Similarly, duration of symptoms is with a significantly increased likelihood stated to be unimportant. In fact, the of breast cancer in a population, this proportion of patients with cancer is not of diagnostic help to a clinician. shows a trend related to symptom dura- One cannot be more concerned with a tion, decreasing from 15% in patients 35% risk than a 28% risk, even though with a symptom duration of less than the difference will be significant in a 1 month, to 12% for 1 month to 1 population of sufficient size. It is wrong to try to compare the year, and 8% for more than 1 year; again this is unlikely to be a chance oral contraceptive users with the nonfinding (X2 = 7.2; 2 degrees of free- users in my study as Dr. Elwood has. The users were naturally all young, and dom; P < 0.05). Also ignored is the finding that a young women do not commonly have history of hysterectomy appears to breast cancer. The nonusers were wommake cancer less likely; 1% of such en of all ages, including older women, women had cancer, compared with who have a greater likelihood of having 19% of other women aged 45 to 54 breast cancer. Any group of young (X2 = 5.3; 1 degree of freedom; P K women, hormone users or not, will have a lower prevalence of breast cancer 0.05). On the other hand, a history of than a group of older women. Apples nipple discharge is stated to virtually cannot be compared with oranges. In the diagnostic value of the duraguarantee innocence of the lesion; however, the data show that 10% of those tion of symptoms Dr. Elwood has again with such a discharge had cancer, com- missed the point. The practising physipared with 13% of those who did not cian will not be able to decide that a have a discharge, a difference that is patient with symptoms for less than 1 very likely due to chance (X2 = 0.3; month has cancer because 56% of .he cancer patients as opposed to 45% of 1 degree of freedom; P = 0.6). Dr. Devitt has also implied that his the patients with benign breast disease findings contradict other descriptions of had histories of less than 1 month. Nor "risk factors" for breast cancer. How- would many clinicians take seriously ever, his study essentially compares pa- his category for symptom duration of tients with breast cancer and patients 1 month to 1 year for breast disorders. Dr. Elwood has also missed the statewith benign breast disease; women representative of the general population ment that the 4 cancer patients among are not compared. Thus a feature that the 40 with nipple discharge each had appears to be a risk factor for both a breast mass. Thus, the statement that benign and malignant breast disease discharge as the only presenting symp(e.g., age at menarche or nulliparity) tom virtually guarantees innocence of will show no association with breast the lesion remains wholly justified. Finally, my paper addressed itself to cancer in his study population. The confusion arising from the lack of an helping doctors in their offices decide association of previous benign breast which women have breast cancer, not disease and breast cancer in this study, which women may get it. Dr. Elwood's and the demonstration of increased risk comments on "risk factors" in women of subsequent breast cancer in women who may get breast cancer are therewith benign breast disease as compared fore irrelevant to the points I discussed. with women in the general population,2 J.E. DEvrvr, MD, CM, M Sc, may thus be explained. It seems likely FRCS (EDIN), FRC5[C] Department of surgery that women with benign breast disease Ottawa Civic Hospital have an increased risk in later life of Ottawa, Ont. both breast cancer and further benign lesions. Cholera and noncholera J. MARK ELwooD, MD, FRCP[C] Epidemiology unit Cancer Control Agency of British Columbia 686 W Broadway, #700 Vancouver, BC
References I. VESSEY MP, DOLL R, SUTrON PM: Oral contraceptIves and breast neoplasia: a retrospective study. Br Med J 3: 719, 1972
2. MoNsoN RR, YEN S. MACMAHON B: Chronic mastitis and carcinoma of the breast. Lancet 2: 224, 1976
To the editor: Dr. Elwood has missed entirely the point of my paper. He has confused epidemiologic data about who will get breast cancer with information usable in the physician's office to make a diagnosis of a patient's breast problem. For example, while nulliparity has been well demonstrated to be associated
To the editor: Having dealt with three illnesses with the clinical features of cholera that proved to be caused by vibrios acquired while the patients travelled abroad, we have found the current epidemiologic practice of classifying these illnesses as "noncholera" to be potentially confusing. Vibrios from these cases do not agglutinate with sera that are presently available, and are referred to by microbiologists as nonagglutinable strains. Prior to Koch's1 description of vibrios from cholera cases in 1883, all cholera outbreaks were reported on the basis of clinical findings. In 1906 Gotschlich2 described a vibrio that differed from the classical Vibrio chalerae
and this variant has since been referred to as biotype El Tor, particularly since 1939, when it was shown to be the causative agent in a severe epidemic in Indonesia. In 1961, after many minor outbreaks, a major epidemic of El Tor cholera occurred in Borneo and the Celebes. This cholera spread in waves in succeeding years and reached its peak as a pandemic by 1972-73. Epidemiologic and laboratory studies have demonstrated that the El Tor vibrios tend not to be as infective as the classical V. cholerae strains. Thus. the study by Mosley3 suggests that exposure to V. cholerae produces 1 case of acute cholera for every 1.3 cases of diarrhea and every 2 mild or asymptomatic cases, whereas the El Tor vibrio produces 1 case of acute cholera for every 4.3 cases of diarrhea and every 19 mild or asymptomatic cases. On the other hand, other workers4 have shown that the disease processes are based on the production of similar enterotoxins. This is borne out by the mortality data in outbreaks such as that at Lake Chad in 1971, where there were 4464 cases and 1482 deaths, the El Tor vibrio having been the causative agent.5 Mostly because of the El Tor pandemic there has been a great deal of research in the last 10 years aimed at explaining the pathogenesis, side effects and immunology of cholera. At present it is generally agreed that the production of an enterotoxin by the vibrio is at least one of the main factors in the production of clinical cholera. Enterotoxin production varies in amount from strain to strain and from time to time with the same strain. Santos, Palchaudhuri and Maas6 claimed that the ability to produce enterotoxin can be transferred to a nonproducing strain by plasmids - a process that could enhance pathogenicity endemically. The latest patient in Montreal, a member of a group that had visited Brazil, was infected with a nonagglutinable vibrio with the laboratory-test characteristics of Heiberg group 2 a strain that has been reported from outbreaks in other countries. The strain from this patient (and from a companion in the group) was reported to Seah and colleagues7 by the national enteric reference centre, Laboratory Centre for Disease Control, Health and Welfare Canada, to be a producer of enterotoxin. The clinical picture was typical of cholera. The patient had profuse diarrhea (at least 20 watery stools) with abdominal cramps and vomiting day and night for 2 days before being seen by a physician. He was found to have hemoconcentration (hemoglobin value, 18.5 g/dL; hematocrit, 65%). The leukocyte count was 8.5 x 109/L with a normal dif-
CMA JOURNAL/AUGUST 20, 1977/VOL. 117 325
Indodd
(indomethacin, MSD Std.) Indications INDOCID. (indomethacin, MSD Std.) has been found effective in the symptomatic treatment of selected cases of rheumatoid arthritis, ankylosing (rheumatoid) spondylitis, gout, selected cases of severe osteoarthritis including degenerative disease of the hip. INDOCID* should be used in those cases of severe osteoarthritis which do not respond to treatment with other drugs such as the salicylates. In these conditions it may on occasion replace other commonly used agents such as corticosteroids, salicylates, phenylbutazone-like compounds, and colchicine. Dosage Summary For Adults In chronic rheumatoid arthritis and ankylosing (rheumatoid) spondylitis: Start with 25 mg b.i.d. or tid. If response is inadequate, add 25 mg daily each week until an adequate response is obtained or a dosage of 150 to 200 mg is reached. In acute rheumatoid arthritis and acute flares of chronic rheumatoid arthritis: Start with 25mg bid. or tid. If response is inadequate, add 25 mg each day until an adequate response is obtained or until a total daily dose of 150-200 mg is reached. Maintenance corticosteroids can often gradually be reduced 25 to 50 percent and completely discontinued over several weeks or months in some patients. In severe osteoarthritis and degenerative disease of the hip: Start with 25 mg bid. or tid. If response is inadequate, increase the daily dosage by 25 mg at about weekly intervals until an adequate response is obtained or until a dosage of 150 to 200 mg is reached. In acute gout: 50 mg t.i.d. until all signs and symptoms subside. INDOCID* Suppositories: 100 mg to 200 mg a day. May be administered one at bedtime, and if necessary one the following morning. Also may be used in combined administration with Capsules: 100 mg suppository at bedtime, supplemented the following day by 25 mg capsules as needed up to a total of 150 to 200 mg (capsules and suppositories) of indomethacin. Note: In chronic disorders, it is important to start with low dosage and increase gradually for best resuIts with fewer adverse reactions. Always give INDOCID* with food or immediately after meals or with antacid to reduce gastric irritation. As with all drugs, the lowest possible effective dose should be utilized for each individual patient. Contraindications Active peptic ulcer, gastritis, regional enteritis, ulcerativecolitis, diverticulitis and if there is a recurrent history of GI. lesions. Also contraindicated in patients allergic to a.s.a. or indomethacin. Safety of indomethacin for use in pregnancy or lactation has not been established. Indomethacin suppositories are contraindicated in subjects with a history of recent rectal bleeding. SHOULD NOT BE ADMINISTERED TO PEDIATRIC AGE GROUPS. Warning Patients who experience dizziness, lightheadedness, or feelings of detachment on indomethacin should be cautioned against operating motor vehicles, machinery, climbing ladders, etc. Use cautiously in patients with psychiatric disturbances, epilepsy, or parkinsonism. Precautions Indomethacin should be used with caution because of the possible occurrence of gastrointestinal reactions, the incidence of which may be decreased by glying the drug immediately after meals, with food or antacids. The risk of continuing therapy with indomethacin in the face of such symptoms must be weighed against the possible benefits to the individual patient. Indomethacin suppositories should be given with caution to patients with any anal or rectal pathology. Discontinue if GI. bleeding occurs. Peptic ulcer has been reported. Hemorrhage and perforation have occurred in patients with history of peptic ulcer (see Contraindicatlons) or in patients receiving steroids or salicylates concomitantly. In some patients there was no history of peptic ulcer or of other drugs being given. As a result of GI. bleeding some patients may manifest anemia and, for this reason, appropriate blood determinations are recommended periodically. Headache may occur, usually early in treatment. Discontinue therapy if headache persists despite dosage reduction. In common with other drugs which have anti-inflamma-
tory, analgesic and antipyretic properties, indomethacin possesses the potential of masking the signs and symptoms which ordinarily accompany infectious disease. The physician must be alert to this possibility to avoid undue delay in initiating appropriate treatment of the infection. Indomethacin should be used with caution in patients with existing, but controlled infections. Where therapy is prolonged, ophthalmological examinations are desirable at periodic intervals (see Eye Reactions). Since advancing years appear to increase the possibility of adverse reactions, indomethacin should be used with greater care in the elderly. As with any drug, patients should be followed carefully to detect unusual manifestations of drug sensitivity. Adverse Reactions Central Nervous System: Commonly seen, headache (usually more severe in morning), dizziness, and lightheadedness. Infrequently observed: mental confusion, syncope, drowsiness, convulsions, coma, depression which may be severe, and other psychic disturbances, such as depersonalization. The severity of these effects may occasionally require cessation of therapy and rarely, admission to hospital. Gastrointestinal: include nausea, anorexia, vomiting, epigastric distress, abdominal pain, and diarrhea, which are not uncommon. Single or multiple ulceration of esophagus, stomach, duodenum orsmall intestine, perforation and hemorrhage have occurred. A few fatalities have been reported. Hemorrhage without obvious ulceration. Increased abdominal pain in patients with ulcerative colitis. Indomethacin has been suspected of precipitating the symptoms of ulcerative colitis or regional ileitis but causal relationship not proven. Rarely reported, intestinal ulceration followed by stenosis and obstruction. Least frequent reactions: ulcerative stomatitis, bleeding from sigmoid colon or diverticuli, perforation of pre-existing sigmoid lesions, e.g., diverticuli or carcinoma. With the use of indomethacin suppositories, pruritus ani, tenesmus, and irritation of the rectal mucosa reported occasionally; rectal bleeding rarely. However, sigmoidoscopic examination in a number of patients did not reveal any significant changes of rectal mucosa. Hepatic: Toxic hepatitis and jaundice of uncertain etiology, including severe and fatal cases. Cardiovascular-Renal: Infrequently, edema, elevation of blood pressure, and hematuria. Dermatologic-Hypersensitivity: Infrequently, pruritus, urticaria, angioneurotic edema, angiitis, erythema nodosum, skin rashes, loss of hair, and acute respiratory distress including sudden dyspnea and asthma. Hematologic Reactions: Infrequently leukopenia, purpura and thrombocytopenia. Rarely agranulocytosis, hemolytic anemia, but definite relationship to drug not established. Anemia secondary to obvious or occult gastrointestinal bleeding. It is advisable to perform periodic blood counts (including platelet) in patients on long term therapy. If signs or symptoms of above reactions appear, discontinue drug and institute appropriate hematological investigations. Ear Reactions: Tinnitus infrequently, and deafness rarely. Eye Reactions: Retinal disturbances, including those of the macula, and corneal deposits have been observed. Some of these changes regressed after discontinuation of therapy. Infrequently, blurred vision, orbital and penorbital pain. Miscellaneous: Rarely, vaginal bleeding, hyperglycemia, glycosuria and peripheral neuropathy, and epistaxis. DETAILED INFORMATION AVAILABLE ON REQUEST. How Supplied Ca 8662.lNDOClD* Capsules 25 mg each, are opaque, blue and white, imprinted with an MSD trademark and potency, and are supplied in bottles of 50 and 500. Ca 8663..lNDOClD* Capsules 50 mg each, are opaque, blue and white, imprinted with an MSD trademark and potency, and are supplied in bottles of 50 and 250. Ca 8711.lNDOClD* Suppositories 100 mg each, are white opaque suppositories, supplied in boxes of 12 or 30. 'Trademark
O MERCK I SHARP I & DOHME CANADA LIMITED
Pointe Claire, Quebec (MC 941 a)
328 CMA JOURNAL/AUGUST 20, 1977/VOL. 117
ferential. Serum electrolyte concentrations were not measured. The stools resembled cloudy urine containing flakes of solid material. He was able to maintain a high fluid intake by drinking large amounts of fruit juices with added salt and other electrolytes. He was treated with tetracycline and his condition improved rapidly. Stool cultures yielded large numbers of V. cholerae. No other intestinal pathogens, including parasites, were found. The clinical disease produced by at least some nonagglutinable strains, particularly Heiberg groups 1 and 2, is similar to that reported in El Tor epidemics, and the potential infectivity of such strains appears to resemble that of the El Tor vibrio if Mosley's figures are accepted.3 Of the 18 people in the group visiting Brazil, 1 became acutely ill, 6 had diarrhea and 11 were asymptomatic. In the preliminary report7 the last sentence reads, "Brazil is not considered to be an infected area with regard to Cholera." From the point of view of warning travellers and of alerting Canadian physicians to what travellers in Brazil may bring home this "noncholera" terminology appears to be misleading. STANLEY SEAH, MD Consultant, department of medicine D.H. STARKEY, MD Director of laboratories Queen Mary Veterans *iospital Montreal, PQ
References 1. KOCH R: Disch Med Wochenschr 9: 615, 743, 884; 10: 63, 111, 191, 221, 725; 1883 2. GOTSCHLIcH F: Z Hyg Infect Kr 53: 281, 1906 3. Mos...' WH in CRAIG JP: United StatesJapan cholera conference. I Infect Dis 125: 570, 1972 4. WnsoN GS, MILES A (eds): Topley & Wilson's Principles of Bacteriology, Virology & Immunity, 6th ed, Baltimore, Williams & Wilkins, 1975, pp 666-8 5. Cholera today - worldwide. Morbid Mortal Wkly Rep 20: 244, 1971 6. SANTOS DS, PALCHAUDHURI 5, MAAS WK: Genetic and physical characteristics of an enterotoxin plasmid. I Bacteriol 124: 1240,
1975 7. Non-cholera vibrio importation - Montreal. Can Dis Wkly Rep 3: 80, 1977
Measurement of nitrous oxide concentrations in operating-room air To the editor: We wish to draw the attention of your readers to two aspects of the use of the Miran 101 infrared analyser for measuring nitrous oxide concentrations in the ambient air of operating rooms, as recommended by Dr. J.L. Oulton in his recent article "Operating-room venting of trace concentrations of inhalation anesthetic agents" (Can Med Assoc 1 116: 1148, 1977). First, the infrared method is subject to interference, and this detector not only responds to nitrous oxide but also gives a small response to vapours aris-
References I. VESSEY MP, DOLL R, SUTrON PM: Oral contraceptIves and breast neoplasia: a retrospective study. Br Med J 3: 719, 1972
2. MoNsoN RR, YEN S. MACMAHON B: Chronic mastitis and carcinoma of the breast. Lancet 2: 224, 1976
To the editor: Dr. Elwood has missed entirely the point of my paper. He has confused epidemiologic data about who will get breast cancer with information usable in the physician's office to make a diagnosis of a patient's breast problem. For example, while nulliparity has been well demonstrated to be associated
To the editor: Having dealt with three illnesses with the clinical features of cholera that proved to be caused by vibrios acquired while the patients travelled abroad, we have found the current epidemiologic practice of classifying these illnesses as "noncholera" to be potentially confusing. Vibrios from these cases do not agglutinate with sera that are presently available, and are referred to by microbiologists as nonagglutinable strains. Prior to Koch's1 description of vibrios from cholera cases in 1883, all cholera outbreaks were reported on the basis of clinical findings. In 1906 Gotschlich2 described a vibrio that differed from the classical Vibrio chalerae
and this variant has since been referred to as biotype El Tor, particularly since 1939, when it was shown to be the causative agent in a severe epidemic in Indonesia. In 1961, after many minor outbreaks, a major epidemic of El Tor cholera occurred in Borneo and the Celebes. This cholera spread in waves in succeeding years and reached its peak as a pandemic by 1972-73. Epidemiologic and laboratory studies have demonstrated that the El Tor vibrios tend not to be as infective as the classical V. cholerae strains. Thus. the study by Mosley3 suggests that exposure to V. cholerae produces 1 case of acute cholera for every 1.3 cases of diarrhea and every 2 mild or asymptomatic cases, whereas the El Tor vibrio produces 1 case of acute cholera for every 4.3 cases of diarrhea and every 19 mild or asymptomatic cases. On the other hand, other workers4 have shown that the disease processes are based on the production of similar enterotoxins. This is borne out by the mortality data in outbreaks such as that at Lake Chad in 1971, where there were 4464 cases and 1482 deaths, the El Tor vibrio having been the causative agent.5 Mostly because of the El Tor pandemic there has been a great deal of research in the last 10 years aimed at explaining the pathogenesis, side effects and immunology of cholera. At present it is generally agreed that the production of an enterotoxin by the vibrio is at least one of the main factors in the production of clinical cholera. Enterotoxin production varies in amount from strain to strain and from time to time with the same strain. Santos, Palchaudhuri and Maas6 claimed that the ability to produce enterotoxin can be transferred to a nonproducing strain by plasmids - a process that could enhance pathogenicity endemically. The latest patient in Montreal, a member of a group that had visited Brazil, was infected with a nonagglutinable vibrio with the laboratory-test characteristics of Heiberg group 2 a strain that has been reported from outbreaks in other countries. The strain from this patient (and from a companion in the group) was reported to Seah and colleagues7 by the national enteric reference centre, Laboratory Centre for Disease Control, Health and Welfare Canada, to be a producer of enterotoxin. The clinical picture was typical of cholera. The patient had profuse diarrhea (at least 20 watery stools) with abdominal cramps and vomiting day and night for 2 days before being seen by a physician. He was found to have hemoconcentration (hemoglobin value, 18.5 g/dL; hematocrit, 65%). The leukocyte count was 8.5 x 109/L with a normal dif-
CMA JOURNAL/AUGUST 20, 1977/VOL. 117 325
Indodd
(indomethacin, MSD Std.) Indications INDOCID. (indomethacin, MSD Std.) has been found effective in the symptomatic treatment of selected cases of rheumatoid arthritis, ankylosing (rheumatoid) spondylitis, gout, selected cases of severe osteoarthritis including degenerative disease of the hip. INDOCID* should be used in those cases of severe osteoarthritis which do not respond to treatment with other drugs such as the salicylates. In these conditions it may on occasion replace other commonly used agents such as corticosteroids, salicylates, phenylbutazone-like compounds, and colchicine. Dosage Summary For Adults In chronic rheumatoid arthritis and ankylosing (rheumatoid) spondylitis: Start with 25 mg b.i.d. or tid. If response is inadequate, add 25 mg daily each week until an adequate response is obtained or a dosage of 150 to 200 mg is reached. In acute rheumatoid arthritis and acute flares of chronic rheumatoid arthritis: Start with 25mg bid. or tid. If response is inadequate, add 25 mg each day until an adequate response is obtained or until a total daily dose of 150-200 mg is reached. Maintenance corticosteroids can often gradually be reduced 25 to 50 percent and completely discontinued over several weeks or months in some patients. In severe osteoarthritis and degenerative disease of the hip: Start with 25 mg bid. or tid. If response is inadequate, increase the daily dosage by 25 mg at about weekly intervals until an adequate response is obtained or until a dosage of 150 to 200 mg is reached. In acute gout: 50 mg t.i.d. until all signs and symptoms subside. INDOCID* Suppositories: 100 mg to 200 mg a day. May be administered one at bedtime, and if necessary one the following morning. Also may be used in combined administration with Capsules: 100 mg suppository at bedtime, supplemented the following day by 25 mg capsules as needed up to a total of 150 to 200 mg (capsules and suppositories) of indomethacin. Note: In chronic disorders, it is important to start with low dosage and increase gradually for best resuIts with fewer adverse reactions. Always give INDOCID* with food or immediately after meals or with antacid to reduce gastric irritation. As with all drugs, the lowest possible effective dose should be utilized for each individual patient. Contraindications Active peptic ulcer, gastritis, regional enteritis, ulcerativecolitis, diverticulitis and if there is a recurrent history of GI. lesions. Also contraindicated in patients allergic to a.s.a. or indomethacin. Safety of indomethacin for use in pregnancy or lactation has not been established. Indomethacin suppositories are contraindicated in subjects with a history of recent rectal bleeding. SHOULD NOT BE ADMINISTERED TO PEDIATRIC AGE GROUPS. Warning Patients who experience dizziness, lightheadedness, or feelings of detachment on indomethacin should be cautioned against operating motor vehicles, machinery, climbing ladders, etc. Use cautiously in patients with psychiatric disturbances, epilepsy, or parkinsonism. Precautions Indomethacin should be used with caution because of the possible occurrence of gastrointestinal reactions, the incidence of which may be decreased by glying the drug immediately after meals, with food or antacids. The risk of continuing therapy with indomethacin in the face of such symptoms must be weighed against the possible benefits to the individual patient. Indomethacin suppositories should be given with caution to patients with any anal or rectal pathology. Discontinue if GI. bleeding occurs. Peptic ulcer has been reported. Hemorrhage and perforation have occurred in patients with history of peptic ulcer (see Contraindicatlons) or in patients receiving steroids or salicylates concomitantly. In some patients there was no history of peptic ulcer or of other drugs being given. As a result of GI. bleeding some patients may manifest anemia and, for this reason, appropriate blood determinations are recommended periodically. Headache may occur, usually early in treatment. Discontinue therapy if headache persists despite dosage reduction. In common with other drugs which have anti-inflamma-
tory, analgesic and antipyretic properties, indomethacin possesses the potential of masking the signs and symptoms which ordinarily accompany infectious disease. The physician must be alert to this possibility to avoid undue delay in initiating appropriate treatment of the infection. Indomethacin should be used with caution in patients with existing, but controlled infections. Where therapy is prolonged, ophthalmological examinations are desirable at periodic intervals (see Eye Reactions). Since advancing years appear to increase the possibility of adverse reactions, indomethacin should be used with greater care in the elderly. As with any drug, patients should be followed carefully to detect unusual manifestations of drug sensitivity. Adverse Reactions Central Nervous System: Commonly seen, headache (usually more severe in morning), dizziness, and lightheadedness. Infrequently observed: mental confusion, syncope, drowsiness, convulsions, coma, depression which may be severe, and other psychic disturbances, such as depersonalization. The severity of these effects may occasionally require cessation of therapy and rarely, admission to hospital. Gastrointestinal: include nausea, anorexia, vomiting, epigastric distress, abdominal pain, and diarrhea, which are not uncommon. Single or multiple ulceration of esophagus, stomach, duodenum orsmall intestine, perforation and hemorrhage have occurred. A few fatalities have been reported. Hemorrhage without obvious ulceration. Increased abdominal pain in patients with ulcerative colitis. Indomethacin has been suspected of precipitating the symptoms of ulcerative colitis or regional ileitis but causal relationship not proven. Rarely reported, intestinal ulceration followed by stenosis and obstruction. Least frequent reactions: ulcerative stomatitis, bleeding from sigmoid colon or diverticuli, perforation of pre-existing sigmoid lesions, e.g., diverticuli or carcinoma. With the use of indomethacin suppositories, pruritus ani, tenesmus, and irritation of the rectal mucosa reported occasionally; rectal bleeding rarely. However, sigmoidoscopic examination in a number of patients did not reveal any significant changes of rectal mucosa. Hepatic: Toxic hepatitis and jaundice of uncertain etiology, including severe and fatal cases. Cardiovascular-Renal: Infrequently, edema, elevation of blood pressure, and hematuria. Dermatologic-Hypersensitivity: Infrequently, pruritus, urticaria, angioneurotic edema, angiitis, erythema nodosum, skin rashes, loss of hair, and acute respiratory distress including sudden dyspnea and asthma. Hematologic Reactions: Infrequently leukopenia, purpura and thrombocytopenia. Rarely agranulocytosis, hemolytic anemia, but definite relationship to drug not established. Anemia secondary to obvious or occult gastrointestinal bleeding. It is advisable to perform periodic blood counts (including platelet) in patients on long term therapy. If signs or symptoms of above reactions appear, discontinue drug and institute appropriate hematological investigations. Ear Reactions: Tinnitus infrequently, and deafness rarely. Eye Reactions: Retinal disturbances, including those of the macula, and corneal deposits have been observed. Some of these changes regressed after discontinuation of therapy. Infrequently, blurred vision, orbital and penorbital pain. Miscellaneous: Rarely, vaginal bleeding, hyperglycemia, glycosuria and peripheral neuropathy, and epistaxis. DETAILED INFORMATION AVAILABLE ON REQUEST. How Supplied Ca 8662.lNDOClD* Capsules 25 mg each, are opaque, blue and white, imprinted with an MSD trademark and potency, and are supplied in bottles of 50 and 500. Ca 8663..lNDOClD* Capsules 50 mg each, are opaque, blue and white, imprinted with an MSD trademark and potency, and are supplied in bottles of 50 and 250. Ca 8711.lNDOClD* Suppositories 100 mg each, are white opaque suppositories, supplied in boxes of 12 or 30. 'Trademark
O MERCK I SHARP I & DOHME CANADA LIMITED
Pointe Claire, Quebec (MC 941 a)
328 CMA JOURNAL/AUGUST 20, 1977/VOL. 117
ferential. Serum electrolyte concentrations were not measured. The stools resembled cloudy urine containing flakes of solid material. He was able to maintain a high fluid intake by drinking large amounts of fruit juices with added salt and other electrolytes. He was treated with tetracycline and his condition improved rapidly. Stool cultures yielded large numbers of V. cholerae. No other intestinal pathogens, including parasites, were found. The clinical disease produced by at least some nonagglutinable strains, particularly Heiberg groups 1 and 2, is similar to that reported in El Tor epidemics, and the potential infectivity of such strains appears to resemble that of the El Tor vibrio if Mosley's figures are accepted.3 Of the 18 people in the group visiting Brazil, 1 became acutely ill, 6 had diarrhea and 11 were asymptomatic. In the preliminary report7 the last sentence reads, "Brazil is not considered to be an infected area with regard to Cholera." From the point of view of warning travellers and of alerting Canadian physicians to what travellers in Brazil may bring home this "noncholera" terminology appears to be misleading. STANLEY SEAH, MD Consultant, department of medicine D.H. STARKEY, MD Director of laboratories Queen Mary Veterans *iospital Montreal, PQ
References 1. KOCH R: Disch Med Wochenschr 9: 615, 743, 884; 10: 63, 111, 191, 221, 725; 1883 2. GOTSCHLIcH F: Z Hyg Infect Kr 53: 281, 1906 3. Mos...' WH in CRAIG JP: United StatesJapan cholera conference. I Infect Dis 125: 570, 1972 4. WnsoN GS, MILES A (eds): Topley & Wilson's Principles of Bacteriology, Virology & Immunity, 6th ed, Baltimore, Williams & Wilkins, 1975, pp 666-8 5. Cholera today - worldwide. Morbid Mortal Wkly Rep 20: 244, 1971 6. SANTOS DS, PALCHAUDHURI 5, MAAS WK: Genetic and physical characteristics of an enterotoxin plasmid. I Bacteriol 124: 1240,
1975 7. Non-cholera vibrio importation - Montreal. Can Dis Wkly Rep 3: 80, 1977
Measurement of nitrous oxide concentrations in operating-room air To the editor: We wish to draw the attention of your readers to two aspects of the use of the Miran 101 infrared analyser for measuring nitrous oxide concentrations in the ambient air of operating rooms, as recommended by Dr. J.L. Oulton in his recent article "Operating-room venting of trace concentrations of inhalation anesthetic agents" (Can Med Assoc 1 116: 1148, 1977). First, the infrared method is subject to interference, and this detector not only responds to nitrous oxide but also gives a small response to vapours aris-
