0

incleraF (PROPRANOLOL)

A beta-adrenergic receptor blocking agent for the treatment of angina pectorls. INDERAL, given daily, prophylactically, reduces the incidence of anginal pains and the requirements for nitroglycerin tablets. Exercise tolerance and physical activity are increased. In many cases, pulse rate may be reduced. Dosage should be adjusted to patient's requirements for maximal benefit with minimal adverse effects (see PRECAUTIONS). Dosage and administration: First day 20mg; then increase by 20mg per day for one week. Then 40 mg four times daily before meals and at bedtime. Occasionally, in resistant cases, doses as high as 320-400 mg per day have been administered safely with beneficial results. If treatment is to be discontinued, reduce dosage raduall over a period of about two weeks (see RECAUTIO NS). CautIon: Abrupt Cessation of INDERAL Therapy in Angina Peotoris There have been reports of severe exacerbation of angina and myocardial infarction occurring in patients with angina pectoris following abrupt discontinuation of INDERAL. Therefore, when discontinuation of INDERAL is planned in patients with angina pectoris, the dosage should be gradually reduced over a period of about two weeks and the patient should be carefuily observed. The same frequency of administration should be maintained. In situtations of greater urgency, INDERAL therapy should be discontinued stepwise and under close observation. If an gins markedly worsens or acute coronary in sufficiency develops, it is recommended that treatment with INDERAL be reiostituted promptly, at least temporarily, in addition, patients with angina pectoris should be warned against abrupt discontinuation of INDERAL Note: The CAUTION concerning the abrupt cessation of INDERAL therapy referred to under ANGINA PECTORiS (see above) need not apply to patients with hypertension provided they have no angina pectoris. Contraindicatlons: Bronchial asthma. Aliergic rhinitis during the pollen season. Sinus bradycardia and g reaterthan second degree or total heart block. Cardiogenic shock. Right ventricular failure secondary to pulmonary hypertension. Congestive heart faliure unless the failure is secondary to a tachyarrhythmia treatable with INDERAL. In chloroform and in ether anesthesia. Precautions: Occasionally, INDERAL has caused sinus bradycardia due to unopposed va.al activity which has been corrected by atropine. A resting pulse of 55-60 is frequentiy associated with INDERAL therapy. Patients without a previous history of cardiac failure have occasionally developed failure, or patients in incipient failure have developed overt congestive failure after treatment with INDERAL. In such cases, if the response is unsatisfactory, INDERAL should be stopped immediately. If a good response is obtained, patients should be fully digitalized and observed closely. If failure persists, INDERAL should be withdrawn completely. The number of patients with such difficulties is small compared with the total number treated. The safety of INDERAL in pregnancy has not been established. INDERALahouId be administered cautiously to children, patients subject to hypoglycemia, patients on hypoglycemic agents, patients with impaired renal or hepatic function, uncontrolled diabetes, shock, metabolic acidosis, and to patients undergoing elective surgery. Patients receiving catecholamine-depleting drugs, such as reserpine, should be closely watched when INDERAL is given concomitently. Adverse reactions: Epigastric distress; dry mouth; mild diarrhea; constipation; lightheadednesa; dizzinesa. H ypotension, con.estive heart failure and marked bradycardia, including sinus arrest, have been reported. Bronchospasm and, rarely, respiratory distress and laryngospasm have occurred, particularly in patients with bronchial asthma. During anesthesia, INDERAL may produce bradycardia due to unopposed vagal activity, reversible with atropine. A few cases of marked bradycardia have resulted while on INDERAL in the presence of hypovolemia and a vasoconstrictor. For other, rarely observed adverse reactions see Product Monograph. Supplied: Tablets of 10 mg and 40 mg in bottles of 100 and 1000; tablets of 80 m. in bottles of 100. Also INDERAL Starter Pak-incremental dosage for first weekof therapy in push-through blister pack.

AYERST LABORATORIES Division of Averat. McKenna & Harrison Limited Montreal. Canada Made in Canada by arrangement with IMPERIAL CHEMICAL INDU STRI ESL MIT ED Product Monograph available on request Reg d

troduce new ideas and bring about development without suppressing local initiative. Accordingly, after 4 years the team was withdrawn slowly, the last MEDICO physician leaving in 1968. Since that time the hospital has been without any foreign staff. This policy was adhered to despite many requests for a longer period of service and such local comment towards the end of the project as "this hospital will stop developing as soon as you leave." In November 1976 I returned to the Kluang District Hospital to see what had happened to our project and to visit old friends. I found that progress had continued at a rapid rate and that all the innovations we had introduced were functioning in an expanded form. The central sterile supply room has operated at full capacity since we left and now supplies two operating rooms instead of one. The blood bank was functioning well. An enlargement to the library and a lecture room had been added. A completely new and larger laboratory had been built, was well staffed and was capable of carrying out an extensive range of complex bacteriologic studies. Two roentgenogram machines were functioning and the intensive care unit was busy and had been moved closer to the operating room. Full electronic monitoring and resuscitation were available. The change was remarkable considering the situation in 1964 when the hospital had only a small outpatient department with dispensary, several wards, only one operating room and a small laboratory where only a few tests could be performed. It was the opinion of the medical staff that CARE-MEDICO had shown the way with a pilot project of hospital development that was later duplicated in many district hospitals in the region. It was encouraging that many young, recently graduated physicians at one time considered the addition of a laboratory, an intensive care unit, a central sterile supply room and an improved operating room to be the norm in hospital development. The lessons we learned from this undertaking can be summarized as follows: 1. Development plans should be instituted in consultation with the local government and only after considerable time is spent working in the hospital to reach conclusions as to what the hospital can best use. 2. Several hospital departments should be developed to a certain equal level simultaneously rather than in sequence, on the principle that, for example, the operating room, laboratory, blood bank, hospital wards and intensive care unit are interdependent.

3. The medical development team should provide for a flexible, planned phase-out period in order to afford predictability and avoid suppressing local initiative. 4. An educational program must be conducted on a continuous basis as it is essential that permanent trained counterpart personnel be available. 5. Outsiders should never compete with the locally available service but add to it something that is new and unavailable. 6. It is bad policy to supply disposable equipment funded from abroad; only reusable equipment should be introduced. Unquestionably the great improvement in economic conditions in Malaysia in the last decade has resulted in improvement of medical services and has been the most important factor in the improvement of Malaysian medicine. However, the Kluang District Hospital would never have progressed without the help and leadership of the CARE-MEDICO team. It was the opinion of the physicians and other hospital staff that CARE-MEDICO had concentrated the development into a short space of time, after which progress was easier. Thanks go to the many individual donors, volunteers and staff of CAREMEDICO and particularly to the many interested Malaysians, both in government and in the private sector, who helped over the last decade to make this Canadian project a success. JOHN R. TAYLOR, MD, FRCS[c] 6700 Finch Ave. W Toronto, Ont.

Hair dyes and bladder cancer To the editor: Recent work has demonstrated the mutagenicity of hair dyes in bacterial mutant systems.1'2 By far the greatest number of dyes are known to be absorbed through the skin and, therefore, on the assumption that most carcinogens are also mutagens,3 dyes must be regarded as potential carcinogens in man. It is speculated that the carcinogenic or mutagenic effects of these chemicals may be due to their extensive reaction with deoxyribonucleic acid.4'5 Although the results of earlier tests performed on dogs and rodents did not indicate that hair dyes are carcinogens6'7 there is some preliminary epidemiologic evidence for this belief in the higher incidence of bladder cancer in barbers, hairdressers and beauticians.8'9 However, a study from Massachusetts discovered no excess risk among female hairdressers.10 Searle and colleagues11 found some carcinogenic activity in their tests on mice. Four

CMA JOURNAL/NOVEMBER 19, 1977/VOL. 117 1131

Maalox '

MAGNESIUM ALUMINUM

DIMETHYLPOLYSILOXANE ANTACID/ANTIFIATULENT

Indications: The treatment and relief of symptoms of peptic ulcer, gastritis, hyperacidity, and the management of gastrointestinal disorders accompanied by excessive gas or flatus.

ContraIndications: Alkalosis; hypermagnesemia; where distention may be due to partial or complete intestinal obstruction. Not recommended for severely debilitated patients or those with impaired renal function.

Precautions: Magnesium salts, in the presence of renal insufficiency, may cause ONS depression. Aluminum hydroxide, in the presence of low phosphorus diets, may cause phosphorus deficiency. Aluminum salts tend to cause constipation. Antacids can interfere with the absorption of iron preparations and/or tetracyclines.

Dosage: Suspension: Adults, 2 to 4 teaspoonfuls taken 20 minutes to 1 hour aher meals and upon retiring. May be mixed with milk or water, except in gastritis, when undiluted administration is recommended.

Tablets: Each tablet is approximately equivalent to 1 teaspoonful of the suspension. Two to 4 tablets well chewed, 20 minutes to 1 hour aher meals and at bedtime. May be followed with water or milk.

Supplied: Suspension: Each 5 ml of peppermint or lemon swiss creme flavoured, creamy, colloidal suspension contains: 200 mg of magnesium hydroxide, aluminum hydroxide (equivalent to dried gel U.S.P.) 228 mg and dimethylpolysiloxane 25 mg. Sodium content: 2.5 mg/S ml (peppermint): 2.25 mg/5 ml (lemon swiss creme). Available in 340 ml bottles. Protect from freezing.

Tablets: Each round, pink-and-white (peppermint) or yellow and white (lemon swiss creme) two layer, monogrammed tablet contains: magnesium hydroxide 200 mg aluminum hydroxide dried gel 200 mg and dimethylpolysiloxane 25 mg Sodium content: 1 mg/tablet (peppermint); 0.83 mg/tablet (lemon swiss creme). Available in boxes of 50

5. KIRKLAND DJ, VaNrrr 5: Cytotoxicity of hair different hair dyes tested were mutacolourant constituents: chromosome damage induced by two nitrophenylenediamines in genic in Drosophila melanogaster." cultured Chinese hamster cells. Mutat Res Such findings indicate an urgent need 40: 47, 1976 6. KINKEL HJ, HOLZMANN 5: Study of long to re-evaluate the toxicology and carciterm percutaneous toxicity and carcinogenicity of hair dyes (oxidizing dyes) in rats. Food nogenicity of the constituents of hair Cosmet Toxicol 11: 641, 1973 colourants in a human population be7. BURNETT CN, LANMAN B, GIovAccHINs R, et al: Long term toxicity studies on oxidation fore any safety standards can be eshair dyes. Food Cosmet Toxicol 13: 353, 1975 8. WYNDER EL, ONDERDONK J, MANTEL N: An tablished.13 epidemiological investigation of cancer of the We conducted an investigation to debladder. Cancer 16: 1388, 1963 DUNHAM LI, RABSON AS, STEWART HL, et 9. termine the role of hair dyes in the al: Rates, interview and pathology study of cancer of the urinary bladder in New Orleans, production of bladder cancer. All the J Nati Cancer Inst 41: 683, 1968 patients and a control group who had 10. Louisiana. COLE P, HOOVER R, FRIEDELL GH: Occupation and cancer of the lower urinary tract. Cancer participated in a previous retrospective 29: 1250, 1972 SEARLE CE, HARNOEN DG, VENUrr 5, et al: study of transitional cell carcinoma of 11. Mutagenicity of hair dyes. Lancet 2: 226, the urinary bladder14 were contacted by 1975 12. BLIJLEvEN WHG: Mutagenicity of four hair telephone. Each patient was matched dyes in Drosophila melanogaster. Mutaf Res 48: 181, 1977 to a control of the same sex and similar age (± 5 years). Male controls were patients with benign prostatic hypertrophy; female controls had been seen Anderson report on anesthesia for problems of stress incontinence. A total of 107 patients and an equal num- To the editor: The editorial comment ber of matched controls were analysed on the Anderson report on anesthesia by Dr. J.H. Feindel (Can Med Assoc I with respect to the use of hair dyes. A McNemar chi-square test was used 117: 312, 1977) suggests that Saskatand no statistically significant differ- chewan's committee for the study of ence was found between cancer patients anesthetic and operative deaths is a and the control group in their reported model that should be duplicated in exposure to hair dyes. There were 19 other provinces. For the information discordant pairs and for those using of your readers I point out that in 1952 hair dyes the relative risk estimate of in Alberta Dr. E.A. Gain founded the 1.1 had a 95% confidence limit of Alberta Medical Association's committee on anesthetic and operative 0.41 to 3.03. Our data on humans are dissimilar deaths, which functions in collaborato the findings reported on bacterial tion with the College of Physicians and and mice systems. Although our find- Surgeons of Alberta. This committee, ings suggest that hair dyes are not albeit with changing membership, has responsible for any appreciable pro- been active since its inception and has portion of cases of bladder cancer the achieved considerable success in reachpossibility still exists that prolonged ing its objective. Annual reports and occupational exposure could be danger- occasional reviews of its activities are ous, perhaps for cancer of another published. It has always collaborated organ. Also, the upper confidence limit actively with educational efforts in the of 3.03, being greater than 1.0, does field of anesthesia, an aspect that is not exclude the possibility that the risk currently being emphasized. Administratively this program is sifor those individuals using hair dyes is higher than that for those not using milar to the one in Saskatchewan. How hair dyes. However, the lower limit of it compares qualitatively is difficult to say. We certainly pursue the same ob0.41 does not exclude the converse. jective. All anesthetists wish patients MEERA JAIN, PH 13 to receive the best possible anesthetic Epidemiology unit care and Dr. Feindel does all of us a National Cancer Institute Toronto, Ont. great service by emphasizing the importance of peer review bodies and ROBERT W. MORGAN, MD LYNN ELINsoN, MA education in the provision of patient Department of preventive medicine care. and biostatistics University of Toronto Toronto, Ont.

Department of anesthesia

Faculty of medicine

University of Alberta Edmonton, Alta.

References

cellophane-wrapped tablets.

1. SEARLE CE, HARNDEN DG, VaNIrr 5, et al: Carcinogenicity and mutagenicity tests of some hair colourants and constituents. Nature 255: 506, 1975 2. AMES BN, KAMMEN HO, YAMASAKI E: Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc Nati Acad Sci USA 72: 2423, 1975

William H. Rorer (Canada) Ltd. Bramalea, Ont. L6T 1 C3

Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Nati Acad Sci USA 70: 2281, 1973 4. MCCAAN J, AMES BN: Detection of carcinogens as mutagens in the salmonella-microsome test. 2. Assay of 300 chemicals - Discussion. Proc Nati Acad USA 73: 950, 1976

U

J.W.R. MCINTYRE, MD, FRCP[C]

3. AMES BN, DURSTON WE, YAMASAKI E, et at:

Communicating with patients To the editor: With reference to the letter from Dr. JE. Kapsos (Can Med Assoc 1 117: 584, 1977) my own personal experience has been that notifying patients of test results by mail has been fairly reliable. For the past 12 months I have in-

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