ELOSEF for Injection: For use in serious and life-threatening infections .... that many major science libraries housed in ... supplement the research library's copy.
LOSEF 250 CAPSULES LOSEF 500 CAPSULES Cephradlne Capsules LOSEF 125 FOR ORAL SUSPENSION LOSEF 250 FOR ORAL SUSPENSION radine for Oral Suspension LOSEF FOR INJECTION, 500 mg and 1 g radine for Injection CTION: Cephradlne is a semi-synthetic, cephalosporin antibiotic xhibiting bactericidal activity through inhibition of cell-wall ntheais. NDICATlONS: Infections in the respiratory and genitourinary racts, and in the akin and soft tissues, due to susceptibte rganisms. Sensitivity tests should be performed: therapy may be instituted before receiving the results. ONTRAINDICATIONS: Hypersensitivity to the cephalosporin roup of antibiotics. ARNINGS: There is evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Therefore, cephrame should be used with caution in patients with known hypersensitivity to penicillins. Antibiotics, including cephradine, should be used cautiously and only when abeolutely necessary in patients with a history of ellergies, perticularly to drugs. Usage during pregnancy and lactation: Safety for use of this product during pregnancy has not been established. Cephradine is secreted in breast milk. PRECAUTIONS: Patients should be obeerved carefully during therapy. Allergic reactions require discontinuation of VELOSEF and ppropriate treatment. rolonged use of VELOSEF may result in overgrowth of nonusceptible organisms: appropriate measures should be Instituted. urlng long-term therapy, hematological, renal and hepetic unctions should be monitored periodically. Patients with known or uspected renal impairment should be obeerved carefully since ephradlne may accumulate in the serum and tissues unless osage is suitably reduced. See DOSAGE AND ADMINISTRATION ction. ndlcated surgical procedures should be performed in conjunction ith antibiotic therapy; e.g., the incision and drainage of bscesses. After treatment with cephalosporins, a false-positive eaction for glucose in the urine may occur, but not with enzymeased tests. A false-positive Coomba' test has also been reported. ELOSEF for Injection is not compatible with Lactated Ringer's olution or other calcium-containing infusion fluids. DVERSE REACTIONS: Usually limited to gastrointestinal disturbnces and occasional hypersensitivity, but may include hematolocal and hepetobiliary disturbances, as well as elevated BUN, LDH serum creatinine; superinfection; vaginitis and joint pains. Thromphlebitis following IV. injection and sterile abacesses after f.M. njection have occurred. nly occasionally severe enough to warrant cessation of therapy SAGE AND ADMINISTRATION: The presence of food in the astrointestinal tract delays the absorption and reduces the peak level but does not affect the total amount of cephradine absorbed. ELOSEF Capsules and VELOSEF for Oral Suspension dults: Respiratory tract infections: 250 mg, q6h. Pneumococcal lobar pneumonia: 500 mg, q6H. enitourinary tract infections: 500 mg, q6h. Prolonged therapy is adviasble for the treatment of prostatitis and epididymitis. Children: 25 to 50 mg/kg/day, divided into four equally spaced oses, e.g.: VELOSEF for Oral Suspension Child's Weight 125 mg/5 ml 250 mg/5 ml 10kg (22 be) ½tol tsp. q6h 20kg(.lbs) lto2tsp.q6h /2toltsp.q6h 4Okg(881ba) 2to4tsp.q6h 1 to2tsp.q6h maller doses than those indicated above should not be used. For otitis media due to H. influenzae, doses from 75 to 100 mg/kg/day are recommended. ELOSEF for Injection: For use in serious and life-threatening infections or where oral therapy is not possible. Average adult daily ose is 2 -4 g, depending on the infection. In children, a daily dose 50- 100 mg/kg is recommended. II patients: all formulations: rger doses (up to 1 g q6h in adults or up to 25 mg/kg q6h in hildren) may be given for severe or chronic infections: maximum ally dose should not exceed 4 g. Therapy should be continued for minimum of 48 to 72 hours after the patient becomes asymptoatic or evidence of bacterial eradication has been obtained. In nfections caused by hemolytic streptococci, a minimum 10-dayreatment period is recommended. Stubborn infections may require restment for several weeks with frequent bacteriological and clinial appraisal. modified dosage schedule in patients with decreased renal unction is necessary. Each patient should be considered individuIly: the following schedule is recommended as a guideline. Initial oading dose: 750 mg. Maintenance dose: 500 mg at the time intersIB listed below: Creatinine Clearance Time Interval (ml/min/1.73m2) > 20m1/min 6-l2hours 15-19m1/min 12-24hours 10-14 mI/mm 24-40 hours 5-9 mI/mm 40-50 hours < Smi/min 50-70hours SAGE FORMS: Capsules of 250 mg and 500 mg in bottles of 50, nd bottles of VELOSEF 125 and 250 for Oral Suspension which, her reconstitution, provide 100 ml of pleasantly flavoured suspenion containing 25 mg/mI and 50 mg/mi respectively. ELOSEF for Injection is provided as a sterile powder for reconstituion in vials containing 500 mg or t g. Consult Product Monograph or reconstitution procedure. roduct Monograph available to physicians and pharmacists on request.
E R SQUIBB & SONS LTD. 2365 COTE DE LIESSE, MONTREAL, QUE. H4N 2M7
Metoclopramide hydrochloride and galactorrhea To the editor: The array of new medications marketed by drug companies produces an increasing number of problems for the unsuspecting physician as side effects come to light. A new problem that has recently come to our attention is galactorrhea following administration of metoclopramide hydrochloride (Maxeran). A 41-year-old housewife was admitted to hospital in November 1975 for investigation of persistent hypokalemia, ultimately diagnosed as Bartter's syndrome, which responded to administration of spironolactone and a potassium supplement. An incidental complaint was the occurrence for more than 20 years of persistent headaches lasting 3 to 4 days and associated with nausea and vomiting. We referred her to a neurologist, who made a diagnosis of migraine headaches and prescribed metoclopramide and ergotamine tartrate (Gynergen). She was readmitted to hospital in March 1976 with a new complaint of galactorrhea associated with breast enlargement. Her headaches and associated nausea had decreased in frequency and severity with the prescribed medications. Ingestion of metoclopramide hydrochloride varied from 10 to 40 mg orally 1 to 4 times per week. Results of investigation of pituitary function were normal except for low gonadotropin values (follicle-stimulating hormone, 62 ng/ml; luteinizing hormone, 18.2 ng/ml) and elevated prolactin value (175 ng/ml; normal, 25 ng/ml). Galactorrhea ceased within a week of withdrawal of metoclopramide. Normal regulation of prolactin secretion is by the hypothalamus, which produces prolactin-inhibiting factor (PIF) and probably prolactin-releasing factors. Thyrotropin-releasing hormone (TRH), which has been shown experimentally to be a potent stimulant of prolactin release, may be implicated. A number of nonspecific stressful stimuli, such as operations, exercise and uremia, have been shown to cause prolactin secretion. In addition, a number of drugs that affect dopaminergic mechanisms have been shown to affect prolactin secretion, by either increasing (dopamine and cholinergic drugs) or decreasing (methyldopa, chlorpromazine and reserpine) PIF secretion. Metoclopramide hydrochloride, a procaine derivative, was extensively reviewed in the Journal in 1975.1 Reported side effects include lassitude, drowsiness, gastrointestinal disturbance and extrapyramidal syndromes. It is structurally related to sulpiride, a potent stimulator of prolactin,2 and has been shown to produce significant prolactin release.3'4 Metoclopramide probably acts as a dopamine antagonist, for pretreatment with levodopa abolishes
the effects of metoclopramide (and TRH) on prolactin secretion, atropine in a dose of 1 mg fails to block metoclopramide-induced prolactin release, bethanechol chloride (a cholinergic drug) does not stimulate prolactin release and, in rats, metoclopramideinduced prolactin release can be abolished by administration of 2-bromoa-ergocryptine.5 Long-term administration of metoclopramide has been associated with galactorrhea and its use has been advocated for the prevention of premature weaning.6 In the long term it may prove to be a useful test of prolactin reserve. W.A. FINNIs, MD G.E. BIRD, MD D.L. WILSON, MD Division of endocrinology Department of medicine Queen's University Kingston, Ont.
References 1. BADLEY BWD: Some aspects of medical management of gastrointestinal disease. Part I. Can Med Assoc J 112: 200, 1975 2. THORNER MO, BEssER GM, HAGAN C, et al: Introduction of a new stimulation test for
prolactin. J Endocrinol 61: 132, 1974
3. MCNEILLY AS, THORNER MO, VOLANS G, et al: Metaclopramide and prolactin. Br Med J 2: 729, 1974
4. MCCALLUM RW, SowaRs JR, HER5HMAN JM,
et al: Metoclopramide stimulates prolactin secretion in man. I Clin Endocrinol Metab 42: 1148, 1976 5. YAMAUCHI J: Stimulation of prolactin secretion by metoclopramide in man and rats
(abstr 30) in V International Congress ol Endocrinology, Giessen, West Germany,
Bruhlsche Universitatsdruckerei, 1976, p 12 6. SousA PLR: Metoclopramide and breast-
feeding. Br Med 1 1: 512, 1975
Inequity in current library regulations To the editor: I read with great interest the recent letter from Dr. Philip Eibel (Can Med ASSOC J 115: 391, 1976) and, as a librarian, have certain comments on some of the points he raised. Eibel refers to decisions made at numerous institutional libraries that restrict availability of the latest information on medical subjects. His argument can be extended one step further in that many major science libraries housed in institutional settings restrict in toto the removal of journals, no matter what vintage! However, I do not wish to enhance this viewpoint but rather to comment on why this seemingly restrictive policy has been adopted by numerous North American biomedical libraries. First, library budgets have been adversely affected by inflation. A subscription to the average medical journal (if there is one) now costs approximately $48 a year. This represents a 144% increase since 1969. As a result, fewer "pocket collections" and individual subscriptions are available to supplement the research library's copy. Second, the explosion in information
CMA JOURNAL/NOVEMBER 6, 1976/VOL. 115 845
has necessitated that libraries subscribe to an increasing number of specialized journals if we are to fulfil the requirements of our users. Third, the development of computerized bibliographic services has greatly expanded the information needs of clinicians and researchers. These facts may hold little interest for the medical scientist who prefers the perusal of medical journals "within the quiet sanctuary of [his] home". It is indeed regrettable, as Eibel points out, that libraries are no longer able to provide this sanctuary thanks to "congestion created by budding prescribers of pills and nostrums". Young students are frequently the products of a McLuhanesque educational process that requires the presence of televisions, slides, tapes, and other noisome instruments in the library. Librarians have little choice in all this. If committed to their professional role in the university they are obligated to provide access to information. How can this role best be filled? While a journal sits in the quiet of a physician's study it is available to him alone. When a physician reads a journal in the library, albeit with difficulty, or obtains a photocopy of the desired article, the journal becomes available to numerous other users within hours. Technology in the form of excellent xerographic processes has enabled libraries to disseminate information rapidly. The role of a major scientific library in an institutional setting is complex and precarious. It is complex because of the multifaceted interests and information needs of the users, the location of users vis . vis the library and the potential for conflict between institutional goals and professional commitments. It is precarious because of the failure of our governments to acknowledge financially the role of major science libraries as regional resource centres. Things are not always what they seem. The move by libraries to restrict journal circulation is a move to increase rather than decrease the availability of scientific information to those who rely upon libraries for that information. FRANCES GROEN Life science area librarian Medical library McGill University 3655 Drummond St. Montreal, PQ
To the editor: I think Frances Groen for her painstakingly detailed letter even if some of her ideas about the new library regulations are at variance with mine. I ascribed these measures largely to an effort to thwart or impede the founding of private libraries from the
accumulated stocks of p.arent institutions. Ms. Groen does not mention the purloining of library contents as a reason for the new regulations rather strange when one considers all the stratagems in a well run modern library to catch thieves - but she blames, as do many people, inflation. Inflation, as our Prime Minister indicates every day, is indeed undesirable and has caused the price of medical journals to soar, but I fail to see how the cost of these journals could be reduced by curtailing the right to peruse them in the solitude of one's home. However, the main reason for the new regulations is not the cost but the supposed lack of readily available library materials under conditions of free circulation. Nothing is more galling for an investigator than to find that an article essential for his work is temporarily out on loan. This is a valid argument but it is doubtful that, under the old system at McGill University wherein journals other than current ones could circulate for 2 or 3 weeks, a Nobel prize was ever lost because a reader or would-be author had to wait a few days for the return of a journal. There are other arguments in Ms. Groen's letter to vindicate the new regulations: the imperative need to cope with the information explosion, the niggardly amounts of money given by our governments for proper library maintenance, and the new disciplines requiring expensive esoteric journals. For the greater part I agree with Ms. Groen except that I yearn for the missing journals in the sanctuary of my study. However, I realize that the good old days when one could walk out of a library with an armful of journals are probably gone forever. PHILIP EIBEL, MD, FRC5[C] Ste. 370, 5845 Cote des Neiges Montreal, PQ
Medical information systems To the editor: Occasional papers appear in the Journal regarding medical information systems. Currently there is a multitude of data systems in Canada ranging from that for individual hospitals to the statutory systems at the provincial and federal government levels. The data collections have different purposes, the quality of the data is uneven and the systems are not linked. This means that the information has limited worth for research work. This is particularly true of the statutory mortality and morbidity data collected by governments that are faithfully filed away and published in selective form. Access to this material is possible and in our experience civil servants are invariably receptive and
846 CMA JOURNAL/NOVEMBER 6, 1976/VOL. 115
helpful. The data, however, are stored by event (hospital admissions and discharges) rather than as a cumulative record for individual patients. Therefore, special time-consuming and costly analyses have to be made for cohort studies or detailed accounts of care patterns. Furthermore, the analyses have to be paid for by the researchers. There are several principal data systems in Ontario, including those for the Ministry of Health, the Ontario Health Insurance Plan and the Hospital Medical Records Institute. These appear to be independent and are not used routinely for evaluative research. Epidemiologic surveys and evaluation of health care would, however, be greatly facilitated by reliable, linked information systems. A health identification number could be developed for each person in order to record all contacts with medical services. Reliability and confidentiality are complex and important but could be ensured with proper planning. Informal contacts made at scientific meetings indicate that there are people across the country interested in information systems but there is insufficient coordination of their concerns. This is a pity since Canada is one of the few Western countries with comprehensive health care statistics on the total population and it is wasteful for these data not to be put to good use. We would be glad to hear from others, particularly in Ontario, who are interested in the promotion of a linked medical data base. MR. EASTwOOD, MD, FRCP[C], MRC PSYCH
B.A. M4UtflN, MD, FRCP[CJ H.M.R. MEIER, MB, CH B, MRC PSYCH
C.M. WOOGH, MD, M sc
Clarke Institute of Psychiatry 250 College St. Toronto, Ont. Correction
In the summary of the paper "Beclomethasone dipropionate aerosol in allergic rhinitis" by Cockcroft and colleagues (Can Med Assoc J 115: 523, 1976) the fourth sentence should read as follows: "Patients in the BDA group had significantly less (P < 0.05) sneezing, rhinorrhea and nasal stuffiness on 36 days, cough on 10 days and antihistamine consumption on 17 days" (our italics). S.milarly, in the Results section in the analysis of diary cards the second and fourth sentences should read as follows: "Patients receiving BDA had significantly lower mean scores than those receiving placebo (P < 0.05) for sneezing and stuffy, runny nose on 36 days" (our italics) and "The BDA group also had significantly less (P < 0.05) cough on 10 days and antihistamine tablet consumption on 17 days" (our italics). We apologize to the authors for these errors.
