2P71 47

LIBRARY GENERAL FUNDS

Luther S. Bent Binding Fund William T. Carter Catalogue Endowment Louis A. Duhring W. V. & J. M. Keating Henry Leffman

Library Endowment Morris Longstreth Phila. Med. Society Charles H. Vinton Douglas Stockton Warren J. William White Caspar Wistar

LIBRARY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA

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Research Triangle Park North Carolina 27709

New York State Journal of Medicine (ISSN 0028-7628)

Published monthly with the Minutes of the House of Delegates added February by the Medical Society of the State of New York. Copyright 1980 by the Medical Society of the State of New York. All material covered by copyright in the New York State Journal of Medicine may be photocopied for noncommercial scientific or educational use only. Special arrangements and permission are required from the author(s ) of the particular article and from the editor for any other purpose. Editorial. Circulation, and Advertising Offices: 420 Lakeville Rd , Lake Success, N.Y. 11042. Change of Address: Notice should state whether or not change is permanent and should include the old address. Six weeks notice is required to effect a change of address. Fifty cents per copy — $3.50 per year. Foreign subscriptions: $3.50 subscription plus $1.50 for mailing. Second-class postage paid at New Hyde Park, N. Y., and additional mailing office. POSTMASTER: Send POO form 3579 to New York State Journal of Medicine, 420 Lakeville Rd., Lake Success, N.Y 11042.

Contents

JANUARY 1980

VOLUME 80 NUMBER 1

The Editors of the Journal assume no responsibility for opinions and claims expressed in the arti- cles contributed by individual authors. Contributions accepted for original publication only.

Scientific Articles

19 Effect of Furosemide on Acute Renal Failure in Dogs; Induced by mercuric chloride

Joseph M. Charxdrankunnel, M.D., Seymour Saxanoff, M.D., Sandra W. Moss, M.D., Philip Rosenzweig, M.D., Millicent Snyder, and Robert P. Eisinger, M.D.

22 Bilirubin Metabolism in Obstructive Jaundice Allan W. Wolkoff, M.D.

25 Transversalis Fascia Hernioplasty

Stanley D. Berliner, M.D., and Leslie Wise, M.D.

29 Hypertension in Perioperative Period

Joseph L. Seltzer, M.D., John I. Gerson, M.D., and Alan W. Grogono, M.D.

32 Cancer Effects of Low-Level Radiation; Theoretic considerations in competing causes of death A. M. Stewart, M.D.

36 Total Knee Arthroplasty; Update

Kenneth M. Chekofsky, M.D., W. Norman Scott, M.D., and John Insall, M.D.

39 Master Two-Step Test; Present status

Jules Constant, M.D., F.A.C.C.

47 Multiple Foci of Colorectal Carcinoma; Argument for subtotal colectomy Richard Fogler, XI. D., F.A.C.S., and Edward Weiner, M.D.

53 Child Abuse; Prevention in teen-age parent Vincent J. Fontana, M.D.

School Health

57 Drugs in Sports

Howard C. Mofenson, M.D., and Joseph Greensher, M.D.

Electrocardiograms of the Month

61 Questions 283 and 284

Ira L. Rubin, M.D., and Julian Frieden, M.D., Editors

Radiologic Problem of the Month

63 Crumbled Head of Humerus

Kakarla Subbarao, M.D.

Sexually Transmitted Diseases

64 Yehudi M. Felman, M.D., F.A.C.P., and James A. Nikitas, M.A., F.R.S.H.

Case Reports

67 Hematuria Secondary to Perivesical Tumors

David V. Schapira, M.D., Ch.B., Robert F. Asbury, M.D., John C. Wandtke, M.D., and Peter K. Macintosh, M.B., Ch.B.

70 Dramatic Response of Cancer to Localized Hyperthermia

John S. Stehlin, Jr., M.D., F.A.C.S., Pierre J. Greeff, M.D., Beppino C. Giovanella, Ph.D., and Leo J. Williams, Jr., M.D.

73 Legionnaires’ Disease After Immunosuppression; Response to erythromycin

Lillian Pothier, M.D. , F.A.C.P., Marshall Clinton, M.D., F.A.C.P., and Martin E. Plaut, M.D., F.A.C.P.

2r.71 47

AUG 181981

January 1980/New York State Journal of Medicine 1

' Tho Family of Man" by Roberto Moretti, a statuary in crystal symbolizing the broad range of hypertensive patients eligible for therapy with Catapres

The Alpha

Advantage:

It’s for all kinds of hypertensives

Unlike beta blockers, Catapres' has no contraindications. Catapres can be useful even in these patients with:

Congestive heart failure Allergic rhinitis

Ventricular hypertrophy Hepatic disease

Hyperglycemia Hyperuricemia

Diabetes mellitus Gouty arthritis

Bronchial asthma Sulfonamide hypersensitivity

Like any antihypertensive, use with caution in severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure.

WOrk/play— normal hemodynamic responses to exercise maintained.

love — low incidence of impotence and/or loss of libido:

2.8% in 1 ,923 patients studied.1

Cardiac output— tends to return to control values during long-term therapy, blood flow— preserved in kidney.

No Single Advantage Determines Drug Choice.

Other factors must include:

The drug’s effectiveness in a given patient, its side effects, warnings, precautions, tolerance, etc. A rational therapeutic choice depends on a careful assessment of all such factors.

'Central alpha-adrenergic stimulation decreases sympathetic outflow from the brain, as shown in animal studies

1 Data on tile at Boehringer Ingelhcim Ltd

Please see last page for brief summary, including warnings, precautions, and adverse reactions.

Biiaw available in new a

^mm£m

®S«|j Wtf/j

Tablets of 0.1, 0.2, 0.3 mg

Catapre

(clonidine HCI)i

The Alpha Advantage

It’s for all kinds of hypertensives

■ Tablets of 0.1, 0.2, 0.3 mg

(clonidine HC1)

Hypertension

• No contraindications.

• Effective in all degrees of hypertension. It is mild to moderate in potency.

The usual starting dose of Catapres is 0.1 mg at breal< fast and 0.1 mg at bedtime. Some patients may benef from a starting dose of 0.1 mg at bedtime.

Usual daily dose range — 0.2 — 0.8 mg

• Low incidence of depression, impotence, orthostatic hypotension — no fatal hepatotoxicity.

• Preserves kidney blood flow.

Most common side effects are dry mouth, drowsiness, and sedation which generally tend to diminish with time

Maximum daily dose — 2.4 mg

Doses as high as this have rarely been employed.

For optimal results, the dose of Catapres must be adjusted according to the patient’s individual blood pressure response.

Catapres®

(clonidine hydrochloride)

Tablets of 0.1, 0.2, 0.3 mg

Indication: The drug is indicated in the treatment of hypertension. As an anti- hypertensive drug, Catapres (clonidine hydrochloride) is mild to moderate in potency. It may be employed in a general treatment program with a diuretic and/or other antihypertensive agents as needed for proper patient response.

Warnings: Tolerance may develop in some patients necessitating a reevaluation of therapy

Usage in Pregnancy: In view of embryotoxic findings in animals, and since information on possible adverse effects in pregnant women is limited to uncon- trolled clinical data, the drug is not recommended in women who are or may become pregnant unless the potential benefits outweigh the potential risk to mother and fetus.

Usage in Children No clinical experience is available with the use of Catapres (clonidine hydrochloride) in children

Precautions: When discontinuing Catapres (clonidine hydrochloride), reduce the dose gradually over 2 to 4 days to avoid a possible rapid rise in blood pressure and associated subjective symptoms such as nervousness, agitation, and headache. Patients should be instructed not to discontinue therapy without consulting their physician. Rare instances of hypertensive encephalopathy and death have been recorded after cessation of clonidine hydrochloride therapy A causal relationship has not been established in these cases It has been demonstrated that an excessive rise in blood pressure, should it occur, can be reversed by resumption of clonidine hydrochloride therapy or by intravenous phentolamine Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of the sedative effect This drug may enhance the CNS- depressive effects of alcohol, barbiturates and other sedatives Like any other agent lowering blood pressure, clonidine hydrochloride should be used witfi caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure As an integral part of their overall long-term care, patients treated with Catapres (clonidine hydrochloride) should receive periodic eye examinations While, except for some dryness of the eyes, no drug-related abnormal ophthalmologic findings have been recorded with Catapres (clonidine hydrochloride), in several studies the drug produced a dose-dependent increase in the incidence and severity of

spontaneously occurring retinal degeneration in albino rats treated for 6 montl longer

Adverse Reactions: The most common reactions are dry mouth, drowsiness sedation. Constipation, dizziness, headache, and fatigue have been repo Generally these effects tend to diminish with continued therapy. The folio reactions have been associated with the drug, some of them rarely. (In s instances an exact causal relationship has not been established.) These incl Anorexia, malaise, nausea, vomiting, parotid pain, mild transient abnormality liver function tests; one report of possible drug-induced hepatitis without ict and hyperbilirubinemia in a patient receiving clonidine hydrochloride, c thalidone and papaverine hydrochloride. Weight gain, transient elevation of b glucose, or serum creatine phosphokinase: congestive heart failure, Raynj phenomenon; vivid dreams or nightmares, insomnia, other behavioral chan nervousness, restlessness, anxiety and mental depression. Also rash, gioneurotic edema, hives, urticaria, thinning of the hair, pruritus not associ with a rash, impotence, urinary retention, increased sensitivity to alcohol, dryr itching or burning of the eyes, dryness of the nasal mucosa, pallor, gynecome weakly positive Coombs' test, asymptomatic electrocardiographic abnorma manifested as Wenckebach period or ventricular trigeminy.

Overdosage: Profound hypotension, weakness, somnolence, diminished o; sent reflexes and vomiting followed the accidental ingestion of Catapres (clom hydrochloride) by several children from 19 months to 5 years of age. Ge lavage and administration of an analeptic and vasopressor led to completi covery within 24 hours Tolazoline in intravenous doses of 10 mg at 30-mi intervals usually abolishes all effects of Catapres, (clonidine hydrochloride) < dosage

How Supplied: Catapres, brand of clonidine hydrochloride, is available as 0.1 (tan) and 0.2 mg (orange) oval, single-scored tablets in bottles of 100 and 1000. available as 0.3 mg (peach) oval, single-scored tablets in bottles of 100.

For complete details, please see full prescribing information.

Under license from Boehringer Ingelheim GmbH

Boehringer Boehringer Ingelheim L

Ingelheim Ridgefield, CT 06877

79 Tumors of Small Intestine; Seek and ye shall find Bruce S. G ingold. M l).

85 Meningitis and Bacteremia; Induced by Bacillus cereus

Brijesh Mittel, M.D., and John Lusins, M.D., F.A.C.P.

87 Unusual Imperforate Anus

Umesh B. Patil, M I)., and John K. Kavouksorian, M L).

89 Hypereosinophilic Syndrome

Bernard Peison, M l)., and Barry Benisch, M.D.

Special Articles

96 The Fight for Continued Medical Privacy

Elemer R. Gabrieli, M.D.

101 Re: Interest on Unpaid Compensation Awards; Order of the chairman Arthur Cooperman

103 Health Care Delivery; Common problems throughout the world Harmen A. Tididens, M.D.

113 Still More Principles of Medicine

Robert Matz, M.D.

History of Medicine

1 17 Cupping in New York State — 1978; Historic review

David B. Stoeckle, M.D., and Rodman D. Carter, M.D., F.A.C.S.

121 Oliver Wendell Holmes, M.D. (1809-1894); Medical and literary knowledge intertwined Rosaly T. Kurth, Ph D., and Donald J. Kurth, M.D.

Contemporary Nutrition

140 Lactase Deficiency

Albert D. Newcomer, M.D.

	Editorials	126	Obituaries
		129	Medical News
12	Masthead	133	Annotations of Books Received
13	Information for Authors	136	Books Reviewed
15	Privacy and confidentiality William A. Bauman, M.D.	138	Letters to the Editor
16	Ghost medicine?	142	Month in Washington
	Mack Lipkin, M.D.		Index to Advertising
	General	11	Index to Advertisers
6	State Society Officers	149	Classified Advertising
7	Medical Meetings
8	Abstracts	159	WHAT GOES ON
10	Abstracts in Interlingua	163	Physicians’ Placement Opportunities

APRIL 25-26-27, 1980

MEDICAL SOCIETY OF THE STATE OF NEW YORK 1980 CME SPRING ASSEMBLY CME PROGRAMS (all CATEGORY I) • SCIENTIFIC AND TECHNICAL EXHIBITS The Rye Town Hilton (Town of Rye)

Port Chester, New York

Applications for Scientific Exhibits are available on request from: Thomas S. Bumbalo, M.D., Chairman, Scientific Exhibits Committee, MSSNY 420 Lakeville Road, Lake Success, N.Y. 11042. Applications will be accepted until February 15, 1980.

January 1980/New York State Journal of Medicine 5

Medical Society of the State of New York

Officers

G. Rehmi Denton, M.D., Albany George T. C. Way, Jr., M.D., Dutchess Ralph M. Schwartz, M.D., Kings Milton Rosenberg, M.D., Suffolk Victor J. Tofany, M.D., Monroe Allison B. Landolt, M.D., Westchester Warren A. Lapp, M.D., Kings John A. Finkbeiner, M.D., New York Joseph F. Shanaphy, M.D., Richmond Richard D. Eberle, M.D., Onondaga

Councilors

Term Expires 1980 John H. Carter, M.D., Albany Morton Kurtz, M.D., Queens Robert A. Mayers, M.D., Westchester Stanley A. Steckler, M.D., Suffolk

Term Expires 1981

Edgar P. Berry, M.D., New York

Joseph R. Fontanetta, M.D., Kings

George Lim, M.D., Oneida

Charles D. Sherman, Jr., M.D., Monroe

Term Expires 1982 CHARLES N. Aswad, M.D., Broome Kenneth H. Eckhert, M.D., Erie Sears E. Edwards, M.D., Nassau Daniel F. O’Keeffe, M.D., Warren

Trustees

LYNN R. Callin, M.D., Monroe, Chairman David Kershner, M.D., Kings Paul M. DeLuca, M.D., Broome George L. Collins, Jr., M.D., Erie Arthur H. DiEDRIGK, M.D., Westchester Ralph S. Emerson, M.D., Nassau Bernard J. Pisani, M I), New York

The Council is compost’d of the officers, I hr councilors, and the chairman of the Hoard of Trustees.

President Past-President President-Elect Vice-President Secretary

Assistant Secretary Treasurer

Assistant Treasurer Speaker Vice-Speaker

Headquarters

420 Lakeville Road, Lake Success, New York 11042 Tel. 516-488-6100

Staff

Henry I. Fineberg, M.D.

Executive Vice-President

Edward Siegel, M.D.

Deputy Executive Vice-President

Alfred A. Angrist, M.D., Director

Division of Scientific Publications and Editor of the New York State Journal of Medicine Directing Librarian

Guy D. Beaumont, Director

Division of Communications

J. RICHARD Burns, J.D. General Counsel

Eugene S. Dombrowski, M.B.A.

Director and Comptroller, Division of Finance

George W. Forrest, Jr., Director

Division of Management Services

Robert J. O’Connor, M.D., Director

Division of Medical Services

Bernard M. Jackson, C.L.U., Director

Division of Insurance and Membership Benefits

George J. Lawrence, Jr., M.D., Director

Division of Scientific Activities

Martin J. Tracey, J.D., Director

Governmental Affairs

I hma Erickson Executive Associate

6 New York State Journal of Me e/January 1980

Medical Meetings

Five-day postgraduate course

The ACP (American College of Physicians) will sponsor a five-day postgraduate course “Problems in Gastroen- terology: A Clinical and Pathological Approach,” Feb- ruary 4-8, 1980, in Keystone, Colorado.

The postgraduate session is one of approximately 45 to be sponsored by the ACP in the United States and Canada during the 1979-80 academic year. Their purpose is to give specialists in internal medicine and related fields an op- portunity to review basic information and to find out what is new in medical diagnosis and therapy.

The Colorado course entitled, “Problems in Gastroen- terology: A Clinical and Pathological Approach,” is being planned by Seymour M. Sabesin, M.D., from Memphis, Tennessee.

For Information and Registration: Registrar, Post-

graduate Courses, ACP, 4200 Pine Street, Philadelphia, PA 19104.

Seminars in oncology

Seminars in oncology, category 1 credit granted, will be presented by the Department of Medical Education, Peninsula Hospital Center. On February 6, Wednesday, at 3 p.m., Perlberg Auditorium, Marvin Kuschner, M.D., will discuss “Environmental Cancer.” On April 17, Thursday, at 3 p.m., in the Perlberg Auditorium, Ron Spiro, M.D., will discuss “Problems in Diagnosis of Head and Neck Cancer.” On June 11, Wednesday, in the Perlberg Auditorium, Ezra Greenspan, M.D., will present "Role of Chemotherapy in Treatment of GI Malignancies” at 3 p.m.

For further information contact: Bernard Lanter, M.D., Peninsula Hospital Center, 51-15 Beach Channel Drive, Far Rockaway, New York 11691; telephone: (212) 945- 7100, extension 377.

Announcement and invitation

The combined meeting of the New York Downstate I and II Regions of the American College of Physicians w ill be held on Tuesday, February 12, 1980, at the New York Hilton Hotel, 1335 Avenue of the Americas, New York, N.Y. 10019. The Fellows, Members, and Associates of the New York Downstate I and II Regions extend a special invitation to all interested physicians, especially those in residency and fellowship training, and hope that their schedules can be arranged so that as many as possible may attend the meeting. Six CME credits will be given.

The topics of this year’s meeting are the ABC of Hepa- titis and Gastrointestinal Causes of Pain. The program committee has assembled an interesting series of “Updates” on these two timely topics in the field of Gas- troenterology. The first session, beginning at 9 a.m., concerns the exciting rapidly developing advances in Viral Hepatitis. The audience will be able to hear directly from the newsmakers some of the promises of prevention and

Material for inclusion in the medical meetings section must be received eight weeks prior to publication date.

therapy. Saul Krugman, M.D., professor of pediatrics, New York University School of Medicine, will deliver the annual American College of Physicians Lecture on Vac- cines for Viral Hepatitis. The second session, at 2 p.m., describes the advances in the causation and relief of pain of gastrointestinal origin. The discoveries of new bio- chemical and physiological pathways have led to the evo- lution of revised concepts of gastrointestinal function and dysfunction.

For further information, call Fenton Schaffner, M.D., F.A.C.P., Governor, Downstate I, at (212) 369-6433.

Review course

A review course for the American College of Physicians’ Medical Knowledge Self-Assessment Program V (MKSAP V) will he held February 29-March 1, 1980, at the Main Auditorium, Arizona Health Sciences Center, Tucson.

The Tucson course (No. B-08) deals with hematology, cardiovascular diseases, pulmonary diseases, and ne- phrology.

The course director is Jay W. Smith, M.D., F.A.C.P., professor of medicine, University of Arizona College of Medicine.

Additional information about MKSAP V courses is available from the American College of Physicians, 4200 Pine Street, Philadelphia, PA 19104.

The New York Arthritis Foundation;

Long Island Division

Future meetings of the New York Arthritis Foundation, Long Island Division, 501 Walt Whitman Road, Melville, N.Y. 11746, will be held on February 26, March 25, April 22, May 20, and June 24.

Review course

A review course for the American College of Physicians’ Medical Knowledge Self-Assessment Program V (MKSAP V) will be held March 3-4, 1980, at the Basic Science Building, Main Auditorium, CMDNJ-Rutgers Medical School, Piscataway, N.J.

MKSAP V is a personal, self-contained, comprehensive program for updating a physicians’ knowledge in internal medicine.

Modern medicine changes rapidly, and physicians have to constantly update their knowledge to keep up with new developments. They receive credits in various categories for these efforts in continuing education. A physician who enrolls in MKSAP V receives a sequence of materials for home study and has the opportunity to attend special re- view courses in many cities around the country.

The Piscataway course deals with hematology, cardio- vascular diseases, pulmonary diseases, and nephrology.

The course directors are Hadley L. Conn, Jr., M.D., F.A.C.P., professor of medicine and chairman, Department of Medicine, CMDNJ-Rutgers Medical School, Piscata-

continued on pane 84

January 1980/New York State Journal of Medicine 7

Abstracts

Chandrankunnel, J. M., Saxanoff, S., Moss, S. W., Rosenzweig, P., Snyder, M., and Eisinger, R. P.: Effect of furosemide on HgC^; Induced acute renal failure in dogs, New York State J. Med. 80: 19 (Jan.) 1980.

Acute renal failure was induced with HgCl-2 (corrosive mercuric chloride) in six dogs and treated with furosemide. Magnification angiography demonstrated impaired cortical perfusion during renal failure and improvement in five after six days of cortical perfusion after furosemide. Im- proved peripheral perfusion, however, was associated with decreased caliber of intrarenal arteries. Urine flow did not consistently improve when cortical perfusion was en- hanced.

Wolkoff, A.: Bilirubin metabolism in obstructive jaun- dice, New York State J. Med. 80: 22 (Jan.) 1980.

The accumulation of bilirubin in the tissues of patients with liver disease is a frequent occurrence. This accounts for a long-standing interest in its metabolism. Biliary obstruction, in particular, is often associated with very high levels of serum bilirubin. To understand bilirubin me- tabolism in this pathologic condition, normal bilirubin metabolism must first be understood. Bilirubin, which is formed in the reticuloendothelial system, is a nonpolar molecule. In the normal state, it is removed from the cir- culation by the liver, conjugated with glucuronic acid to form a more polar compound, and excreted into bile. Al- though much of the biochemistry of these processes is known, this remains a field of ongoing investigation.

Berliner, S. D., and Wise, L.: Transversalis fascia her- nioplasty, New York State J. Med. 80: 25 (Jan.) 1980.

The socioeconomic implications of inguinal hernia dis- ability are enormous. The operation is the commonest major general surgical procedure performed and comprises 9.2 percent of all primary operations. Transversalis fascia hernioplasty, as popularized by E. E. Shouldice, is receiving increasing clinical trial in this country. It is anatomically correct because it bridges the direct defect between transversus abdominis and iliopubic tract. It is physio- logically sound because there is no tension on suture lines. Anesthesia is local, and rehabilitation is rapid. Our ex- perience is with 900 transversalis fascia hernioplasties followed for 12 to 88 months. This represents a mean follow-up of 50 ± 2.5 months (standard error of mean). There have been 16 recurrences, that is a 1.8 percent failure rate.

Seltzer, J. L., Gerson, J. I., and Grogono, A. W.: Hy- pertension in the perioperative period, New York State J. Med. 80: 29 (Jan.) 1980.

I he incidence of hypertension in the perioperative pe- riod was examined by a retrospective review of 1 ,038 elec- tive (nonopen heart) cases receiving general anesthesia. Hypertension occurred in either the operating room and/or the recovery room in 94 patients (9 percent). Those pa-

tients who had a preoperative history of hypertension had a significantly greater incidence of hypertensive episodes (21.5 percent). In patients with no history of hypertension, an elevated preoperative blood pressure was not associated with a greater incidence of hypertensive episodes. Bal- anced anesthesia (nitrous oxide, thiopental sodium, with or without narcotics, and muscle relaxants) was associated with a greater incidence of hypertension in patients with and without a history of hypertension.

Stewart, A. M.: Cancer effects of low-level radiation; theoretic considerations in compet ing causes of death, New York State J. Med. 80: 32 (Jan.) 1980.

Studies of delayed effects of radiation are reviewed. Surveys with negative findings for small-dose effects have usually relied on extrapolations from large-dose effects and ignored two causes of nonrecognition of cancers in these situations: latent period deaths due to noncancer effects of the radiation, and latent period deaths due to the con- ditions which necessitated the exposures. Surveys with positive findings for low-level radiation suggest that the end results of such doses, delivered at a slow rate, may be very different from the end result of much larger doses delivered at a fast rate and that the difference is related to cell death effects of the radiation.

Chekofsky, K. M., Scott, W. N., and Insall, J.: Total knee arthroplasty; update, New York State J. Med. 80: 36 (Jan.) 1980.

The abundance of total knee prostheses and their di- versity of design has presented a challenging problem to the orthopedist. Since the early nineteenth century dif- ferent approaches have been used toward replacement of the articulating surfaces of the knee. Our study included 48 patients undergoing 57 prosthetic operations; 80 percent of the patients were male and 20 percent were female. Osteoarthritis was the diagnosis in 89 percent of the cases, rheumatoid arthritis in 11 percent, and 5 were revisions of failed operations. The overall results were good or excel- lent in 90 percent of the cases. The complications were few and included: delayed wound healing (5 cases), pulmonary embolus (1), peroneal palsy (1), and hepatitis (1).

Constant, J.: Master two-step test; present status, New York State J. Med. 80: 39 (Jan.) 1980.

The Master two-step test can never give the information about cardiovascular fitness, cardiac function, or ar- rhythmias that can be gained from a progressive treadmill or bicycle stress test. In diagnosing the presence of coro- nary disease and suggesting the prognosis for future coro- nary events, however, the augmented double Master two- step compares favorably in both sensitivity and specificity, especially if attention is paid to the postexercise rate. Risk ratios have also been shown to he not significantly different for the double Master and progressive exercise tests.

continued on pane 11

8 New York State Journal of Med cine/January 1980

brand of

timetidine

How Supplied:

Pale green 300 mg. tablets bottles of 100 and Single Unit Packages of 100 (intended for institutional use only). Injection, 300 mg./2 ml., in single-dose vials and in S ml. multiple-dose vials, both in packages of 10.

a SmithKIine company

Abstracts in Interlingua

Chandrankunnel, J. M., Saxanoff, S., Moss, S. W., Rosenzweig, P., Snyder, M., e Eisinger, R. P.: Effecto del furosemida supra le HgCU; insufficientia renal acute inducite in canes, New York State J. Med. 80: 19 (Janu- ario) 1980.

Le insufficientia renal acute inducite con HgCU (chloride de mercurio corrosive) in 6 canes esseva tractate con fu- rosemida. Le angiographia magnificate demonstrava un perfusion cortical deteriorate durante le insufficientia renal e un melioramento de iste perfusion in 5 del canes depost de 6 dies de tractamento con furosemida. Nonobstante, iste melioramento esseva associate con un diminution del calibre del arterias intrarenal. Le fluxo urinari non mel- iorava de maniera uniforme quando le perfusion cortical esseva reforciate.

Wolkoff, A.: Metabolismo del bilirubina in le ictericia obstructive, New York State J. Med 80: 22 (Januario)

1980.

Le accumulation del bilirubina in le texitos del patientes con morbo hepatic es frequente, e ha causate interes, per longe tempore, in le metabolismo del bilirubina. Le ob- struction biliari, in particular, es frequentemente associate con nivelos multe elevate del bilirubina seric. Pro com- prender le metabolismo del bilirubina in iste morbo, debe primemente comprender se le metabolismo normal de iste composto. Le bilirubina que es formate in le systema re- ticuloendothelial, es un molecula non polar. In le stato normal, le bilirubina es separate del circulation per le fi- cato, conjugate con le acido glucoronic pro formar un composto plus polar, e depost es excretate con le bile. Nonobstante, multe es cognoscite supra iste processos biochemic que totavia sigue investigante se.

Berliner, S. D., e Wise, L.: Hernioplastia con le fascia transversalis, New York State J. Med. 80: 25 (Januario) 1980.

Le implications socio-economic del disabilitate per hernia inguinal es enorme. Le operation es le procedi- mento chirurgic plus commun e representa le 9.2 pro cento de omne primari operationes. Le hernioplastia con le fascia transversalis, popularisate per E. E. Shouldice, es recipiente de un crescente numero de studios clinic in iste pais. Iste procedimento es anatomiemente correcte per que copera directemente le orificio hernial inter le ab- dominis transversus e le tracto iliopubic. Le procedi- mento, etiam, es physiologic per que non ha tension in le lineas de sutura. Nostre experientia include 900 patientes operate de hernia usante le fascia transversalis e seguite de 12 a 18 menses postoperatorimente. Isto representa un promedio de observationes ulterior de 50 ±2.5 menses. Habeva 16 recurrentias que representa 1.8 pro cento de fallimentos.

Seltzer, J. L., Gerson, J. I., e Grogono, A. W.: Hyper- tension in le periodo perioperatori, New York State J. Med. 80: 29 (Januario) 1980.

Le frequentia del hypertension in le periodo periopera- tori esseva examinate mediante un revision retrospective de 1038 casos selective (non chirurgia a corde aperte) op- erate infra anesthesia general. Le hypertension esseva observate in le salla de operationes o in ille de recuperation in 94 patientes (9 pro cento). Le patientes con anteced- entes de hypertension preoperatori habeva un frequentia significativemente plus elevate de episodios hypertensive (21.5 pro cento). In le patientes sin antecedentes de hy- pertension, le elevation preoperatori del tension arterial non esseva associate con un major frequentia de episodios hypertensive. Le anesthesia equilibrate (oxido nitrose, thiopental sodic, con o sin narcoticos, e relaxantes mus- culari) esseva associate con un major frequentia de hy- pertension in patientes con o sin antecedentes de hyper- tension.

Stewart, A. M.: Effectos carcinogenic de radiationes de nivello basse; considerationes theoretic in competition con causas de morte, New York State J. Med. 80: 32 (Janu- ario) 1980.

Le studios supra le effectos tardive del radiationes es revistite. Le observationes con trovatos negative corres- pondente al effectos de parve doses de radiationes es gen- eralmente basate in extrapolationes relationate con le ef- fectos del radiationes a doses elevate, ignorante se duo causas de canceres non recognoscite: le periodos de la- tentia al morte debite al effecto non carcinogenic del ra- diationes, e illes debite al morbo mesme causante del ne- cessitate del exposition al radiationes. Le studios con trovatos positive relationate con le radiationes a nivello basse suggere que le resultatos final de tal doses, donate a velocitate lente, pote esser multe differente de illes rela- tionate con doses elevate facite a velocitate rapide, e que le differentia es relationate al morte cellulari debite al ra- diationes.

Chekofsky, K. M., Scott, W. N., e Insall, J.: Arthro- plastia total del genu; stato actual, New York State J. Med. 80: 36 (Januario) 1980.

Le abundantia de prosthesis total del genu e le diversi- tate del designos ha presentate un problema defiante pro le orthopedistas. Desde le principio del seculo 19, dif- ferente approaches ha essite usate pro le remplaciamento del superficies articulari del genu. Un studio includeva 48 patientes que habeva 57 operationes prosthetic; 80 pro cento de iste patientes esseva homines e 20 pro cento, feminas. Osteoarthritis esseva diagnosticate in 89 pro cento del casos, e arthritis rheumatoide in 1 1 pro cento, e 5 pro cento correspondeva a operationes fallite. Le re- sultato total esseva bon o excellente in 90 pro cento del casos. Le complicationes esseva parve e includeva retardo del cicatrisation del ferita operatori (5 casos), embolia pulmonari (1 caso); paralysis peroneal (1 caso) e hepatitis (1 caso).

continued on page 145

10 New York State Journal of Medicine/January 1980

Index to Advertisers

continued from pane 8

Methods of standardization by the use of a metronome without Master’s tables and of achieving maximum safety are described.

Fogler, R., and Weiner, E.: Multiple foci of colorectal carcinoma; argument for subtotal colectomy, New York State J. Med. 80: 47 (Jan.) 1980.

A review of 50 consecutive colon resections with refer- ence to the status of multiple malignant foci within the specimens is presented. Significant findings were that 80 percent of cases had associated benign polypoid lesions; 14 percent had invasive carcinoma within villous adenomas; 4 percent had superficial carcinoma within pedunculated polyps; 2 percent had an early mucosal carcinoma; and 14 percent had a second invasive carcinoma. Thus, a total of 84 percent of these patients had more than one focus of malignant disease within the resected colon. Preoperative evaluation with complete colonoscopy seems mandatory in any patient with a known malignant lesion within the colon. When indicated, subtotal colectomy preserving the rectum seems to be a reasonable resection of choice when more than one lesion is indicated.

Fontana, V. J.: Child abuse; prevention in teen-age parent, New Y’ork State J. Med. 80: 53 (Jan.) 1980.

Teen-age pregnancies have reached epidemic propor- tions. Adolescent parents are at high risk in the mal- treatment of children. At especially high risk are those adolescent parents who have themselves experienced maltreatment in early childhood. Suggested solutions to the child abuse problem include: (1) sessions on “good parenting" in elementary and high school classes; (2) perinatal assessment for high-risk characteristics for po- tential child abusers by hospital personnel; (3) community adolescent maternity health services; (4) preventive ser- vices, for example, shelters for pregnant teen-agers and infant day-care services; and (5) comprehensive education in human sexuality which includes learning to accept re- sponsibility for one’s actions.

Unproved hypothesis:

Sodium intake and hypertension

Observing that the scientific basis for what physicians recommend in the way of treatment will be increasingly demanded, the author examines 4 common assumptions: (1) increased sodium intake is related to hypertension; (2) tonsillectomy prevents respiratory disease; (3) alcoholism is a disease; and (4) dietary fat is related to atherosclerosis. On a strictly scientific basis, he points out, none of these hypotheses are proved. This does not mean, however, that they are rejected. The author’s main point is that perhaps more effort to find definitive evidence one way or the other would not be misspent. Dawber, T. R.: Unproved hy- potheses, New England J. Med. 299: 452 (Aug. 31) 1978.

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Geriatric Pharmaceutical Corp 52

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January 1980/New York State Journal of Medicine 11

New York State Journal of Medicine

420 Lakeville Road, Lake Success, New York 11042 Tel. 516 488-6100 Copyright 1980 by the Medical Society of the State of New York January 1980 Volume 80 Number 1.

“Dedicated to the continuing education of the physician ”

80th year of publication

Published monthly by the Medical Society of the State of New York

HENRY I. Fineberg, M.D., Executive Vice-President JULIUS E. STOLFI, M.D., Associate Editor

Alfred A. Angrist, M.D., Editor Elizabeth C. Smith, Managing Editor

Eugene S. Dombrowski, Business Manager

Alfred A. Angrist, M.D., ex officio

Anthony A. Albanese, Ph.D.

Lloyd T. Barnes, M.D. Jeremiah A. Barondess, M.D. Joshua A. Becker, M.D. Stuart Bondurant, M.D. Albert Cook, M.D. Seymour Cutler, M.D.

William Dock, M.D. Vincent P. Dole, M.D. Steven D. Douglas, M.D.

Aaron Feder, M.D. Vincent J. Fontana, M.D. Lytt I. Gardner, M.D.

PUBLICATION COMMITTEE Milton Gordon, M.D., Chairman Arthur H. Diedrick, M.D.

ASSOCIATE EDITORIAL BOARD

Carl Gemzell, M.D. Carl M. Harris, M.D. Alfred P. Ingegno, M.D. Ralph F. Jacox, M.D. Ira Snow Jones, M.D. Leslie A. Kuhn, M.D. George J. Lawrence, Jr., M.D. Harry M. LeVeen, M.D. Gerald P. Murphy, M.D. Stephen Nordlicht, M.D. Richard H. Orr, M.D. Edmund D. Pellegrino, M.D.

Julius E. Stolfi, M.D., ex officio

Ira Polisar, M.D. Paul Reznikoff, M.D. Howard A. Rusk, M.D. Henry Schutta, M.D. Joseph E. Snyder, M.D. Bjorn Thorbjarnarson, M.D. Vincent Tricomi, M.D. Robert Turell, M.D. James H. Wall, M.D. Robert P. Whalen, M.D. Frank M. Woolsey, Jr., M.D. Melvin D. Yahr, M.D. Alex W. Young, Jr., M.D.

General Information

Published monthly with the Minutes of the House of Delegates added in February. Editorial, circulation, and publication offices: 420 Lakeville Road, Lake Success, New York 1 1042. Copyright 1980 by the Medical Society of the State of New York.

Rates. The subscription rate is $3.50 per year payable in advance. Foreign subscriptions: $3.50 subscription plus $1.50 for mailing. Single copies $0.50. ($3.50 of each member’s dues is applied as a subscription for this publication.) Back issues will he supplied for the past five years at the single copy rate when available. Back issues

prior to 1962 are $2.00 per copy; from 1961 to 1971, $1.00 a copy.

CHANGE OF ADDRESS. Notice should be sent to the circulation office, 420 Lakeville Road, Lake Success, New York 1 1042. Old and new addresses should be included as well as a statement whether or not change is permanent. Six weeks is required to effect a change of address.

Advertising Representatives: United Media Asso- ciates, Inc., 16 Bruce Park Avenue, Greenwich, Connecticut 06830. Telephone: 203-661-9702.

12

Information for Authors

Manuscripts. Manuscripts will be accepted for consideration with the understanding that they are original, have never before been published nor submitted elsewhere, and are contributed solely to the Nkw York State Journal of Medicine. Original, a copy, and abstract must be included. Address manuscripts to Editor, New York State Journal of Medicine, 420 Lakeville Road, Lake Success, New York 1 1042.

Rejected manuscripts are returned by regular mail. Accepted manuscripts become the permanent property of the JOURNAL and may not be published elsewhere without written permission from both the author and the JOURNAL. The JOURNAL is not re- sponsible for loss of manuscripts through circum- stances that are beyond its control.

Copyright. Material that is published in the New York State Journal of Medicine is protected by copyright. In view of The Copy- right Revision Act of 1976, transmittal letters to the editor should contain the following language: “In consideration of the Medical Society of the State of New York taking action in reviewing and editing my submission entitled (here give title), the author(s) undersigned hereby trans- fers, assigns, or otherwise conveys all copyright ownership to the MSSNY in the event that such work is published by the MSSNY.” We regret that transmittal letters not containing the foregoing language signed by all authors of the submission will necessitate delay in review of the manuscript.

Specifications: Manuscripts must be original typed copy (not all capitals), not carbons, on 8V2- by-ll-inch firm typewriter paper, double spaced throughout (including text, case reports, legends, tables, and references), with margins of at least IV2 inches. Subheads should be inserted at reasonable intervals to break the typographic monotony of lengthy texts. A carbon copy is to be retained by the author. The manuscript should include the title of the article (titles are best brief and concise), the full name of the author (or authors) with degrees, aca- demic or professional titles, affiliations, complete addresses, and any institutional or other credits. Pages should be numbered consecutively. Uncom- mon and parochial or esoteric abbreviations if used must be explained and the generic as well as the trade names of pharmaceutical products given. Italics are rarely used.

Tables: Each table should be typed on a separate sheet of paper, be numbered consecutively, have a brief descriptive title, and its position in text indi- cated. Take care that columns add up correctly and that statistics are consistent in both tables and text.

Permissions: When material is reproduced from other sources, full credit must be given to both author and publisher and written permission from these sources included. Where work is reported from a

governmental service or institution, clearance by requisite authority should accompany the manu- script.

References: References should be limited to

those citations noted in the text. A complete review of the literature is rarely desirable. The references must be typed double-spaced and are to be numbered as they appear consecutively in text, with their po- sitions in the text indicated. An alphabetized bib- liography is used only when the listing is of books suggested merely for supplementary reading. All references must be checked to assure complete ac- curacy (an inaccurate reference is useless to the reader). Each journal reference must include au- thors) and initials, complete title of article, name of publication, volume, first page of article, and date. Complete dates (month, day, as well as year) are to be included with all references that have appeared within the last three years. Include with book ref- erences name of author(s) and/or editor(s) with ini- tials, title of book, edition, location, publisher, year, volume if given, and page. If reference is to a chapter within a book, include the author of the chapter, if this is not the same as the author of the book, and the title of the chapter, if any.

Illustrations: Authors are urged to use the ser- vices of professional illustrators and photographers when possible. Drawings and charts should always be done in black ink on white paper. Clear, glossy photographs, black on white, should be submitted and such illustrations numbered consecutively and their positions indicated in text. Original magnifi- cations should be noted. Please do not deface il- lustrations by writing on front or back, nor should they be scotch-taped or pasted to paper. They may be pasted carefully on cardboard. The figure num- ber, indication of the top, and the author’s name are to be attached to the back of each illustration. Legends for illustrations should be typewritten in a single list, with numbers corresponding to those on photographs and drawings. Recognizable photo- graphs of patients are to be masked and should carry with them written permission for publication. Special arrangements must be made with the Editor for excessive illustrations or color plates.

Responsibility. Manuscripts are subject to editorial modification and such revisions as bring them into conformity with JOURNAL style. How- ever, neither the editors nor the publishers nor the Medical Society of the State of New York will accept responsibility for statements made or opinions ex- pressed by any contributor in any article or feature published in the pages of the JOURNAL.

When revisions and alterations, not on the original copy, are made by authors on the galleys sent them for corrections, these are chargeable to the au- thors.

Reprints. An order form for reprints is at- tached to the galleys returned to authors for correc- tion and approval.

January 1980/New York State Journal of Medicine 13

km you prescribing a regimen of

P AM ASPIRIN EVERY DAY?

BUFFERIN' WAS SIGNIFICANTLY BETTER TOLERATED IN LONG-TERM ADMINISTRATI

In a particular series of 14-day gastric tolerance studies among 182 normal subjects, 49% suffered G.I. upset from plain aspirin. Most of these subjects took BUFFERIN without discomfort.

Subjects in these controlled trials, which utilized a crossover design, were given Bufferin and Bayer " Aspirin for two weeks each in a balanced order of administration. The cumulative gastric tolerance superiority of Bufferin over plain aspirin was significant (P= < .01 ) from day one and persisting through each day of the study This superiority for an extended period could be of particular

importance to patients on repeat-dosage schedules.

For full aspirin benefits, together with excellent gastric tolerance, Bufferin should be your brand of choice. If you are prescribing a regimented daily dose of aspirin, prescribe Bufferin— the repeat-dosage aspirin — instead.

BUFFERIN: The Repeat-Dosage Aspirin.

For complimentary samples of Bufferin and Arthritis Strength Bufferin, please write: Bufferin, RO. Box 65, Elizabeth, New Jersey 07207. Composition Each Bufferin tablet contains aspirin 324 mg. and the antacid Di-Alminate® (Bristol-Myers’ brand of Aluminum Glycinate 48 6 mg and Magnesium Carbonate 97 2 mg.). ©1978, Bristol-Myers Co.

Editorials

Privacy and confidentiality

With regard to confidentiality, we physicians continue to endorse the 2,000 year-old Hippocratic Oath, even though it antedates modern medical practice, computers, and third parties involved with healthcare. The Oath declares: “All that may come to my knowledge . . . which ought not to be spread abroad, I will keep secret ... .” The Oath leaves

it to practitioners to determine which information must be kept secret. Some may argue that this part of the Oath is obsolete because circumstances are different today. However, it is difficult to support this argument.

Need for confidentiality

Despite scientific and technical advances and the changes in our social, political, and economic envi- ronment that have occurred since Hippocrates, physicians still depend on information obtained from their patients. Patients must feel free to provide accurate health data about themselves to enable their physicians to arrive at appropriate medical decisions. Often patients disclose sensitive information which, if made public, could damage their reputations. They expect their physicians to keep such personal information confidential unless disclosure is for the patient’s direct benefit. To act otherwise, physicians would jeopardize patient relationships, lose the lat- ter’s confidence, and become liable for unauthorized disclosure. Patients realize that if they withhold or falsify historical data, their physician will be misled and render inappropriate or possibly detrimental care.

Third parties (insurers, attorneys, health-care administrators, researchers, and health agencies), however, need medical data to fulfill their functions. Many third-party agencies have taken steps to safeguard sensitive medical data. Because of the rapid growth of information technology, they have come to rely heavily on computers and copying equipment to gather and transfer the data.

Controls

Aware that automation of medical data could fa- cilitate abuses, the Committee on Information Technology of the Medical Society of the State of New York (formerly the Committee on Medical Data Processing) turned its attention in 1970 to issues of confidentiality. The committee recognized both the ease with which primary patient information could

be copied and t ransferred and the difficulty of com- pletely safeguarding the stored data. Committee members reviewed existing policies and procedures of hospital medical records and information de- partments, and learned that these departments ad- hered stringently to codes of ethics on confidentiality as related to medical records. Custom and regula- tions prohibited disclosure of the contents except to those who had the right to know. Medical infor- mation could be released outside the hospital only with patient consent or where medical necessity could be demonstrated. Hospital administrators were legally bound to adhere to these principles. These controls have minimized disclosure of confi- dential medical data. The committee endorsed these policies and procedures and recommended that they be extended to computer-based systems.

At about the same time, the computer industry began to enhance methods to protect computer- stored data. During the ensuing decade, corporate espionage, bugging, shredding, credit bureau abuse, the Privacy Act, and the Sunshine Law provided impetus to the computer industry’s development of security techniques.

The publicity given to the private health problems of Messrs. Eagelton, Ellsberg, and former District Attorney Hogan created an outcry of protest, as did the release of the names of women who had had abortions, names of applicants rejected for life in- surance, and lists of patients suffering from epilepsy. Westin* cites additional cases where threats to the security of personal health data would undermine basic rights of citizens.

The Committee on Information Technology, in its annual reports to MSSNY (Medical Society of the State of New York), has presented its own views and recommendations. In 1977, the MSSNY cospon- sored a joint task force on computerized medical records which has evolved into the New York State Association for Confidentiality of Health Data, Inc. Members of the committee have provided input to other deliberations related to confidentiality. At the 1978 annual meeting of MSSNY’s House of Dele- gates, the committee endorsed Resolution 78-65 opposing disclosure to the State of New York De- partment of Health of patient identification except with informed consent and with a statement of the

* Westin, A. F.: Computers, Health Records and Citizens

Rights, Monograph 157, U.S. Department of Commerce, Bureau of Standards, 1976.

January 1980/New York State Journal of Medicine 15

purpose for which data will be used. The committee supports the regulations of the Department of Health, Education, and Welfare to protect confi- dential health data of the National Center for Health Statistics and of the Professional Standards Review Organizations. We are following proposed Federal and New York State legislation to limit availability of confidential, individually identified, medical in- formation.

Recommendations

As observers and participants in discourses con- cerning confidential medical data, the committee has developed certain concepts and has made recom- mendations. We recognize that physicians acquire primary health information from their patients and, as guardians, they are obliged to safeguard and con- trol access to this information. They may disclose information only for the patient’s benefit; for other purposes, they should remove all personal identifiers prior to disclosure, or obtain prior consent from the patient. Only by court order in cases of alleged criminal activities can they be required to supply information without patient consent. The principles and procedures for data protection apply to infor- mation in any form: written, computerized, taped, or remembered.

Ghost medicine?*

Last year, the TV show “Sixty Minutes” portrayed an episode at the Strong Memorial Hospital in which a surgical patient stated his belief that the chief surgeon had operated on him, while actually it was the surgical resident. This vignette revealed, in a sense, the old “ghost surgery” in reverse. Instead of a better-trained surgeon than the one the patient had engaged doing the operation, a less-experienced surgeon operated. Of course, surgeons in training can become competent only by operating, preferably under close supervision. The objection to both kinds of ghost surgery is the deception of the patient, whatever the motive.

A somewhat similar practice on the medical units of many of our teaching hospitals, which might be called “ghost medicine,” forbids the patient’s per- sonal physician to write orders; only the intern or resident may do so. Though it has attracted little attention or comment, this practice deserves scruti- ny, as it has unfortunate effects.

House staff supervisors try to justify the exclusion of the personal physician by saying that residents

' Reprinted from The Pharos of Alpha Omega Alpha, Summer 1979, vol. 42, number 9, page 30, with permission of the Editor and the Author.

A dilemma has arisen because we physicians are licensed and responsible to society. Occasionally agency requirements conflict with our patient’s needs. In such cases, we must decide which of the two masters we will serve; we should do so on a case-by-case basis, bearing in mind our moral and legal obligations. We could resolve the dilemma by not possessing or by always withholding sensitive data; or we could release personal information only if we know exactly what uses would be made of the data.

Conclusion

In the final analysis, we must exercise our own judgment and act responsibly, measuring the needs of our patients against those of society, and always trying to preserve our relationship with our patients. If we fail, we can lose our most valuable source of medical information, the patient himself. Now is the time to let our voices be heard. Let our patients know how we feel, and remember to keep secret that which ought not to be spread abroad.

WILLIAM A. BAUMAN, M.D.

( Chairman , Committee on Information Technology in Medicine, Medical Society of the State of New York, Lake Success) 326 West 42nd Street New York, N. Y. 10036

must learn to take responsibility and can only learn by taking responsibility; and, further, that residents insist on this practice and will choose other institu- tions if this privilege is denied. Residents concur, saying that having total responsibility is the best way to learn. This is open to question. In foregoing the opportunity to observe experienced clinicians in ac- tion, house officers are compelled to learn partly by making the mistakes the experienced have learned to avoid. A fortune cookie message advised, “Learn from others’ mistakes. There isn’t time to make them all yourself.”

The first rule of responsibility for patients is that their welfare take precedence over every other con- sideration. Do hospital authorities, in depriving patients of the care of their own doctors, give house officers a contradictory message, namely, that their training is as important, or more so, than the pa- tient’s peace of mind? Although medical students are exhorted to pay close attention to the importance of the patient-physician relationship, they too ob- serve t he primary, personal physician being excluded from the care of the hospitalized patient, who then has no single trusted and familiar physician to whom to turn.

16 New York State Journal of Medicine/January 1980

The personal physician is far more likely to be aware of the psychologic and social factors sur- rounding his patient’s illness then is the full-time academic clinician, who, because of his interest in teaching and research, is apt to have mostly brief, episodic, rather than long-term contact with a large number of patients. Medical care can become fo- cused on the disease process, with neglect of other aspects of the illness. Patients are exposed to un- necessary procedures, often expensive and frequently hazardous. Paul Beeson has commented, “Anyone who makes ward rounds today cannot fail to be im- pressed by the significant fraction of the work de- voted to counteracting unwanted effects of diagnostic or therapeutic procedures.” House officers tend to feel inadequate if any other physician can think of a test not yet carried out, no matter how obscure, and will use any new procedure that might conceivably add another bit of information, needed or not. In many hospitals, the patient needs an advocate-pro- tector, a function best served by the personal physi- cian.

That the personal physician assumes ethical and legal responsibility for his private patient in the hospital should be clearly understood by everyone concerned with that patient. The hospital staff is responsible for weeding out incompetent attending physicians or insisting on supervising any who un- dertake treatment beyond their competence. In many hospitals general practitioners may perform only selected procedures.

I can think of few devices more likely to cause widespread loss of confidence among patients than to allow the resident on duty to take complete charge, only to replace him the next week or month by an- other resident who may not know the cases thor- oughly. To be sure, many residents are well in- formed, conscientious, cooperative, tactful, humble,

and eager to learn. Some are not. Residents give similar descriptions of some attending physicians. But is it fair to the patient to insist that control of his or her care be surrendered to the house staff re- gardless of the ability of whichever resident happens to be on duty? Has any veteran attending physician who has thus surrendered control of his patient not witnessed bad practice resulting from a house offi- cer’s lack of experience, or judgment, or knowledge of the patient?

Much has been said about honest dealing with patients. How many teaching hospitals would be willing to present these facts to incoming patients: a member of our house staff will be in direct charge of your care. The resident will be one to four years out of medical school. He or she may be an excellent doctor or not. You will have no voice in deciding which one will take care of you, no matter whether you like or dislike, trust or distrust him or her. Your personal physician will not be allowed to prescribe tests or treatment for you. Can you hear the outcry if these practices were to become public knowledge? Is it time they were amended?

I suggest that the senior person, preferably the personal physician, remain in charge, assigning as much responsibility to residents as they are ready for. He could countermand orders, which usually should be written by the house staff, but be expected to ex- plain why. Irreconcilable differences of opinion would be referred to the chief of service or his sur- rogates, preferably the most respected and experi- enced staff members available. This plan seems to me to promise better patient care and better teaching.

MACK LIPKIN, M.D.

The Commonwealth Fund New York, New York

January 1980/New York State Journal of Medicine 17

only

BRONKODYL

brand of

theophylline, USP (anhydrous)

BREON LABORATORIES INC.

90 Park Avenue. New York. N Y 10016

is 100% micro-pulverized, anhydrous theophylline, in capsules

Bioavailability equal to an elixir1 Achieves blood levels rapidly1

1 Tinkelman, D.G . Carroll. M S . Vanderpool. G . Jones. M . The bioavailability of theophylline in elixir and micro-pulverized forms. Medical Challenge 10 24-26. 1978.

BRAND OF THEOPHYLLINE, USP (ANHYDROUS)

Before prescribing, please consult complete prescribing information, a sum- mary of which follows:

For relief and/or prevention of bronchospasm associated with bronchial asthma, chronic bronchitis and emphysema

Hypersensitivity to any of

its components

Theophylline should be used with caution in children and in others who are currently taking bronchodilator products, especially in rectal dosage form, which may contain theophylline or related drugs

Status asthmaticus is a medical emergency Addi- tion of corticosteroids and other medications to bronchodilator therapy may be required Serum theophylline levels should be monitored at appropriate intervals for dosage adjustment High serum levels of theophylline and resultant toxicity may occur with conventional doses in patients with decreased theophylline clearance as found with cardiac failure, liver disease, chronic obstructive pulmonary disease, and in geriatric patients Early signs of theophylline toxicity, such as nausea and restlessness may not occur prior to convul- sions or ventricular arrhythmias Pre-existing

arrhythmias may be worsened by theophylline

Theophylline safety in preg- nancy has not been established Use of Bronkodyl during lactation or in women of childbearing poten- tial requires that possible benefits of the drug be weighed against possible hazards to fetus or child Smokers may require larger doses of theophylline because of a shorter half-life in these patients

Theophylline should not be administered con- currently with other xanthines Caution should be observed in patients with cardiac disease, severe hypoxemia, hypertension, hyperthyroidism, acute myocardial injury, cor pulmonale, congestive heart failure, liver disease, peptic ulcer, and in the elderly and neonates Pa- tients with congestive heart failure in particular may have markedly prolonged serum half-lives of theophylline

Most adverse reactions to theophylline are seen with serum levels exceed- ing the therapeutic range. Gastrointestinal: nausea, vomiting, epigastric pain, hematemesis. diarrhea CNS: headache, irritability, restlessness, insomnia, reflex hyperexcitability, muscle twitching, clonic and tonic generalized convulsions Cardiovascular: palpitations, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, ventricular arrhythmias which may be life-threatening Respir- atory tachypnea Renal: diuresis, albuminuria Other hyperglycemia, inappropriate ADH

secretion

Toxic synergism with ephedrine and other sympathomimetic bronchodilators may occur.

A If potential oral overdose is established and seizure has not occurred: 1) Induce vomiting

2) Administer a cathartic. 3) Administer ac- tivated charcoal

B If patient is having a seizure: 1) Establish an airway 2) Administer O2 3) Treat the seizure with intravenous diazepam, 0 1 to 0.3 mg/kg up to 10 mg 4) Monitor vital signs, maintain blood pres- sure and provide adequate hydration

C Post-seizure coma: 1) Maintain airway and oxy- genation 2) If a result of oral medication, follow above recommendations to prevent absorption of drug, but intubation and lavage will have to be performed instead of inducing emesis, and the cathartic and charcoal will need to be intro- duced via a large bore gastric lavage tube

3) Continue to provide full supportive care and adequate hydration while waiting for drug to be metabolized In general, the drug is metabolized sufficiently rapidly so as to not warrant consider- ation of dialysis

Bronkodyl 100 mg,

brown and white capsules in 100's Code 1831

Bronkodyl 200 mg,

green and white capsules in 100's Code 1833

Scientific Articles

Effect of Furosemide on Acute Renal Failure in Dogs

Induced by mercuric chloride

Acute renal failure was induced with HgCl2 (corrosive mercuric chloride ) in six dogs and treated with fu- rosemide. Magnification angiography demonstrated impaired cortical perfusion during renal failure and improvement in five after six days of cortical perfu- sion with furosemide. Improved peripheral perfu- sion, however, was associated with decreased caliber of intrarenal arteries. Urine flow did not consis- tently improve when cortical perfusion was en- hanced.

JOSEPH M. CHANDRANKUNNEL, M.D. SEYMOUR SAXANOFF, M.D.

SANDRA W. MOSS, M.D.

PHILIP ROSENZWEIG, M.D.

MILLICENT SNYDER ROBERT P. EISINGER, M.D.

Piscataway, New Jersey

From the Department of Medicine, College of Medicine and Dentistry of New Jersey, Rutgers Medical School

Reduction of renal cortical blood flow is a feature of acute renal failure of various etiologies.1 Hence, it seems possible that restoration of cortical perfusion may favorably alter the course of this condition. Since furosemide increases cortical blood flow, its role in the therapy of acute renal failure has been scrutinized.- Some investigators have suggested that treatment with furosemide may indeed significantly alter the course of acute renal failure.3’4 Other data, however, in an animal model of ischemic acute renal failure, indicate that furosemide, while increasing urine flow and sodium excretion, does not improve urea clearance.5 Epstein, Schneider, and Befeler6 studied the effect of intrarenal infusion of furosemide on renal function and intrarenal blood flow patterns, and concluded that furosemide administration offers no benefit in the course of acute renal failure or on intrarenal hemodynamics. Since radioactive mi- crospheres may not accurately evaluate regional renal blood flow and xenon washout curves do not specify what factors have affected flow, we elected to observe directly the action of furosemide on renal vasculature in acute renal failure by using magnification angi- ography; this would allow visual appraisal of the drug’s effects on intrarenal vascular caliber.8

Methods

Six mongrel dogs weighing 19 to 27 kg. were de- prived of water for 24 hours, and then injected in- travenously with HgCL (mercuric chloride) in a dose of 4.5 mg. per kilogram. Prior to injection blood was withdrawn from a foreleg vein for determination of BUN (blood urea nitrogen) and creatinine. For the next 48 hours the dogs were kept in a metabolic cage, and urine flow was monitored. After 48 hours, BUN and creatinine again were determined. Anesthesia was then induced by intravenous pentobarbital so- dium injection (Nembutal). A polyethylene catheter was placed in a foreleg vein for administration of drugs and fluids. The bladder was catheterized to monitor urine flow. A catheter was introduced into a renal artery under fluoroscopic guidance using the Seldinger technique. The dog was placed on an ad- justable plastic cradle to obtain maximum magnifi- cation. Ten ml. of diatrizoate meglumine and dia- trizoate sodium injection (Renografin-76) was then given intrarenally using a cordis automatic injector, and two films were exposed per second for three seconds. This procedure was repeated in three dogs. From 80 to 100 mg. furosemide (Lasix) were then administered intravenously. After a delay of 45 minutes to 1 hour, magnification angiography was repeated.

Results

All six dogs developed oliguria and significant az- otemia. Prior to injection of HgCU blood urea ni- trogen was from 9 to 19 mg. per 100 ml. (mean 14 mg. per 100 ml.) and serum creatinine from 0.9 to 1.2 mg. per 100 ml. (mean 1 mg. per 100 ml.). Forty-eight hours after administration of the toxin, urine flow

January 1980/New York State Journal of Medicine 19

TABLE I. Effects of furosemide on acute renal failure in six dogs studied with magnification angiography

Urine Flow

BUN , — Serum Creatinine — N (milliliter per minute)

Dog	(mg. per 100 ml.) Pre Post HgCl2 HgCl2	(HgCl2, mg. per 100 ml.) Pre 48 Hours HgCl2 Post HgCl2	Post 48 Hours HgCl2	Post Furosemide	r Magnification Angiography Pre Furosemide Post Furosemide
1	13	42	1.1	3.6	0.3	0	Decreased cortical perfusion	Increased cortical perfusion, decreased diameter of intra- renal vessels.
2	15	52	0.9	3.6	0.2	0	Decreased cortical perfusion	Decreased cortical perfusion. Increased diameter of interlobar, interlobular, and arcuate vessels.
3	19	75	1.0	4.4	0.16	2.4	Decreased cortical perfusion	Increased cortical perfusion. Decreased caliber of arcuate, and interlobular vessels.
4	9	52	1.0	3.7	0.06	4.8	Decreased cortical perfusion	Increased cortical perfusion. Decreased caliber of interlobular and arcuate vessels.
5	12	70	0.9	3.8	0.3	1.06	Decreased cortical perfusion	Increased cortical perfusion. Decreased caliber of interlobular and arcuate vessels.
6	15	103	1.2	7	0.2	0	Decreased	Increased cortical perfusion.

cortical Decreased caliber of intrarenal

perfusion vessels.

FIGURE 1. Magnification angiogram from dog 1 in acute renal failure.

ranged from 0.06 to 0.3 ml. (mean 0.2 ml.) per minute; blood urea nitrogen was from 42 to 103 mg. per 100

ml. (mean 66 mg. per 100 ml.), and creatinine was from 3.6 to 7 mg. per 100 ml. (mean 4.4 mg. per 100 ml.). With the injection of furosemide, urine flow improved in three of the six dogs (Table I).

Findings on magnification angiography confirmed that all six dogs had developed significant cortical ischemia (Fig. 1). No change in perfusion pattern was observed merely with repeated contrast injec- tions into the renal artery in three dogs. Systemic, intravenous administration of furosemide, however, improved the peripheral cortical perfusion pattern in five dogs. Nevertheless, the intrarenal vessels — interlobar, interlobular, and arcuate arteries — ap- peared to narrow (Fig. 2). In the remaining dog, cortical perfusion decreased further following in- jection of furosemide, while intrarenal arteries di- lated. There was increased flow of urine in three of the five dogs with improved cortical perfusion. However, the remaining two dogs continued to be oliguric despite similar enhancement of cortical blood flow.

Comment

Cantarovich et al., 3 and Fries et al.4 have reported that high doses of furosemide have a favorable effect on the clinical course of acute renal failure. Epstein et al.6 examined the effect of intrarenal administra- tion of furosemide on acute renal failure in man, and found that the drug did not modify the clinical course of this condition or alter the renal hemodynamics.

We have examined the vasculature of various compartments of the dog kidney by magnification angiography. Intravenous injections of furosemide improved cortical perfusion in five of the six dogs with acute renal failure, despite demonstrable nar- rowing of the interlobar, interlobular, and arcuate arteries. These changes could not be attributed to the contrast injections alone. These findings are

20 New York Stale Journal of Medicine/January 1980

FIGURE 2. Magnification angiogram from same dog after administration of furosemide.

thus consistent with those of Birtch et al.2 who found varying effects of furosemide on different vascular levels in normal dogs. Although urine flow at times increased with improved cortical perfusion, it did not regularly do so.

Ludens et al.8 have suggested that the capacity of furosemide to enhance renal blood flow could be re- lated to the initial resistance of certain vascular segments; the higher the initial resistance, the greater the effect of this agent on blood flow. This concept

might account for disparate effects on different an- imals, and also different effects on different levels of the renal vascular tree.

Summary

Magnification angiography was used to study the renal vasculature in canine acute renal failure, in- duced by HgCl2 (mercuric chloride) and treated with furosemide. All dogs developed cortical ischemia and acute renal failure. In five of six dogs adminis- tration of furosemide enhanced cortical perfusion, while interlobar, arcuate and interlobular vessels narrowed. In the remaining dog cortical perfusion further decreased after injection of furosemide, while larger intrarenal vessels appeared to dilate. Urine flow did not consistently improve with enhancement of cortical perfusion. Since furosemide may improve cortical perfusion without enhancing urine (low, it appears either that its salutary effect in acute renal failure may not be mediated solely via its vasoactive properties, or that additional factors intervene to sustain acute renal failure once it is established by cortical hypoperfusion.

Division of Nephrology College of Medicine & Dentistry of New Jersey Rutgers Medical School Piscataway, New Jersey 08854 (DR. EISINGER)

References

1. Hollenberg, N. K., et al.: Acute oliguric renal failure in man: evidence for preferential renal cortical ischemia, Medicine 47: 455 (1968).

2. Birtch. A. G., Zakheim, R. M., Jones, L. G., and Barger, A. C.: Redistribution of renal blood flow produced by furosemide and ethacrynic acid. Circulation Res. 21: 869 ( 1967).

3. Cantarovich, F., et al.: Furosemide in high doses in the treatment of acute renal failure. Postgrad. Med. suppl. 47: 13 (1971).

4. Fries, D., Pozet, N., Dubois, N., and Trager, J.: The use of large doses of furosemide in acute renal failure, ibid. supp. 47: 18 (1971).

5. Papadimitriou, M., Milionis, A., Sakellariou, G., and Met- axas, P.: Effect of furosemide on acute ischemic renal failure in the dog, Nephron 20: 157 (Mar.) 1978.

6. Epstein, M., Schneider, N. S., and Befeler, B.: Effect of intrarenal furosemide on renal function and intrarenal hemody- namics in acute renal failure, Am. J. Med. 58: 510 (1975).

7. Bankir, L., Tan, M. M., and Griinfeld, J. P.: Measurement of glomerular blood flow in rabbits and rats: Erroneous findings with 15-^m microspheres, Kidney Int. 15: 126 (Feb.) 1979.

8. Ludens, J. H., Hook, J. B., Brody, M. J., and Williamson, H. E.: Enhancement of renal blood flow by furosemide, J. Phar- macol. & Exper. Therap. 163: 456 (1968).

January 1980/New York State Journal of Medicine 21

Bilirubin Metabolism in Obstructive Jaundice *

ALLAN W. WOLKOFF, M.D.

The Bronx, New York

From the Department of Medicine and Liver, Research Center, Albert Einstein College of Medicine

Results of studies of bilirubin metabolism may suggest, but are never diagnostic of, biliary obstruc- tion in a jaundiced patient. Bilirubin is a yellow pigment. Its accumulation in tissues is frequent in patients with liver disease, and this accounts for long-standing interest in its metabolism. To un- derstand bilirubin metabolism in biliary obstruction, normal bilirubin metabolism must first be under- stood.

Bilirubin metabolism

Clinical chemistry. In normal individuals, bil- irubin is excreted almost exclusively by the liver which converts the nonpolar bilirubin molecule into a water-soluble conjugate with glucuronic acid. The diazo (van den Bergh) reaction is the procedure used to measure serum bilirubin in most clinical labora- tories. Conjugated bilirubin is water soluble and reacts with the diazo reagent almost immediately, resulting in a purple product; this is the direct reac- tion. Unconjugated bilirubin is minimally soluble in aqueous solution and reacts slowly with the diazo reagent. If an accelerator, such as alcohol or caffeine, is added to the diazo mixture, unconjugated as well as conjugated bilirubin quickly reacts. When ac- celerator is added, total bilirubin, both conjugated and unconjugated, is quantitated. If the direct re- action is performed first to quantitate conjugated bilirubin, and this result is subtracted from total bilirubin obtained using accelerator, the amount of indirect, or unconjugated, bilirubin is quantitated. Normally, there is no conjugated bilirubin in serum as determined by sensitive biochemical tests. The diazo reaction, however, may show a small amount of direct reaction, which accounts for 10 percent or less of total bilirubin.1

Annual Alberl F. It. Andresen Memorial Lecture, presented at the 172nd Annual Meeting of the Medical Society of the State of New York, New York ( ity, Section on Gastroenterology and Colon and Rectal Surgery, Wednesday, October 25, 1978.

* Supported by the National Institutes of Health Grants AM28026, AM02019, and AM 17702.

When conjugated and total bilirubin levels are elevated, conjugated hyperbilirubinemia is said to be present. There are many disorders of hepatobiliary function which are manifested by conjugated hy- perbilirubinemia. These disorders may be primarily intrahepatic, for example, hepatitis, Dubin-Johnson syndrome, drug cholestasis, primary biliary cirrhosis, or intrahepatic biliary atresia. Conjugated hyper- bilirubinemia may also result from lesions of the extrahepatic biliary tree, which include sclerosing cholangitis, cholangiocarcinoma, pancreatic carci- noma, and cholelithiasis. There is no simple bio- chemical differentiation between intra- and extra- hepatic jaundice. Similar patterns of serum-con- jugated and unconjugated bilirubin may be seen in all these disorders.

Formation. Bilirubin is formed from heme. It is derived predominantly from hemoglobin released from senescent red cells, and is synthesized in the reticuloendothelial system. In hemolysis, or pre- mature destruction of red cells, bilirubin production is increased, and this may result in unconjugated hyperbilirubinemia in an otherwise normal individ- ual. If hemolysis occurs in a patient with obstructive jaundice, serum bilirubin may reach very high levels. In this situation, conjugated bilirubin regurgAate? from the liver cell back into plasma, resulting in in- creased serum-conjugated as well as unconjugated bilirubin.1-3

After formation, bilirubin is released into the pe- ripheral circulation. As noted, it is a nonpolar mol- ecule and is virtually insoluble in aqueous solutions at physiologic pH. In plasma, bilirubin binds strongly to albumin, allowing it to circulate without precipitating in the vascular system. It is this binding of bilirubin to albumin which largely pre- vents its permeation into organs other than the liver. This is especially important in neonates who may be at risk for the development of kernicterus, or biliru- bin encephalopathy.

Hepatic metabolism. Bilirubin is metabolized almost exclusively by the liver cell. The normal pathway for metabolism of bilirubin by the liver is shown in Figure 1. The first step in hepatic metab- olism of bilirubin is uptake from the circulation into the liver cell. This process is rapid and involves re- moval of bilirubin from its albumin carrier. Some organic anions such as sulfobromophthalein compete with bilirubin for hepatic uptake. Others, such as bile acids, appear to enter the liver cell by a different mechanism.4 The kinetics of hepatic bilirubin transport have been extensively studied, and suggest carrier mediation.5 Study of the interaction of bil- irubin with proteins on the outer surface of the liver cell is a field of ongoing research with the aim of identifying a receptor(s) which mediates organic anion uptake.

As early as one and one-half minutes after the in- travenous injection of 3H-bilirubin into rats, close to 40 percent of the dose is recovered in the liver, where

22 New York State Journal of Medicine/January 1980

The accumulation of bilirubin in the tissues of pa- tients with liver disease is a frequent occurrence. This accounts for a long-standing interest in its me- tabolism. Biliary obstruction, in particular, is often associated with very high levels of serum bilirubin. To understand bilirubin metabolism in this patho- logic condition, normal bilirubin metabolism must first be understood. Bilirubin, which is formed in the reticuloendothelial system, is a nonpolar molecule. In the normal state, it is removed from the circulation by the liver, conjugated with glucuronic acid to form a more polar compound, and excreted into bile. Al- though much of the biochemistry of these processes is known, this remains a field of ongoing investiga- tion.

SINUSOID HEPATOCYTE CANALICULUS

FIGURE 1. Normal hepatic transport and metabolism of bilirubin. Bilirubin (B) circulates in vascular system bound to albumin. First step in hepatic metabolism is uptake into liver cell (1), by process having carrier-mediated kinetics. Within liver cell, bilirubin accumulates or is "stored” bound to ligandin (2). Within cell, bilirubin conjugated with glucu- ronic acid forms bilirubin monoglucuronide (BMG) (3). Re- action catalyzed by enzyme UDP-glucuronyl transferase (G-T) and requires UDP-glucuronic acid (UDPGA). Prior to ex- cretion most BMG converted to bilirubin diglucuronide (BDG) by plasma membrane enzyme, bilirubin glucuronoside glu- curonosyl transferase (BGGT) (4). Small amount of BMG may be excreted unchanged (5).

it resides for a relatively long period of time.6 Just as unconjugated bilirubin in plasma requires albumin to keep it in solution, it should be expected to require solubilization within the hepatocyte as w'ell. Arias et al. ‘ homogenized a rat liver after intravenous in- jection of radioactive bilirubin. The homogenate was centrifuged to obtain soluble cellular proteins. These proteins were separated on a column by gel chromatography. Radioactive bilirubin eluted from the column in two predominant peaks which w7ere called Y and Z peaks, and corresponded to two pro- teins, the Y and Z proteins. In later studies, it was found that Y protein is the major organic anion- binding protein within the liver. It represents 5 percent of the liver’s soluble protein, and in light of its ability to bind many compounds, including cor- tisol and carcinogens, has been renamed ligandin. It also has glutathione transferase enzymatic activity and is important in metabolism of various drugs and toxins."

After bilirubin enters the liver cell, the next step in its metabolism is conjugation with glucuronic acid. Whereas unconjugated bilirubin is lipid soluble, conjugated bilirubin is water soluble. Normally, virtually no unconjugated bilirubin is present in bile, and conjugation of bilirubin is obligatory for its ex- cretion. Bilirubin diglucuronide is the predominant conjugate of bilirubin found in rat and human bile. It had been thought until recently that a single en- zyme, bilirubin UDP (uridine diphosphate)-glucu- ronyl transferase was responsible for conversion of bilirubin to its diglucuronide. Recent investigation has demonstrated that conjugation of bilirubin oc- curs in two steps.8 The first step, resulting in for- mation of bilirubin monoglucuronide, occurs in the endoplasmic reticulum of the cell and is catalyzed by the enzyme, UDP-glucuronyl transferase. This re- action requires UDP-activated glucuronic acid. The

second step, resulting in formation of the diglucu- ronide, is catalyzed by a newly discovered enzyme termed bilirubin glucuronoside glucuronosyl trans- ferase, which is present on the surface, or plasma membrane, of the liver cell. This reaction does not require activated glucuronic acid, but involves the interaction of two bilirubin monoglucuronide mole- cules to form one molecule of bilirubin diglucuronide and one molecule of unconjugated bilirubin. Gunn rats and patients with Crigler- Najjar syndrome have very severe unconjugated hyperbilirubinemia, lack the first-step enzyme, UDP-glucuronyl transferase, and are unable to form bilirubin monoglucuronide. However, normal activity of the second-step enzyme is present in liver biopsies. Gunn rats also convert exogenously administered bilirubin monoglucuro- nide to diglucuronide.

The rate-limiting step in bilirubin transport by the normal liver is excretion of conjugated bilirubin from the cell into the bile canaliculus. Bilirubin must be conjugated to be excreted into bile, and this excretion is thought to be an active, energy-requiring process. Much of our understanding of canalicular excretion of bilirubin has come from studies of patients with the Dubin-Johnson syndrome.9 This is a chronic, benign disorder characterized by conjugated hy- perbilirubinemia and a grossly black liver. Results of other liver function tests in these patients are normal, and hyperbilirubinemia results from markedly re- duced canalicular excretion of bilirubin. Inter- estingly, serum bile acid levels are normal, implying that they are excreted by a different mechanism from bilirubin. For many years, this syndrome was as- sumed to be an autosomal dominant disorder. Possible carriers or heterozygotes for Dubin-Johnson syndrome, assuming recessive inheritance, could not be detected by any means. It was then discovered that these patients have abnormal urinary excretion of coproporphyrin, in a pattern different from that seen in any other hepatobiliary disorder or porphyria.

January 1980/New York State Journal of Medicine 23

Nonjaundiced parents and children of patients with the disorder have abnormal coproporphyrin excre- tion in a range intermediate between that seen in normal and in affected individuals. Family study of this coproporphyrin abnormality demonstrated an autosomal recessive pattern of inheritance. The relationship of the coproporphyrin abnormality to the pathogenesis of the excretory defect in Dubin- Johnson syndrome is not clear. Further studies are being performed at present to elucidate this ques- tion.

After excretion of conjugated bilirubin into bile, it traverses the intestine where a large portion is metabolized by colonic bacteria, and urobilinogen is formed.1’3 Approximately 20 percent of urobilino- gen is reabsorbed in the colon and, if the liver is normal, is reexcreted into the bile. In obstructive or other liver disease, urobilinogen reexcretion is poor, and it appears in urine in large amounts. With complete obstruction to bile flow, bilirubin no longer reaches the colon, urobilinogen production ceases, and urinary urobilinogen may then be undetectable. Thus, in obstructive jaundice without urinary uro- bilinogen, complete obstruction is likely.

Conclusion

Bilirubin has been followed from its site of for- mation in the reticuloendothelial system through the circulation where it is bound to albumin, and into the liver cell. Within the cell, bilirubin is bound to li- gandin and subsequent conjugation converts it into a water-soluble molecule. Conjugation of bilirubin is obligatory for its excretion into bile.

In obstructive jaundice, the block to bile flow means that biliary excretion of conjugated bilirubin is reduced. If hemolysis, even of low grade, compli- cates the clinical picture, the degree of hyperbiliru- binemia is greatly exaggerated. Bilirubin which is conjugated in the liver cannot be excreted due to the

mechanical block and regurgitates back into the circulation, from which it can be removed by the kidneys. Urinary excretion of conjugated bilirubin is an important alternate means for elimination of bilirubin in obstructive jaundice. In cases compli- cated by renal failure, serum bilirubin levels may rise to very high levels.

Thus, to understand bilirubin metabolism in ob- structive jaundice or any other hepatobiliary disor- der, mechanisms of bilirubin transport and metab- olism by the normal liver must be understood. Much of the biochemistry of these processes is known, but more insight remains to be gained.

Liver Research Center Albert Einstein College of Medicine 1300 Morris Park Avenue The Bronx, New York 10461

References

1. Schmid, R., and McDonagh, A. F.: Hyperbilirubinemia, in Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S., Eds.: Metabolic Basis of Inherited Disease, New York, McGraw-Hill Book Co., 1978, p. 1221.

2. Berk, P. D., Wolkoff, A. W., and Berlin, N. I.: Inborn errors of bilirubin metabolism, M. Clin. North America 59: 803 (1975).

3. Berk, P. D., Howe, R. B., and Berlin, N. I.: Disorders of bilirubin metabolism, in Bondy, P. K., and Rosenberg, L. E., Eds.: Duncan’s Diseases of Metabolism, Philadelphia, W. B. Saunders Co., 1974, p. 825

■*. Alpert, S., et al.: Multiplicity of hepatic excretory mecha- nisms for organic anions, J. Gen Physiol. 53: 238 (1969).

5. Scharschmidt, B. F., Waggoner, J. G., and Berk, P. D.: Hepatic organic anion uptake in the rat, J. Clin. Invest. 56: 1280 (1975).

6. Wolkoff, A. W., et al.: Hepatic accumulation and intra- cellular binding of conjugated bilirubin, ibid. 61: 142 (Jan.) 1978.

7. Arias, I. M., et al.: On the structure, regulation, and func- tion of ligandin, in Arias, I. M., and Jakoby, W. B., Eds.: Gluta- thione: Metabolism and Function, New York, Raven Press, 1976, p. 175.

8. Chowdhury, J. R., et al.: Hepatic conversion of bilirubin monoglucuronide to diglucuronide in uridine diphosphate-glu- curonyl transferase-deficient man and rat by bilirubin glucuro- noside, glucuronosyltransferase, ibid. 62: 191 (July) 1978.

9. Wolkoff, A. W., Cohen, L. E., and Arias, I. M.: Inheritance of the Dubin-Johnson syndrome, New England J. Med. 288: 113 (1973).

24 New York State Journal of Medicine/January 1980

The socioeconomic implications of inguinal hernia disability are enormous. The operation is the com- monest major general surgical procedure performed and comprises 9.2 percent of all primary operations. Transuersalis fascia hernioplasty, as popularized by E. E. Shouldice, is receiving increasing clinical trial in this country. It is anatomically correct because it bridges the direct defect between transversus ab- dominis and iliopubic tract. It is physiologically sound because there is no tension on suture lines. Anesthesia is local, and rehabilitation is rapid. Our experience is with 900 transuersalis , fascia her- nioplasties followed for 12 to 88 months. This rep- resents a mean follow-up of 50 ± 2.5 months (stan- dard error of mean). There have been 16 recurrences, that is, a 1.8 percent failure rate.

Transversalis Fascia Hernioplasty

STANLEY D. BERLINER, M.D.

New Hyde Park, New York

LESLIE WISE, M.D.

New Hyde Park, New York

From the Department of Surgery, Long Island Jewish-Hillside Medical Center

The enormous socioeconomic implications of

hernia disability call for a procedure that allows rapid rehabilitation with minimal failures. We reviewed the Professional Activities Study (PAS) statistics for 1976 at three local university-affiliated medical centers. It indicated that inguinal hernia surgery comprised 9.3 percent, that is, 1,558 of 16,744 of all primary operative procedures and ranked third in frequency only to dilatation and curettage and cir- cumcision. We also reviewed 11,377 consecutive major general surgical operations performed at the Long Island Jewish-Hillside Medical Center during the five-year period from January 1, 1972, through December 31, 1976; 3,265, or 28.7 percent of these operations were inguinal herniorrhaphies. One- stage bilateral procedures were counted as one op- eration; 1,770 herniorrhaphies, or 15.6 percent, were on patients over the age of 18. This figure outranked that for all breast surgery, 14.3 percent, and that for all biliary tract surgery, 12.3 percent, carried out at that institution.

Transversalis fascia hernioplasty as popularized at the Shouldice Clinic in Toronto is being given in- creasing clinical trial in the United States; and al- lowing for inadequate documentation concerning follow-up in some series, very low recurrences are being reported.1’2 This procedure places reemphasis on the transversalis fascia, which is an investing sheath of connective tissue that is quite thin at the site of the direct hernia (Fig. 1A). Therefore, it might appear paradoxic that this structure would be effective when utilized as a primary line of defense in hernia surgery.

In 1887, Marcy3 used transversalis fascia to close the internal ring snugly. It is probably true that this procedure, combined with a high dissection of the indirect sac, is the most important step in an indirect inguinal hernia repair. However, it does not address the problem of a direct floor weakness. At the turn

of the century, Ferguson,4 emulating Marcy, rec- ommended tightening the internal ring by plicating the transversalis fascia. Ferguson also recognized the futility of subcutaneous transplantation of the cord in an attempt to reinforce the direct repair with the aponeurosis of the external oblique. In 1920 Downes,5 concerned about direct recurrences, excised the direct sac and repaired the resultant defect in the transversalis fascia with a continuous suture. Downes found that it was not helpful to divide the epigastric vessels, but it w'as important to dissect these vessels away from the transversalis so that a new internal ring could be constructed safely.

In 1945, Shouldice6 altered a modified Bassini procedure, and over a period of six or seven years he evolved a technique of overlapping the transversalis fascia as the first and second layers of the repair.7 Both Downes and Shouldice reinforced the floor with a Bassini-type repair, namely, the approximation of the conjoined tendon to the undersurface of the ex- ternal oblique adjacent to the inguinal ligament. They replaced the cord in its normal subfascial po- sition as urged by Ferguson.

In a series of anatomic dissections, Anson and McVay,8,9 Nyhus, Condon, and Harkins,10 and Condon11 demonstrated that the major etiologic factor in the development of a direct inguinal hernia in the male is a deficiency in the musculo-aponeurotic fibers of the transversus abdominis. It appears reasonable therefore that the meticulous overlapping of transversalis fascia without tension will correct the defect. This bridges the gap between the lateral or inferior ligamentous thickening of the transversalis. fascia, that is, the iliopubic tract, which lies posterior to the inguinal ligament, and the medial or superior transversalis fascia with its overlying ridge of transversus abdominis (Fig. IB).

Two popular operative procedures for the repair

January 1980/New York State Journal of Medicine 25

FIGURE 1. Transversalis facia. (A) Inguinal ligament divided to show three faces: (1) site of direct hernia; (2) iliopubic tract; and (3) femoral sheath. (B) Transversalis fascia opened to show undersurface of medial (superior) leaf and ridge of transversus abdominis (arrows).

of inguinal hernias are the Bassini12 and the Cooper’s ligament repairs.13 The former “hides” the direct defect by suturing conjoined fibers to the inguinal ligament. The inguinal ligament is not within the transversalis lamina of the groin, and as Nyhus, Condon, and Harkins10 cautioned, the repair violates the principle of restoration of the anatomic integrity of transversalis fascia and its analogues. The Coo- per’s ligament repair, as championed by Anson and McVay8’9 in this country, sutures conjoined tendon or rectus sheath to the superior pubic, Cooper’s ligament. The concept is anatomically acceptable,

but it is not physiologically sound because tension results which may require a generous rectus relaxing incision.

The transversalis Shouldice operation embodies the principle of repairing the primary transversalis- transversus abdominis defect without tension. Since 1973 we have been using a three-layer repair. After a careful high dissection of the indirect component, the transversalis fascia is opened and overlapped for the first and second layers. The first layer closes the defect anatomically; it unites the lateral, inferior, leaf to the undersurface of the medial, superior, leaf.

TABLE I. Comparative review

Author, Year	Type of Repair	Number of Cases	Number of Patients	Follow- Up	Number of Recur- rences	Percent of Cases Recurred	Patients Lost for Follow- Up	Number of Patients Who Died	Percent Followed	Method of Follow-Up
Skinner and Duncan. 194515	Halsted	1,126	1,105	6 months to 3 years	14	1.4	250	NR	75	Letter, 75 percent; examination, 25 percent
Clear, 1951 16	Halsted	1,048	771	10 years +	114	11	368	NR	55	Letter, 39 percent; examination 61 percent
Hagan and Rhoads, 1953 17	Several	1,082	957	2 years	NR	Direct. 5.1; indirect 4.1; recurrent, 21 14.3	191	NR	71	Examination, 100 percent
Shuttleworth and Davies, I96018	Several	355	266	4 to 12 years	48	5	5	96	Examination, 100 percent
Marsden, 196219	Several	2,000	NR*	3 years	109	6.8	398	Excluded	80	Examination, 100 percent
Shearburn and Myers, 19691	Shouldice	550	NR	0 to 13 years	1	0.2	NR	NR	96	NR
Lichtenstein and Shore, 1 97620	Mesh	627	NR	1 to 9 years	15	2.4	6	NR	99	NR
Halverson and McVay, 197021	Abdominal, ring or Cooper’s ligament	1,211	1,008	1 to 22 years	42	3.5	88	156	76	Letter and exami- nation
Palumbo and Sharpe, 197 l22	Modified Bassini/ Halsted	3,572 Primary Hernias	3,155	1 to 16 years	37	1	NR	NR	91	Letter and exami- nation
Cl a show, 19732	Shouldice	2,748	2,270	7 years	19	0.7	898	263	55	Letter and exami- nation
Berliner, Burson, Katz, and Wise, 197823	Bassini or Cooper’s ligament	720	526	4 to 9 years	83	11.5	33	16	93	Examination. 90 percent
Berliner, Burson, Katz, and Wise, 197H23	Transversalis (Shouldice)	591	494	2 to 5 years	16	2.7	18	6	96	Examination, 95 percent

* NR = Not recorded.

26 New York State Journal of Medicine/January 1980

'Phis bridges the gap between the transversus ab- dominis ridge medially and the iliopubic tract lat- erally. The iliopubic tract is the lateral thickening of the transversalis which lies behind the inguinal ligament. Contrary to the belief of some, we have found in over 1,000 cases that the inferior segment of transversalis usually holds sutures well. This was also noted by Glassow14 of the Shouldice Clinic, in a personal series of 15,000 operations. Therefore, the more remotely situated Cooper’s ligament can be ignored and tension avoided.

The second layer of the transversalis repair joins the medial, superior edge of transversalis to transversalis laterally where available and also to the inguinal ligament. The third and final suture, Bassini layer, approximates the conjoined fibers to the undersurface of the external oblique adjacent to the previous suture line. The inguinal ligament at- tachment of the second layer and the third Bassini layer serve to stabilize and reinforce the transversalis repair. A continuous nonabsorbable polyester su- ture of 3-0 Teudek is used for all three layers. This has the added effect of creating a mesh support for the posterior wall of the inguinal area.

A comparative review of some of the larger and better documented series during the past 30 years reflects the difficulty of follow-up (Table I).1*2,15-23 From our own experience, it is the patients who are usually reported as lost to follow-up that are the most likely to have had a recurrence of their hernia. During a four- to nine-year follow-up of a group of patients with Bassini or Cooper ligament repairs, 68 patients were eventually traced with much difficulty; 21 of this group, or 31 percent, had a recurrence of their hernia and had been reoperated by another surgeon or were living with a truss.23

A retrospective review of our own cases suggests the superiority of the transversalis, Shouldice repair. The recurrence rate was 11.5 percent for 720 Bassini or Cooper’s ligament repairs followed four to nine years compared to 2.7 percent for 591 transversalis fascia hernioplasties followed from two to five years.23 The current personal experience of one of the authors (S.B.) is with 900 Shouldice-type repairs followed for 12 to 88 months. This represents a mean follow-up of 50 plus or minus 2.5 months (standard error mean). There have been 16 recur-

rences, that is, a 1 .8 percent failure rate. The oper- ation is performed under local anesthesia, the patient goes home on the second postoperative day, and he may resume his usual activities when comfortable.

58-47 Francis Lewis Boulevard Fresh Meadows, New York 11564 (DR. BERLINER)

References

1 . Shearburn, E. W., and Myers, R. N.: Shouldice repair for inguinal hernia. Surgery 66: 450 (1969).

2. Glassow, F.: The surgical repair of inguinal and femoral hernias, Canad. M. A. J. 108: 308 (1973).

3. Marcy, H. O.: The cure of hernia, J.A.M.A. 8: 589 (1887).

4. Ferguson, A. H.: Oblique inguinal hernia. Typic oper- ation for its radical cure, J.A.M.A. 33: 6 ( 1899).

5. Downes, W. A.: Management of direct inguinal hernia, Arch. Surg. 1: 53 ( 1920).

6. Shouldice, E. E.: Surgical treatment of hernia, Ontario med. Rev. 12: 43(1945).

7. Welsh, D. R.: Inguinal hernia repair: a contemporary approach to a common procedure, Mod. Med. 42: 49 (1974).

8. Anson, B. J., and McVay, C. B.: Inguinal hernia. The anatomy of the region, Surg. Gynec. & Obst. 66: 186 (1938).

9. McVay, C. B., and Anson, B. J.: Aponeurotic and fascial continuities in abdomen, pelvis and thigh, Anat. Rec. 76: 213 (1940).

10. Nyhus, L. M., Condon. R. E., and Harkins, H. N.: Clinical experiences with preperitoneal hernial repair for all types of hernia of the groin, with particular reference to the importance of transversalis fascia analogues, Am. J. Surg. 100: 234 (1960).

1 1. Condon, R. E.: Surgical anatomy of the transversus ab- dominis and transversalis fascia, Am. Surgeon 173: 1 (1971).

12. Bassini, E.: Uber de Behandlung des Leistenbruckes, Arch. klin.Chir. 40: 429 (1890).

13. Lotheissen, G.: Zur Radikaloperation der Schenkelher- nien, Zentralbl. Chir. 25: 548 (1898).

14. Glassow, F.: Inguinal hernia repair. A comparison of the Shouldice and Cooper ligament repair of the posterior inguinal wall. Am. J. Surg. 131: 306 (1976).

15. Skinner, H. R., and Duncan, R. D.: Inguinal hernia. Report of 1 126 cases, S. Clin. North America 25: 219 (1945).

16. Clear, J. J.: Ten year statistical study of inguinal hernias. A comparison of the rate of recurrence following repair by the Halsted 1 and other operations, Arch. Surg. 62: 70 (1951).

17. Hagan, W. H., and Rhoads, J. E.: Inguinal and femoral hernias; a follow-up study, Surg. Gynec. & Obst. 96: 226 ( 1953).

18. Shuttleworth, K. E., and Davies, W. H.: Treatment of inguinal herniae, Lancet 1: 126 (1960).

19. Marsden. A. J.: Inguinal hernia, a three-year review of 2000 cases, Brit. J. Surg. 49: 384 ( 1962).

20. Lichtenstein, I. L., and Shore, ■). M.: Exploding the myths of hernia repair. Am. J. Surg. 132: 307 ( 1976).

21. Halverson, K., and McVay, C. B.: Inguinal and femoral hernioplasty, Arch. Surg. 101: 127 (1970).

22. Palumbo, L. T., and Sharpe, W. S.: Primary inguinal hernioplasty in the adult, S. Clin. North America 51: 1293 (1971).

23. Berliner, S., Burson, L., Katz, P., and Wise, L.: An ante- rior transversalis fascia repair for adult inguinal hernias, Am. J. Surg. 135: 633 (May) 1978.

January 1980/New York State Journal ot Medicine 27

Hie primary beneficiaries of

ORAL

HYDERGINE -

Each 1 mg Hydergine tablet contains dihydroergocornme mesylate 0 333 mg, dihydro- ergocristine mesylate 0.333 mg,anddihydroergocryptine(dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine in the proportion of 2:1) mesylate 0.333 mg, repre- senting a total of 1 mg.

They're in their late sixties, the beneficiaries of more lib- eral retirement laws and more enlightened attitudes toward the elderly. They’re leading socially pro- ductive lives. But recently, without any clear cause, they had each begun to experience mild ^ episodes of symptoms such as confusion, mood-depression, and dizziness. Their ability to function could have been jeopardized. That’s when they be- came the beneficiaries of oral Hydergine therapy.

The still-functioning geriatric can benefit from Hydergine treatment

It is quite common for cognitive and emotional symp- toms of deterioration to manifest gradually in the elderly. During this early stage, such symptoms are mild and more amenable to treatment. It is at this stage that Hydergine therapy has proved most effective. Patients tend to respond better, and with symptoms effectively relieved— or at least their progression retarded— the ability to function can be maintained.

Oral Hydergine tablets promote better patient compliance

Compared with the sublingual form, dosage administra- tion is easier, with less need for supervision.

Contraindications: Hypersensitivity to the drug.

Precautions: Because the target symptoms are of unknown etiology, careful diagnosis should be attempted before prescribing Hydergine tablets and sublingual tablets.

Adverse Reactions: Serious side effects have not been found Some sublingual irritation, transient nausea, and gastric disturbances have been reported. Hydergine tablets and sublin- gual tablets do not possess the vasoconstrictor properties of natural ergot alkaloids Dosage and Administration: 1 mg three times daily Alleviation of symptoms is usually gradual and results may not be observed for 3-4 weeks How Supplied: Hydergine tablets (for oral use) 1 mg, packages of 100 and 500 Hydergine sublingual tablets 1 mg, containing dihydroergocornine mesylate 0.333 mg, dihydroergocristine mesylate 0.333 mg, and dihydroergocryptine (dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine in the proportion of 2:1) mesylate 0 333 mg, representing a total of 1 mg, packages of 100, 500, and 1000 Hydergine sublingual tablets 0.5 mg, contain- ing dihydroergocornine mesylate 0 167 mg, dihydroergocristine mesylate 0.167 mg, and di- hydroergocryptine (dihydro-alpha-ergocryptine and d i hydro-beta-ergocryp ' in the proportion of 2:1) mesylate 0167 mg, representing a total of 0.5 mg, packages of 100 and 1000.

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Hypertension in Perioperative Period

The incidence of hypertension in the perioperative period was examined by a retrospective review of 1,038 elective ( nonopen heart) cases receiving general anesthesia. Hypertension occurred in either the operating room and/or the recovery room in 94 pa- tients (9 percent ). Those patients who had a pre- operative history of hypertension had a significantly greater incidence of hypertensive episodes (21.5 percent). In patients with no history of hyperten- sion, an elevated preoperative blood pressure was not associated with a greater incidence of hypertensive episodes. Balanced anesthesia (nitrous oxide, thiopental sodium, with or without narcotics, and muscle relaxants) was associated with a greater in- cidence of hypertension in patients with and without a history of hypertension.

JOSEPH L. SELTZER, M.D.a

Syracuse, New York

JOHN I. GERSON, M.D.a

Syracuse, New York

ALAN W. GROGONO, M.D.b

Syracuse, New York

From the Department of Anesthesiology, State University of New York Upstate Medical Center. a Assistant Professor. b Associate Professor.

It has become increasingly apparent that hyper- tension in the perioperative period may be undesir- able and it may be advisable to appropriately lower the blood pressure.1 Hypertension is anticipated during endotracheal intubation in normal and in hypertensive subjects.2’3 Hypertensive events occur at other times as well. We explored the incidence of hypertensive events in the perioperative period as related to preexisting hypertension and anesthetic techniques, with a retrospective review of anesthetic records.

Methods

The preanesthetic assessments, intraoperative anesthetic charts, and recovery room records, were reviewed for each patient receiving a general anes- thetic during two separate two-month periods. Patients undergoing open-heart surgery or emer- gency surgery were excluded. A blood pressure of 140/90 mm. Hg was considered the upper limit of normal. Patients with normal preoperative blood pressures and no previous history of hypertension were placed in Group 1. Those with a history of hypertension or who were taking antihypertensive agents were placed in Group 2. Group 3 consisted of patients with an elevated preoperative blood pressure but no history or symptoms related to hy- pertension. The highest blood pressure of the preanesthetic period was taken as the patient’s baseline pressure. In most patients, pressures were obtained by the Riva-Rocci method. However, when an arterial line was in place, it was used to measure the blood pressure.

A hypertensive episode in the perioperative period was judged to have occurred when there were three

consecutive five-minute blood pressure readings which exceeded the baseline level by 20 percent and exceeded 140/90 mm. Hg. The incidence of hyper- tensive episodes was recorded for the three groups and for the type of anesthetic used: balanced anes- thesia (nitrous oxide and thiopental sodium, with or without narcotics, and muscle relaxants) and inha- lational anesthesia (enflurane or halothane regardless of adjunctive agents). Statistical significance was determined by chi-square analysis.

Results

A total of 1,038 cases were reviewed. Hyperten- sion lasting for 10 minutes or longer occurred in 94 patients (9 percent). Forty-one episodes (3.9 per- cent) occurred intraoperatively, and 62 episodes (6 percent) postoperatively in the recovery room. Nine patients had hypertensive episodes in both the op- erating room and the recovery room. The incidence of patients developing perioperative hypertension is shown in Table I. Patients with an elevated pre- operative blood pressure but no hypertensive history (Group 3) had an incidence of hypertension similar to patients with no previous hypertensive history (Group 1). Accordingly, these two groups were subsequently considered as a single group. The in- cidence of perioperative hypertension was signifi- cantly greater in those patients with a positive history

TABLE I. Incidence of patients developing perioperative hypertension.

	T Hypertensive Episodes-]
Group	L Patients PercentJ

1	(862)	69	8
2	(93)	20	21.5*
3	(83)	5	6
Total	(1,038)	94	9

*p <0.001 compared to groups 1 and 3.

January 1980/New York State Journal of Medicine 29

TABLE II. Comparison of anesthetic agents.

Anesthetic	Patients	Perioperative Patients	Hyper- tension Percent
Group 1 plus 3 (945)
Inhalation	778	48	6
Balanced	167	26	15.5*
Group 2 (93)
Inhalation	80	10	12.5
Balanced	13	10	77 1

* p <0.001 comparing inhalation to balanced technique for Group 1 plus 3.

+ p <0.001 comparing inhalation to balanced technique for Group 2.

of hypertension, Group 2, when compared with Groups 1 and 3 (p <0.001).

The incidence of hypertension was also related to the choice of anesthetic technique (Table II). Bal- anced anesthesia was associated with a significantly higher incidence of hypertension in all groups, but particularly in Group 2 where a majority of the pa- tients, 10 of 13, had hypertensive episodes.

Comment

There is no well-defined blood pressure threshold which divides normal from hypertensive. There is, however, a relationship between increasing levels of blood pressure and morbidity and mortality rates in the general population.4 We chose 140/90 mm. Hg as the upper limit of normal because it is in the middle of a number of suggested values quoted by Pickering.4 We realize that the upper level of normal chosen will change the incidence of hypertension. We also arbitrarily chose a 20 percent rise above the highest preanesthetic blood pressure to represent perioperative hypertension. At higher baseline systolic pressures, such as 165 mm. Hg, this meant the patient’s pressure would have to go to very high levels (over 198 mm. Hg) to be included. Two sep- arate two-month periods were analyzed to see whether or not the incidence of hypertension changed as our residents’ experience increased. The data for both periods was consistent and has, there- fore, not been presented separately.

It was impossible to judge what was the cause of the hypertensive episodes we recorded by reviewing the records. The increased incidence of hyperten- sion in patients receiving balanced anesthesia may, in part, be due to catecholamine release. This has been documented for droperidol and fentanyl in combination5 and for high doses of morphine.6 The effect of small doses of narcotics used for balanced anesthesia has not been reported. However, Nikki et al. ' have shown that elevation of blood pressure during nitrous oxide, oxygen, or relaxant anesthesia was associated with increase in catecholamine levels. There is evidence that adequate treatment of hy- pertension prevents increases of catecholamines during balanced anesthesia.8 However, in our pa-

tients who were hypertensive and receiving treat- ment, there was still a greater incidence of hyper- tension in those receiving a balanced anesthetic. In our institution, as is obvious from the data, the vast majority of patients received an inhalation anes- thetic. It is, therefore, conceivable that lack of fa- miliarity with balanced anesthesia could have con- tributed to the difference.

Goldman and Caldera9 have recently reported a group of 676 patients with an overall incidence of perioperative hypertension of 12 percent. In their series, 8 percent of normotensive patients became hypertensive. Their hypertensive patients were divided into three groups. First, those receiving therapy and now normotensive had a 27 percent in- cidence of hypertension; second, those still hyper- tensive in spite of therapy had a 25 percent incidence; and finally those who were hypertensive and un- treated had a 20 percent incidence. If all these pa- tients are added together to make one group, the incidence of hypertensive episodes in this group was 23 percent which is consistent with our finding of 21.5 percent among patients in Group 2. Equally im- portant, they found no increase in cardiovascular complications among hypertensive patients whose diastolic pressure was less than 110 mm. Hg.

Hypertension in recovery room patients had been reported by Gal and Cooperman.10 They reported a 3.25 percent incidence of blood pressures greater than 190/100 mm. Hg for greater than 10 minutes. Pain, hypoxia, emergence excitement, and reaction to the endotracheal tube were felt to be the main etiologic factors. In their series, the agent associated with the greatest postoperative hypertension was fluroxene, followed by halothane, cyclopropane, methoxyflurane, diethyl ether, and then nitrous oxide, including supplementation with muscle re- laxant, thiopental sodium, and narcotics. We could show no statistical difference for hypertension in the recovery room between balanced and inhalation anesthesia. However, it is a common practice at our institution to administer a narcotic intravenously toward the end of an operative procedure to provide postoperative analgesia. Of the patients with re- covery room hypertension in Gal and Cooperman’s10 series, 58 percent had a previous history of hyper- tension. This concurs with our findings that patients with an established history of hypertension are more prone to perioperative hypertension.

An interesting finding was that patients with a high preoperative blood pressure, but no history or symptoms of hypertension, had no greater incidence of perioperative hypertension than those with normal preoperative blood pressures. In contrast, a patient with a history of hypertension, with or without treatment, was more likely to develop perioperative hypertension. Finally, we found that balanced an- esthesia was more often associated with perioperative hypertension than inhalational anesthesia. We re- alize that in a retrospective study, the selection of

30 New York State Journal of Medicine/January 1980

balanced or inhalational anesthesia could have been influenced by a preoperative history of hypertension. However, in all three groups there was a greater in- cidence of hypertension in patients who received balanced anesthesia.

The clinical significance of the hypertensive epi- sodes reported in this study is not known; we have no evidence of untoward events traceable to any of these episodes. However, it is well known that sudden increases in blood pressure can be associated with myocardial ischemia, decreased cardiac output in valvular lesions such as mitral or aortic insufficiency, cerebral vascular accidents, and increased surgical bleeding. It is likely that these complications were not observed by us because most episodes were rel- atively short owing to the fact that hypertension in the perioperative period is easily controlled. Before initiating treatment, the adequacy of ventilation must be evaluated to rule out hvpoxia or hypercapnia as precipitating factors. During a surgical procedure, deepening the anesthesia by either inhalation or in- travenous agents will almost always return the blood pressure to the normal range. In the recovery room, emergence excitement terminates itself rapidly as the patient awakens. Postoperative pain may be treated with analgesics. If precipitating factors are con- trolled, and the hypertension persists at dangerous levels, either an injection of diazoxide or an infusion

Final elimination of measles by 1982 held attainable goal

The United States can eliminate measles by 1982, the Surgeon General of the United States declares in an edi- torial in the September 14 Journal of the American Medical Association.

”1 think the elimination of indigenous measles in this country is indeed a realistic goal,” says Julius B. Richmond, M.D., U.S. Surgeon General.

Dr. Richmond’s editorial accompanies a study of the effort to eliminate measles by the Center for Disease Control, Atlanta. Alan R. Hinman, M.D., and colleagues trace the efforts to halt measles in the past year and con- clude that complete elimination in this country is fea- sible.

Levels of immunization already are quite high among American children and cases of measles have dropped sharply, Dr. Richmond points out. Of 46 states surveyed in the fall of 1978, he says, 29 reported that 90 percent or

of sodium nitroprusside will act rapidly and is ef- fective for short-term control. Persistent postop- erative hypertension should be evaluated and treated in the usual fashion.

References

1. Hamilton, W. K.: Editorial: Do let the blood pressure drop and do use myocardial depressants!, Anesthesiology 45: 273 (1976).

2. Takeshima, K., Noda, K., and Higaki, M.: Cardiovascular response to rapid anesthesia induction and endotracheal intuba- tion, Anesth. & Analg. 43: 201 (1964).

3. Prys-Roberts, C., Greene, L. T., Meloche, R., and Foex, P.: Studies of anesthesia in relation to hypertension. II. Hae- modynamic consequences of induction and endotracheal intu- bation, Brit. J. Anaesth. 43: 531 (1971).

4. Pickering, G.: Hypertension. Definitions, natural

histories and consequences, Am. J. Med. 52: 570 (1972).

5. Giesecke, A. H., Jr., Jenkins, M. T., Crout, J. R., and Col- lett, J. M.: Urinary epinephrine and norepinephrine during In- novar-nitrous oxide anesthesia in man, Anesthesiology 28: 701 (1967).

6. Hasbrouck, J. D.: Morphine anesthesia for open-heart surgery, Ann. Thorac. Surg. 10: 364 (1970).

7. Nikki, P., Takki, S., Tammisto, T., and Jaattela, A.: Effect of operative stress on plasma catecholamine levels, Ann. Clin. Res. 4: 146 (1972).

8. Jaattela, A., et al.: Effect of operative stress on plasma catecholamines in treated and untreated hypertensive patients, ibid. 4:84 (1972).

9. Goldman, L., and Caldera, D. L.: Risks of general anes- thesia and elective operation in the hypertensive patient, Anes- thesiology 50: 285 (Apr.) 1979.

10. Gal, T. J., and Cooperman, L. H.: Hypertension in the immediate postoperative period, Brit. J. Anaesth. 47: 70 (1975).

more of children entering school for the first time had re- ceived measles vaccine. In 16 of these states the level was 95 percent.

Measles have been declining for 15 years, since the ad- vent of the vaccine, and the public has tended to forget that the disease, while mild for most, still can cause complica- tions leading to encephalitis, mental retardation, and even death, the Surgeon General points out.

It is feasible to vaccinate virtually all American children and to halt spread of infection within this nation, but there will continue to be frequent importations of measles from other countries, and it will be essential to maintain sur- veillance systems and immunization programs, the Federal report says.

In 1978 there were 26,795 cases of measles reported, a decline of 53 percent from the previous year. Three states, New Mexico, South Dakota, and Wyoming, were free of reported measles throughout the year. In the first 26 weeks of 1979 only 10,686 cases were reported, an all-time low.

January 1980/New York State Journal of Medicine 31

Cancer Effects of Low-Level Radiation

Theoretic considerations in competing causes of death

A. M. STEWART, M.D.

Edgbaston, Birmingham, England

From the Regional Cancer Registry, University of Birmingham

Ionizing radiations are powerful carcinogens, and, provided the age and species of the recipients are held constant, there is probably a middle range of radiation doses where cancer mortality effects are directly proportional to the dose. Nevertheless, in spite of radiation dose effects having been intensively studied by scientists from two disciplines, radio- biology and epidemiology, there is still uncertainty about whether or not to expect any cancer-induction effects from x-ray examinations or the doses en- countered by workers in certain industries. Ac- cording to one school of thought there is no danger at these low dose levels, a concept known as the safety threshold or nonlinear hypothesis. However, there is a rival school which believes that the cancer in- duction effects of radiation remain directly propor- tional to the dose however small, this concept known as the no safety threshold or linear hypothesis.

The two theories are mutually exclusive since one, the linear hypothesis or no safety threshold, would allow a single nonlethal mutation to initiate a cancer process, and the other, the nonlinear hypothesis or safety threshold, would require a different mecha- nism which is compatible with cancer induction’s being the result of a particular sequence of cell changes. Meanwhile, in relation to the cancer effects of low-level radiation, radiobiologists have had con- sistently negative findings, and epidemiologists are still making contradictory claims. One of the surveys with positive findings may have ascribed to radiation the effects of other carcinogens,1 and another may have placed too much reliance on retrospective data.2 However, there is no proof that this is so, and we are clearly dealing with a situation in which there is more scope for false negative than false positive find- ings.

Studies of delayed effects of radiation are reviewed. Surveys with negative findings for small-dose effects have usually relied on extrapolations from large-dose effects and ignored two causes of nonrecognition of cancers in these situations: latent period deaths due to noncancer effects of the radiation, and latent pe- riod deaths due to the conditions which necessitated the exposures. Surveys with positive findings for low-level radiation suggest that the end results of such doses, delivered at a slow rate, may be very dif- ferent from the end result of much larger doses de- livered at a fast rate and that the difference is related to cell death effects of the radiation.

Neither in animals nor man can the origins of cancers be deduced from their clinical or pathologic manifestations. Therefore, even radiobiologists, who are free to experiment with the situation, have been forced to look for causal associations between ra- diation exposures and subsequent events; to use as indices of cancer induction either cancer mortality rates or prevalence; and to accept the fact that there will only be recognition of radiogenic and spontane- ous cancers at a group level. There have been two approaches to the problem of small-dose effects: follow-up studies of human or animal populations exposed to uniform or variable doses, that is, pro- spective surveys; and case history studies of cancer patients, or retrospective surveys. Since intervals between cancer induction and diagnosis or death are of uncertain duration, both approaches require rec- ognition and control of numerous factors related to cancer prevalence and mortality rates.

In planned studies the two groups of cancers which are otherwise indistinguishable, spontaneous and radiogenic, necessarily have different age distribu- tions since, by definition, one consists of cases ini- tiated at the time of the exposure and the other by different initiations. This is important for several reasons, including the possibility that cancers have sufficiently long latent periods for competing causes of death to be significant and even important sta- tistical factors, and the possibility that some dis- turbance of general health, that is, changed reactions to diseases in general, occurred before a cancer de- veloped to the point of being clinically recogniz- able.

The risk of dying from all causes is a function of infection susceptibility which is negatively correlated with age during the period of growth and develop- ment, that is, between conception and puberty, and positively correlated with age thereafter. Therefore, even on the assumption of no deterioration in health before a cancer is diagnosed, the proportion of both unrecognized and recognized cancer inductions, due to competing causes of death, would be different for spontaneous and radiogenic cases. Furthermore, the differences between the two groups would be con-

32 New York State Journal of Medicine/January 1980

stantly changing since they would depend on several factors, including exposure, age, duration of the fol- low-up, the prevalence of other causes of death before and after radiologic exposure, and the intensity of the exposures.

The last factor is important and has often been overlooked by research workers whose estimates of small-dose effects were based on extrapolations from large doses. Cancers are far from being the only in- jurious effects of radiation, and we can be reasonably certain that all cell-damage effects are directly pro- portional to the dose. Therefore, extrapolations from high doses could be dangerous unless one allows for the possibilities that the proportion of unrecog- nized cancer inductions due to competing causes of death could be positively correlated with the radia- tion dose, different for radiogenic and spontaneous cases due to age differences, and different for internal and external radiation due to the different properties of alpha and gamma rays.

The cancers most likely to have changed reactions to other diseases before they are clinically recogniz- able are cancers of lymphatic and hemopoetic tissues, that is, RES (reticuloendothelial system) neoplasms. In one half of these cases there is no question of a painful lump being detected at a relatively early stage of the disease, and in all of them there is direct in- volvement of the immune system and a possibility of total loss of immunologic competence within a few weeks of confirmation of the diagnosis. Since an important component of the RES, bone marrow, heads the list of tissues which are exceptionally sensitive to the cancer-induction effects of radiation,3 even a small increase in infection sensitivity during the latent phase of a bone marrow cancer such as myeloid leukemia or myelomatosis, would allow competing causes of death to have a selective harmful effect on the incidence and type of radiogenic can- cers.

Finally both infections and cancers are under the control of the immune system. Therefore, it is pos- sible that cancer sensitivity bears a similar relation to age as sensitivity to infection and is greater at the beginning than at the end of fetal life and prepuberty. An important cause of early death is a difficult de- livery, and the usual time for x-raying pregnant women is toward the end of the gestation period. Therefore, in studies of the cancer effects of these in utero x-ray exposures allowance should be made for the following possibilities: (1) more cancer induc- tions during the first compared with the incidence in the second half of fetal life and different clinical forms of radiogenic cases between the earlier and the later initiations; and (2) more unrecognized cancer inductions following difficult than easy deliveries and more involvement of spontaneous than radiogenic cases in these early deaths.

Thus far, prospective surveys with negative find- ings for low-level radiation have been the sole source of guidelines for radiation protection purposes.4-5

Risk estimates in support of these guidelines, usually in the form of maximal permissible doses, have ac- cepted that the cancer effects of radiation are directly proportional to the dose. Therefore, are they ex- aggerating the risks with the safety threshold hy- pothesis, or are they understating the risks with re- jection of a safety threshold?

Linear hypothesis (no safety threshold)

Surveys with positive findings for the hazard of low-level radiation have not relied on extrapolations from high doses. Since this is a constant feature of animal experiments, the main support for the linear hypothesis has come from (1) a follow-up of A-bomb survivors exposed to less than 10 rads, that is, the Japanese data; (2) several studies of the cancer ef- fects of obstetric radiography, that is, fetal irradia- tion; and (3) a study of radiation doses of workers in the nuclear industry, known as the Hanford data.

Japanese data. For two groups of A-bomb sur- vivors, at Hiroshima and Nagasaki, who were prob- ably exposed to less than 10 rads in August, 1945, leukemia mortality rates during a 22-year period from October, 1950, to December, 1972, were in- creased by a significant amount compared with unexposed Japanese national rates.6 The increase was greater for Hiroshima, 0.88 expected and 1.48 observed, than Nagasaki, 1.11 expected and 1.78 observed, but both differences were statistically significant.

Fetal irradiation. The most consistent findings for cancer effects of low-level radiation have come from case history studies of children who died from cancers before 10 years of age and who were x-rayed in utero for obstetric reasons.2-7-8 The retrospective surveys have always shown higher exposure rates for these children than healthy controls, but an equiv- alent series of prospective surveys, that is, follow-up studies of in utero exposures, has yielded less con- sistent positive findings, even when the postexposure period was as long as the longest predeath period in the retrospective surveys.

There have been only three occasions when all the children in a prospective survey were followed for 10 years.9-11 In two of the surveys, the source of the radiation was an x-ray examination. These expo- sures, which showed the usual bias in favor of third- trimester x-rays, had two groups of children, one with low rates of general mortality, whites in the United States, and one with high mortality rates, blacks in the United States. On the third occasion the chil- dren were A-bomb survivors who were exposed to a wide range of doses at different times between con- ception and birth and a grossly abnormal environ- ment for at least five years after birth. For blacks in the United States and A-bomb survivors there was no evidence of any cancer effects from the in utero exposures, but for the two groups of whites in the United States there was definite evidence of such an effect.

January 1980/New York State Journal of Medicine 33

For many years the positive findings for fetal ir- radiation were ascribed either to biased data sources or to the reasons requiring the x-rays.5 Neither reason was likely, but both remained in circulation in the literature until the original retrospective sur- vey2 was in a position to include in a series of Man- tel-Haneszel analyses, all factors suspected of having associations either with the exposures or the can- cers.12-15

Each analysis took the form of a rigidly controlled test of a null hypothesis, and the series as a whole led to the following conclusions. The association be- tween fetal irradiation and cancer was a direct one and was stronger for multiple than single exposures, and much stronger for near-conception than near- birth exposures. For a rare group of cancers with fetal manifestations, for example, teratomas, the cancers were the reason why the mothers were x- rayed, but otherwise the association was stronger for routine x-ray studies with normal findings than for special x-ray studies with abnormal findings. Yet “obstetric disproportion” as an x-ray finding, which has exceptionally strong associations with difficult deliveries, actually showed a negative correlation with childhood cancers.

Hanford data. Support for the linear hypothesis has come from a branch of the nuclear industry which has been kept under continuous surveillance since 1944. li16 It was originally intended to compare ac- tual with expected cancer deaths by a method which is well known to cancer epidemiologists, but is slow to recognize small differences between observed and expected numbers of cancer deaths, determined by the SMR (standardized mortality ratio) method. However, the records included annual radiation doses of badge-monitored workers. Therefore, it was possible to make a forecast of mortality trends by comparing the radiation doses of workers who had died from stated causes.

According to these forecasts, cancer risks for workers in the nuclear industry are directly propor- tional to the dose and are related to age. At present, the showing is that cancers most likely to be caused by radiation are bone marrow, pancreas, and lung, but this could be a temporary phenomenon due to the fact that other cancers have longer latent periods.

Nonlinear hypothesis ( safety threshold)

Quite apart from surveys with negative findings for fetal irradiation, there are many observations which favor the safety threshold model of radiation carcinogenesis. Most of the evidence comes from animal experiments, but the Japanese survey of A- bomb survivors has been quoted in this context as well as spondylitic data, that is, a survey of patients with ankylosing spondylitis who were given thera- peutic doses of radiation with temporary relief of pain.

Japanese data. The ratio of observed to expected cancer deaths has always been lower in Nagasaki

than in Hiroshima, but the proportion of acute leu- kemias has always been biased in the opposite di- rection.4 These differences are supposed to be due to the different neutron content of the two bombs, but they could equally well be due to different con- centrations of radioactive dust in the two situa- tions.

The Hiroshima bomb fell on a flat plain and caused more injuries than the Nagasaki bomb, which fell in deep valley. Therefore, the hills must have offered some protection against the blast. By the same token, there must have been more radioactive dust in the valley than the plain. Therefore, we should expect troubles due to ingestion or inhalation of “hot” particles, that is, beta emitters, to be much greater in Nagasaki than in Hiroshima. This aspect of the bombing receives no mention in ABCC (Atomic Bomb Casualty Commission) publications, but it is nevertheless true that bone-marrow effects of beta emitters include permanent loss of immu- nologic competence, due to myelofibrosis, as well as acute myeloid leukemia.

In both cities residual effects of the blast were still being felt in 1960. Therefore, although the ABCC study population was not assembled until October, 1950, there was ample opportunity for radiation- induced loss of immunologic competence, or delayed effects of unmeasured doses of internal radiation, to prevent recognition of other delayed effects.

Spondylitic data. In the survey of patients with ankylosing spondylitis, everyone received a tissue- destructive dose to the spinal bone marrow. Also, the more crippled the patient, the greater the prob- ability of receiving more than one course of radio- therapy. Therefore, there were two dose-related reasons why the proportion of unrecognized cancers due to latent period deaths should be increased: loss of immunologic competence due to radiation-induced myelofibrosis and similar effects due to the disease- causing rigidity of the thoracic cage.

In relation to this survey, there has only been mention of factors which might have added to the cancer risks. For example, the possibility of a direct connection between ankylosing spondylitis and leukemia has been mentioned, as well as the possi- bility of the use of drugs with carcinogenic properties, and the possibility that a rigid chest might increase a smoker’s risk of lung cancer.417 But the possibility that any disease requiring exposure to tissue-de- structive doses of radiation could make it difficult to arrive at a true estimate of the cancer effects of ra- diation has been completely overlooked. Such an effect would be strongly age-related, and so this could he the reason why risk estimates based on spondylitic patients show much less variation with age than ones based on workers in the nuclear industry. For Hanford workers, the risk of premature death was small even compared with all men of working age, reflecting the so-called “healthy worker effect,” and this could be the reason why an SMR analysis of

34 New York State Journal of Medicine/January 1980

Hanford data actually found evidence of radiation effects for two rare groups of cancer, myelomatosis and pancreas, even though the overall cancer death rate was well below the national average.18

Comment

The fact that radiation has immediate as well as delayed health effects means that even if each effect were directly proportional to the dose, this would not be true of the net effect. It also means that the higher the dose the smaller the net effect per unit dose. The “cell death” component of this difference is well known, hut there is no comparable recognition of the fact that tissue destruction by radiation need not be obvious to have lifelong effects. This un- comfortable fact is due partly to the extreme sensi- tivity of bone marrow but also to the strong affinity between radioactive substances and the inner lining of bone, which is also the outer lining of bone marrow.

We have yet to prove that there has been, in A- bomb survivors, both cancellation of the cancer ef- fects of measured doses of external radiation by bone marrow effects of unmeasured doses of internal ra- diation and heightening of the first effect by the second effect, by the addition of bone-marrow can- cers. But we can be reasonably certain that, even in relation to nonradiogenic cancers, there are changed reactions to other diseases during periods of cancer latency. These changes are more typical of leukemia than solid tumors. But for all forms of cancer there is an appreciable risk of dying from the effects of the disease before it can be recognized, and this risk is much greater in infancy and old age than it is during the intervening period.

Therefore, in any study of the cancer mortality effects of radiation it is important, not only to allow for inevitable age differences between spontaneous and radiogenic cancers, but also to remember that there will always be four factors influencing the proportion of unrecognized cancer initiations: the intensity of the exposures, the exposure age, the length of the postexposure period, and the general mortality rate.

University of Birmingham Edgbaston Birmingham, England

References

1. Mancuso, T. F., Stewart, A., and Kneale, G.: Radiation exposures of Hanford workers dying from cancer and other causes, Health Physics 33: 369 (Nov.) 1977.

2. Stewart, A., Webb, J., and Hewitt, D.: A survey of child- hood malignancies, Brit. M. -I. 1: 1495 (1958).

3. Radiosensitivity and Spatial Distribution of Dose, Pub- lication 14, The International Commission on Radiological Pro- tection, Elmsford, New York, Pergamon Press, 1969.

4. The effects of Populations of Exposure to Low Levels of Ionizing Radiation, BIER (Biological Effects of Ionizing Radia- tion) report, Washington, D.C., National Research Council, 1972.

5. Review of NCRP Radiation Dose Limit for Embryo and Fetus in Occupationally Exposed Women, Report 53, Washington, D.C., National Council on Radiation Protection and Measure- ments, 1977.

6. Pochin, E. E.: Malignancies following low radiation ex- posures in man, Brit. J. Radiol. 49: 577 (1976).

7. Ford, D. D., Paterson, J. C., and Treuting, W. L.: Fetal exposure to diagnostic x-rays, and leukemia and other malignant diseases in childhood, J. Nat. Cancer Inst. 22: 1093 (1959).

8. Graham S., et al.: Epidemiological approaches to the

study of cancer and other chronic diseases, in Preconception, In- trauterine and Postnatal Irradiation as Related to Leukaemia, monograph 19, National Cancer Institute, 1966, p. 347.

9. MacMahon, B., and Hutchinson, G. B.: Prenatal x-ray and childhood cancer: a review, Acta Unio internat. contra can- crum 20: 1172 (1964).

10. Diamond E. L., Schmerler, H., and Lilienfeld, A. M.: The relationship of intra-uterine radiation to subsequent mortality and development of leukemia in children. A prospective study, Am. J. Epidemiol. 97: 283 (1973).

11. Jablon, S., and Kato, H.: Childhood cancer in relation to prenatal exposure to atomic-bomb radiation, Lancet 2: 1000 (1970).

12. Kneale, G. W., and Stewart, A. M.: Mantel-Haenszel analysis of Oxford data. I. Independent effects of several birth factors including fetal irradiation, J. Nat. Cancer Inst. 56: 879 (1976).

13. Ibid.: II. Independent effects of fetal irradiation sub- factors, ibid. 57: 1009 (1976).

14. Idem: Age variation in the cancer risks from foetal irra- diation, Brit. J. Cancer 35: 501 (Oct.) 1977.

15. Idem: Pre-cancers and liability to other diseases, ibid. 37: 448 (Mar.) 1978.

16. Kneale, G. W., Stewart, A. M., and Mancuso, T. F.: Re- analysis of data relating to the Hanford study of the cancer risk of radiation workers, IAEA-SM-224/5, Vienna Congress, March 13 to 17, 1978.

17. Brown, W. M., and Doll, R.: Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis, Brit. M. J. 2: 1327 (1965).

18. Gilbert, E. S., and Marks, S.: Cancer mortality in Hanford workers, IAEA-SM-224/4, ibid.

January 1980/New York State Journal of Medicine 35

Total Knee Arthroplasty

Update

KENNETH M. CHEKOFSKY, M.D.a

New York City

W. NORMAN SCOTT, M.D.b

New York City

JOHN INSALL, M.D.C

New York City

From the Departments of Orthopedic Surgery, Lenox Hill Hospital and Hospital for Special Surgery.

a Resident, Lenox Hill Hospital.

b Assistant Adjunct, Lenox Hill Hospital; Assistant, Hospital for

Special Surgery.

c Associate, Hospital for Special Surgery.

Successful knee arthroplasty requires painless motion and stability; since the nineteenth century there have been numerous attempts to realize this goal.1 Interposing membranes such as pig bladder, nylon, fascia lata, gold, cellophane, and other sub- stances have been used unsuccessfully. Resection of the arthritic joint was often done but did not pro- vide stability. Knee arthrodesis was the procedure of choice until the middle of the twentieth cen- tury.

Although fusions provided a painless and stable knee, the adverse long-term effects of this operative procedure encouraged further interest in a more physiologic result. Any arthroplasty consisting of replacing the femoral surface alone or the medial and/or lateral plateaus became more successful with use of better metallic alloys. Introduction of a con- strained hinge replacement allowing biaxial motion represented the beginning of total knee arthroplasty as it is known today.

Hinge replacements, such as the Walldius, Shiers, Guepar, and many others, were quite successful when applied to less-active rheumatoid arthritis patients.1 The rigid articulation with subsequent transmission of forces along the stems and the cement bone bond has always been a concern for potential loosening. Indeed, long-term experience with these has pro- duced a rather high rate of loosening. The experi- ence gained with this group of prostheses led to the development of a nonarticulated tibiofemoral re- placement by Gunston in the 1 960s. 1 Using the same materials and concept of low-friction arthroplasty as applied to total hip replacements, and recognizing

the importance of maintaining the instant center of rotation for knee motion, the polycentric replace- ment became the prototype of future surface re- placements. The cruciate-retaining (Geometric) replacement developed by five prominent orthopedic surgeons in the United States enticed many investi- gators to further refine a prosthesis that would allow for painless and stable knee arthroplasty.1

Although most endeavors were directed toward developing a cruciate-retaining tibiofemoral re- placement such as the Geometric, there were few attempts to develop a nonarticulated cruciate-sac- rificing prosthesis; Freeman must be credited with the latter concept. The Freeman-Swanson ICLH prosthesis challenged the basic concept that func- tioning cruciate ligaments were required for a suc- cessful nonarticulated replacement.1 Further re- finement of this idea, recognizing that prosthetic conformity could provide optimal stability, has led to the most rapid advances in this field.

Any joint includes both the tibiofemoral and patellofemoral articulations. In 1974, the first patellofemoral articulation knee arthroplasty was inserted.1 For the first time, the entire knee joint was successfully replaced.

In 1975, there were almost 300 available prosthetic designs, many of which had no resemblance to each other.1 Today, the number is fewer, and the pros- theses have many similar design features. Un- doubtedly, refinements will continue to be intro- duced, but for the first time it is safe to say that success with certain knee replacements has ap- proached the quality of results achieved with total hip arthroplasty.

Although there is still an abundance of prostheses, there is a useful classification. All the prostheses can be subdivided into four categories: Group 1 — cru- ciate retaining, Group 2 — cruciate sacrificing, Group 3 — constrained, and Group 4 — hinge replacements. Each of these group has respective advantages and disadvantages, but it was decided to use a cruciate- sacrificing replacement, the TCP (total condylar prosthesis), for our patients.

Description of TCP method

The TCP is a nonhinged, nonarticulated, cru- ciate-sacrificing prosthesis, with a curvature that roughly approximates the average, normal knee.2 The femoral component consists of a cobalt, chrome, and molybdenum alloy; the patella and tibia are made of high-density polyethylene (Fig. 1).

Surgical technique

The TCP uses perpendicular and parallel bone cuts to position the components so that the collateral ligaments are taut in extension with 90 degrees of flexion.3 The tibia is cut perpendicular to the long axis in both the coronal and sagittal planes; the an- terior and posterior femur are sectioned parallel to the shaft. The distal femur is cut to correct align-

36 New York State Journal of Medicine/January 1980

FIGURE 1. Total condylar prosthesis, from top to bottom: patella, femoral, and tibia replacements.

ment and flexion deformities. With severely de- formed knees, the basic technique is supplemented by an understanding of the deformity. Arthritic deformities are more accurately described in terms of imbalance rather than instability. On the concave side, the ligamentous and capsular structures become shortened. On the convex side, the ligaments stretch and lengthen from the stresses of weight-bearing. Shortening procedures have failed; releasing proce- dures have been successful. Varus release involves the periosteum, pes tendons, and superficial medial collateral ligament. Valgus release is done proximal to the knee joint and includes isolation of the pero- neal nerve and release of iliotibial band, lateral cap-

The abundance of total knee prostheses and their diversity of design has presented a challenging problem to the orthopedist. Since the early nine- teenth century different approaches have been used toward replacement of the articulating surfaces of the knee. Our study included 48 patients undergoing 57 prosthetic operations; 80 percent of the patients were male and 20 percent were female. Osteoarthritis was the diagnosis in 89 percent of the cases, rheumatoid art hritis in 1 1 percent, and 5 were revisions of failed operations. The overall results were good or excel- lent in 90 percent of the cases. The complications were few and included: delayed wound healing (5 cases), pulmonary embolus ( 1 ), peroneal palsy (1), and hepatitis (1).

sule, lateral collateral ligament, and posterior capsule of the femur.

Patient data

Of the 48 patients who underwent the operation with 57 prostheses, 80 percent were female, 20 per- cent male. Osteoarthritis was the diagnosis in 89 percent of the cases, and rheumatoid arthritis in 11 percent. Revisions of failed knee replacements ac- counted for five of the procedures and an infected prosthesis for one. There were 23 patients with varus deformity, maximum 20 degrees, and 34 pa- tients with valgus deformity, maximum 25 degrees. Each of the patients was evaluated using the Hospital for Special Surgery knee-score sheet. The score sheet quantitates the patients’ level of pain, function, range of motion, muscle power, deformity, and in- stability. A score of 85 to 100 is excellent, 70 to 84 is good, 60 to 69 is fair, and below 60 is poor.

All our patients had preoperative evaluation by an internist or rheumatologist: 30 percent were being treated for hypertension, 6 percent had previously documented ischemic cardiac disease, and 10 percent were diabetic. All the patients were placed on pre- operative and postoperative antibiotics. Postoper- atively, the patients were placed on aspirin prophy- laxis.

Results

The average preoperative knee score was 53: 34 in the rheumatoid patients and 57 in the osteoar- thritic patients. The postoperative score average was 82: 74 in the rheumatoid arthritis and 87 in the osteoarthritic patients. The overall results were good or excellent in 90 percent of cases.

Complications

The number of complications were few. Delayed wound healing, present in five cases, was the major problem, but was handled successfully in all cases.

January 1980/New York State Journal of Medicine 37

There was one pulmonary embolus, no deep infec- tions, and one peroneal palsy in a patient with a valgus knee who did not have a lateral release and isolation of the nerve. One patient developed a metastatic superficial infection after a distal stasis ulcer, and another developed a case of hepatitis at three months postoperatively. Thirty percent of patients required manipulation.

Comment

Our results are indeed comparable to the larger series previously reported.2

Venous thrombosis and its ensuing complication is different both in its etiology and occurrence when comparing the orthopedic and general surgical pa- tient.4 The rate of positive findings on venograms in the total knee-replacement patient is 35 percent.2 The venous thrombosis can occur not only from re- traction or direct manipulation but also from the heat produced by methylmethacrylate.5 All our patients had preoperative and postoperative phleborheo- grams. None showed a positive result.

The average blood loss per case was 1.3 units. There were no cases of postoperative myocardial ischemia, and all our patients have postoperative electrocardiograms on a routine basis.

Since this is an older group of patients, the therapy

Treatment for Hodgkin’s disease causes loss of sexual function

Chemical castration is the price of the “cure” of Hodg- kin’s disease, says an article in the October 26 Journal of the American Medical Association. And it doesn’t have to happen.

For more than 30 years medical science has been able to prolong life and sometimes virtually cure this serious cancer of the lymph nodes. But only now physicians are discovering that the drugs that are used in the treatment often destroy the sexual function of the patient.

The studies are the work of Ramona M. Chapman, M.D., and Simon B. Sutcliffe, M.D., at St. Bartholomew’s Hos- pital, London. Dr. Chapman is now at Walter Reed Army Medical Center, Washington, and Dr. Sutcliffe is at Prin- cess Margaret Hospital, Toronto.

It is not the disease itself that damages hormone func- tion, says Dr. Chapman. It is the drugs used to treat the disease.

Under the drug treatment, the disease responds well, but “young women show a pattern of progressive ovarian fail- ure accompanied by severe estrogen deficiency and lack of libido. The loss of ovarian function seems to result from the chemotherapy.”

The researchers cited many instances of marriage

must be attuned to their medical as well as orthope- dic needs. A bilateral procedure at the same sitting is done only if (1) the first side is completed within one hour and forty-five minutes, and (2) there are no signs of extreme blood loss or hypotension. In a re- cent total condylar study comparing unilateral and bilateral knee replacements, the rate of blood loss was 0.7 units for unilateral and 2.4 units for bilateral.6 Our overall results were good or excellent in 90 per- cent of cases.

Therefore, the TCP has been shown to be highly effective in relief of pain and improvement of func- tion for the arthritic knee.

References

1. Scott, W. N., Tria, F., and Insall, J.: Total knee arthro- plasty, past, present and future, Orthop. Surv. 3: 135 (Sept.- Oct.) 1979.

2. Insall, J., Scott, W. N., and Ranawat, C. S.: The total condylar knee prosthesis. A report of two hundred and twenty cases, J. Bone & Joint Surg. 61: 173 (Mar.) 1979.

3. Insall, J., Ranawat, C. S., Scott, W. N., and Walker, P.: Total condylar knee replacement, Clin. Orthop. 120: 149 (1976).

4. Gitel, S. N., et at: The effect of total hip replacement and general surgery on antithrombin III in relation to venous throm- bosis, J. Bone & Joint Surg. 61: 653 (July) 1979.

5. Stamatakis, J. D., et al.: Failure of aspirin to prevent postoperative deep vein thrombosis in patients undergoing total hip relacement, Brit. M. J. 1: 1031 (Apr. 22) 1978.

6. Scott, W. N., Insall, J., Zeno, S., and Koslin, B.: Unilateral and bilateral total knee replacement, J. Bone & Joint Surg., to be published.

problems and failures and other social ills among women “cured” of Hodgkin’s disease by drug treatment. The reluctance of the patients to talk with their physicians about it caused great anguish and suffering among patients for the past 30 years, she declares. The physicians did not know of the sexual malfunction.

Now that the side effect of the drugs is known, it usually is possible to offset the sexual loss by hormonal replace- ment, accompanied by appropriate counseling so that the patient will understand that loss of libido is to be expected during drug treatment, and can be corrected by hor- mones.

In an accompanying editorial, William H. Crosby, M.D., of La Jolla, California, declares:

“We were unaware that the pulses of drugs used in Hodgkin’s disease destroyed libido, ruining personal relations and disrupting families — this in addition to causing sterility. An unbelievable amount of human misery has been silently borne by the patients of three decades.”

Now that the problem is known to physicans and hor- monal replacement is available for those receiving drug treatment for Hodgkin’s disease, the response has been gratifying.

“They come in like shrinking violets; we treat them and they come back like English roses.”

38 New York State Journal of Medicine/January 1980

Master Two-Step Test

Present status

The Master two-step test can never give the infor- mation about cardiovascular fitness, cardiac func- tion, or arrhythmias that can be gained from a pro- gressive treadmill or bicycle stress test. In diag- nosing the presence of coronary disease and suggesting the prognosis for future coronary events, however, the augmented double Master two-step compares favorably in both sensitivity and specific- ity, especially if attention is paid to the postexercise rate. Risk ratios have also been shown to be not significantly different for the double Master and progressive exercise tests. Methods of standard- ization by the use of a metronome without Master’s tables and of achieving maximum safety are de- scribed.

JULES CONSTANT, M.D., F.A.C.C.

Buffalo, New York

From the Department of Medicine, State University of New York at Buffalo School of Medicine

The relatively simple Master two-step is still such a popular office test throughout the world that it is important to see if any new developments in the step test can allow it to compete with the treadmill or bi- cycle stress tests, which are not only more time- consuming and expensive but are not generally suitable as an office procedure. The two-step test can never replace a monitored treadmill or bicycle stress test for learning about ventricular function, physical fitness, or the analysis of exercise-induced arrhythmias. But as a test for the presence of sig- nificant coronary disease and for the prognosis of future coronary events, the Master two-step test must be compared with the progressive stress tests to see if it should be abandoned for these purposes also.

Physiology

Heart rate changes during test. In normal subjects a mean maximum heart rate of 144 beats per minute or 85 percent of predicted maximal, 220 minus the age, for a 50-year-old man occurs during a DM (double Master) or three-minute two-step test. However, subjects with angina performing a DM tend to have slower heart rates which approximate about 80 percent of the predicted maximum for a man of 50 years. Younger subjects tend to reach only about 75 percent, while some young and many older subjects reach 100 percent of predicted maximum at these work loads.1

The heart rate almost always reaches a plateau by the last minute of the DM. Therefore, aerobic con- ditions and a steady state apparently are obtained by the third minute.2 A training effect can be seen so that a lower heart rate may occur with a DM than with a single Master done a few days before.

It may not be important to reach the high maximal heart rates achieved with treadmill testing. This is suggested by the finding that the exercise-induced maximum heart rate is 15 to 20 percent lower in pa- tients with ischemic heart disease than in normal subjects.3,4 In another treadmill study of 651 subjects with ischemic chest pain, only about 40

percent achieved 85 percent of age-predicted heart rate in two separate tests conducted six weeks apart. Only 15 percent could reach the predicted maximum heart rate despite the fact that about 45 percent were on vasodilators.5 Therefore, most coronary patients may reach their near-maximum capabilities with a DM two-step test.

Master6 also noted that in a two-step test a fast heart rate was not always necessary because the amount of S-T depression in 200 patients with classic angina bore no relation to the maximum heart rate or to the percentage of maximum over their resting rate as recorded in monitored tests.

Oxygen consumption and work done during DM two-step test. The DM requires approxi- mately 8.5 calories per minute, or an oxygen uptake of about 20 ml. per kilogram per minute, that is, about 5 to 6 METS. ' This is about 50 percent of the maximum VO2 (oxygen consumption) measured during progressive exercise stress tests in sedentary middle-aged men.

Post-DM heart rate and pressure changes.

Although the postexercise heart rate of a DM may only reach 50 to 60 percent of predicted maximum heart rate, the coronary circulation may be inade- quate in the postexercise period.8 This may be be- cause the postexercise tension time index, the best index of oxygen consumption, which reaches a maximum by the second minute in normal subjects and by the fifth minute in coronary patients is also greater in coronary patients due to an increased ejection time and a rise in peripheral resistance. In coronary patients after a DM, unlike normal subjects, total peripheral resistance rises significantly above resting levels by the second minute, and the blood pressure, heart rate, and cardiac output take about eight minutes to return to resting value.9 In normal subjects the heart rate usually returns to resting rates by about three minutes.

Comparison studies

Comparison of in-exercise versus postexercise electrocardiographic monitoring. In one study

January 1980/New York State Journal of Medicine 39

TABLE I. Sensitivity for DM with angiogram correlations

	ECG	Per
	Criteria	cent
	(mm.	Sensi-
Chief Investigator	Depression)	tivity
Aronow et al.15	0.5	67
Cohn et al.16	0.5	84
FitzGibbon et al.17	0.5	62
McConahay, McCallister, and Smith18	0.5	60
Schweitzer et al.19	0.5	39
Ascoop et al.20	1	77
Cohn et al.16	1	77
Demany, Tambe, and Zimmerman21	1	64
Most, Kemp, and Gorlin22	1	50
Average		64
TABLE II. Sensitivity for bicycle tests with angiogram
correlations
	ECG
	Criteria Percent
	(mm.	Sensi-
Chief Investigator	Depression)	tivity
Kassebaum, Sutherland, and Judkins23	0.5	73
Mason et al.24	0.5	88
Schweitzer et al.19	0.5	45
Ascoop et al.20	1	60
Borer et al.25	1	33
Kassebaum, Sutherland, and -Judkins23	1	71
Likoff et al.26	1	58
Average		61

of over 5,000 DM and 200 submaximal treadmill or bicycle tests, only one patient had ischemic S-T segments during and not after exercise, and 98 per- cent occurred after exercise alone.10

Master and Rosenfeld,11 using a V5 lead with a V5r negative electrode in 52 patients with angina, found 40 positive tests during exercise and 49 positive tests in the postexercise tracings. Mattingly12 found that the S-T interval that persists for two to four minutes after exercise when the rate has decreased is more specific than the S-T depression that occurs during exercise.

The oxygen demands of a treadmill test may be different from that of a DM because most treadmill testing employs a warm-up and gradual increase in the amount of exercise. The immediate exercise at the maximal level for the DM protocol may cause an unfavorable shift in myocardial oxygen supply and demand not seen with some treadmill protocols. It is known that a sudden, vigorous exercise can pro- duce abnormal cardiogram findings in 60 percent of healthy men.13

Comparative sensitivity and specificity of bi- cycle, treadmill, and DM exercise tests. The DM

was compared with progressive exercise tests in re- spect to their ability to predict: (1) the presence of significant coronary vascular obstruction; (2) the degree of obstruction, for example, how many vessels are involved and at what site; and (3) the presence of latent coronary disease or prognosis for future coro- nary events.

Sensitivity of DM versus bicycle or treadmill testing for diagnosing the presence of coronary disease.

40 New York State Journal of Medicine/January 1980

TABLE III. Sensitivity for treadmill tests with angiogram correlations: ECG criteria 1 mm. S-T depression

Chief Investigator	Protocol	Percent Sensitivity
Bartel et al.27	Maximum	65
Cole et al.28	Maximum	95
Ellestad et al.29	Maximum	76
Goldman, Tselos, and	90 percent	80
Cohn30	maximum
Goldschlager, Selzer, and	85 percent	64
Cohn31	maximum
Kansal, Roitman, and	90 percent	92
Sheffield32	maximum
Martin and McConahay33	Maximum	62
McHenry34	90 percent maximum	72
Nasrallah et al.35	Maximum	67
Roitman, Jones, and Sheffield36	Submaximum	92
Average		77

Sensitivity tells you how often a test result is pos- itive in a group of patients with the disease; that is, it reflects how good the test is at avoiding false neg- ative findings.

Friedberg et al. in 1962, 14 using only clinical cri- teria, found a 90 percent sensitivity for the DM when 0.5-mm. S-T depression criterion was used. The sensitivity of eight other DM studies using coronary angiograms to decide the presence of significant coronary disease had an average sensitivity of 64 percent with a range from 39 to 84 percent (Table I). The study with the highest sensitivity, 84 percent, excluded all tests with a postexercise heart rate of less than 110 beats per minute.16

In seven bicycle studies, the sensitivity ranged from 33 to 88 percent, or an average of 61 percent (Table II).

In 10 treadmill reports, the sensitivity ranged from 62 to 95 percent with an average of 77 percent (Table III).

Comparing only those studies in which coronary angiograms were used as the criteria for coronary disease, most of the nine DM studies were as sensitive as most bicycle tests but not as sensitive as most treadmill studies. When, however, the DM study which eliminated patients with postexercise heart rates of less than 110 beats per minute was compared with graded exercise tests, it was more sensitive than 6 out of 7 bicycle tests and 7 out of 10 treadmill tests.16 This suggests that when the postexercise heart rate was less than 110, the test was not stressful enough. The use of the augmented DM will be dis- cussed later.

In multiple-vessel disease the DM becomes even more sensitive if the postexercise heart rate is 110 or more because then the DM has a 91 percent sensi- tivity. If an S-T depression of 2 mm. or more was recorded, there was a 95 percent chance of finding significant disease in two or three coronary ves- sels.16

Specificity of DM, bicycle, and treadmill tests in diagnosing the presence of coronary disease.

TABLE IV. Specificity for DM with angiogram correlations

Chief Investigator	ECG Criteria (mm. S-T Depression)	Percent (Specificity) |(0.5 1 mm.)\
Aronow et al.15	0.5 and 1	94	96
Ascoop et al.20	0.5	92
Cohn et al.16	0.5 and 1	73	88
Demany, Tambe, and Zimmerman21	1		70
FitzGibbon et al.17	0.5	67
Kemp et al.39	0.5	83	100
McConahan, McCallister, and Smith18	0.5 and 1	83
Schweitzer et al.19	0.5	87
Average		82	88

The specificity of a test tells you how often a group of patients free of the disease have a negative test; that is, it reflects how often a false positive response will occur.

When only clinical criteria and no angiograms were used, three studies showed that the DM had a spec- ificity of 55, 88, and 95 percent, with an average of 80 percent.1 4-37-38 When angiograms w'ere used, eight DM studies showed a range of 67 to 100 percent w'ith an average of 85 percent (Table IV).

All bicycle and treadmill studies had angiographic correlations. Five bicycle studies showed a speci- ficity range of 55 to 97 percent, with an average of 79 percent (Table V). Eight treadmill studies showed a specificity range of 70 to 96 percent, with an average of 81 percent (Table VI).

Thus there was no significant difference in speci- ficity between the DM and graded exercise tests. The specificity was influenced more by the protocol used and the selection of patients than by the type of test.

Comparison of treadmill tests with respect to sensitivity, specificity, and risk ratios in detecting latent coronary disease.

The sensitivity of the DM for the prediction of future coronary events, mostly in asymptomatic men, in five studies varied from 27 to 40 percent, with an average of 32 percent.12-39-12 For four treadmill tests the sensitivity was remarkably constant at about 60 percent.39-41-43-44

The specificity for the DM in four studies varied from 93 to 99 percent.12-42-45-46 For four treadmill tests it varied from 75 to 92 percent, with an average of 87 percent.39-41 -43-44

Thus, the treadmill test is almost twice as sensitive as the DM in predicting future events but is not necessarily more specific; that is, there were just as many or more false positive results. This suggests that a more vigorous exercise test than the routine DM is necessary to equal the predictive value of a treadmill test for future events, at least in asymp- tomatic men. Thus, there is a probability that just as a postexercise heart rate should equal at least 110 to give a good sensitivity for detecting the presence of coronary disease, this same goal should probably be attained if we wish to use it to predict future

TABLE V. Specificity for bicycle tests with angiogram correlations: ECG criteria 1 mm. S-T depression

Chief Investigator		Percent Specificity
Borer et al.25		55
Kassebaum, Sutherland, and Judkins23	97
Likoff et al.26		68
Mason et al.24		89
Schweitzer et al.19		86
Average		79
TABLE VI. Specificity for treadmill with angiogram
correlations: ECG criteria 1 mm. S-T depression
		Percent
Chief Investigator	Protocol	Specificity
Ascoop et al.20	Maximum	73
Bartel et al.27	Maximum	92
Cole et al.28	Maximum	87
Ellestad et al.29	Maximum	76
Kansal, Roitman, and	Near maximum	75
Sheffield32
McHenry34	90 percent	95
	maximum
Nasrallah et al.35	Maximum	85
Roitman, Jones, and	Submaximum	70
Sheffield36
Average		81

events with a DM.

Comparison of risk ratios for DM, bicycle, and treadmill tests.

By risk ratio is meant the percentage of patients with a positive test finding who develop the disease compared to the number of patients with a negative test result who develop the disease.

Risk ratios for 1 1 DM studies for periods of 1.5 to 10 years varied from 2:1 to 18:1 for coronary events, with an average of 11, and went even as high as 40:1 for coronary deaths.12-15-40-42-45-50 There were no significant differences between risk ratios in asymptomatic men and those with known coronary disease.

The risk ratios for one bicycle and seven treadmill studies over periods of two and one-half to six years in asymptomatic men varied from 3:1 to 15:1, with an average of 12:1, with the one exception of the study by Aronow51 carried over two and one-half years on 100 patients with the risk ratio of 23:

l 15,25,29,41,43,44,52,53

Thus, risk ratios have not been shown to be sig- nificantly better with either a treadmill, bicycle, or DM and probably depend on the protocol used and the selection of patients.

Advances in methods of doing the Master two-step test

Number of trips. Master’s assumption that a heavier subject does more work over a fixed distance than does a lighter subject disregards the increases in muscle mass, heart weight, and stroke volume that compensate for increased weight. Also, the in- creased heart rate in an exercise test depends mostly on the rate of work. The total oxygen uptake for a heavier person doing the same rate of work will be greater, but the adjusted VO-2 to kilogram body

January 1980/New York State Journal of Medicine 41

weight will be identical. Using Master’s tables, the oxygen requirements per kilogram of body weight are much higher for lighter subjects who are made to do enough trips to approach their maximum oxygen uptake, as much as 10 METS, than for the heavier subjects who do many fewer trips and are farthest from their maximum, some as low as 5 METS.54

As for age, there is no evidence for a decrease in the mechanical efficiency in response to a fixed task from teens to about age 70.55 It has been shown that if all subjects with different weights and ages do 20 trips for a single, 1.5-minute, test and 40 trips for a DM, that is, the number of trips from Master’s tables for a 150-pound man aged 50, there is much less varia- tion in total net oxygen consumption when expressed per unit of body weight when different numbers of trips are used according to Master’s tables.54

Timing trips. The easiest way to make sure that the patient completes 20 trips, that is, the single Master two-step, in exactly 1.5 minutes is to have the patient climb each step to the rhythm of a metro- nome set at a rate of 66. If a subject takes one beat to turn, the test will be completed in the exact period of time. If Master’s original age and weight tables are used, then the number of trips for a 1.5-minute test should be multiplied by ten-thirds to get the correct metronome setting.

Augmenting DM trips. The best DM sensitivity for the prediction of coronary disease by angiography was obtained when a rate of at least 110 beats per minute was reached post exericse.16 Therefore, a negative DM test result with a rate of less than 110 should be considered an inadequate test, and a more strenuous exercise should be done.

Master1 found that an augmented test of 15 per- cent more steps than in his tables did not produce an unacceptable number of false positive test findings. If, however, the quadriceps muscles will not tolerate an increase in the number of trips, a practical modi- fied augmented step test can be used. The patient walks at a brisk pace over the steps for 10 minutes or until chest pain if that comes first. He returns to the starting point by walking around on the floor and avoids vertigo by turning clockwise and then coun- terclockwise as he returns to his starting point.

How to make the two-step test safe. Myocar- dial infarction, ventricular fibrillation, and death have occurred with the performance of a step test.56 A defibrillator and personnel trained in cardiopul- monary resuscitation should be nearby. Several precautions are necessary to emulate Master’s claim that he did 20,000 tests without a mishap. If the clinical history suggested definite angina, he always did a single, 1.5-minute test first, and only if that result was negative or equivocal did he do a double test.57’58 However, it saves time to do an augmented DM, (46 trips) immediately on a patient with nonanginal chest pain and no obvious coronary dis- ease.

The diagnosis of nonanginal chest pain may be made if any one of the following is present: ( 1 ) the pain is too short, that is, less than five seconds, or too long on many occasions, that is, over one-half hour;

or (2) the pain increases with one inspiration or can be brought on by bending forward, local pressure, or one movement of the chest or arm. Beware of the patient who has more than one pain or exercise- induced pain that disappears in less than five seconds if the patient stops immediately at its onset.

If the 1.5-minute test finding is negative, then an augmented DM may be done safely. The test should be stopped at the onset of pain or excessive dyspnea. A report by Master concerned a patient who was told to keep walking until exhaustion or pain occurred. He would have done only 38 trips according to Mas- ter’s tables. He collapsed on the fifty-eighth trip with a heart rate of 20. Fortunately, he recovered, but there have been myocardial infarctions reported in patients subjected to continuous unmonitored step exercise until pain or exhaustion.59

In one report of myocardial infarction associated with a Master test, the subject had reported experi- encing nocturnal angina for four months after an infarction. After eight trips he developed unusual dyspnea without pain.56 This suggests that excessive dyspnea should also be an end-point and that if a patient has a history strongly suggestive of coronary disease, that is, past infarction or classic angina, Master’s original precaution of doing the 1.5-minute test in a fasting state should probably be rigidly ad- hered to.

Accelerating angina is also a contraindication to performing the test. Of 50,000 DM tests reported in the literature, there were six myocardial infarctions either on the day of or following the test. In all of these either the resting ECG or symptoms had sug- gested the presence of acute coronary insufficiency. A recent infarction subject should probably have at least four weeks of convalescence before a Master step test is done. An exercise test done any earlier after infarction should probably be a carefully monitored low-level treadmill or bicycle test.

How to avoid false positive findings in pre- dicting future events. The incidence of false positive results for detecting future coronary events in bicycle and treadmill studies ranged from 8 to 25 percent.39,51 For the DM the range was from 1 to 7 percent.42,46

To prevent false positive findings in predicting future events, it is helpful to use ancillary predictive factors.

1. If the test result is positive, take into account the patient’s risk factors and the past history of heart disease. For a cholesterol of over 275 mg. per deciliter compared to 200, the risk ratio for developing ischemic heart disease was 6:1. For 40 percent over ideal weight and for smoking, the risk ratios were 4:1.

2. Use postexercise ECG changes other than S-T depression. While ordinary postexercise premature ventricular contractions have no significant effect on risk ratio, if they are in higeminy there is an increased risk ratio.50’52’5'1’60

3. Use symptoms during exercise. If there is angi- na at the time of a treadmill S-T depression, there is a 50 percent chance of a coronary event occurring within

42 New York State Journal of Medicine/January 1980

a year.61 This was two and one-half times the inci- dence of coronary events with only a positive test re- sult. Also, if the pain occurred at a low work load, there was an even higher incidence of coronary events.

How to avoid a false negative Master two- step test finding for detecting the presence of coronary disease. The incidence of false negative DM test findings ranges from 16 to 67 percent. Therefore the cause of false negative findings in double- and triple-vessel disease may be partly due to techniques of doing and interpreting the test.

There are several precautions that can be taken to avoid false negative results:

1. Take the leads that are most likely to show is- chemic changes. V5 picks up about 90 percent of all positive findings, We picks up 70 percent, and V.t about 55 percent. Then come V3, lead II, lead III, and a Vf. Occasionally each of these may be the only lead to show S-T abnormalities.62 Therefore, to pick up 110 percent of positive results one must do the chest leads, V5, We, V4, and V3, and the limb leads, II, III, and a Vf, preferably in that order.

2. If the 46-trip augmented DM yields a negative finding but the postexercise rate is less than 100 per minute, increase the amount of exercise by the "walk- around” 10-minute step test described previously.

DM as test of fitness. Although an accurate ex- ercise prescription can be given only after a bicycle or treadmill test, a DM can be used as an office screening test. The equivalent of a DM to a tread- mill is a brisk walk at about three miles per hour at a 5-percent grade for 10 minutes, or about 4.5 miles per hour on the level. This would be equal to mod- erately heavy work and is roughly equivalent to climbing up and down two flights of stairs in about one minute.63 Any patient able to complete a DM with slight symptoms is likely able to meet the de- mands of any light jobs, such as light industry tasks, retail, and distribution work. These jobs are clas- sified as not requiring either over 5 cal. per minute or a heart rate of over 110.63

Indications for a Master two-step test

The significant number of false positive and neg- ative results with every type of exercise test in trying to predict the presence of significant coronary disease limits their value in telling you the cause of chest pain. As high as 25 percent false negative findings can occur with a maximal Bruce protocol, the most strenuous and anaerobic of all TM protocols, even in the presence of triple-vessel disease. False positive findings can occur even with a downsloping S-T segment.27 64 The routine evaluation of chest pain should, therefore, be based mainly on history, physical examination, x-rays, the resting ECG, sys- tolic time intervals, and echocardiography findings. An ECG taken during an episode of spontaneous pain can help rule out variant angina.

Of more value is the use of an exercise test to in-

dicate prognosis and to help decide who should have angiography with a view to bypass surgery. A posi- tive stress perfusion scintogram result with thallium occurs in about 15 percent of patients with only one- or two-vessel disease and in only 45 percent of pa- tients with left-main or three-vessel disease.65 Therefore, it is of limited value in deciding which patients are in a high-risk group anatomically. It is also unknown whether the positive scintogram finding has any prognostic value. There is, however, suggestive evidence that degrees of positivity in an exercise test finding has prognostic value. This is suggested by the correlation between the degree and slope of S-T depression and prediction of future events found in several studies.

Robb and Marks,50 in a DM study of 3,300 men, one half with atypical pain and 25 percent with no pain but an abnormal ECG finding, found that over an average of nine years the risk ratios for coronary events increased with increasing S-T depression. The risk ratio for an S-T depression from 0.1 to 0.9 mm. was 2:1; for an S-T depression of 1 to 1.9 mm. it was 3:1; and if 2 mm., it was 10:1. For coronary deaths alone the risk ratios were two to three times higher for each of the aforementioned categories of S-T depression.

Punsar, Pyorala, and Siltanen66 reported that if the S-T segment sloped up to a T that began below the base line, there was a 25 percent increase of cor- onary events or grossly abnormal cardiogram findings within five years. If the S-T segment was horizontal or downsloping, there was a 50 percent increase in coronary events or abnormal cardiogram results, while with no S-T depression, there was only a 7 percent incidence.

Ellestad and Wan67 showed that after a six-year follow-up an S-T depression of 0.5 to 1.4 mm. had a risk ratio of 4:1, but if 1.5 mm. or more, it was 7:1. Also a negative test result showed a 3-percent-per- year incidence of coronary deaths, w'hile a 1-, 2-, and 3-mm. depression resulted in an 8-, 10-, and 13-per- cent yearly mortality rate from coronary disease.67 They found that with maximum exercise the degree of S-T depression did not correlate with either the severity of coronary disease or future events, but with less strenuous exercise, the degree of S-T depression gave a fair correlation.67 Therefore, a test some- where between the routine, moderate DM and the more strenuous maximum treadmill protocol seems to be a suitable compromise. Such augmented step tests were discussed in the Methods section.

It is generally agreed by those who believe that aortic-coronary bypass surgery can prolong life, that patients with either two- or three-vessel disease or main left coronary disease will probably live longer after bypass surgery. The degree and slope of S-T depressions may not only give you prognostic criteria but can also tell you the probability of finding a de- gree of coronary obstruction which, if bypassed, will prolong life.

The degree and slope of S-T depression does seem to correlate with the severity of coronary disease. A

January 1980/New York State Journal of Medicine 43

2-mm. S-T depression after a submaximal treadmill test was associated with a 75 percent incidence of critical obstruction to the anterior descending main left coronary artery.68 A 3-mm. or more S-T de- pression after a maximal treadmill test in one study always indicated two- or three-vessel disease with invariable involvement of the proximal anterior de- scending artery.69 In another study a downsloping S-T segment persisting for eight minutes into re- covery was associated with not only a 99 percent chance of being a true positive result but also with an over 85 percent chance of having two- or three-vessel or main left coronary artery disease.70

Pain with the S-T depression also has anatomic predictive value. Of patients with pain accompa- nying ischemic S-T depression, 90 percent not only have significant coronary disease, but most have two- or three-vessel disease.71

Since the degree and shape of the S-T depression and the reproduction of pain does appear to correlate with future events and the severity of obstruction, it suggests the possibility of using the DM as an indi- cator as to when to do coronary angiography with bypass surgery in mind. If the test result is markedly positive, that is, there is a persisting 2-mm. or more downsloping S-T depression, especially if accompa- nied by chest pain and a fourth heart sound, then the prognosis is probably bad enough to warrant coro- nary angiography.

One DM study found that of patients with signif- icant three-vessel disease, one third had a normal result, one third had a 1-mm. or less S-T depression, and one third had at least a 2-mm. S-T depression.22 Therefore, if the degree of S-T depression does in- deed correlate with the future development of coro- nary events, then there must be considerable vari- ability in the life expectancy of patients with three- vessel disease. A marked S-T depression of over 2 mm. following a step test should at least call for the anatomic prognostic data provided by angiog- raphy.

There is more to be learned from a progressive stress test with constant monitoring of blood pressure and ECG than can be learned from the unmonitored step test, but if all you wish to know is whether there is ischemia due to coronary disease, or what the prognosis is for future coronary events in an attempt to help you decide whether a patient should have coronary angiography, there is no proof that a proh gressive stress test is superior to an augmented DM two-step test. If a Master two-step test finding is markedly positive, then coronary angiography may well he indicated as the next step in the management of that patient. If, however, the step test shows only a moderate S-T depression of 1 to 2 mm. then per- haps a progressive exercise test with monitoring of blood pressure, testing of cardiovascular fitness, and even thallium scanning is indicated as the next step. If the augmented Master two-step test result is negative despite a postexercise rate of at least 110, it is questionable whether anything more than

medical management of symptoms and risk factors is necessary.

100 High Street Buffalo, New York 14203

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64. Kurita, A., Chaitman, B. R., and Bourassa, M. G.: Sig- nificance of exercise-induced junctional S-T depression in eval- uation of coronarv artery disease, Am. J. Cardiol. 40: 492 (Oct.) 1977.

65. Dash, H., Massie, B. M., Botvinick, E. H., and Brundage, B. H.: The noninvasive identification of left main and three-vessel coronary artery disease by myocardial stress perfusion scintigra- phy and treadmill exercise electrocardiography. Circulation 60: 276 (Aug.) 1979.

66. Punsar, S., Pyorala, K., and Siltanen, P.: Classification of electrocardiographic S-T segment changes in epidemiological studies of coronary heart disease. Preliminary evaluation of a new. modified classification, with particular reference to the prognostic significance of different types of S-T segment changes, Ann. Med. Int. Fenniae 57: 53 (1968).

67. Ellestad, M. H., and Wan, K. C.: Predictive implications of stress testing. Follow-up of 2700 subjects after maximum treadmill stress testing, Circulation 51: 363 (1975).

68. Cheitlin, M. D., et al.: Correlation of “critical" left coro- nary artery lesions with positive submaximal exercise tests in patients with chest pain, Am. Heart J. 89: 305 (1975).

69. Williams, D. O., Capone, R. J., and Most, A. S.: The “strongly positive exercise test”; an indication for aggressive management of angina pectoris, abstract 10, Circulation (supp. 2) 53: 10 54:10 (1976).

70. Goldschlager, N., Selzer, A., and Cohn, K.: Treadmill stress tests as indicators of presence and severity of coronary artery disease, Ann. Int. Med. 85: 277 (1976).

71. Weiner, D. A., et al.: The predictive value of chest pain as an indicator of coronary disease during exercise testing, abstract 10, Circulation (supp. 2) 53: 10 54: 10 (1976).

January 1980/New York State Journal of Medicine 45

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Multiple Foci of Colorectal Carcinoma

A review of 50 consecutive colon resections with ref- erence to the status of multiple malignant foci within the specimens is presented. Significant findings were that 80 percent of cases had associated benign polypoid lesions; 14 percent had invasive carcinoma within villous adenomas; 4 percent had superficial carcinoma within pedunculated polyps; 2 percent had an early mucosal carcinoma; and 14 percent had a second invasive carcinoma. Thus, a total of 34 percent of these patients had more than one focus of malignant disease within the resected colon. Pre- operative evaluation with complete colonoscopy seems mandatory in any patient with a known ma- lignant lesion within the colon. When indicated, subtotal colectomy preserving the rectum seems to be a reasonable resection of choice when more than one lesion is indicated.

Argument for subtotal colectomy

RICHARD FOGLER. M.D., F.A.C.S.

Brooklyn, New York

EDWARD WEINER, M.D.

Brooklyn, New York

From the Departments of Surgery and Pathology, The Brookdale Hospital Medical Center

Excluding skin cancer, carcinoma of the colon and rectum afflicts more patients than any other malig- nant disease in the United States.1 The five-year survival rate of carcinoma of the colon has not changed in the past 20 years,2 despite major advances in surgery, chemotherapy, immunology, and radia- tion therapy. In general, the stage of the disease at the time of initial surgery is the prime factor in the patient’s ultimate prognosis.2-4

Unfortunately, in many cases, the results are less than satisfactory. Controversy concerning ancillary therapeutic modalities as well as the extent of sur- gical resection for a particular lesion continues. In addition, the concept of the colon as a premalignant organ capable of producing multiple foci of malignant change remains an enigma because of the markedly variable statistics concerning the incidence of this phenomenon in the general population. In an at- tempt to crvstalize a “tailored” approach to treat colon cancer, all patients referred to Dr. Fogler with this problem since January, 1973, were thoroughly investigated for potential second cancers.

Subtotal colectomy, that is, colonic resection to the peritoneal reflection with ileoproctostomy, was ar- bitrarily chosen as the surgery of choice for carcinoma of the colon. The selection of cases depended on the points emphasized in the accompanying protocol.

Materials and methods

After routine history and physical examination, all patients underwent digital rectal examination with guaiac test, sigmoidoscopy, and barium enema ex- amination with air contrast as the initial screening procedures.

Protocol. Any patient with a lesion proximal to the splenic flexure of the colon or the suggestion of other colonic lesions, that is, polyps, carcinomas, and so forth, or the persistence of guaiac-positive stool or frank rectal bleeding in the absence of positive x-ray findings, were examined by colonoscope preopera- tively.

Patients with nonobstructing distal colonic lesions were also studied by colonoscopy on occasion, but not patients with obstructing or partially obstructing colonic lesions.

Subtotal colectomy was chosen as the procedure of choice for any of the following situations:

1. Patients with suspicious multiple colonic le- sions.

2. Patients in good health, with no life-shortening medical contraindications, no matter what the location of the colonic lesion, that is, above the peritoneal re- flection.

3. At laparotomy, the absence of extracolonic evi- dence of carcinoma.

4. Patients who, by all routine parameters, such as age, medical illness, and extent of disease, would prob- ably be five-year survivors.

The thrust of the pathologic and histologic stud- ies was designed to identify synchronous malignant lesions of the colon. Although 40 of the 50 cases in this series had associated polypoid lesions, only those with malignant change were considered in the mul- tiple primary statistics. Thus, colons that contained

FIGURE 1 . Panoramic view of subtotal colectomy specimen with demonstration of 3 invasive carcinomas.

January 1980/New York State Journal of Medicine 47

FIGURE 2. Flat cecal lesion. (A) Section showing in situ malignant change, in continuity with normal mucosa (hematoxylin and eosin stain). (B) High-power view showing well-circumscribed, early malignant change with multiple mitotic figures and gland in gland pattern (hematoxylin and eosin stain, original magnification X 410).

FIGURE 3. Sections. (A) Mixed villoadenomatous polyp demonstrating progression from cellular atypia to early car- cinoma. (B) Through base of villous adenoma with frank invasive carcinoma. (Hematoxylin and Eosin Stain)

a symptomatic malignant lesion plus one or more other histologically malignant lesions represented by ( 1 ) a second invasive carcinoma, as shown in Figure 1; (2) a de novo carcinoma in situ, as illustrated in Figure 2; (3) a villoadenomatous polyp with super- ficial carcinoma (Fig. 3A); and (4) villous adenomas with malignant change, as shown in Figure 3B, were classified as multiple primary cases. The raw data concerning the 50 consecutive cases of carcinoma of

the colon seen and treated by resection from January, 1973, to September, 1977, are summarized in Tables I and II. There were 28 males and 22 females, with ages ranging from 36 to 94 years. All cases of resec- tion with anastomosis were performed with the Gastrointestinal Anastomosis Instrument (GIA Autosuture device). Two patients included in the subtotal colectomy statistics actually had total proctocolectomy and ileostomy, and one other pa- tient had a Hartmann operation.

Results

The overall operative mortality rate for the 50 cases was 4 percent. Two patients requiring seg- mental resection for perforated carcinoma expired after prolonged hospitalization. There were no op- erative deaths in the subtotal colectomy group, and morbidity statistics, including those reflecting pro- longed postoperative diarrhea, were minimal. Of the 15 subtotal colectomy patients, 3 required antidiar- rheal medication while in the hospital. No patient required routine antidiarrheal medication after discharge.

Seventeen patients had multiple malignant lesions by our criteria. Nine patients were known to have two or more malignant foci preoperatively, while the other eight were discovered at laparotomy or after resection. These eight patients are further sub- classified as follows:

1. Seven patients were operated on prior to the avail- ability of routine colonoscopy. Of these:

TABLE I. 50 colonic resections for cancer

Category	Number (Percent)
Sex
Male	28(56)
Female	22(44)
Mult iple lesions	17(34)
Recognition
Preoperative	9(18)
Postoperative	8(16)
Subtotal colectomy	15(30)

48 New York State Journal of Medicine/January 1980

TABLE II. Summary of multiple-lesion patients

Patient Known

Num- Initial Primary Second Malignant Other Colonic Preoper- Miscellaneous

ber Lesion Focus Lesions atively Operation Information

1	Adenocarcinoma of	Villous adenoma with		+	Rectal resection Refused laparotomy
	rectum	carcinoma in transverse colon
2	Adenocarcinoma of	Extensive cecal		-	Subtotal
	sigmoid colon	adenocarcinoma			colectomy
3	Adenocarcinoma of	Villous adenomas with	Numerous benign	-	Subtotal	Multiple carcinoid tumors
	rectum	invasive carcinoma in	pedunculated		colectomy	of small bowel
		ascending colon	polyps
4	Adenocarcinoma of	Adenocarcinoma of	Numerous benign	-	Subtotal
	descending colon	cecum and sigmoid	pedunculated polyps		colectomy
5	Adenocarcinoma of	Adenocarcinoma of	Benign pedunculated	+	Subtotal	Anterior resection for
	hepatic flexure of	distal and descending	polyps		colectomy	adenocarcinoma of recto-
	colon	colon				sigmoid two years prior
6	Adenocarcinoma of Adenocarcinoma of	0	-	Subtotal	Adenocarcinoma of small
	descending colon	cecum			colectomy	bowel at this time; anterior resection for adenocarcinoma of recto- sigmoid four years prior
7	Irreducible hernia	Adenocarcinoma of	0	-	Right	Fatjent’s chief complaint
		cecum and in villous			hemicolecto-	was irreducible right
		adenoma distal			my	inguinal hernia
8	Adenocarcinoma of Adenocarcinoma of	0	-	Left
	sigmoid colon	descending colon			hemicolecto-
9	Mucoepidermoid	Invasive	0	+	Total proctoco-	Anal tumor discovered
	carcinoma of	mucoepidermoid			lectomy and	in fistulous tract
	anus	carcinoma in villous adenoma of descending colon			ileostomy
10	Obstructing	Numerous villous	Benign polyps	+	Subtotal	Primary villous adenoma
	adenocarcinoma	adenomas with			colectomy	of appendix also present
	of sigmoid colon	carcinoma
11	Obstructing	Superficial	Two benign polyps	-	Subtotal
	adenocarcinoma	adenocarcinoma of			colectomy
	of sigmoid colon	cecum
12	Superficial	Adenocarcinoma of	Multiple minute	+	Subtotal
	adenocarcinoma	transverse colon	sessile adenomas		colectomy
	of sigmoid colon		with marked atypia
13	Obstructing	Three villous adenomas	Two benign villous	+	Left
	adenocarcinoma	with adenocarcinoma	adenomas, several		hemicolecto-
	of splenic flexure	of descending colon	pedunculated		my
	of colon		polyps
14	5 X 8-cm. of benign Two villoadenomatous	Several	+	Subtotal
	villous adenoma	polyps with	villoadenomatous		colectomy
	of hepatic flexure	adenocarcinoma in	polyps with atypia
	of colon	transverse colon
15	Adenocarcinoma of Adenocarcinoma of	Benign pedunculated	+	Right	Adenecarcinoma of prostate
	transverse colon	midtransverse colon	polyps		hemicolecto-
16	Obstructing	Villoadenomatous polyp		—	my Segmental
	adenocarcinoma	with superficial			resection
	of rectosigmoid	carcinoma in sigmoid			(Hartmann)
	with perforation	colon
17	Adenocarcinoma of Two sessile villous	Multiple benign	+	Total
	rectum	lesions with superficial sessile and		proctocolectomy,
		carcinoma	pedunculated polyps		ileostomy

A. Four patients had the second lesion missed by barium enema.

B. Three patients had obstructing lesions on