Sinequar. It works safely Indications The antidepressant and anxiolytic properties of Sinequan (doxepin) have been found to be of value in the drug treatment of: 1. Psychoneurotic patients with anxiety and I or depressive reactions; Anxiety neurosis associated with somatic disorders; Alcoholic patients with anxiety and/or depression. 2. Psychotic depression, including manicdepressive Illness (depressed type) and involutional melancholia. Contraindications Sinequan is contraindicated in individuals who have shown hypersensitivity to the drug. It Is not recommended for children under 12 years of age, since sufficient data on its use in this age group is not yet availableBecause of its antich olinergic activity Sinequan should not be administered to patients with glaucoma or a tendency to urinary retention. Tricyclic agents are generally contraindicated in patients with a history of blood dyscrasias and severe liver diseaseSinequan should not be administered concomitantly with MAO inhibitors, since such a combination may cause a syndrome of intensive sympathetic stimulation. Drugs of this type should be discontinued at least two weeks before instituting therapy with Sinequan. PrecautIons and Warnings The safety of Sinequan in pregnancy has not been established and therefore it should be used in pregnant women only when, in the judgment of the physician, it is essential for the welfare of the patientsSince drowsiness may occur with the use of this drug, patients should be warned of the possibility of this occurring early in the course of treatment, and cautioned against driving a car or operating machinery. Combined use with other drugs acting on the central nervous system should be undertaken with due recognition of the possibility of potentiation. The response to alcohol may also be modified. As with other antidepressant agents, the possibility of activation of psychotic symptoms should be borne in mindAppropriate supervision is required when treating depressed patients, and alternate forms of management should be considered in treating severely depressed patients because of the inherent suicidal risk. Tricyclic agents may lower the convulsive threshold and should therefore be used with caution in patients with convulsive disorders- Sinequan should be used with caution in patients with cardiovascular disorders- At doses of 300 mg I day or above, it may block the antihypertensive effect of guanethidine and related compounds. The use of Sinequan on a once-a-day dosage regimen in geriatric patients, patients with intercurrent illnesses, or patients taking other medications should be adjusted carefully, based on the patient's condition- This is especially important if the patient is receiving other medications with anticholinergic effects. Adverse Reactions Sinequan is generally well tolerated- The following adverse reactions have been reDorted:

Behavioral Effects: agitation, restlessness, excitement, activation of psychotic symptoms and toxic confusional state. Anticholinergic Effects: dry mouth, blurred vision, constipation, and genito-urinary disorders. Central Nervous System Effects: drowsiness, insomnia, extrapyramidal symptoms. Cardiovascular Effects: dizziness, hypotension, tachycardia. Miscellaneous: fatigue, weight gain, increased sweating and other secretory effects, nausea, heartburn, rash and pruritus, paresthesia, edema, flushing, chills, tinnitus, photophobia, decreased libido.

Dosage and Administration An optimum daily dosage of Sinequan depends on the condition which is being treated and the response of the individual. Some patients respond promptly; others may not respond for 2 weeks or longer. An initial dosage of 25 mg t.i.d. is recommended in most patients. This dosage should be increased as required by 25 mg increments at appropriate intervals until a

therapeutic response is obtained. The usual optimum dosage range is 100-150 mg per day. In some patients, up to 300 mg per day may be required, but there is rarely any benefit to be obtained by increasing this dosage. In elderly patients it is advisable to proceed more cautiously with dosage increments and to initiate treatment with a lower dosage. Once a satisfactory therapeutic response has been obtained, it is generally possible to reduce the dosage and still maintain this effect. For maintenance therapy in depressed patients, the total daily dosage, up to 150 mg, may be given on a once-a-day schedule. This dosage should be established as described above and should preferably be given at bedtime. Oral Concentrate: SINEQUAN Oral Con-

centrate is available in 120 ml bottles with an accompanying dropper calibrated at 5 mg, 10 mg, 15 mg, 20mg, and 25mg. Each ml contains doxepin H Cl equivalent to 10 mg doxepin. SINEQUAN Oral Concentrate should be diluted with water or suitable juices just prior to administration. Preparation and storage in bulk dilutions is not recommended.

Dosage Forms

SINEQUAN Capsules contain doxepin hydrochloride equivalent to 10, 25, 50 and 100 mg of doxepin in bottles of 100 and 500. SINEQUAN Oral Concentrate is available in bottles of 120 ml. Each ml of SINEQUAN Oral Concentrate contains doxepin hydrochloride equivalent to 10 mg of doxepin. Bibliography 1. PRODUCT MONOGRAPH 2. GERSON, IM. et al: Non-Antagonism of An-

tiadrenergic Agents by a Dibenzoxepine, Diseases of the Nervous System, Volume 31, pp. 780-782, November 1970. 3. PRANGE, A.J., Jr.: The Use of Antidepressant Drugs in the Elderly Patient. In Eisdorfer, C. and Fann, W.E. (Eds): Psychopharmacology and Aging, New York, Plenum Press, 1973, p.232. 4. AYD, F.J., Jr.: Maintenance Doxepin (Sinequan) Therapy for Depressive Illness, Diseases of the Nervous System, Volume 36, No.4, pp. 109.114, March 1975. 5. AYD, F.J., Jr.: Recognizing the Depressed Patient, New York, Grune & Stratton, Inc., p. 26, 1961. 6. GOLDBERG, H.L. and FINNERTY, R.J.: Doxepin in a Single Bedtime Dose in Psychoneurotic Outpatients, Arch. Gen. Psych., Vol. 31, p. 513, October 1974. 7. SMITH, J.A. and RENSHAW, D.C.: Insomnia - A Signal Symptom, Scientific Exhibit presented at the 127th Annual Meeting of the American Psychiatric Association, May 5-9, 1974. 8. DAVIES, B.M.: The Effects on the Heart of Dif. ferent Tricyclic Antidepressants, Reprinted from Sinequan" (doxepin HCI) Excerpla Medica, 1975. 9. Official Health Protection Branch Product Monographs for amitriptyline, clomipramine, desipramine, nortriptyline, protriptyline, trimipramine and imipramine. trademark authorized user

PHARMACEUTICAL DIVISION Montreal, Canada

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tion where they received no treatment except continuation of medication and exposure to the community indicates that this exposure may be beneficial. I hope that in the future we will see intensive evaluation, probably in general hospital units for acutely ill psychiatric patients, followed by appropriate placement, be it admission to a small psychiatric hospital or a foster home, or return to the family, according to indications only now being worked out. I don't think the foster care system should be abandoned for either persons currently in mental hospitals or patients placed in foster homes directly from a general hospital setting. A.S. MACPHERSON, MD 1650 Cedar Ave. Montreal General Hospital Montreal, PQ

Slide test for a-fetoprotein To the editor: Denver Laboratories (Canada) Limited recently circulated a letter to physicians in Canada offering a new slide test for the detection of a-fetoprotein (AFP). We believe the marketing of this product has been taken over recently by Frank W. Homer Limited. This test is described in the letter as "so straightforward that results are read in five minutes". They suggest that "by testing maternal sera during the early stages of pregnancy you may be aided in the antenatal detection of anencephaly and spina bifida". They also say the test is sensitive to concentrations as low as approximately 250 ng/ml and as accurate as the more complex test using counterimmunoelectrophoresis. It is not, however, sensitive enough to be used for the detection of neural tube defects in fetuses because the upper limit of normal for AFP values in women 16 to 18 weeks pregnant is well below 250 ng/ml. Only the more substantial elevations of AFP could possibly be detected. In fact, many false-negatives have been reported when maternal blood AFP values are used to predict the presence of a defect, even when the most sensitive technique available - namely, radioimmunoassay - is used.1 We are greatly concerned that this slide test might be used by physicians who think they can then reassure pregnant women that they are not carrying a fetus with a neural tube defect. We are also concerned that, because of this test, women at risk might not have amniocentesis. Estimation of the concentration of AFP in the amniotic fluid is the only proven way of biochemically detecting neural tube defects. Regrettably, this test can only be offered to women proven to be at risk (those having a previously affected

child or a strongly positive family history). Although screening of maternal serum for AFP may be available in future, we all feel strongly that this test is not appropriate for detection of congenital defects at present. PATlUcIA A. BAIRD, MD, CM DA. APPLEGARTH, PH D

R.B. LOWRY, MB J.R. MILLER, PH D P.M. MACLEOD, PH D Department of medical genetics University of British Columbia Vancouver, BC

Reference 1. SELLER MJ: Screening for neural-tube defects (C). Lancet 2: 1141, 1975

[A revised statement concerning the principle of the AFP slide test and its valid applications is under preparation by Frank W. Homer Limited. - Ed.]

Infection due to Bacillus cereus To the editor: Infections due to Bacillus species other than B. anthracis are rare but do occur.1'2 They may be localized or generalized3 and they may occur in immunologically compromised patients or in those with malignant disease.4 There is also some association of these infections with instruments such as indwelling intravascular catheters,5 hemodialysis apparatus0 and cerebrospinal fluid shunts.7'8 However, of the 98 shunt infections described by Schoenbaum, Gardner and Shillito,8 only one was due to B. subtilis, and the case report of Cox, Sockwell and Landers7 referred to only one case of B. subtilis shunt infection. The nomenclature of the genus Bacillus has, in the past, been somewhat confused. Generally, for purely medical purposes, the significant member of the group is considered to be B. anthracis, the others being regarded as B. subtilis.2'7'9 It is possible, therefore, that an organism called B. subtilis in some of the literature may, in fact, be B. cereus.3 Because of the rarity of infection with Bacillus species and the importance of recognizing the possibility of B. cereus septicemia and meningitis in a child with a cerebrospinal fluid shunt and the striking effect of removing the infected tube, the following case is of interest. A baby girl was first admitted to hospital when a few days old with a large head (head circumference, 38 cm) and suspected hydrocephalus. Subsequently she was readmitted several times but on each occasion there was some reason for not performing a ventriculogram. When she was 8 months old ventriculography was performed and the radiologist was satisfied that the findings were consistent with

a communicating type of hydrocephalus. A few days later a ventriculoperitoneal shunt was inserted and this was followed by fever (temperature, up to 390C), vomiting and increased fontanelle tension. There was radiologic evidence of pneumonitis. Blood samples were drawn for culture; several were discarded because they were contaminated with Bacillus species. Cerebrospinal fluid (CSF) contained 3.24 x 10./l leukocytes (52% polymorphs and 48% monocytes); glucose concentration was 46 mg/dl and protein concentration, 28 mg/dl; no organisms were seen and the culture was sterile. Serum immunoglobulin concentrations were normal and, although the child was anemic (hemoglobin value at admission, 8.6 g/dl), on several occasions polymorphonuclear leukocytosis was noted in the peripheral blood. The child was treated with ampicillin, 500 mg intravenously (IV) immediately and 500 mg IV q6h, and gentamicin, 20 mg IV immediately and ql2h. A reservoir was inserted between the ventricular catheter and the shunt valve some 2 weeks after the first operation. Two days later seizures occurred but diazepam therapy controlled them. Culture of CSF was sterile, although a blood culture at this time grew a Bacillus sp. and the child was febrile. The fever settled. A month after the first operation she again became feverish. CSF contained 297 x 108/1 leukocytes (50% polymorphs and 50% lymphocytes) and numerous gram-positive rods apparently in chains; glucose concentration was 66 mg/dl and protein concentration, 20 mg/dl. Culture yielded a Bacillus organism. The child was given trimethoprim-sulfamethoxazole, ½ tsp. orally bid, and gentamicin, 15 mg intramuscularly bid. At this point one of the blood cultures that we had considered contaminated and were discarding was rescued when we realized the "contaminant" was pathogenic. The surgeon removed the shunt and from its tip a growth of Bacillus sp. was obtained. Immediately after the shunt was removed the child's condition improved appreciably, and she was discharged from hospital 3 days later. The organisms isolated from the blood, CSF and shunt tubing were sent for identification to Dr. W.A. Black of the University of Western Ontario, on whose advice they were sent to Dr. E. Gordon of Rutgers University, New Brunswick, New Jersey, who identified the organisms as B. cereus. STANLEY S. RAPHAEL, MB, FRCP[C] MERILYN DONAGHUE, RT Department of pathology Hotel Dieu of St. Joseph 1030 Oucllette Ave. Windsor, ON

References 1. PEARSON HE: Human infections caused by organisms of the Bacillus species. Am I Clin Pathol 53: 506, 1970 2. FARRAR WE: Serious infections due to "nonpathogenic" organisms of the genus Bacillus: review of their status as pathogens. Am I Med 55: 839, 1973 3. GOULLET P, PEPIN H: Bacillus cereus septicaemia. Lancet 1: 761, 1974 4. IHDE DC, ARMsTRONG D: Clinical spectrum of infection due to Bacillus species. Am I Med 55: 839, 1973

5. FREEMAN R, KING B: Isolations of aerobic sporing bacilli from the tips of indwelling intravascular catheters. / Clin Pathol 28: 146, 1975 6. CURTIS JR, WING AJ, COLEMAN IC: Bacillus cereus bacteraemia: a complication of intermittent hemodialysis. Lancet 1: 136, 1967 7. Cox R, SOCKWELL G, LANDERS B: Bacillus subtilis septicemia: report of a case and review of the literature. N Engi / Med 261: 894, 1959 8. SCHOENBAUM SC, GARDNER P. SHILLITO J: Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations and therapy. J Infect Dis 131: 543, 1975 9. Wan..s.rarn L, COLBURN CG: Bacillus subtills meningitis and bacteremia; report of a case and review of the literature on "subtilis" infections in man. Arch Intern Med 86: 585, 1950

Anatomical musings To the editor: I was delighted to read "On learning that his professor of anatomy is now a vigorous octogenarian" (Can Med Assoc J 114: 985, 1976), by an old friend, Dr. Kenneth M. Leighton. It set me to thinking of my own student days and also to reviewing the present status of my ana: tomical knowledge. My professor of anatomy seemed at the time an awesome figure, certainly chock-full of minute structural detail, which he presented with authoritarian certainty and most definitely with not the faintest hint of apology. I can't recall that he engendered much affection, but later on, in my more senior years, when he would give me a nod as we passed in the corridors, my feelings mellowed. Now, of course, time has taken the process further still. I believe he has passed on, and at a much younger age than Dr. Leighton's spritely octogenarian mentor. If I am even a minute fragment of his monument, how has he fared? Not very well, I'm afraid. My recollections of body structure are about the anatomic equivalent of the history student's "1066 and All That". But, of course, a few bits still stick - a couple of mnemonics, for example. I can still remember the reported outraged cry of Wharton's duct on finding itself double-crossed and also the outrageous conduct of Timothy towards all nervous housemaids. In fact, one of the few (and quite endearing) stories told of my old professor of anatomy related to that last mnemonic. A student undergoing the trial by ordeal known as "orals" was doing rather badly with a difficult set of relations and eventually ground to a halt. He received a little memory prod: "Come, come! - Timothy, Mr. Smith, Timothy!" What else has lingered? Well, had I expired prior to my anatomy years and met in the next (?nether) world a Roman - say the centurion who stood such faithful guard at Pompeii - what could I have said to him? About my only conversational essay would have been "Omnis Gallia in tres partes divisa

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