definite rela- tionship between dosage and body weight was ob- served. The average total dose for the first forty- eight hours was 46.5 mg. The mean effective
After the therapeutic range had been achieved, forty-three of the fifty-two patients, or 81 per cent, escaped at one time or another above the 30 per cent level, and fourteen patients, or 27 per cent, were below the 10 per cent level on at least one occasion. There was a total of 525 days of maintenance therapy during which the prothrombin concentration was above 30 per cent on 143 days, or 27 per cent of the time, and be- low 10 per cent on eighteen days, or 3 per cent of the time. Following the discontinuance of therapy the average time for the prothrombin concentration to return to above 40 per cent was thirty-six hours.
Bleeding, limited to mild epistaxis and hema- turia occurred in nine patients, or 17 per cent. Though this is slightly higher than found with the other agents, the number of patients ob- served was not large enough to make it statis- tically significant, and it is doubtful if bleeding is more apt to occur with Sintrom therapy. As noted with other anticoagulants, bleeding usually occurred when the prothrombin concentration was 10 per cent or below. The hypoprothrombino- penia induced by Sintrom was rapidly corrected by oral or intravenous Vitamin Kj (Mephyton)
(Fig. 2).
No evidence of toxicity was noted though ther- apy was continued in one patient for fifty-three
50
TMSMS
CLINICAL EVALUATION OF SINTROM (G-23350)— POLHEMUS ET AL
days. Pre-treatment and post-treatment renal and liver function studies, consisting of creatinine clearances, urinalyses and Bromsulfalein excre- tions, were performed in two patients without
parallel the decrease in prothrombin activity as reflected by the one stage (Quick) and two stage methods. No significant change in Factor V could be detected.
DAYS
* VITAMIN K, (MEPHYTON-MERCK) AS *»B20863 44 S THROMBOPHLEBITIS
Fig. 2. The excessive prothrombin time resulting from Sintrom was rapidly reversed by 15 mg. of vitamin Ki orally with prompt cessation of hematuria.
evidence of change. No absolute resistance to Sintrom was noted.
In addition to daily Quick one-stage prothrom- bin determinations, several patients had simultane- ous prothrombin evaluations by the Owren one- stage P and P method,4 the Ware modification of the Owren one stage method5 and the two stage method of Ware and Seegers.6 As previous- ly reported by Duff,1 when the prothrombin level was within therapeutic range (10 to 30 per cent) by the Quick one-stage and two-stage methods, the corresponding values by the Owren and Ware methods were definitely below the recommended safe level. The Quick method of prothrombin determination, which is the simplest and most widely used, though not specific, was found to be satisfactory for control of Sintrom.
Two patients had daily Factor V (Proacceler- and) and Factor VII (Proconvertin) determina- tions. A fall in Factor VII activity was noted to
Sintrom was the most potent anticoagulant evaluated, milligram for milligram. Though it probably is more rapid in action than Dicumarol and similar to Dipaxin, it is not as rapid as Tromexan and PID. The return to normal pro- thrombin levels following the discontinuance of drug administration would appear to be as rapid with Sintrom as with any of the other anticoagu- lants. Unfortunately in our experience there does not seem to be a uniform response to a specific dosage from patient to patient nor in the same patient. This characteristic makes se- lection of a maintenance dose difficult and prob- ably accounts for the high incidence of escape from therapeutic levels.
Summary
1. Sintrom, an oral anticoagulant, was given to seventy-two patients. The results in fifty-two of ( Continued on Page 56)
January, 1957
51
Diuretics in the Treatment of Congestive Heart Failure
/^\NE of the cardinal manifestations of con- gestive heart failure is edema. The raw materials for this edema, chiefly sodium and water, are provided by the abnormal retention, by the kidney, of these substances. This retention is due to two factors: decrease in the glomerular filtra- tion rate, and increase in the tubular reabsorption of sodium and water. These two factors are more or less operative in all cases of congestive heart failure, and are secondary to the failure of the heart to maintain an adequate circulation.
The primary effort in the therapy of congestive heart failure, then, should be directed toward the correction of the damaged pump. Unfortu- nately, the types of heart disease for which we have a specific cure are few, indeed. Commis- surotomy for mitral stenosis, thiamin for beri- beri heart disease, subtotal thyroidectomy or therapeutic doses of radioactive iodine for thy- rotoxic heart disease are examples of specific corrective measures. For the majority of oases of heart failure, digitalis is a nonspecific but highly effective medication to improve the effi- ciency of the failing myocardium. These spe- cific measures plus digitalis, then, constitute the primary weapons against congestive heart failure; their use usually improves the circulation suffi- ciently to reverse the mechanisms which caused the edema, resulting in diuresis.
Frequently, however, a direct approach to the elimination of the excess sodium and water is made. This may be accomplished in two ways: reducing the intake of sodium, and promoting the excretion of sodium and water. The absorp- tion of sodium into the body may be reduced by low-sodium diets and by the use of cation-ex- change resins. The increased removal of edema fluid may be accomplished by mechanical means,
From the Departments of Medicine, City of Detroit Receiving Hospital and Wayne State University Col- lege of Medicine, Detroit, Michigan.
Supported in part by grants from the National Institutes of Health ( H- 1471) and the Michigan Heart Association.
Presented on Heart Day, Michigan Clinical Institute, Detroit, March 8, 1956. Heart Day was supported by the Michigan Heart Association.
By Yoshikazu Morita, M.D.
Detroit, Michigan
such as abdominal paracentesis,1 or by diuretics, which promote increased renal excretion of edema fluid. In most patients, diuretics permit a more rapid recovery from congestive heart failure than would be possible without their use, and in some patients, diuretics are necessary if any improve- ment at all is to be noted. The diuretics which are commonly used in the therapy of congestive heart failure are shown in Table I.
TABLE I. COMMONLY AVAILABLE DIURETICS IN THE
TREATMENT OF CONGESTIVE HEART FAILURE
I. Organic mercurials
A. Parenteral
B. Oral
II. Acetazoleamide (Diamox)®
III. Aminometramide (Mictine)®
IV. Ammonium chloride
V. Aminophylline
The injectable organic mercurial preparations are the most effective of the diuretics. Oral mercurial compounds, Diamox® and Mictine,® are less effective but useful compounds, since they may be administered by mouth. Ammonium chloride and aminophylline are not very potent diuretics in themselves, but are important ad- juncts in the optimal use of mercurials, and will be discussed more in detail below.
Organic mercurial preparations act by depress- ing the reabsorption of chloride, sodium, and water by the renal tubules, thereby producing an increase in the urinary excretion of these in- gredients of edema. The exact biochemical locus of action is still in doubt.2,3 It usually promotes a greater excretion of chloride than of sodium;4’5 the result frequently is a depletion of chloride from the body. There is also an increased excre- tion of acid in the urine. These two actions lead to the development of hypochloremic alkalosis, which is the most common electrolyte disturbance produced by the use of a mercurial diuretic. Its recognition is important in that it results in a refractoriness to further injections of the same compound. This refractoriness may be the re- sult of the decrease in the chloride load filtered by the glomeruli,6 and/or of the shift of intra- cellular pH toward alkalinity.7 Correction of this
52
TMSMS
DIURETICS IN CONGESTIVE HEART FAILURE— MORITA
electrolyte disturbance may be simply made by the administration of ammonium chloride. En- teric coated tablets, in the dose of 2.0 grams four times a day, should be given for two to three days.
A second type of electrolyte disturbance some- times attributed to the use of mercurials is hypo- natremia. The appearance of this condition is usually due in part to other factors, such as markedly restricted salt intake, extrarenal salt loss, and internal shifts of electrolytes, and it is difficult to blame the diuretic alone. Mild hyponatremia of about 125 to 130 mEq. per liter does not usually prevent an adequate response to mer- curials, provided the chloride level is not low. Severe hyponatremia of less than 120 milliequiva- lents per liter may reflect an actual deficit of total body sodium, as may be the case in a patient who has been eating little and receiving frequent injections of mercurials. Physical examination of such a patient would reveal evidence of de- hydration and possibly collapse, or of normal hydration. Replenishing the sodium supply may improve the clinical picture almost immediately. The following formula may be used as a guide to determine the amount of sodium to be given to raise the plasma level by a given amount. Six-tenths milliequivalent of sodium should be given for each kilogram of body weight to raise the plasma sodium level by 1 milliequivalent per liter. If it is desired to raise the plasma sodium level in a 70 kilogram man by 10 milliequivalents per liter, 0.6 x 70 x 10 or 420 milliequivalents of sodium should be given. The sodium may be given chiefly as the chloride, bicarbonate or lac- tate, depending upon the relative deficits of bi- carbonate and chloride in the plasma. It is advisable to proceed cautiously when administer- ing large amounts of sodium; an attempt to correct the plasma sodium level completely to normal in one step should not be made. It is suggested that about one-half of the amount needed for complete restitution be given as the first dose. Further doses may be given if a good clinical response occurs, and incomplete correction of the hyponatremia is found. A patient with congestive heart failure, who still has moderate to marked edema and who has severe hypona- tremia, probably does not have a deficit of total sodium, but actually has an excess of total body sodium. In the extracellular fluid, the excess of water, however, is relatively greater than the
excess of sodium, resulting in hyponatremia. The giving of sodium to such a patient is very much like giving an additional weight for the left hand to a man who is carrying a heavy package in his right hand. The added burden, by restoring better balance, may result in more efficient carry- ing ability; however, there is the danger that the man may not be able to lift the total load at all! In patients with congestive heart failure, the in- fusion of hypertonic saline may result in a tem- porary increase in urinary output of water and sodium; however, usually the net loss of edema is nil.8 Frequently, patients who develop this type of electrolyte disturbance are critically ill, and the giving of hypertonic saline does not prevent a continuing downhill course.9 It is possible that in such patients the hyponatremia is a reflection of decreased osmolarity of the intracellular fluid, and therefore not amenable to correction by the addition of sodium to the extracellular fluid. If it has been decided to give sodium to the edematous patient with hypo- natremia, the amount of sodium required should be calculated from the above formula. Since water is already present in large excess, the in- take of water must be kept at a minimum; the sodium should be given intravenously, slowly, as a hypertonic solution, such as 5.8 per cent saline, which contains 100 milliequivalents of sodium per 100 ml.
A third type of electrolyte disturbance which may develop during mercurial therapy is hypopo- tassemia. Under certain conditions, mercurials may inhibit the tubular secretion of potassium.4’10 However, in most patients with congestive failure, there is an increase in potassium excretion. This increased excretion is not very marked in most patients. Hence, in a patient who is eating nor- mally, marked potassium depletion does not oc- cur. Nevertheless, even a modest loss of potas- sium in a patient who is fully digitalized may lead to cardiac manifestations of digitalis intoxi- cation,11 such as frequent ventricular premature beats. This is due to the opposing effects which potassium and digitalis exert upon myo- cardial function.
During the development of congestive heart failure, there is usually a negative potassium balance.22 In subjects in whom this deficit be- comes very large, perhaps due, in part, to poor intake of food, a marked decrease in intracellular potassium occurs. Extracellular sodium may
Jan UARY, 1957
53
DIURETICS IN CONGESTIVE HEART FAILURE— MORITA
migrate into the cellular space under such condi- tions, resulting in hyponatremia. In such cases, the hyponatremia cannot be corrected until the intracellular potassium deficit is remedied.12
Diuresis with mercurial plus aminophylline Rheumatic 8 hypertensive heart disease
Fig. 1. Diuresis produced by the combined use of a mercurial diuretic plus aminophylline.
Where potassium lack is deemed to be clinically significant, potassium chloride, enteric coated, should be given in a dosage of 2.0 grams three to four times daily until the deficit is corrected.
Before discussing a plan for the use of mercurial diuretics, the value of aminophylline as an ad- junct to mercurial diuretics should be discussed. When given parenterally, aminophylline has two effects on the kidney: first, it increases renal plas- ma flow and glomerular filtration rate,8 both of which are usually depressed in congestive heart failure; and, secondly, it inhibits tubular reab- sorption of sodium. The first is by far the more important factor. Since filtration is the first
step in the production of urine, a diminution of this function, such as occurs in congestive heart failure, hinders the removal of sodium and water and, thus, of edema, by the kidneys. Of the diuretics commonly used, aminophylline is the only one which increases glomerular filtration. Figure 1 illustrates the use of this drug. The patient was a woman with hypertensive and rheumatic heart disease, with severe congestive heart failure. It is to be noted that with amino- phylline alone or with mercurial alone, there was no loss of edema, as indicated by daily body weight measurements; however, the combination of the two drugs resulted in a good diuretic re- sponse repeatedly. The increase in glomerular
filtration, brought about by the aminophylline, plus the inhibition of tubular reabsorption of salt and water, accomplished by the mercurial, resulted in diuresis, where either one alone failed.
Table II is a suggested regimen for the use of injectable mercurial diuretic in congestive heart failure; it embodies the principles of its use out- lined above.
TABLE II. SUGGESTED REGIMEN FOR PARENTERAL MERCURIAL DIURETIC
I. 2 ml. intramuscularly every third morning.
II. If response, as measured by increase in urinary volume and/or decrease in body weight is poor, give enteric coated ammonium chloride, 2.0 grams four times a day, for three days preceding each dose of the mercurial.
III. It the response is still poor, give aminophylline,
0.5 to 1.0 gram, in 300 ml. of 5 per cent glucose in water intravenously over a three-hour period, starting simultaneously with the dose of mercurial.
In more urgent cases, mercurial injections may be given oftener than indicated; however, more frequent injections are more likely to lead to electrolyte disturbances, resulting in refractoriness, and may result in mercurialism if renal function is markedly impaired. Aminophylline need not be given as an infusion, but may be given in one 0.5 gm. dose intravenously about one to two hours after the mercurial. If intravenous injection is not feasible, aminophylline, 0.5 gm. in 2 ml., may be administered intramuscularly together with the mercurial in the same syringe13; however, this is not a recommended procedure, since intra- muscular injections of aminophylline are painful. Orally administered aminophylline is poorly ab- sorbed, and therefore has little beneficial effect. It should be stressed again that the patient should be at rest, reclinining, for several hours to obtain a maximal glomerular filtration rate and maximal diuresis.
The procedure just outlined is designed for the initial treatment of a patient with congestive heart failure. For maintenance, less strenuous measures may suffice. Many patients may remain edema-free with digitalis, adequate rest, salt re- striction, and one of the oral diuretics.
Oral mercurial preparations are not as effective as their injectable counterparts.14’15 Moreover, there is a higher incidence of side reactions, not- ably gastrointestinal disturbances, which attend their use.16 Gastrointestinal manifestations include stomatitis and gingivitis, nausea, vomiting, ab- dominal pain, and diarrhea. Dermatitis, albu- minuria and hematuria also have been reported. Mercurials are also prepared as rectal supposi-
54
TMSMS
DIURETICS IN CONGESTIVE HEART FAILURE— MORITA
ories. Their efficacy is of the same order as hat of the oral diuretics.23
Acetazoleamide, or Diamox. is another recently ntroduced oral diuretic. This interesting com- xmnd is an inhibitor of the enzyme carbonic mhydrase, which is found in the cells of the •enal tubules. One of the numerous functions )f the distal renal tubules is the acidification of mine. This function and the reabsorption of ome of the sodium in the tubular urine are ntermeshed in an operation which requires car- tonic anhydrase for its functioning. In the tubu- ar cell, this enzyme catalyzes the production of :arbonic acid from the ever present raw materials, vater and carbon dioxide. The carbonic acid, n turn, dissociates to yield hydrogen ion and ticarbonate ion. The hydrogen ion is secreted nto the tubular urine in exchange for sodium on. The operation results in the excretion of icid and the conservation of sodium ion to the >ody. When Diamox is administered, this enzyme 5 blocked. The production of carbonic acid de- ceases and, consequently, the availability of tydrogen ion in the tubular cell is decreased, exchange of sodium for hydrogen is thereby re- luced, allowing more sodium to remain in the ubular fluid. The result is the excretion of ncreased amounts of sodium and, with it, water, "urther, since hydrogen ion secretion is depressed, he urine becomes less acid, and frequently al- aline. A consequence of the use of this com- >ound, therefore, is the production of hyper- hloremic acidosis.17 This is the exact opposite if the electrolyte disturbance produced by mer- urials.
In clinical trials,18’20 Diamox has been found o be a mild to moderate diuretic. It is said to le more effective in failure due to cor pulmonale han in ordinary types of heart failure.19 The typerchloremic acidosis produced is usually mild nd asymptomatic; however, it will result in re- ractoriness to the diuretic action of the drug. In irder to allow the body to recover from the acido- is and thus again become responsive to the drug, he compound should not be given more often han once every other day. The side effects of he drug in the doses recommended below are nild, and consist of paresthesia of the circumoral rea and the extremities.
Aminometramide, or Mictine, is another useful >ral diuretic.21 It acts by inhibition of tubular re- .bsorption of sodium and water, and no electrolyte
disturbance has been reported following its use. Because the side effects are chiefly referable to the gastrointestinal tract, the drug should be given with meals to minimize this. Doses larger than that recommended below will give a high inci- dence of undesirable reactions; nausea and vom- iting were found in 31 per cent of patients re- ceiving 1.5 gm. of Mictine per day.21 On the basis of preliminary observations, Rolicton,® which is closely related chemically to Mictine, seems to be as effective as, and less likely to cause nausea and vomiting than, Mictine, when 500 mgm. are given three times a day with meals.
Table III summarizes the doses and suggested plan for the use of the oral diuretics discussed.
table in
I. Mictine®
200 mg. t.i.d. with meals, every other day
II. Neohydrin®
3 to 8 tablets after breakfast, every other day
III. Diamox®
250 or 500 mg. every other morning
In general, if possible, all diuretics should be given in the morning, or not later than mid- afternoon, to allow the patients uninterrupted sleep at night. In the case of Mictine, gastro- intestinal disturbances dictate administering the drug with meals. With oral mercurials, the larg- er doses indicated should not be continued in- definitely, since gastrointestinal symptoms of mer- curialism are more apt to develop. Furthermore, in patients with elevated blood urea nitrogen or nonprotein nitrogen, there may be an impaired ability to excrete mercury, and mercurial diure- tics, oral or parenteral, should not be used in high doses. The importance of bed rest for at least a few hours after administration, to obtain max- imal effect, has been stressed above.
Summary
In conclusion, diuretics are important, although secondary, therapeutic measures in the treatment of congestive heart failure. Parenteral organic mercury preparations are the most potent diuretics known. In the absence of severe organic renal disease, mercurials, used with ammonium chloride and aminophylline, as indicated, will produce diuresis in most patients with severe congestive heart failure. The oral diuretics are less effective than injectable mercurials; however, in moder- ately severe cases, their use may reduce or nullify the requirement for injections. Each of the di- uretics must be used with a full understanding of its mode of action and its shortcomings.
[anuary, 1957
55
DIURETICS IN CONGESTIVE HEART FAILURE— MORITA
References
1. Schemm, F. R., and Camara, A. A.: The relief of resistant edema by utilization of a sump phe- nomenon. Circulation, 11:411, 1955.
2. Dale, R. A., and Sanderson, P. H.: The mode of action of a mercurial diuretic in man. J. Clin. Invest., 33:1008, 1954.
3. Wesson, L. G., Jr., and Anslow, W. P., Jr.: Effect of osmotic and mercurial diuresis on simultaneous water diuresis. Am. J. Physiol., 170:255, 1952.
4. Welt, L. G.; Goodyer, A. V. N. ; Darragh. J. H. ; Abele, W. A. ; and Meroney, W. H. : Site of salure- tic action of an organic mercurial compound. J. Appl. Physiol., 6:134, 1953.
5. Schwartz, W. B., and Wallace, W. M.: Electrolyte equilibrium during mercurial diuresis. J. Clin. In- vest., 30: 1089, 1951.
6. Goodman, L. S., and Gilman, A.: The Pharmaco- logical Basis of Therapeutics, 2nd Ed., p. 848. New York: The Macmillan Co., 1955.
7. Mudge, G. H., and Hardin, B. : Response to
mercurial diuretics during alkalosis: A comparison of acute metabolic and chronic hypokalemic alka- losis in the dog. J. Clin. Invest., 35:155, 1956.
8. Weston, R. E.; Escher, D. J. W. ; Grossman, J.; and Leiter, L. : Mechanisms contributing to unre- sponsiveness to mercurial diuretics in congestive failure. J. Clin. Invest., 31:901, 1952.
9. Uricchio, J. F., and Calenda, D. G.: The failure of hypertonic saline in the treatment of hypona- tremia and edema in congestive heart failure. Ann. Int. Med.. 39:1288, 1953.
10. Mudge, G. H.; Ames, A.; Flulks, J.; and Gilman, A. : Effect of drugs on renal secretion of potassium in the dog. Am. J. Physiol., 161:151, 1950.
11. Lown, B. ; Salzber, H.; Enselberg, C. D.; and
Weston, R. E.: Interrelation between potassium
metabolism and digitalis toxicity in heart failure. Proc. Soc. Exper. Biol. & Med., 76:797, 1951.
12. Cort, J. H., and Matthews, H. L.: Potassium de- ficiency in congestive heart failure. Lancet., 1:1202, 1954.
13. Vogl. A., and Esserman, P. : Aminophylline as
supplement to mercurial diuretics in intractable
congestive heart failure. J.A.M.A., 128:12, 1951.
14. Moyer, J. H. ; Handley, C. A.; Seiber, H. A.; and Snyder, H B. : Electrolyte, water and mercury ex- cretion after oral administration of neohydrin. Arch. Int. Med., 92:847. 1953.
15. Moyer, J. H.; Handley, C. A.; and Wilford, I.: Results over a two-year period on three experimen- tal diuretics administered orally to patients with cardiac failure. Am. Heart J., 44:608, 1952.
16. Evans, J. M., and Massumi, H. A.: The long-term use of the oral diuretic 3-chloro-mercuri-2-methoxy- propylurea (Neohydrin) in ambulatory patients. Ann. Int. Med., 44:124, 1956.
17. Leaf, A.; Schwartz, W. B. ; and Reiman, A.: Oral administration of a potent carbonic anhydrase in- hibitor (“Diamox”). New England J. Med., 250: 759, 1954.
18. Reiman, A.; Leaf, A.; and Schwartz, W. B. : Oral administration of a potent carbonic anhydrase in- hibitor (“Diamox”). II. Its use as a diuretic in patients with severe congestive heart failure. New England J. Med., 250:800, 1954.
19. Schwartz, W. B. ; Reiman, A. S.; and Leaf, A.: Oral administration of a potent carbonic anhydrase inhibitor (“Diamox”). III. Its use as a diuretic in patients with severe congestive heart failure due to cor pulmonale. Ann. Int. Med., 42:79, 1955.
20. Friedberg, C. K.; Taymor, R.; Minor, J. B.; and Halpern, M. : The use of Diamox, a carbonic an- hydrase inhibitor, as an oral diuretic in patients with congestive heart failure. New England J. Med. 248:883, 1953.
21. Caccamo, L. P. ; Pringle, B. H.; and Hissong, D.
E.: A therapeutic evaluation of l-allyl-3-ethyl-6-
aminotetrahydropyrimidinedione (Mictine), a new oral diuretic. (To be published).
22. Iseri, L. T. ; Boyle, A. J.; and Myers, G. B. : Water and electrolyte balance during recovery from severe congestive failure on a 50 mgm. sodium diet. Am. Heart J., 40:706, 1950.
23. Makons, N. ; Jennings, P.; Frank, E. H., Jr.; and Vander Veer, J. B.: A clinical evaluation of the use of a rectal mercurial diuretic in patients with chronic congestive heart failure. Am. J. M. Sc., 231:86, 1956.
SINTROM, A NEW ORAL ANTICOAGULANT
(Continued from Page 51)
these were compared with those obtained in other patients receiving Dicumarol, Hedulin or Indon (phenylindandione) , Dipaxin and Tromexan.
2. On the basis of the mean effective dose, the drug was found to be the most potent of any of those studied.
3. A maintenance dose was difficult to estab- lish which resulted in a high incidence of escape from therapeutic range.
4. Toxicity was not encountered and the in- cidence of bleeding (17 per cent) was in the general range reported with other anticoagulants.
5. The excessive effect of Sintrom could be rapidly reversed by oral or intravenous Vitamin
Kv
6. A decrease in Factor VII activity paral- leled the hypoprothrombinemia produced.
References
1. DufT, I. F.; Gamble, J. R. ; Willis, P. W., Ill; Hodgson, P.; Wilson, W. S. ; and Polhemus, J. A.: The control of excessive effect by anticoagulants. Ann. Int. Med., 45:955, 1955.
2. Geigy Pharmaceuticals: Personal communication.
3. Moeschlin, S., and Schorno, H. : Clinical experi- ence with a new 4-oxycumarin derivative — Sintrom. Schweiz, med. Wchnschr., 85:590-592 (June 11) 1955.
4. Owren, P. A., and Oas, K.: The control of
Dicumarol therapy and the quantitative determina- tion of prothrombin and proconvertin. Scandinav. J. Clin, and Lab. Invest., 3:201, 1951.
5. Ware, A. G., and Stragnell, R.: Improved one- stage prothrombin method. Am. J. Clin. Path., 22: 791, 1952.
6. Ware, A. G., and Seegers, W. H.: Two stage procedure for the quantitative determination of prothrombin concentration. Am. J. Clin. Path., 19:471, 1949.
7. Wright, I. S.: The use of anticoagulants in the treatment of diseases of the heart and blood ves- sels. Ann. Int. Med., 30:80, 1949.
56
JMSMS
Interatrial Septal Defect
Course and Surgical Correction
By James B. Blodgett, M.D.
Detroit, Michigan
T NTERATRIAL septal defect is an important ■** cardiac anomaly because it usually causes death in early adult life and it is subject to surgi- cal correction. It is one of the most common of the congenital abnormalities of the heart. Gelf- man and Levine1 in studying 453 autopsied cases of congenital heart disease found interatrial septa] defect present in 39 per cent of all cases and in 25 per cent of the cases over two years of age. In a clinical study of 1,395 patients with congeni- tal heart disease, Gasul & Fell2 found interatrial ;eptal defect to be the fourth commonest lesion, occurring in 9.6 per cent of their series.
The life expectancy in interatrial septal defect varies as it does with other congenital cardiac de- pots, but average life expectancy is between thirty- our3 and forty4 years. Death is preceded by a lumber of years of increasing cardiac disability.
The pathologic physiology is a consequence of he anatomic defect and the associated abnormal oemodynamics. The primary hemodynamic ab- lormality is an enormous flow of blood from the eft atrium to the right. This is referred to as a eft to right interatrial shunt. The great quantity rf this shunt was demonstrated by Healy, Dow, iosman and Dexter5 who calculated the volume }f the flow per minute by obtaining the difference between the pulmonary flow and the peripheral low in liters per minute. The flow through the hunt in their patients was commonly 6 to 8 liters aer minute and not infrequently as high as 25 o 28 liters per minute. This large volume of nteratrial flow is added to the normal inflow af the right atrium. Consequently, the minute volume flow through the right atrium, the right /entricle, pulmonary vascular system and the left itrium is very large. The left ventricular and irterial flow is reduced in quantity by the inter- itrial shunt. The increase in pulmonary flow aroduces the enlargement of the pulmonary vas-
Dr. Blodgett is Associate Surgeon, Grace Hospital and \ssistant Surgeon, Children’s Hospital Detroit, Michigan.
Presented on Heart Day, Michigan Clinical In- stitute, Detroit, March 8, 1956. Heart Day was sup- aorted by the Michigan Heart Association.
January, 1957
culature, as seen by x-ray and also produces the vascular pulsation which is occasionally seen, and is known as “hilar dance.” The reduced peri- pheral arterial flow is the cause of the easy fatigue in these patients and the general underdevelop- ment. It has been shown by Edwards,6 Dam- mann,7 and others, that large increases in volume of pulmonary flow eventually produce obliterative vascular changes which increase resistance and consequently elevate the pulmonary artery pres- sure. Concomitantly there is elevation in right ventricular pressure and increased work for the right ventricle. There follows right ventricular hypertrophy and dilatation and eventual incom- petence of both the pulmonary and tricuspid valves. At some stage in this sequence the right atrial pressure rises and clinical signs of peripheral congestive failure ensue. In the late stages, the right auricular pressure may rise to such levels that the volume of the shunt is very much re- duced if not completely eliminated and there is occasional reversal of the shunt so that blood flows from the right atrium to the left, with the appearance of cyanosis. Death is the ultimate consequence of this pathophysiologic progression.
The anatomic consequence of the interatrial shunt is enlargement of the pulmonary artery and its radicals, enlargement of the right ventricle, the right auricle and left auricle. Apparently, as the atria dilate, the defect in the interatrial sep- tum also enlarges, that is, it is stretched along with the atrial walls and septum. This increases the amount of the shunt. The mitral valve has been commonly found to be abnormally small, but not the seat of pathologic abnormality. The probable reason for this is that since the flow through the mitral valve into the left ventricle has always been small, the valve has not en- larged at the normal rate. As the individual grows, there is greater disproportion between the mitral valve which remains relatively infantile and the interatrial defect which enlarges as the atria dilate. The effect of this is an increasing per cent of left to right shunt.
57
INTERATRIAL SEPTAL DEFECT— BLODGETT
As a means of correction of this anomaly, clo- sure of the interatrial septal defect is obviously necessary. Open heart surgery with inflow occlu- sion may occasionally be necessary, but for the
Fig. 1. Interatrial defects; closed methods of repair. The four drawings illustrate the placement of the cir- cumferential suture and the dissection behind the vena cava into the posterior portion of the interatrial septum, which permits closure of the defect by tying the suture.
commoner atrial defects the closed method has proven very safe and effective. The closed method of interatrial repair depends upon a technique developed by Sondergaard, presented by Bjork and Craford.8 Briefly, the method of Sondergaard depends upon the fact that the pos- terior portion of the interatrial septum reaches the atrial wall at a point between the vena cava and the right pulmonary veins. Thus, by dis- secting up the vena cava away from the pulmon- ary veins at the hilum of the lung, the dissection is carried essentially into the back portion of the interatrial septum. Once this dissection has been made, sutures can be placed from the outside of the atrium, which can close the septal defect. The needle is guided by the finger introduced into the right atrium through the auricular ap- pendage. Through the septal defect both sides of the interatrial septum can be palpated as the sutures are being placed. These sutures can be placed in a variety of ways and the completeness of the closure can be clearly appreciated by the palpating finger. The closure can be accom- plished without interference with the vena caval
inflow and should not of course interfere with the AV conduction system, or the outflow of the coronary sinus. Before the closure it is possible to pass the intracardiac finger through the auricu-
Fig. 2. Interatrial defects; closed methods of repair. Drawings A and B illustrate placement of mattress su- tures from the Sondergaard dissection to close the de- fect. Drawings C and D illustrate the technique of Lam for closing the defect with the double ended needle.
lar defect and palpate the mitral valve and to palpate any possible tricuspid insufficiency. As the defect is closed the distention of the right atrium becomes noticeably less, and the color of the blood as the finger is withdrawn from the right atrial appendage is dark venous in appear- ance rather than bright red as when the finger was introduced. We have also noted, in cases where a pulmonary arterial thrill had been palp- able, that this has disappeared upon interatrial closure. Suturing and manipulation from the right side of the heart is attended with very little rhythm irregularity and the cardiac function has been well maintained during surgery. Figures 1 and 2 illustrate three methods of suture place- ment. All start from the Sondergaard dissection. The lower two illustrations in Figure 2 show the method of suture placement devised by Lam9 which uses a double-ended needle. In cases where the septal wall is thick enough, this method has been very useful.
The indication for surgical closure of an inter- atrial septal defect would appear to be the presence of the defect in any patient who has
58
JMSMS
INTERATRIAL SEPTAL DEFECT— BLODGETT
not progressed to the stage of such elevated ir- reversible pulmonary hypertension that operation can produce little or no improvement. Ideally the closure should be effected before the second- ary anatomic results of the massive shunt and chamber enlargement have occurred. There is no doubt that the operative procedure is easier and less hazardous when undertaken on the small hearts of children rather than upon the tremen- dously enlarged hearts of adults. Our present feeling is that parents with children who have interatrial septal defects should be advised to have operative closure for the following reasons:
1. The expectation is that the individual will die before the age of forty without closure.
2. Early operation prevents:
(a) Progressive enlargement of the inter- atrial defect.
(b) Increasing disproportion of the mitral valve and the defect.
(ci) Progressive pulmonary vascular changes and pulmonary hypertension.
(d) The clinical complications of the dis- ease such as recurrent pneumonia, pul- monary thrombosis, and hemoptysis.
3. The child can regain his normal growth curve.
4. The operation is technically easier and less hazardous in childhood.
Surgery is contraindicated if the pulmonary pressure, as measured by catheterization, is con- siderably elevated. The reason for this is that irreversible pulmonary vascular changes have oc- curred and the right heart symptoms will not abate as a result of closure of the defect. Pul- monary hypertension is clinically suggested by signs of right cardiac failure, a very large heart and if the patient is over forty years of age.
Case Reports
The following three cases are presented to il- lustrate the previous points.
Case 1. — This was a forty-two-year-old woman who had had progressive disability for six years, character- ized by breathlessness, fatigue, dependent edema and ascites. She entered the hospital completely incapac- itated and was maintained in an oxygen tent. Roent- genogram showed tremendous enlargement of the heart (Fig. 3). Angiography demonstrated trichamber en- largement with a very large pulmonary arterial tree. Catheterization findings by Dr. Harper Hellems showed that there was a left-right shunt of 4.7 liters per minute and that the pulmonary artery pressure was 97/36. Op- eration was carried out April 19, 1955. At this time a
tremendous right auricle was demonstrated. The defect by palpation was felt to be 4 to 5 cm. in diameter. There was definite tricuspid regurgitation. The de- fect was completely closed with mattress sutures.
Fig. 3. Case 1. Preoperative chest radiograph.
Following operation the patient was improved. Her respiration was considerably easier. She could be out of her oxygen tent, was up and around, and the edema of the extremities cleared somewhat. She was discharged on the twentieth postoperative day. At home, the signs of right-sided failure gradually increased, and the pulmonary symptoms did not reappear. The patient died suddenly at home four months following operation.
Comment : This was an advanced phase of inter-
auricular septal defect with high pulmonary pressure. The operation was undertaken because of the high vol- ume of the shunt and the precarious condition of the patient. In the presence of tricuspid insufficiency, clos- ure of the shunt did not correct the right-sided failure and operation was too late to be of benefit to this patient.
Case 2. — This patient is a thirty-six-year-old mother of five children, who had had progressive symptoms for four years, consisting of easy fatigue, dyspnea, tachy- cardia and hemoptysis. On examination, she had signs of atrial septal defect, and catheterization by Dr. Harper Hellems proved the presence of the defect. There was a left to right shunt of 9.1 liters per minute, but the pulmonary artery pressure was 27/11, indicating not more than minimal pulmonary vascular obstructive changes. Operation was carried out June 14, 1955. The interatrial defect was found to be 2.4 cm. in size. The mitral valve opening was about a finger and a quarter in size. The interatrial septal defect was closed with three mattress sutures. The patient did well fol- lowing operation. She was discharged on the tenth
January, 1957
59
INTERATRIAL SEPTAL DEFECT— BLODGETT
postoperative day. The x-ray taken two months post- operatively is reproduced with the preoperative film (Fig. 4). The transverse diameter had decreased 1.8 cm. Following operation the patient has had occasional
Case 3. — This is a five-year-old girl who had rather slow physical development and frequent colds. She was found to have an enlarged heart with a systolic murmur. Catheterization was carried out January 17,
Fig. 5. Case 3. Chest radiographs. Six days postoperative (It) and two months postoperative (rt) when heart size was normal.
tachycardia but no pulmonary difficulty, no fatigue, and felt considerably improved. Two months following op- eration the patient became pregnant and was delivered of an eight pound, six ounce, child in breech presenta- tion. There were no signs of failure during the preg- nancy or during or following delivery. At present the patient is caring for her six children and feels well.
Comment : This is an example of an adult in whom
closure of the defect has been corrective, since there had not been significant increase in pulmonary pressure.
1955, by Dr. Anthony Nolke; angiocardiography was done February 23, 1955, by Dr. John Hertzler. These tests were consistent with interatrial septal defect. Op- eration on January7 9, 1956, demonstrated a defect of 1 J/2 cm. in diameter, well above the tricuspid valve, which was closed without difficulty with through-and- through mattress sutures. The murmurs disappeared She was discharged home on the ninth postoperative day. The two-months’ follow-up roentgenogram appears with one taken shortly after operation (Fig. 5). It shows the change in size and contour of the heart to ( Continued on Page 90)
60
JMSMS
Familial Heights as a Useful Guide
in the Diagnosis of Genitourinary Anomalies
By Robert C. Moehlig, M.D.
Detroit, Michigan
TTAVING observed certain congenital urinary anomalies in association with familial height, it was deemed worth while to report these ob- servations. Many years ago I called attention to the selective action of the endocrine glands on various tissues depending upon their embryo- logic origin.1
In the present article, a brief resume will be given showing the relationship of the pituitary gland to the genitourinary tract and the relation of the familial height to anomalies of this tract. A potent argument favoring the view that the pituitary affects mesodermal tissues (of which the genitourinary tissues are a part) is seen in the anencephalic fetus with pituitary defects.1 The pituitary maldevelopment in these fetuses pro- duces an aplasia of the genitourinary tract with small kidneys, defects in the genitalia and ad- renal cortex hypoplasia.
It has been shown that pituitary defects result in genitourinary defects as well as mesodermal defects in general. It is also true that pituitary hyperfunction results in hyperplasia of the genito- urinary system as well as hyperplasia of the ad- renal cortex. The adrenal cortex, a mesodermal derivative, has a selective action on a division of the mesoderm, namely the mesothelium. From this are derived the following tissues:
1. Peritoneum.
2. Pleura.
3. Pericardium.
4. Urogenitals: (a) Wolffian body; (b) Kid-
ney; (c) ovary; (d) oviducts, uterus, and vagina.
5. Striated muscles: (a) Skeletal: (b) cardiac
muscle.
The important feature to be discussed is the pituitary, the controlling gland of the mesoderm and the mesodermal subdivision, the mesothelium.
In discussing the relationship between the pi-
From the Department of Medicine, Harper Hospital and Wayne University, Detroit, Michigan.
January. 1957
tuitary and adrenal cortex I said that anterior cerebral defects which include pituitary defects are in turn accompanied by adrenal cortex defects.1 In 1943, discussing renal rickets, I stated that a congenitally deformed pituitary gland is frequent- ly associated with congenital cerebral defects such as anenecephalus and hydrocephalus. Such a pituitary defect is associated with a secondary genitourinary tract defect in the form of kidney malformation, dilatation of the kidney pelves and the bladder. Agenesis of the adrenal cortex is also usually present. A further association of the pituitary to the genitourinary tract and skeletal system is seen in renal rickets or renal dwarfism. In this disease, diabetes insipidus is frequently present, indicating a posterior lobe defect since these cases respond to vasopressin and are not the result of the renal defect such as is present in nephrogenic diabetes inspidus. This presumes that the anterior pituitary lobe, while defective in development, is not completely so; otherwise, there would be no diabetes insipidus. The same holds true for the kidney, that is some functioning renal tissue must be present albeit the kidneys are small and aplastic.
Chown,2 in commenting in his studies of renal dwarfism, came to the conclusion that the disease is the result of a pituitary-diencephalon disturb- ance. He said “The argument in proof of the thesis that a lesion of the pituitary-diencephalic mechanism is the primary cause of the symptom complex called renal rickets is then as follows:
1. Malformation of the pituitary has been found in these cases;
2. The associated symptoms of the dwarfing infantil- ism and urinary tract dilatation can be caused by such a lesion;
3. The nephritis is not primary but is secondary to an abnormal metabolism, itself the result of faulty bone growth;
4. The faulty bone growth therefore not being due to the nephritis, and the remaining symptoms be- ing due to pituitary-diencephalic disease. It is to be presumed that the bone disease is due to the same cause.”
61
DIAGNOSIS OF GENITOURINARY ANOMALIES— MOEHLIG
In reviewing some of the literature on renal rickets, I was impressed with the fact that devel- opmental defects of the kidneys, urinary tract and skeleton are important features of the disease as- sociated with defects in the pituitary-hypothalamic region. For instance, hydrocephalus may be as- sociated with a pituitary defect and this in turn with an anomalous development and aplasia of the adrenal cortex, urinary and genital organs.3
Davis, ■' in his study of kidneys and ureters found coexisting abnormalities of the genital organs. He reported cases of urinary bladder dilatation and kidney anomalies associated with hydrocephalus. Increased intracranial pressure from whatever cause during the early developmental period of life results in pituitary disturbance with conse- quent genitourinary anomalies and defects. Con- genital hypopituitarism of various degrees, even to the extent of complete apituitarism, results in aplasia of the adrenal cortex and the genitourinary tract.
A congenitally small pituitary or underactive deformed pituitary is, therefore, most likely to be associated with maldevelopment of the kidneys and genitalia, such as aplastic malformations which usually include the adrenal cortex.
By the same reasoning and based on clinical evidence, hyperfunction of the pituitary is most likely to be associated with overdevelopment of the kidneys, genitalia and adrenal cortex. This is well illustrated in acromegaly and gigantism. In these diseases the growth hormone affects the whole body structure, increasing the size of the viscera and, of course, this includes the kidneys. It is known that anterior pituitary extracts can increase the size of the kidneys.5
If the pituitary activity is reflected in the gen- itourinary tract, then familial heights may give a clue to urinary pathology. As we know, the pitui- tary is a most important factor in the development of the skeletal system so that heights of the imme- diate family may guide one in suspecting what type of genitourinary pathology may be present. This may be briefly summarized by stating that familial shortness of stature is associated with congenital underdevelopment of the kidneys such as is present in renal dwarfism, and that familial tallness is associated with overdevelopment of the kidneys such as supernumerary multiple kidneys, and multiple ureters. Likewise, polycystic kid- neys are associated with familial tallness.
The constitutional hereditary background is shown by the familial heights of greater than average sampling of the population. In the First World War the average height of the male recruits was 67 inches and in the Second World War it was 68 inches. In the immediate family it is usually found that the male members are 72 inches or more in height. This could be inter- preted as indicating a constitutional familial back- ground of skeletal overactivity as compared with the normal skeletal activity. This, then could indicate a pituitary hereditary factor as respon- sible for the kidney anomalies, if one grants that the pituitary is necessary for genitourinary de- velopment. Applying this same principle to the underdeveloped anomalous defects of the genito- urinary tract, it is found that this occurs in the shorter than normal male members of the imme- diate family. It is of some interest and impor- tance that individuals with a high arched palate usually have pituitary disturbances. This holds for both hypofunction and hyperfunction of the gland. Elsewhere1 it was stated that, since the anterior lobe of the pituitary develops from the roof of the mouth, the high arched palate indicates a congenital pituitary background that is a pre- disposition to a disturbance of this gland. It is seen in individuals with migraine, epilepsy, reti- nitis pigmentosa, arachnodactyly, and in many in- dividuals with an allergic condition, the latter probably being due to a pituitary-hypothalamic disturbance. Individuals with genitourinary de- fects have, as a rule, a high arched palate.
It should be stated that the short asthenic built individual is the one who suffers from underdevel- opment of the genitourinary tract. However, short, stocky individuals who have characteristics of pituitary basophilism are apt to have double ureters, reduplication of pelves and horseshoe kid- neys, the same as the individual with a tall back- ground. This is due probably to the overactivity of the pituitary before puberty resulting in rapid ossification and shortness of stature. They are the pyknic type of individual. As an example of familial height giving a clue to genitourinary path- ology is a family of two boys and a girl, each of whom had two kidneys and two ureters on the left side and a normal kidney and ureter on the right.
The genetic constitutional inheritance factor is shown by the familial heights. Both the father’s and mother’s height was 72 inches, the two boys
62
TMSMS
DIAGNOSIS OF GENITOURINARY ANOMALIES— MOEHLIG
were 72 inches and 74 inches respectively, and the girl 71 inches.
The familial height has been very useful in directing and anticipating genitourinary diagnoses so that attention is directed to this feature as a diagnostic aid.
Summary
Based on clinical and embryologic observations it was found that the state of the pituitary gland is related to the development of the genitourinary tract. Congenital defects of the pituitary gland are associated with congenital genitourinary de- fects as well as aplasia of the adrenal cortex.
Overactive pituitary function of a congenital nature is associated with overdevelopment of the genitourinary tract and adrenal cortex hyper- plasia. Because of the relationship of the pitui- tary glands to both the osseous system and the genitourinary tract, it has been found over a period of many years that the familial heights are a useful guide to genitourinary anomalies.
The pituitary’s selective action on mesodermal tissues (the osseous system, genitourinary tract and adrenal cortex are mesodermal in origin) fur- nishes an understanding of these mesodermal anomalies.
In a general way, it can be said that familial shortness of stature associated with an asthenic habitus is accompanied by developmental defects of the genitourinary tract, such as renal rickets, aplasia and hypoplasia of the kidneys. However, familial shortness of stature in asthenic built indi- viduals with suggestive pituitary basophilism symptoms results in overgrowth of the genito- urinary tract, since the overactive pituitary in these individuals produces early and rapid ossifi- cation with shortness of stature. They are there- fore, comparable to the tall individual in respect to genitourinary anomalies.
Attention was called to the fact that individ- uals with a high arched palate usually have pi- tuitary disturbances.
This is true for both hypofunction and hyper- function. The reason for this high arched palate is believed to be due to the fact that the an- terior pituitary lobe develops from the roof of mouth. Individuals with genitourinary defects, have, as a rule, high arched palates.
Conclusion
Familial heights are a useful guide in diagnosing congenital genitourinary anomalies.
References
1. Moehlig, Robert C.: A study of the ductless glands. Detroit M. J.. 14:268-289, 1914.
Ductless Gland Cell Control. Monograph, Town- send Press, 1918.
Clinical notes on selective tissue action of posterior pituitary gland. M. J. & Rec., 120:55-59, 1924 Selective action of suprarenal cortex secretion on mesothelial tissues. Am. I. M. Sc.. 168:553-564, 1924.
Embryohormonic relations of pituitary gland to mesenchymal tissues. Ann. Int. Med., 1:400-411, 1927; 1:563-576; 828-834, 1928.
Pituitary gland and suprarenal cortex. Arch. Int. Med., 4:339-343, 1929.
Renal dwarfism or renal rickets. Am. J. Roent- genol., 50:582-601, 1943.
Significance of high arched palate. Harper Hosp. Bull., 4:168-173, 1946.
Hyperthyroidism. Clinics, 1:1115-1167; 2:423-497, 1943.
2. Chown, B. : Renal rickets and dwarfism: A pitui- tary disease. Brit. J. Surg., 23:552-566, 1935-1936.
3. Krause, E. J.: Die Entwicklungstorungen der Hy- pophyse. Die Morphologie des Missbildungen des Menschen und der Tiere. 3:483-524. Jena; G. Fish- er, 1929.
4. Davis, J. E.: Surgical pathology of malformations in kidneys and ureters. J. Urol., 20:1-25, 155-183, 283-331, 1928.
5. Putnam, T. J.; Benedict, E. B. ; and Teel, H. M.: Studies in acromegaly; Experimental canine acro- megaly produced by injection of anterior lobe pituitary extract. Arch. Surg., 18:1708-1736 (Apr.) 1929.
964 Fisher Bldg.
Detroit 2, Michigan
TUBERCULOSIS PROBLEM NOT SOLVED
Despite a gratifying decline in the death rate, the tuberculosis problem in this country will not approach acceptable solution until the morbidity rate demon- strates a corresponding decline. Over the last five years, deaths from tuberculosis have declined between 15 and 20 per cent each year. The morbidity rate, however,
has declined only three to four per cent per year over the same period of time. At this rate, more than a quarter century will be required to equal the same per cent reduction in morbidity that has been achieved in mortality in the past five years alone. — Annual Report , Special Health Services, U. S. Department of Health, Education , and Welfare, Washington, D. C. (1954-1955)
January, 1957
63
Paroxysmal Tachycardia in Infants
By Irving F. Burton, M.D., and Morris Starkman, M.D.
Detroit, Michigan
T7ARLIER writers have pointed out that the
' counting of pulse rates in infants is a much neglected procedure. When the counting is done routinely, the incidence of cardiac arrhythmias is found to be higher than the medical literature would indicate. Of the arrhythmias, the one most frequently occurring is paroxysmal tachycardia. Since this type of arrhythmia often terminates fa- tally, failure to recognize the excessive heart rate is unfortunate inasumch as the prognosis with treatment is excellent.
Because of the general unfamiliarity with this disease, we are presenting four cases and are taking this opportunity to review this syndrome.
Case Presentation
Case 1. — A thirteen-month-old, white male infant was admitted to Harper Hospital, July 6, 1955, with the diagnosis of an acute upper respiratory infection. The baby had been well until three hours prior to admis- sion. At that time, the mother had noticed labored breathing, increased irritability and a short interval of cyanosis. On physical examination, the infant appeared acutely ill and in marked respiratory distress. He seemed very toxic with a fixed apprehensive stare. His temperature was 102.6° F. by rectum. His respiratory rate was 40 per minute, regular and with symmetrical excursion of the chest. Occasional rales were heard in both bases. The pulse rate was counted at 200 per minute. The liver and spleen were not enlarged. No cyanosis or signs of heart failure were apparent. The balance of the examination was noncontributory. An electrocardiogram taken on admission showed a tachy- cardia of 180 per minute of supraventricular origin. No other cardiac abnormalities were found. The white blood cell count showed no significant altera- tion in number or in cell components. Urinalysis, throat and blood culture and a chest roentgenogram showed no abnormalities.
The infant was placed in an oxygen tent. 300,000 units of procaine penicillin were administered intramus- cularly. Digitoxin was administered orally on the basis of 0.05 mg. per kg. body weight and given in three doses at eight-hour intervals. The first dose contained one-half the calculated digitalizing dose. The second and third doses each contained one quarter of the calculated dose. One-tenth of the calculated dose per day was given for maintenance. Within twenty-four
From the Division of Pediatrics, Harper Hospital Detroit, Michigan.
64
hours, the pulse rate was 110 per minute. The symp- toms of dyspnea, toxicity, and elevated temperature all subsided correspondingly. The digitoxin was discon- tinued on the third hospital day. Subsequent examina- tions showed no evidence of underlying heart disease. A second electrocardiogram taken on the fifth hospital day was normal. The patient was discharged on the seventh hospital day. No recurrence of this disease has been noted to the present time.
Case 2. — A three-and-one-half-month-old, white male infant was admitted to Harper Hospital, July 26, 1955, with a history of intermittent cyanosis, vomiting, and a temperature of 104° F by rectum for two days. On physical examination, the infant appeared acutely ill, cyanotic, and extremely toxic. His pharynx was mod- erately injected. His respiratory rate was 48 per min- ute, regular, and with symmetrical excursion of the chest. No rales or pulmonary abnormalities were found. His pulse was counted at 200 per minute. His liver and spleen were not enlarged. No evidence of heart failure was noted. The balance of the examination was noncontributory. An electrocardiogram taken on admission showed a tachycardia of 200 per minute of supraventricular origin. No other cardiac abnormali- ties were found. The white blood cell count showed no significant alteration in number or cell components. Urinalysis, throat and blood culture, and a chest roent- genogram showed no abnormalities.
The infant was placed in an oxygen tent. 150,000 units of procaine penicillin were administered intramus- cularly. Digitoxin was administered intramuscularly on the basis of 0.05 mg. per kg. body weight. The same schedule of administration and dosage was used as in the first case. Within twenty-four hours the pulse rate dropped to a normal value, and the other symptoms correspondingly cleared. The digitoxin was discontin- ued on the third hospital day. Subsequent examina- tions showed no evidence of underlying heart disease. The patient was discharged on the fourth hospital day. No recurrence of this disease has been noted up to the present time.
Case 3. — A three-month-old, white male infant wa 3 admitted to Harper Hospital, August 23, 1955, with a history of the abrupt onset of dysynea, listlessness, pal- lor, and sweating six hours prior to admission. On physical examination, the infant appeared acutely ill, extremely toxic and frighteningly near death. His tem- perature was 103° F by rectum. His respiratory rate was 36 per minute, regular and with symmetrical excur- sion of the chest. His breath sounds were harsh and bronchial in nature. His pulse was counted at 190-200
TMSMS
PAROXYSMAL TACHYCARDIA— BURTON AND STARKMAN
per minute. His liver and spleen were not enlarged. Neither cyanosis nor signs of heart failure were noted. The balance of the examination was noncontributory. An electrocardiogram taken on admission showed a tachycardia of 190 per minute of supraventricular origin. No other cardiac abnormalities were found. The white blood cell count showed no significant alteration in number or cell components. Urinalysis, throat and blood culture, and a chest roentgenogram showed no abnormalities.
The infant was placed in an oxygen tent. 150,000 units of procaine penicillin were administered intramus- cularly. Digitoxin was administered intramuscularly in the same dosage formula and schedule as with the previous cases. Within twenty-four hours, the pulse rate dropped to a normal value and the other symp- toms correspondingly cleared. The digitoxin was dis- continued on the third hospital day. Subsequent ex- aminations showed no evidence of underlying heart dis- ease. The patient was discharged on the fourth hos- pital day. No recurrence of this disease has been noted to the present time.
Case 4. — A two-week-old, white male infant was seen at another hospital three hours following the repair of a unilateral harelip. He had been given 1/800 gr. of scopolamine preoperatively. For anesthesia, he had been given ether by open-drop. On physical examina- tion, the infant appeared acutely ill and extremely toxic with marked dyspnea and sweating. His temper- ature was 104.2°F by rectum. His respiratory rate was 42 per minute, regular and with symmetrical excursion of the chest. No rales or pulmonary abnormalities were found. His pulse was counted at 200 per minute. His liver and spleen were not enlarged. No evidence of heart failure was noted. The balance of the exam- ination was noncontributory. An electrocardiogram taken immediately showed a tachycardia of 200 per minute of supraventricular origin. No other cardiac abnormalities were found. The white blood cell count showed no abnormalities.
The infant was placed in an oxygen tent. 150,000 units of procaine penicillin were administered intramus- cularly. Digitoxin was administered intramuscularly in the same dosage formula and schedule as with the previous cases. The pulse rate dropped to a normal value on the fourth hospital day and the other symp- toms correspondingly cleared. The digitoxin was dis- continued on the fifth hospital day. Subsequent ex- aminations showed no evidence of underlying heart disease. No recurrence of this disease has been noted up to the present time.
Discussion
In 1941, Hubbard1 reported nine cases of par- oxysmal tachycardia in infants under the age of one year. He stressed the acute onset of the at- tack, the alarming clinical picture, and the fre- quency of fatal termination. In his discussion, he pointed out that many cases of a malignant syndrome of unknown etiology in infants reported
in the literature at that time were similar to his cases but that the heart rate had not been counted. On this basis, he felt that the syndrome was much more prevalent than generally reported, probably being overlooked in many cases. In 1952, Nadas and co-workers2 presented a compre- hensive article on this subject with a detailed an- alysis of forty-one cases in infants and children. They were able to form a concise picture of this syndrome which will be presented in outline form and augmented with our own experience.
Age. — Almost all of the cases occurred in in- fants four months of age or younger. Three of our cases were four months of age. One patient was thirteen months of age.
Sex Incidence. — All four of our cases occurred in males. This observation is in agreement with other studies indicating that the male is the most frequently affected.
Etiology. — No apparent single causative factor precipitated the attacks. Many infants seemed well prior to the illness. A few had respiratory' infections which had been considered trivial. One of our cases had sustained his attack following the use of scopolamine in preanesthesia medica- tion. In Nadas’ series, two cases followed anes- thesia, and one had atropine sulfate as prean- esthesia medication. Although congenital heart disease and the Wolff-Parkinson-White syndrome can be the cause of paroxysmal tachycardia, nei- ther is etiologically important in this age group.
Clinical Appearance. — The onset was usually sudden. The infants appeared acutely and criti- cally ill. They were prostrate with a fixed ap- prehensive stare and ashen color. Respiration was rapid and labored. The clinical impression was that of an acute septic disease. Many had an elevation of temperature. The urine was usu- ally normal; the white blood cell count sometimes showed an elevation. The roentgenogram of the chest was normal unless there was congestive heart failure. In advanced cases, there was evi- dence of heart failure with cyanosis, enlargement of the heart and liver, pulmonary congestion, abdominal distension and frequent vomiting. The roentgenogram of the chest may then have shown the heart to be enlarged with both ven- tricles equally involved and congestive changes present in the lung.
January, 1957
65
PAROXYSMAL TACHYCARDIA— BURTON AND STARKMAN
In all cases, the excessive heart rate was out- standing. The rate varied in the individual case. None of the cases had a rate less than 180 per minute, and some had a rate as high as 330 per minute. A heat rate of 180 per minute or higher in an infant should always bring this syndrome to mind.
The appearance of heart failure is dependent on the duration of the attack, not on the rate of the tachycardia. In Nadas’ study, none of the infants showed evidence of heart failure when the attack was less than twenty-four hours’ dura- tion. After forty-eight hours, one-half of the untreated cases showed signs of failure. In Hub- bard’s observation, when the syndrome was less clear and treatment not instituted promptly, the infants either died in heart failure or recovered completely, the attack subsiding spontaneously.
Electrocardiogram. — The only significant find- ing was the tachycardia of supraventricular ori- gin. If other changes should be present, other diseases must be considered. In the Wolff-Park- inson-White syndrome, the characteristic findings are not present during the attack of paroxysmal tachycardia but are revealed only in the electro- cardiogram taken between attacks.3 Repeating the electrocardiogram in these infants when the rate becomes normal is important.
Treatment. — Many methods and drugs can be used for stopping a rapid heart rate. In this syndrome, digitalis has been the most successful and the least dangerous of all therapies. Both Nadas and Hubbard emphasize that the dosage in infants must be higher on a weight basis than
ordinarily used in older children and adults. The recommended dose in children under two years of age is 0.03 to 0.05 mg. per kg. body weight with complete digitalization in twelve to twenty-four hours. Not all observers are in
agreement with the larger dose.4 The daily main- tenance dose is one-tenth of the total digitalizing dose. The infants are maintained on digitalis two to seven days or longer following the return of the normal heart rate. In small infants, digitoxin
intramuscularly is the treatment of choice.
Supportative treatment should also be given. The infants should be placed in oxygen and given antibiotics, if they are indicated.
Summary
Paroxysmal tachycardia in infants is presented as a distinct clinical entity. Counting the pulse rate is a necessary part of an infant’s examina- tion.
Acknowledgment
The authors gratefully acknowledge the generous as- sistance of Dr. Edgar Martmer, chief of the Division of Pediatrics, Harper Hospital, Detroit.
References
1. Hubbard, J. P. : Paroxysmal tachycardia and its
treatment in young infants. Am. J. Dis. Child., 61:687 (Apr.) 1941.
2. Nadas, A. S.; Daeschner, C. W.; Roth, A.; and
Blumenthal, S. L. : Paroxysmal tachycardia in in- fants and children: Study of 41 cases. Pediatrics,
9:167, (Feb.) 1952.
3. Mannheimer, E.: Paroxysmal tachycardia in in-
fants. Acta Ped., 33:38.3, 1946.
4. Ziegler, Robert: Personal communication. (Henry
Ford Hospital, Detroit, Michigan.)
3825 Brush Street Detroit 7, Michigan
IMMUNIZATION
Diphtheria. — The outbreak of diphtheria in Detroit in December suggests some needed statewide remedy. It is not listed as an epidemic but 161 cases have occurred in six special districts, mostly poor and underprivileged. The rate of immunization of school children is below 40 per cent. Only six cases have developed in all other areas where the rate of immunization is mostly around 60 per cent. All doctors treating such children or having influence in neglected districts should urge and adminis- ter toxoid protection. Six deaths have been attributed
to a disease rarely seen because of well-known control methods.
Polio. — This is the recommended season for polio vaccine shots. The vaccine is accumulating rapidly and is being left standing on warehouse shelves. Too many children are still unprotected. The Health Department and the Council of the Michigan State Medical So- ciety are urging that everyone through the early thirties be immunized without delay, and most especially the youth years. It takes about seven months for maximum protection. Now is not too late.
66
JMSMS
Modern Techniques for the Diagnosis of Pheochromocytoma
* I *HE PATIENT with pheochromocytoma pre- sents a potentially curable lesion. In the past ten years considerable advances have been made in the precise diagnosis of this condition. It is the purpose of this article to review these advances for the benefit of the practicing physician.
When To Suspect Pheochromocytoma
All patients with essential hypertension should be viewed as suspects. Cases have been found among both the sustained and labile types. The index of suspicion is generally increased when the patient with hypertension also shows transient glycosuria or hyperglycemia, or when episodes of spontaneous sympathetic and vasomotor activity occur with palpitation, tachycardia, flushing, in- creased perspiration or tremors. It is important to recall that the disease may also occur among apparent normotensives who show blood pres- sure elevations only with attacks. These attacks may vary in their symptomatology but usually include palpitation, flushing, headache, perspira- tion, tremulousness, and abdominal pain. Pres- ence of dizziness, numbness and paresthesia of the fingers and about the mouth denote hyperventila- tion syndrome and are not characteristically caused by pheochromocytoma; relation to meals and relief by ingestion of carbohydrate may de- note hypoglycemic episodes.
Diagnostic Procedures If Systolic Blood Pressure Exceeds 200
1. Regitine Test.- — The best screening test when the blood pressure is substantially elevated (i.e. exceeds 200/110) consists in the slow intravenous injection of 5 mg. Regitine®. Intramuscular injection may lead to a false negative.1
(a) Procedure. — The patient is placed in the resting recumbent state and the blood pressure is taken every 30 seconds. When the readings have
From the Department of Internal Medicine, Univer- sity of Michigan Medical School.
Development of the analytic procedure for catechol amines was greatly aided by a grant from the Michigan Heart Association.
By S. W. Hoobler, M.D., Robert D. Johnson, M.D.,
and Ray Warzynski, M.D.
Ann Arbor, Michigan
stabilized, a venipuncture is done but the drug is not injected until the blood pressure in the oppo- site arm returns to the previous basal level. The drug is then given slowly over a 45-second in- terval, blood pressure and pulse rate being taken every thirty seconds in the opposite arm for a period of five minutes.
(b) Interpretation. — A reduction of 25 mm. in the diastolic blood pressure in at least two suc- cessive readings is considered a positive response.
(c) False positives. — False positives occur in patients under the influence of various antihyper- tensive drugs. They are reported in uremia, but since this rarely coexists with pheochromocytoma, it is not usually necessary to test hypertensive patients with consistently elevated nonprotein ni- trogen in the blood. In the absence of any of these explanations, about 10 per cent of the cases show false positive reactions due, no doubt, to the fact that Regitine, in addition to its adren- olytic properties, has weak ganglionic blocking and direct vasodilator activity. Therefore, a positive Regitine 'test should be viewed as a screening test only. It should be repeated and should be checked with benzodioxane or histamine test.
(d) False negatives. — These are rare. It should be noted that if the blood pressure is not greatly elevated, the Regitine test cannot be posi- tive by definition without inducing considerable hypotension, since a diastolic blood pressure fall of 25 mm. is necessary to qualify as positive.
(e) Contraindications. — These are relative but would include chiefly patients with a history sug- gestive of cardiac arrhythmias or angina pectoris. The drug has excitatory properties. Tachycardia is regularly induced and in at least one instance angina pectoris has followed testing. It is be- lieved that this latter effect is transitory, mild and can be overcome by vasodilators, and that if the test is really indicated, no harm can come of the procedure if proper precautions are taken.
January, 1957
67
PHEOCHROMOCYTOMA— HOOBLER ET AL
2. Benzodioxane Test. — This procedure is indi- cated when the Regitine test has been positive and the blood pressure is substantially elevated. Details of the test procedure, as printed by the manufacturer, have been modified in our clinic as follows:
(a) Procedure. — The calculated amount of the drug is taken up in the syringe and after the basal blood pressure has been determined in the opposite arm, a venipuncture is performed and the blood pressure allowed to return to the basal level. The drug is then injected slowly at a steady rate such that one-half the dose has been administered in the first minute. The blood pressures taken every 30 seconds on the opposite arm are then inspected. If a rise of less than 15 to 30 mm. Hg. systolic or diastolic has occurred, the remainder of the dose is given in the second minute. If such a rise has already occurred, the injection is stopped, since in all likelihood the test will be negative and further injection may only cause distressing side effects (tachycardia and dyspnea) and a further elevation of the blood pressure. Since the blood pressure may arise falsely due to anxiety, it is important that the patient be reassured prior to the injection and that if possible he should not know the moment the injection is started. The more elaborate testing technique of Goldenberg and Aranow2 was devised for this reason.
(b) Interpretation. — According to the origina- tors of the test, a positive reaction can be judged only when it is performed according to their pre- cise technique. In our experience, any reduction exceeding 5 to 10 mm. Hg. of systolic and dias- tolic pressure by our technique should be viewed as a positive reaction.
(c) False negative reactions. — False negative reactions occur with greater frequency than with the Regitine test, probably because the drug has a concomitant central excitatory and hypertensive effect, combined with a weaker adrenolytic and no vasodilator activity.
(d) False positive reactions. — These are said to occur in uremia.
(e) Contraindications. — The drug should be given carefully in extremely hypertensive patients but the procedure outlined above should protect from serious reactions. The central and cardio- excitatory effects on the heart rate might be ad-
verse in angina pectoris, but we have had no such personal experiences.
3. Urinary Catechol Amine Analysis. — Approx- imately 3 per cent of intravenously administered adrenaline or noradrenaline can be recovered in the urine by sensitive bioassay techniques. This recovery is further reduced if the urine is neutral or alkaline and subject to oxidation. There is a wide variation in “normal” 24-hour urine catechol amine excretion, the limits being approximately 10 to 100 micrograms per twenty-four hours.3
(a) Procedures. — During the collection period it is important that each urine specimen be im- mediately acidified to prevent oxidation of cate- chol amines. Fluorescent contaminants present in most stoppers must be excluded by covering with cellophane. After the specimen is collected, an approximate 100 cc. aliquot may be taken for chemical or biologic assay.*
(b) Chemical method. — The urine is passed through an alumina column which adsorbs 90 to 100 percent of catechol amines. It is then eluted with acetic acid and oxidized by the addition of potassium ferricyanide at pH 6.5 to adrenachrome. Ascorbic acid is then added to stop further oxi- dation and the adrenochrome is rearranged to the highly fluorescent adrenolutin by the simultaneous addition of NaOH. The mixture is read in the Farrand photofluorimeter and compared with a similar urine sample which, by omitting the as- corbic acid oxidation, has been permitted to go to complete destruction of the catechol ring struc- ture. Although the norepinephrine derivative possesses only one-fourth of the fluorescent ac- tivity of epinephrine, the two cannot be sepa- rated by this test. For consistency, the result is expressed as micrograms of epinephrine. This is essentially the method of Von Euler et al4 and can be performed using any sensitive photofluor- imeter. Both adrenaline and noradrenaline added to urine are measured accurately by this proced- ure. Other related substances may also contrib- ute to fluorescence. The procedure is not quite the same as that used by Goldenberg, but on the basis of considerable experience we believe that a satisfactory distinction between normal, hyperten- sive, and pheochromocytoma cases can be made.
♦The sample can be sent in a special mailing car- ton provided on request from the Hypertension Unit, University of Michigan Hospital, Ann Arbor, Michigan. The cost of the test is $15.00.
68
TMSMS
PHEOCHROMOCYTOMA— HOOBLER ET AL
rABLE I. RESULTS OF TESTS IN PROVEN CASES OF PHEOCHROMOCYTOMA University Hospital 1956
|
Cases |
Histamine Test |
Regitine Test |
Benzo- dioxane |
24 I Catechol Meg/ |
lour Amines* 24 hr. |
|
Pre- Operative |
Post- Operative |
||||
|
W. H. |
4- |
+ |
645 512 |
46 |
|
|
R. J. |
+ |
+ |
665 502 |
||
|
R. B. |
+ |
+ |
243** 144 118 |
*Of 37 normal persons and pheochromocytoma suspects, the mean ;wenty-four hour excretion of catechol amines, expressed in terms of epinephrine equivalent, was 49.2 micrograms with a range of 9.4 to 107.5. One false positive of 486 is recorded, but subsequent preoperative values were 87 and 44 mcg/24 hours. A bilateral adrenal exploration vas negative.
N*This patient had a small area of adrenal medullary hyperplasia at jperation, but when the adrenal was clamped the blood pressure fell narkedly. The findings did not resemble the usual pheochromocytoma rathologically and her status remains in some doubt.
(c) Biological method. — This is a complex pro- :edure, depending on the contraction of a spirally tut strip from rabbit or rat aorta when solutions :ontaining .01 to .0001 micrograms of adrenaline are compared to the response of the unknown sample eluted from the alumina column. The method used in our laboratory is patterned after the technique of Helmer with certain local mod- ifications. The test is used when the urine sam- ple by the chemical method shows a high output af catechol amines.
(d) Interpretation. — It is evident from the above that unknown contaminants may produce either fluorescent or vasoactive compounds which resemble adrenaline or noradrenaline. No drugs capable of producing fluorescent end products should be given during the urine collection. Fur- thermore, adrenaline and noradrenaline cannot readily be distinguished by these methods but since both are found in varying amounts in cases of pheochromocytoma, this would seem to make little practical difference.
(e) False positives. — False positives may appear as experience with the method increases. For this reason consistency with clinical and pharma- cologic testing should be insisted on before ad- vising adrenal exploration. In one such case, where preoperative catechol amine levels were 486 and 87 micrograms per twenty-four hours, ex- ploration failed to reveal a tumor in the adrenal region. A high level is therefore not certainly diagnostic. In three cases proven at operation, levels have been consistently high (Table I).
(f) False negatives. — False negatives can occur if proper precautions are not taken in the collec- tion. Also, it is possible that during a period of normotension no elevation of urinary catechol amines would occur. In such circumstances it might be better to obtain a specimen during an attack. For this purpose a four hour urine collection test has been devised (vide infra) but we do not yet have sufficient evidence of the normal range of such short collection periods dur- ing “attacks” associated with other causes than adrenaline release. Consequently, normal stand- ards at present must be inferred from our experi- ence with twenty-four hour urine samples. On this basis, a positive test should probably exceed 25 meg. excretion in a four hour collection period.
(g) Contraindications. — None. It is to be em- phasized, however, that this procedure should be done only when clinical criteria and pharmaco- logic testing are compatible, since a negative Regitine or histamine test is extremely unlikely to occur in the presence of a pheochromocytoma. Only when angina pectoris makes the latter tests dangerous to the patient should urine testing pre- cede pharmacologic testing.
Diagnostic Procedures If Systolic Blood Pressure Is Below' 200
1. Histamine Test.5
(a) Procedures. — Histamine acid phosphate solution is used. 0.0275 mg./cc. (= .01 mg. histamine base/ce.) is prepared fresh every month or so and stored in the refrigerator. The dilution represents 1 / 100th the strength of the 1/1000 histamine usually supplied. After the blood pres- sure has stabilized, give in 10 to 20 seconds 2.5 cc. (.025 mg. of the base) intravenously, taking blood pressure every thirty seconds in the oppo- site arm for five to ten minutes.
The usual response is a flush, vasodilator head- ache and transient hypotension lasting one to two minutes, followed by return to normal or slightly supernormal values in next three to five minutes. If the subsequent rise exceeds the pre- injection level by 30/20 mm. Hg., pheochromo- cytoma is suspected. Leave the needle in the vein after injection, so as to be prepared to give Regitine®, 5 mg. intravenously in case of a hyper- tensive reaction.
(b) False positives. — The reactions may be due to anxiety and discomfort from the histamine.
January. 1957
69
PHEOCHROMOCYTOMA— HOOBLER ET AL
Rises usually do not exceed that observed by the cold pressor test. Reassurance, explanation of symptoms to be expected from test, and repetition often are needed to exclude. A certain number occur, nevertheless.
(c) False negatives. — Although rare, these also occur. Check with the Etamon test (see below).
(d) Contraindications:
( 1 ) Rarely give to patients with systolic blood pressure over 200 for fear of excessive hypertension. Have Regi- tine,® benzodioxane, nitrites present for antidotes.
(2) Give rarely or never in the presence of angina or severe asthma. Reduce initial dose in seriously suspected cases or severe hypertension.
(3) Always have Regitine® at hand and be prepared to administer it promptly if an attack is precipitated. Under these circumstances there is no need to fear reactions to this test.
2. T etraethylammonium (Etamon) Test.e
(a) Procedure. — 200 to 300 mg. of tetraethyl- ammonium chloride (Etamon — Parke Davis) is given intravenously twenty to thirty seconds after blood pressure has become basal. The patient will notice paresthesias, blurring of vision and a mild tachycardia, and the blood pressure will fall 10 to 40 mm. systolic and diastolic in normals and mild hypertensives. In uremics and in some elder- ly patients with arteriosclerosis, more marked hypotension will occur but can be corrected promptly with a head down tilt or intravenous vasoconstrictors. Hence, over the age of fifty a dose of 200 mg. intravenously is sufficient for most routine tests. The effects last for 15 to 20 min- utes, and orthostatic hypotension is the last to go away. Hence, these patients should be observed for syncope when they first get up after the test.
(b) Interpretation. — In the presence of pheo- chromocytoma most but not all patients show a marked secondary rise in blood pressure after the period of hypotension. The secondary rise should exceed the pre-injection blood pressure by 20 to 30 mm. Hg. A moderate rise in blood pressure occurring in young persons after tetraethylam- monium, may be the source of a false positives. The test is not as likely to be positive as the his- tamine test.
(c) Contraindications. — None except in pa- tients with extreme arteriosclerosis or angina, who should receive smaller than average doses. If an attack is precipitated, the patient should be made to sit up and hang his legs over the side of the bed, since orthostatic effects may cancel out part of the epinephrine-induced hypertension.
Procedure During Acute Attack of Hypertension
(These first two measures may be done by the patient after proper advance instructions.)
1. Record pulse, blood pressure.
2. Start a four-hour urine collection for cate- chol amines.
If the patient can remember the precise time of preceding voiding, force fluids and continue col- lection into an acidified bottle up to the fourth hour. If the exact time of the previous specimen is uncertain, the patient should void immediately and discard, then collect the following four hours of urine. Water should be taken to provide an adequate four-hour volume.
3. Take an electrocardiogram since transiently peaked T-waves may be associated with the hyperpotassemia of epinephrine release (See be- low) .
4. Draw sample for blood sugar, which may showr transient elevations, or test for glycosuria.
5. Give 2.5 mg. Regitine intravenously in forty- five seconds, recording pulse and blood pressure carefully. Patients in an attack are hypersensi- tive to Regitine, and a brief but marked response to a small dose is of diagnostic help.
6. If attack is serious, the further administra- tion slowly of up to 10 mg. of Regitine should provide relief.
Clinical Observations
In general, it has been our practice to follow the outline above. We screen most patients with labile or established hypertension by means of pharmacologic tests. In our clinic, 136 tests were performed in the year 1956. Five apparent false positives were recorded among eighty-eight hista- mine tests and six among forty-eight Regitine tests. When clinical signs or confirmatory pharm- acologic tests were positive, urinary catechol amines were determined. Table I reviews the
70
JMSMS
PHEOCHROMOCYTOMA— HOOBLER ET AL
hree positive cases which have been encountered luring the past year.
Case Report
The patient described below proved of partic- ilar interest because his presenting complaint vas recurrence of very brief spells of palpitation md irregular pulse on exertion.
R. J., a thirty-two-year-old male laboratory worker or a paint company entered the hospital with the chief omplaint of “high blood pressure and weak spells” ince November, 1954. He was essentially well until hat date, when one afternoon at 3 p.m. he had an pisode of weakness, pallor, perspiration and dizziness asting ten to fifteen minutes after hurrying up a flight if stairs. No similar symptoms occurred until April, 955, when an attack lasted ten minutes and was asso- iated with an excruciating occipital headache. From ^pril through June, 1955, these episodes occurred about weekly and almost exclusively in the late afternoon, ex- ept for one severe headache which awakened him at i a.m. and disappeared spontaneously in about ten ninutes. A sequence of events elicited from the patient ncluded an aura, described as a sensation of “draining if strength,” followed by a throbbing headache, a lowing of the pulse and measured rise in blood pres- ure. At these times his face was observed to be ashen ;rey and his body was drenched with sweat.
Progressive impotence was another presenting symp- om in this young man. Regitine and histamine tests lone at another hospital were reported as “inconclu- ive” and intravenous pyelograms and blood sugar were lormal. The patient’s father had diabetes mellitus.
Examination revealed a healthy appearing and well nuscled man with a casual blood pressure of 160/90 md pulse of 60 per minute. The pupils were dilated md the fundi showed no hypertensive or diabetic ret- nopathy. Skin was warm and moist. There were no remors. The thyroid gland was not enlarged. Heart vas normal in every way, including size, except for he bradycardia. Liver extended 4 to 5 cm. below the ight costal margin, but no other abdominal or flank nasses could be felt. Femoral and peripheral pulses vere normal.
Laboratory studies showed a normal urine, stool and Cahn reaction. White blood count was 9,300, and here was a normal differential, with 18 per cent lym- jhocytes and 1 per cent eosinophils. Serum creatinine vas 1.12 mg. per cent, and the clearance was 187 V24 hours. Nonprotein nitrogen was 33 mg. per cent, fasal metabolic rate was +15 per cent. Bromsulfalein etention in forty-five minutes was 15.9 per cent. Fast- ng blood sugar determination showed 129, 111, 107 'Somogyi-Nelson: normal is 60 to 90 mg. per cent). \ glucose tolerance test run after a standard three- lay preparation diet gave a diabetic type curve: asting blood sugar, 107; at one hour, 250; at one and )ne-half hours, 205; at two hours, 164; at two and one- lalf hours, 138; at three hours, 119; at three and >ne-half hours, 104; and at four hours, 69 mg. per :ent. A 4 plus glycosuria occurred from the first hour
through the second hour. No attack of symptoms of hypoglycemia appeared at the fourth hour.
While in the hospital his temperature reached 99° to 99.2° on only two days, pulse varied from 55 to 90 per minute and the blood pressure varied from 105 to 220 systolic and from 70 to 120 diastolic. A charac- teristic postural change in blood pressure and pulse was found. The recumbent blood pressure was 175/85 with a pulse of 72 per minute; it fell to 120/80 immediately upon standing, with a pulse of 128 per minute and to 145/110 after standing two minutes. During one of his attacks the patient noted a dull pain in the left flank (the side which proved to contain the tumor).
An interesting finding documented both at another hospital and here were the electrocardiographic changes during the attack; these included frequent ventricular premature beats, bradycardia and large narrow upright T-waves, the latter suggestive of an initial hyper- kalemia. A subsequent electrocardiogram was entirely normal after the attack.
Regitine and benzodioxane tests were positive, as well as the aorta strip test. Catechol amines in the urine during an attack were 502 meg. and 665 meg. per twenty-four hour specimen of urine (normal range 10 to 100 meg.). One Regitine test run during an active phase of the disease showed an unusual response. Just before the test dose of Regitine, the blood pressure was running 242-258/100-104 and diaphoresis was evident. Pulse was very slow, 56 to 60 per minute but no ectopic beats were present. Thirty seconds after 5 mgs. of Regitine was given intravenously, the blood pressure fell from 240/76 to 160/66, then rose abruptly to ,300/142 in association with an agonizing headache and abdominal pain, pallor and diaphoresis. Pulse rose to 120. The attack subsided in approximately five min- utes.
On June 28, 1956, after cortisone preparation, a simultaneous bilateral exposure revealed a tumor of the left adrenal gland. During manipulation of the tumor the blood pressure rose to 230/160 and fell to 90/60 as soon as the blood supply to it was clamped. The post- operative course was uneventful and the microscopic material was reported as typical for pheochromocytoma.
Three months later the patient was asymptomatic with a blood pressure of 130/65, and the glucose tolerance test was no longer diabetic in type.
Comment. — This patient presented four un- usual features. His presenting symptoms had fea- tures in common with functional hypoglycemia and with attacks of premature ventricular beats. The complaint of impotence and the presence of an orthostatic blood pressure fall suggested wide- spread inhibition of sympathetic vasomotor tone. The development of upright T-waves of the hyperkalemic type during a paroxysm suggest a possible diagnostic test during an attack, although it must be emphasized that T-wave changes may occur from a variety of causes unrelated to serum ( Continued on Page 83 )
January, 1957
71
Cerebral Angiography
By H. Harvey Gass, M.D. Detroit, Michigan
A LTHOUGH cerebral angiography is now a commonplace procedure, prejudice against its use still lingers in some quarters. In some of the vascular diseases it is irreplaceable, while in the problem of brain tumors, especially those lo- cated supratentorially, it may provide accurate and easy diagnosis, often making the cumbersome, time-honored air study unnecessary. The more one uses cerebral angiography the greater it in- creases in value, not only for positive identifica- tion of existent disease, but also as a survey tool to help exclude the presence of disease resulting in greater reassurance for both patient and doc- tor. That there are limitations to its diagnostic use and associated pitfalls, no one will deny; but as our familiarity with angiography grows these become more readily recognized and unsuspected information about patients is frequently uncov- ered, such as previously unrecognized vascular occlusions, vasospastic tendencies, and collateral circulations. The role of the variability of the caliber of intracranial vessels and rate of cere- bral blood flow are virgin fields in which cerebral angiography may yet find further fruition.
The resistance to the performance of this pro- cedure which the neurosurgeon still encounters from time to time frequently stems from early reports about mishaps associated with its use. Such accidents were not infrequent during the period of introduction of this technique. The high risk conditions were identified which stim- ulated technical refinements and led to the devel- opment of increased safety in cerebral angiog- raphy. Several recent reports attest to this point of view.1'5 To further dispel unwarranted fear about this procedure this report is being made on 500 consecutive angiograms, all performed by the author, with only a single death in which the procedure can be implicated. Technical points which have enabled the achievement of this rec- ord will be discussed.
The 500 cerebral angiograms forming the basis of this report were done in 364 different patients, and all were performed percutaneously. The first sixty-two of these arteriograms were the basis for an earlier report on the use of urokon in cere-
bral angiography.6 In this series, 474 were car- otid angiograms and twenty-six were vertebral. They were performed in fourteen different hospi- tals in the Detroit area, over half of them being done in one institution.*
The subjects were male in 289 of the arterio- grams and female in 211. The age distribution is given in Table I. Of the entire group, 452 were done in patients between the ages of twenty and seventy. The youngest patient was three and one- half years of age and the oldest seventy-nine. A total of three arteriograms were done in two pa- tients aged seventy-nine.
TABLE I. AGES OF PATIENTS
0-9. 10 - 19. 20 - 29. 30 - 39. 40 - 49. 50 - 59. 60 - 69. 70 - 79.
7
28
59
113 128 . 89 . 68
. 13
Total
.500
All the angiograms done on children aged twelve or under were performed under general anesthesia except one done on a twelve-year-old boy who was awake during the procedure. Of the twenty-eight angiograms done in the age group ten to nineteen, seven were given general anesthesia and five were in patients in coma. Of the total group of 500 angiograms, forty-eight were done in patients in coma or under general anesthesia and 452 were done in conscious and re- sponsive patients.
In 133 of the 364 patients receiving angiograms gross lesions were demonstrated (Table II).
TABLE II. PATHOLOGIC LESIONS FOUND BY ANGIOGRAPHY
Lesion No.
Mass 78
Aneurysm _ 29'
Malformation 8
Occlusion * 8
These included seventy-eight mass intracranial lesions, twenty-nine aneurysms, eight vascular mal- formations, and eight major vascular occlusions (either middle cerebral or internal carotid). The
*Mt. Carmel Mercy Hospital.
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CEREBRAL ANGIOGRAPHY— GASS
anterior cerebral or the posterior cerebral system may at times not fill in the arteriogram, and such non-filling alone was not considered diagnostic of occlusion of these arteries. In addition impor- tant information was obtained in thirty-nine addi- tional patients. These included twelve patients in whom a normal angiogram was relied upon to rule out a traumatic intracranial hematoma and twenty-seven patients in whom operative angio- graphic evaluation was essential, as in postopera- tive aneurysm patients to verify satisfactory ob- literation of aneurysms by clips. Thus in 172 of 364 patients, information critical for the pa- tients’ management or diagnosis was revealed by the angiogram. In the remaining 192 patients, normal angiograms were obtained in patients sus- pected of serious gross intracranial disease. In twenty-two patients, the angiogram alone without an air study gave ample information for accurate localization of an intracranial mass, and in an additional seventeen patients angiography alone re- vealed the presence of a surface hematoma. In none of these thirty-nine patients was the angio- gram in error.
Ill effects associated with cerebral angiography may be grouped in the following categories : ( 1 ) discomfort associated with performance of the test, (2) dye sensitivity, (3) air embolism (4) hematoma formation in the neck, (5) minor neu- rologic reactions, (6) major neurologic reactions, and (7) death. The first four of these did not present a serious problem in this series, but will be mentioned in subsequent portions of this paper. Included in minor neurologic reactions are tran- sient neurologic incidents completely reversed in less than twenty-four hours (hemiparesis, hemi- sensory symptoms, aphasia, hemianopia) , precipi- tation of a grand mal seizure without subsequent sequelae, and precipitation of an attack of atypical migraine (one patient). Such reactions occurred in conjunction with twenty-six arteriograms. In three of these patients a brain tumor was present.
The only serious ill effects of cerebral angiog- raphy in our experience in this group concerns the major neurological reactions (neurological in- cident lasting more than twenty-four hours) and death in which the arteriogram is implicated. There were six patients in whom major neuro- logic reactions developed and one patient in whom death occurred following the angiogram. In the latter, death in an already critically ill patient must be considered to have been hastened by the
test. Of the six patients with major neurologic reactions two had brain tumors, one had a rup- tured cerebral aneurysm, and three had serious cerebrovascular disease. Four of these had full recovery of their neurologic incident in less than six months even though subsequent craniotomies were done in two. A fifth patient, a seventy-five- year-old man with left optic atrophy and mild mental changes tolerated the left arteriogram without incident, but on the day following the right arteriogram, despite demonstration of a right internal carotid artery occlusion, he developed weakness of the left upper extremity which was still present one month later. The sixth patient was a fifty-seven-year-old man with a malignant brain tumor, who developed a right hemiplegia and aphasia without loss of consciousness follow- ing the arteriogram. By the following day the hemiplegia had nearly completely recovered, but not the aphasia. His neurologic status was other- wise good. Craniotomy was performed on the next day and the patient expired on the first post- operative day. This was clearly a surgical death, and it is felt that the arteriogram was not a sig- nificant factor as a cause of death. The single death in this series in which angiography is cul- pable occurred in a forty-nine-year-old woman who had a recurrent subarachnoid hemorrhage one week after the initial bleeding. The arterio- gram was done on the following morning and general anesthesia seemed advisable. She ex- pired twelve hours later never having reacted from the anesthetic. In this case two safeguards discussed later were not adhered to: (1) A gen-
eral anesthetic was used which camouflages any untoward reactions to a previous injection, and (2) two additional unnecessary injections were made because of failure of a new radiologic de- vice.
Thus, there was a total of thirty-three reactions to arteriograms in this group of 500, an inci- dence of 6.6 per cent. Only seven of these (1.4 per cent) were serious. The one death consti- tutes an incidence of 0.2 per cent. It must be emphasized that this low rate of complications occurred in a group of patients with a high in- cidence of serious and critical illness. Omitted from consideration in this mortality rate are fifty- four additional patients known to have died at some time subsequent to the arteriogram. In forty-nine of these, death was distantly removed from the arteriogram and in no way could be
January, 1957
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CEREBRAL ANGIOGRAPHY— GASS
Fig. 1. Arteriogram (lateral view) made with 3 cc. of 30 per cent uro- kon. Note “stretched-out” perical- losal artery indicating hydrocephalus.
Fig. 2. Arteriogram (occipital view) made with 3 cc. of 30 per cent urokon. Note elevation of an- terior cerebral artery caused by pi- tuitary tumor.
Fig. 3. Normal venogram (lateral view) made with 3 cc. of 30 per cent urokon.
considered to be influenced by it. In five patients, however, death occurred within twenty-four hours of the arteriogram, but each of these were coma- tose at the time of arteriography and showed no evident reaction to it, the cause of the coma in each being ample cause of his death.
Of the 500 arteriograms, 483 were done with 30 per cent urokon sodium. This became the me- dium of choice, although it should be stressed that the safety of this medium rests to a large measure also on the small quantities per injec- tion which were used. In ten arteriograms, 35 per cent diodrast was employed in part or all of the test. In three arteriograms, lesser dilutions than 30 per cent of urokon6 were used, but the resulting films were not completely satisfactory. Four arteriograms in elderly or severely hyperten- sive patients were done utilizing thorotrast for some or all of the injections. In no instance was thorotrast injected unless the needle was can- nulated far into the artery making extravasation impossible.
Of great importance in maintaining a safe technique is the reduction of trauma to the arte- rial tree not only in performing the arterial puncture, but by the reduction of the overall irri- tating stimuli to the intimal surface of the cerebral vascular system. In this regard, the total num- ber of injections required for the arteriograms, the total quantity of contrast medium used, and the quantity of medium per injection are impor- tant factors. We have become increasingly im- pressed with the importance particularly of the
latter, the quantity of medium used per injection, and have been able to progressively decrease the amount used down to 5 cc. per injection and more recently to 3 cc. per injection and still to obtain good films almost consistently. Only 5 cc. quantities were used in 408 of the angiograms in this series, and in a total of 444 angiograms 5 cc. or less were used per injection. Most of those done using larger quantities were in the first part of this series (twenty-eight of the first forty-one).
Of the last twenty-nine angiograms done in this series, twenty-five were performed utilizing only 3 cc. per injection, and in each good arterial filling was demonstrated (Figs. 1 and 2). Venous visualization was also usually adequate (Fig. 3), but occasionally an injection might have to be re- peated with a delayed exposure to get a good venogram unless a serial technique was used. Sixteen of these last twenty-nine arteriograms re- quired only two injections of 3 cc. each — a total of 6 cc. per arteriogram!
The 500 angiograms required a total of 1281 injections. Two injections only were used for 230 angiograms. Eight patients required over five injections, one patient requiring eight. These excessive numbers of injections were needed for detail in multiple phases and/or perspectives in aneurysms or vascular malformation patients. In sixty-eight angiograms only a single injection was used. Occasionally, the test was stopped after the first injection because of an unfavorable reaction to that injection, but in the majority of instances single injections were used for a single
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CEREBRAL ANGIOGRAPHY— GASS
anterior- posterior view to determine presence or absence of shift of midline vessels or of a sub- dural or extradural hemorrhage. Additional in- jections for lateral views would have been super- fluous.
Early in this series, several instances of a large total quantity of contrast medium being used are on record. In one instance, when injections of 10 cc. quantities were customary, as much as 60 cc. of 30 per cent urokon was used. Most of the other multiple injection arteriograms, however, when smaller quantities were used, do not rep- resent such a large total quantity of medium. Thus, one arteriogram was done using eight injections and a total of 40 cc. of media, another needed seven injections and a total of 35 cc., and four required six injections and 30 cc. each. More recently a six-injection arteriogram was re- quired, in which only 3 cc. per injection was used, or a total of only 18 cc.
Of the 1281 injections of dye made, thirty-two were partly or completely extravascular. Such injections caused immediate increased pain dur- ing and shortly after the injection. Otherwise no other ill effects occurred except in one patient who suffered an immediate minor neurologic re- action with a quick complete recovery. In none of these thirty-two cases was thorotrast used. Sev- eral times x-rays of the neck subsequently dem- onstrated complete absorption of the dye within a few hours. An injection of urokon and diodrast outside the lumen of the carotid artery meets greater resistance and creates severe local pain in the neck, ear and jaw which subsides within a few minutes. An injection outside the lumen of the vertebral artery causes severe pain in the shoulder and arm, which likewise usually subsides in a few minutes. In one such instance, brachialgia lasted several days probably because an associated nerve root at that site was irritated by the dye.
Discussion
A good safety record can be maintained by ad- hering to two prophylactic concepts. The first is care in selection of patients, and where greater risk patients must be subjected to the test, rigid attention to safety features in technique must be applied. The second is a constant respect dur- ing technical performance of the test for its po- tential hazards with corresponding insistence on efficient, safe technique. Despite faithful appli- cation of these two principles, some reactions will
still occur, but with proper safeguards they can ordinarily be rendered innocuous. These conten- tions do not deny the need for still further tech- nical improvements. As of this writing, two major advances are still needed: (1) The devel-
opment of a more perfect contrast medium (one which will provide good contrast, but which is still painless, nonirritating, nonradioactive, and readily excreted or destroyed by the body) ; and (2) a more dependable simple technique for ver- tebral angiography.
In accepting a patient for this test, there is comfort in the knowledge that in most patients there is a large margin of safety with regard to neurologic accidents or fatalities. These patients will tolerate a traumatic arterial puncture, re- peated large injections of contrast medium, extra- vascular injections, and sundry other insults with- out neurologic sequelae. There is a significant number, however, who beforehand give warning of potential complications. These include the aged, the arteriosclerotic, the hypertensive, patients who have recently bled from aneurysm, and the pa- tient with a known intracranial mass lesion. Then there is still another group of patients who give no such warning, but who for some unknown reason tolerate a local vascular insult such as caused by injection of contrast medium less well than others. Patients in whom this is likely to occur cannot be recognized in advance, but will show their intolerance to the procedure by neuro- logic reactions during the performance of the test. In both these latter groups a neurologic reaction following an injection of dye or even to attempted cannulation of the artery is a danger- signal for trouble ahead, which if ignored is apt to lead to a disastrous complication. Thus, a patient who, following the first injection, is unable to move the contralateral extremities fully, or who complains of numbness in those parts, or who is having speech trouble, when subjected to a re- peated vascular trauma with another severe in- jection may have such a transient complication converted to a more permanent one. It is im- portant for the operator to know “where his patient is” after each injection. For this reason we believe that the procedure should be done under local anesthetic in a fully-awake patient whenever possible. It can be made to be nearly pain free and tolerable under local anesthetic only. We do not hold with those that believe that the theoretical benefit of relaxation of cerebral ves-
January, 1957
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CEREBRAL ANGIOGRAPHY— GASS
sels under general anesthesia overcomes the ad- vantage of knowing that your patient has not reacted well to the injection just given. In an anesthetized patient this reaction is masked. When it is necessary to do cerebral angiography in an unconscious patient or in one in whom general anesthesia cannot be avoided, as in children or grossly irrational patients (in whom restraining head and extremity compression straps are in- adequate), it is important that the number of injections (small quantities) be kept to a mini- mum and ample rest periods for recovery be allowed between injections.
Often, therefore, it is possible to cut short the usual technique as soon as the problem is solved. In a stuporous or comatose patient, for example, in whom a surface hematoma is suspected, who shows in the first film (an anterior-posterior view) a significant shift of anterior cerebral arteries to one side with a pathognomonic free space between cortical vessels and calvarium indicating a sur- face hematoma, there is no need to risk a second injection trauma to obtain a lateral view. Angio- grams, therefore, should be done only by those persons who are fully aware of the problems of the case and who will carry out the definitive therapy. In this way, injections which will yield little or no clinical information may be avoided.
Other occasions develop where a purely neuro- surgical decision of clinical management is made during the course of the performance of the test as the wet films are seen following each injection. These may include cessation of the test, need for certain oblique views, demonstration of collateral ability of Circle of Willis, legibility and adequacy of the films, et cetera. This procedure may be accepted once by the patient without much com- plaint, but he is apt to be bitter if a repetition is needed because of some oversight when it was first performed. If the responsibility of this test is placed upon a resident in training, he must be prepared to make accurate and complete neuro- surgical diagnosis as he goes along or have each set of films as they are developed interpreted for him by someone who can.
Technique
One cannot underestimate the importance of technique when considering the safety of cerebral angiography. Unlike some medical investigative procedures, the outcome of this test may depend on the care and efficiency with which it is done
by different operators. Safe angiography may be done in a variety of ways, the differences in tech- nique depending upon the operator’s preferences, the radiologic facilities available, and the pa- tient’s disease. Angiography as done by a single operator always in the same institution may not be suitable for the itinerant neurosurgeon who answers consultations in many institutions. It is not always feasible or safe to transfer a patient who may benefit from the information obtained by the test from one institution to another solely for the performance of angiography. The tech- nique which was developed and has been utilized for most of the patients in this series has proven itself to be safe, reliable and simple, and easily adaptable to any general hospital, even though it is utilized there rarely. Experience with several specially built units for taking multiple serial films has failed to prove their value to the author for routine angiographic diagnosis. In the oc- casional circumstance where interval exposures beyond the customary arteriographic and veno- graphic phases may be needed, they can be readily obtained by another injection and timing of exposures earlier or later than is usual. Thus the elimination of special equipment has enabled increased utility of this test.
Several features of technique deserve comment. Especially in hospitals where the personnel are unfamiliar with cerebral angiography, it is im- portant that the neurosurgeon take complete charge of the procedure, especially from the radio- logic point of view. If he yields to the factors, patient positions, tube position, cassette position imposed by a technician inexperienced in this test and somewhat in variance with his own ex- perience, he will frequently end up with an under- exposed film or one showing the head rotated or not properly centered. If necessary, it is wise before actual performance to take one or more exposures of the head in the test position to per- fect technique. Unnecessary injections which in- crease both the pain and the hazard may be reduced by proper planning.
Preference for local anesthesia has already been stressed in order that greater control over and prevention of untoward reactions may be achieved by the operator. With experience the test may be made to be almost pain free. Ordinarily, aside from the pain associated with the introduc- tion of local anesthesia, there is momentary sharp pain as the needle pierces the carotid artery and
76
TMSMS
CEREBRAL ANGIOGRAPHY— GASS
<«.-■ r*
r:v: 3 the arie: i. uiin.; <■ ct c: .. ,'ieedi e
Fig. 4. Fixing and transfixing the artery.
Imoe
again as the needle is withdrawn at the com- pletion of the test while pressure is being made against the puncture site to prevent local hema- toma. Description of the discomfort associated with injection varies with the patient and the amount, the type and rate of injection of the contrast medium. A rapid injection of 5 cc. of 30 per cent urokon into the common carotid artery is accompanied by a sudden stinging, burn- ing sensation in the homolateral side of the face and behind the eye. It tastes bitter and often induces the sensation of something flushing through the mouth, and the patient may desire to expectorate. A calm stoic patient will report it not to be painful but to burn as though on fire for an instant. In a small per cent of patients a moment or two later there may be nausea or actual gagging. This pain is considerably re- duced when only 3 cc. is used, and the patient verbalizes little distress from the experience.
Although intracarotid injection of thorotrast is painless, it is retained in the body and may be seen years later in quantity in liver and spleen, and its malignancy provoking possibility has been indicted many times. Moreover, in a percu- taneous injection any extravasation could lead to serious late cicatricial changes in the neck. Its use, therefore, may be justified only in elderly patients or severe hypertensives where the danger of immediate reaction is high. The newer media, hypaque and renograffin, are now receiving trial and show promise of being less irritating than 30 per cent urokon.
Fig. 5. Cannulating the artery (See text).
The performance of the test involves two steps: (1) the cannulation of the artery, and (2) the injection. For carotid angiography it is almost always the common, which is more accessible than the internal carotid artery, that is punctured. The demand for vertebral angiography is infre- quent and the technique less dependable. Ex- pertness in performing carotid cannulation ensures a minimum of pain and a maximum of safety and success. Although specially designed needles are preferred by some, an ordinary sharp No. 18 spinal puncture needle has proved adequate in this series. The operator first aims to transfix the artery with the needle, bevel down. This necessitates fixing the artery against lateral or medial movement with perfect control. If it
January, 1957
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CEREBRAL ANGIOGRAPHY— GASS
cannot be readily done between the fingers, the use of an accessory needle placed down to the transverse process medial to the artery against which it may be held, is of inestimable value (Fig. 4) . Successful impaling of the artery is deter-
Fig. 6. Angiogram (lateral view) made with 5 cc. of 30 per cent urokon showing large arterio-venous malfor- mation. Note complete filling of early phase with only 5 cc.
mined by slow withdrawal of the spinal puncture needle with its stilette out until a show of blood is seen at the open bore. After transfixation of the artery has thus been secured, the operator next aims at cannulating the artery as follows. Further slow withdrawal of the needle is continued and while doing so appropriate pressures are exerted against the needle to cause the artery to be raised up by the needle point (Fig. 5) until the needle is felt to “pop"’ into the lumen much as a needle “pops” through the dura in doing a lumbar punc- ture. This is accompanied simultaneously by a pulsating spurt of blood out of the needle, indi- cating the needle bevel to be entirely within the lumen of the artery. The needle may then be threaded up the artery a safe distance to insure total intraluminal injection of dye, usually one- fourth to one-half inches or more. The stilette is then replaced in the needle until the injection is ready to be made. The needle may be left in situ as long as needed.
The injections are made by attaching a 10 cc. plain tip syringe containing the contrast medium directly to the needle. Continuous irrigation of the needle system is thus safely omitted. Elim- ination of the irrigation system not only simplifies the technique, but enables the use of smaller quan-
tities of dye. It is doubtful that uniformly suc- cessful angiograms can be obtained with as little as 3 to 5 cc. of medium if the dead space of irri- gating tubing is interposed between syringe and needle. Moreover, facial petechiae which have been reported after this test do not occur when the irrigation system is eliminated. Evidently their occurrence indicates inadvertent injection of air trapped in the tubing. With the use of small quantities of dye (3 to 5 cc.), care must be taken not to allow blood to enter the syringe in any quantity before the injection is made unless the bolus of dye is diluted. The operator soon becomes proficient in how rapidly to inject the dye and when to make the exposures, and rarely misses obtaining appropriately timed films, both in the arteriographic and venous phases.
It is of interest that huge vascular lesions may be visualized in their entirety in all phases utiliz- ing 5 cc. of dye or less (Fig. 6). It is also prob- ably true that such large lesions may have greater than a 5 cc. total fluid capacity in their arterial or venous phases yet visualize completely with a smaller quantity of contrast medium. This may be due to the fact that the x-ray exposure is not instantaneous and visualizes the dye as it travels through the arterial or venous tree for a given period of time, if only brief. Cinefluorographic angiography7 has shown with what rapidity blood flows through the cerebral vascular system. A quantity of dye insufficient to fill the entire ar- terial system in a given instance may, therefore, during a brief but finite interval, which is being filmed, fill out the entire vascular silhouette.
As a rule it is necessary to make only two in- jections, the first for an arteriographic view in the anterior-posterior projection, and the second for both arteriographic and venous phases in the lat- eral projection. The two phases may be obtained by manually changing the cassettes rapidly and making two properly timed exposures. Individual circumstances may vary this routine, however, since at times more than two injections may "be needed where at other times a single injection for the anterior-posterior view may solve the prob- lem in question. Interval phases between and after the arteriographic and venous phases may be needed for completeness in arteriovenous mal- formations or certain vascular tumors, and addi- tional oblique views are often necessary for com- plete delineation of aneurysms. Flexibility with regard to the number of films and views needed
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CEREBRAL ANGIOGRAPHY— GASS
to answer the special needs of individual cases should be the keynote, bearing in mind at all times, however, that the fewer injections made the less likely the patient will react unfavorably. Adequate rest periods between injections are or- dinarily provided if one waits to develop and view each set of films before proceeding with the next.
It is wise to take the lateral views on grid cassettes without turning the patient’s head to offer less chance for the needle to be dislodged. This also simplifies the manual changing of cassettes for the two routine phases. The anterior- posterior projection, if taken with a 30° to 40° tilt as used in obtaining an occipital or Towne view of the skull, is apt to be more informative than a straight perpendicular projection, since then a longer view is obtained of the important midline pericallosal artery as well as the Syl- vian vessels. Any shift from the midline of the former vessel is more evident in the longer view than when it is foreshortened as in a straight per- pendicular view. Medial displacements of the Sylvian vessels away from the calvarium are sim- ilarly more evident in the longer occipital pro- jection. Moreover, overlapping orbital and front- al sinus bony detail present in a perpendicular anterior-posterior film is thrown out of the field of the arteries in the occipital view.
If the time exposure is kept to one-fourth sec- ond or less, any movement that the patient may make in reacting to the injection will occur after the exposure is complete. He should be fore- warned when the injection is about to be made. These precautions usually suffice in obtaining good quality films without motion, but occasionally head restraints or even general anesthesia are indi- cated.
The operator should be protected by a leaded shield placed over the patient’s chin or neck be- tween the needle and the rest of the patient’s head, or by an extension cone or cylinder reaching nearly to the head which keeps the operator’s hands out of any direct x-ray beam.
A percutaneous vertebral arteriogram technique as reliable, safe and simple as the carotid tech- nique has not been developed. Success in ob- taining good vertebral angiograms may be expect- ed about 75 per cent of the time. Myelographic visualization of the main branches of the basilar artery system for aneurysms and displacement may be safely achieved by the use of the technique of
Mellins,8 but this is of limited value, although not difficult to accomplish.
On withdrawal of the needle following carotid angiography, immediate firm finger pressure at the site of puncture for a few minutes, which is some- what uncomfortable, will prevent any significant hematoma formation. Greater care in this regard is needed in hypertensives and in the aged. Al- though a large number of minor hematomas in the neck have occurred, which contributes to the neck soreness which follows the test for a few days, none in this series has ever caused serious incon- venience nor have any had to be evacuated. Fol- lowing vertebral angiography the site of punc- ture cannot be compressed, yet no ill effects fol- lowing needle removal have been seen. It is rec- ommended that the patient remain recumbent for two hours following angiography.
Summary
The author’s experience with 500 consecutive cerebral angiograms performed in 364 patients is presented from the point of view of safety and yield of information. The total incidence of reac- tion was 6.6 per cent, but only 1.4 per cent for serious reactions, and the single death in which the test might be causally involved constituted an incidence of 0.2 per cent. Details of technique which enabled achievement of this record are dis- cussed, including the recent use of 3 cc. of con- trast media per injection.
Information critical for the diagnosis or the management of the patient was obtained in 172 of the 374 patients. In thirty-nine patients an- giography alone without air study provided ample information for neurosurgical identification and localization of an intracranial mass or a surface hematoma.
Addendum
Since the preparation of this paper, more than 100 additional angiograms have been performed utilizing 3 to 4 cc. of dye per injection. Not a single major complication has occurred. Hypaque sodium (50 per cent) was used in almost all of this group and when injected into the internal carotid artery resulted in excellent contrast without producing pain. In 3 to 4 cc. quantities, it has become our medium of choice.
( Continued on Page 88)
January, 1957
79
Anomalous Left Coronary Artery and Endocardial Fibroelastosis
npo THE PHYSICIAN whose practice is con- ■*- cerned with or limited to patients in the ped- iatric age group, sudden and clinically unexplain- able death in a previously apparently healthy in- fant or child is a most distressing happening.
Farber,1 in his timely work on this problem, refuted the myth of the thymus gland as the cause in itself of sudden death, and cast serious doubts on many of the other more or less accepted reasons for this highly disturbing occurrence. At the same time, Farber quite definitely established the roll of various fulminating and unrecognized infections as the almost universal cause of these “sudden deaths.”
Recently, Adelson and Kinney,2 in a compre- hensive study of 126 consecutive cases of sudden unexpected death in children between the ages of ten days and two years, have again pointed up the almost universal role of severe fulminating infections in all instances of sudden death other than traumatic.
Two of the less frequently occurring and most often unrecognized causes for sudden or very rapidly occurring death in an infant who had pre- viously given no clinical evidence of disease or anomaly, are anomalous left coronary artery and its counterpart in clinical course and manifesta- tions, endocardial fibroelastosis.
This paper presents a review of the literature and cases of each of these uncommon conditions in which the ages, past histories and clinical courses were remarkably similar, and where diag- nosis of the cause of their rapid demise was es- tablished only at the necropsy table.
Historical Data
The first report of anomalous left coronary artery was by Abrikosoff3 in 1911. It was six years later that Heitzmann4 reported an identical case and called attention to the similarity of the
From the Departments of Pediatrics of the St. Law- rence and Edward W. Sparrow Hospitals, Lansing, Michigan.
By John F. Sander, M.D.
East Lansing, Michigan
Ronald C. Peets, M.D.
Lansing, Michigan
pathologic findings to those resulting from coro- nary occlusion in adults. In 1934, this entity was described in detail by Bland, Garland, and White.0 It was from this report that the anomaly received its occasional name of “Bland — Garland — White Syndrome.”
To this date, there have been approximately forty cases of this anomaly reported in the liter- ature. All have essentially similar findings.
The companion entity, endocardial fibroelastosis, was first described in 1818 by Kreysig.6 For a century it seems to have been either unrecognized or considered a facet of myocarditis. Then, in 1918, Potoschnig7 reported this condition and sug- gested that it was noninflammatory and deserved further investigation. There appears to have been further lack of recognition of the entity until 1941 when Gross8 reviewed the subject. Investigators then bestan to consider the condition with the congenital anomalies of the heart. It was given its present name by Weinberg and Himmelfarb9 in 1943. Many more cases have been reported since that time, some of which were suspected clinically and verified at necropsy.
The Clinical Picture
The symptomatology of these two disorders is essentially identical. The infant, usually born normally at full term, appears normal at birth and for several weeks to months thereafter. Then the parents note the onset of attacks of pain, espe- cially at the time of feeding. Respirations become short and grunty and the infant frequently pulls up his knees as if having colic. Later there is sweating, apparent shock and frequently cyanosis. It is now accepted that these attacks represent angina pectoris. Physical examination and chest roentgenogram show evidence of cardiac enlarge- ment. Electrocardiogram shows signs of myo- cardial hypoxia as well as left ventricular hyper- trophy. Cardiac catheterization has been of little help in distinguishing the two entities.
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Pathology
The findings at necropsy are characteristic. There is considerable enlargement of the heart, particularly of the left ventricle, due both to dila- tation and hypertrophy. In the first condition, the changes are predominantly in the distribution of the left coronary artery. The endocardium of the affected area is usually thickened and gray, due to associated endocardial fibroelastosis. The left ventricular myocardium may appear scarred on gross inspection, and usually will exhibit scar- ring on microscopic examination. These are typ- ical of scars due to myocardial infarction and, ac- cording to Bland et al,5 tend to be concentrated near the endocardial side of the myocardium of the left ventricle. The myocardium will frequent- ly also show focal areas of calcification. These are generally thought to be necrotic muscle. Acutely infarcted myocardium is sometimes evi- dent. Endothelial-lined blood-containing sinus- oids are frequently present in the myocardium of the left ventricle and these are quite striking when seen. The pathologic findings typical of endo- cardial fibroelastosis are essentially the same but without the anomalous coronary artery.
We wish to present one case of anomalous left coronary artery, and two cases of endocardial fibroelastosis for the record.
Case Reports
Case 1. — K. J., a four-week-old girl, was born nor- mally of healthy parents. There were no other children. Her course in the hospital was uneventful. She was discharged in apparently good condition, and when ex- amined two weeks later by her physician was in good condition and had made normal progress. When one month of age the parents reported that she was very fussy at feeding time. She would take about one
ounce of formula and would pull up her knees and “scream” as though in great pain. She was given an appointment for office examination but shortly be- fore that time the physician received an “emergency” call, stating the baby had another episode of severe pain, had vomited and then stopped breathing. Prompt and accepted attempts at resuscitation were of no avail.
Necropsy Findings. — Significant abnormalities were limited to the heart. The pericardial cavity was greatly distended and contained 85 cc. of blood-tinged fluid. The greatest transverse diameter was 4 cm.; the weight 42 grams. The coronary arteries were anomalous in that the left coronary originated from the pulmonary trunk. The left coronary was limited to the descend- ing branch. The right coronary originated from the aortic trunk and was normal. The left ventricular wall varied in thickness from 5 to 7 mm.; the right 3 to 4
Fig. 1. (above) Case 1. — Myocardium showing the necrosis and focal calcification in ischemic areas.
Fig. 2. (center) Case 1. — Myocardium showing blood filled, endothelial lines sinusoids (x 150).
Fig. 3. (below) Case 1. — Papillary myocardium ex- hibiting necrosis and focal calcification.
mm. The lateral aspect of the wall of the left ventricle exhibited an area of brownish discoloration 1 cm. in diameter lying beneath the endocardium and extend- ing 2 to 3 cm. into the myocardium. The valves were grossly normal, as were other features of the heart.
Micropathology. — Myocardial fibers were hypertro- phied, particularly of the left ventricular wall. There was a moderate an aunt of generalized interstitial edema.
January, 1957
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Sections through the wall in the area of the above- described discoloration revealed several scars particu- larly beneath the endocardium. In several areas there was necrosis of the myocardial fibers. There were focal
Fig. 4. Case 2. — Ventricular myocardium exhibiting endocardial fibrous thickening and vacuolization of un- derlying myocardium.
areas of calcification among the necrotic muscle bundles. Many of the papillary muscles exhibited focal areas of necrosis and calcification. The endocardium in the areas of myocardial involvement was greatly thickened due to an excess of fibrous and elastic tissue. There was no evidence of inflammatory cell infiltration.
Pathologic Diagnosis. — Anomalous origin of left cor- onary artery from the pulmonary trunk. Coronary artery insufficiency and acute myocardial infarction. Cardiac hypertrophy, dilatation and acute congestive failure.
Case 2. — H. U., a five-month-old, white female child was born by normal spontaneous delivery after a normal pregnancy. No physical abnormalities were noted in the postnatal physical examination. Both parents were in good health. A two-year-old brother, normal and in good health, was the only sibling. She was ex-
amined regularly at monthly intervals according to accepted pediatric standards and her progress was good. Her mental and physical development were normal. She had no illnesses until she was five months old, at which time she had an acute adenotonsillitis, uncom- plicated. She received penicillin therapy and routine symptomatic treatment. Her clinical improvement was prompt and satisfactory for four days, but then she again became febrile, irritable and anorexic. She vom- ited persistently. Her physician was called on the
fifth day and when she was seen was extremely and critically ill. Her color was ashen gray, respirations were rapid, grunting, and labored. Breath sounds were bronchial in character over both upper lung fields more marked on the left. Clinical diagnosis of pneumonia, and dehydration was made, with the possibility of previously unrecognized cardiomegaly.
The infant was promptly hospitalized; placed in oxygen, parenteral fluids started, and she was given streptomycin-penicillin therapy.
Chest roentgenogram showed marked cardiac en- largement involving chiefly the left side of the heart, and bilateral bronchopneumonia.
She remained cyanotic and had increasing respira- tory distress, even in high oxygen concentration, and expired six hours after admission.
Autopsy Findings. — Pathology was limited to the heart and lungs. Both ventricles were markedly dilated.
The mitral valve leaflets and the endocardium showed white fibrous thickening. Microscopically there was edema of the interstitial connective tissue, of the myo- cardium and patchy fibroelastosis throughout. The en- docardium was thickened by fibrosed elastic fibers. Bundles of atypical clear cells were found beneath the endocardum. The mitral valve leaflets were thickened and showed both fibrosis and degenerative changes.
The lungs exhibited a patchy consolidation of all lobes, which microscopically proved to be entirely edema.
Pathologic Diagnosis.— Myocardial failure due to en- docardial and myocardial fibroelastosis.
Case 3. — C. C., a five-months-old, white male infant, was born by normal spontaneous delivery after a normal pregnancy. The mother was Rh negative. Cord blood was Coombs negative and showed a bilirubin of 1.7 mg. per cent. Growth and development were normal during his five months of life. He became ill during the day prior to admission with persistent vomiting, was restless and irritable and cried constantly. The following day his physician was called and he felt that the child’s condition was critical, and advised immediate hospitalization. His temperature was 104° rectally on admission. He was cyanotic, respirations were rapid and labored, and breath sounds were bronchial in char- acter over both upper lobes but more marked on the left. Parenteral fluids, oxygen and vigorous antibiotic therapy was started, but he expired one and one-half hours after admission.
Autopsy Findings. — The pericardial cavity contained 30 cc. of straw-colored fluid. The heart was markedly enlarged and when emptied of its contents weighed 108 grams, with the greatest transverse diameter being 6.5 cm. The coronary arteries were normal in origin and distribution. The myocardium was hypertrophied and flabby. Both ventricles were markedly dilated. There were no anomalies of the heart or great vessels. The endocardium was opaque, white and thickened.
Microscopically the myoeardium of the left ventricular wall showed marked hypertrophy of uneven distribution. The endocardium of the left ventricle was markedly thickened. There were numerous trabeculae of dense connective tissue extending into the myocardium with partial degeneration of some of the myocardial fibers. There was no myocardial infarction, nor any inflamma- tory myocarditis or endocarditis. The lungs, liver, spleen and kidneys showed marked congestion.
The pathologic diagnosis was congenital endocardial fibroelastosis with left ventricular cardiac hypertrophy and acute congestive heart failure.
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Comments and Summary
Sudden and unexpected death in an apparently previously healthy infant or child is a most shock- ing and distressing occurrence to both the phy- sician and the family. For years most of these sudden deaths were attributed to hypertrophy of the thymus gland and/or status thymico lym- phaticus. Since 1924 when Farber first refuted this then current and accepted cause of death, and established fulminating infection as the most universal cause of all sudden, other than trau- matic deaths, numerous articles have been pub- lished confirming his findings.
Three cases of sudden, unexpected and clin- ically unexplained death are reported by us, which are neither on a traumatic or infection basis, and which indicate that in any similar sit- uation, the possibility of endocardial fibroelastosis or anomalous left coronary artery should be in- cluded by the physician in his differential diag- nosis.
Acknowledgment
The authors wish to thank Dr. Leo W. Walker and Dr. Charles E. Black, pathologists at St. Law- rence and Edward W. Sparrow Hospitals re-
spectively, for their kind help and cooperation in the preparation of this paper.
References
1. Farber, S.: Fulminating streptococcus i»fections in infancy as a cause of sudden death. New England J. Med., 211:154-159, 1934.
2. Adelscn, L., and Kinney, E. R.: