Role of the physician in screening for carriers of Tay-Sachs disease.

A screening test for carriers of Tay-Sachs disease has been available in Toronto for more than 6 years. In that time more than 11 000 Jewish residents have been tested. Most had requested testing after hearing about the screening program from friends or the media; few had been advised by their physicians to be tested. To sample the attitudes of physicians in Toronto towards carrier screening, we studied questionnaire responses of 42 physicians whose practices were composed largely of Jewish patients. Only 31% regularly advised their young adult Jewish patients to have a carrier screening test but 76% said they had patients who asked if they should be tested. Of the 14 (33%) who had had one or more patients with Tay-Sachs disease 6 did not advise carrier testing. There was a positive correlation between specialty training and support for the screening program. Methods for increasing physician advocacy of these programs are discussed.     

Strain variation in Hymenolepis diminuta: enzyme profiles

In comparative study of respiratory metabolism, it was established that the relative proportions of respiratory end-products (succinic, acetic and lactic acids) differed consistently in two strains of Hymenolepis diminuta (Toronto and ANU). The ANU strain produced more lactic acid and less succinic acid under aerobic and anaerobic conditions. In the shift from aerobic to anaerobic conditions both strains compensated by increasing their outputs of succinic acid. The ANU strain possessed significantly higher activities of hexokinase, pyruvate kinase, lactate dehydrogenase, cytosolic and mitochondrial malic enzyme and cytosolic α-glycerophosphate dehy drogenase. The Toronto strain had significantly higher activities of fumarase, succinate dehydrogenase, and fumarate reductase. There were no significant differences in the activities of phosphoenolpyruvate carboxykinase and malic dehydrogenase between strains. The fumarase activity in the Toronto strain was 16 times that of the ANU strain, its K_m (malate) was 0.8mM, as opposed to 2.5 mM, and it was less sensitive to inhibition by NAD or ATP. These observations are consistent with the patterns of end-product formation in the two strains. Ratios of end-products and calculations of approximate redox balance suggest that the Toronto strain may have a greater capacity for aerobic metabolism.     

Infant feeding practices: 1984-85 versus 1977-78.

In 1979 and 1980 the Canadian Paediatric Society''s Nutrition Committee published guidelines for professionals counselling mothers of infants on feeding practices. The practices in 1984-85 of mothers in Toronto were determined for comparison with the practices identified in a similar study conducted in Toronto and Montreal in 1977-78 to ascertain if practices had changed in favour of the recommendations. Between July 1984 and February 1985, 404 metropolitan Toronto mothers of infants were interviewed. Compared with the 1977-78 group of mothers, more of the 1984-85 mothers had chosen to breast-feed and fewer had stopped breast-feeding in the first month. As well, fewer of the 1984-85 infants had been fed unmodified cow''s milk in the first 6 months of life and introduced to solid foods before 4 months of age. We conclude that major changes in infant feeding practices had occurred since 1977-78 and that the 1984-85 practices corresponded closely to the infant feeding guidelines.     

The first 10 years of the dialysis-transplantation program at The Hospital for Sick Children,Toronto. 1: Predialysis and dialysis.

Renal dialysis and transplantation have been used for many years for adults with kidney failure but only recently for children. In May 1967 a renal-dialysis-transplantation program was established at The Hospital for Sick Children, Toronto for patients aged 6 to 18 years living within 240 km of Toronto. In 1973, children aged 1 to 5 years began to be accepted into the program, and by August 1977, 90 children (mean age 11 years) from all parts of Canada had been admitted to the program. The creation of vascular access in very small patients is difficult; the most successful types of access have been central shunts (established above the knee or the elbow) and bovine grafts. Specially made dialysis equipment is necessary for young patients. Young children should only be accepted in a dialysis-transplantation program that has a medical staff expert in meeting the specific needs of such children.     

Intestinal parasites in metropolitan Toronto day-care centres.

In 1981, 900 children (aged 3 months to 10 years) and 146 staff attending 22 day-care centres in metropolitan Toronto chosen at random provided a stool specimen in a survey for intestinal parasites. Of the children, 4% to 36% were infected in 20 of 22 centres. Overall, 19% of the children and 14% of the staff had intestinal parasites: 8.6% and 4.0% respectively had Dientamoeba fragilis, and 7.8% and 2.0% respectively had Giardia lamblia. The highest prevalence of dientamebiasis was in the 7- to 10-year-olds, whereas giardiasis was detected most frequently in the 6-year-olds. Infection with intestinal parasites was not correlated with age, sex, duration in the day-care centre, dog ownership, travel history, gastrointestinal symptoms or the proportion of children in the day-care centre who were born in less developed countries. Immigrant children and children of parents born in industrialized countries (including Canada) were more likely to be infected than were children born in Canada of parents from the developing world. Dientamebiasis was associated with cat ownership. Thus, intestinal protozoa--in particular, D. fragilis and G. lamblia--are endemic in Toronto day-care centres.     

Water regulation in aestivating snails

Summary Aestivating snails form abundant lamellate vesicles in the cells of the mantle collar, an epithelium known to regulate the rate at which water is lost from its surface. Since lamellate vesicles are much reduced in hydrated mantle tissue of recently stimulated animals it is tentatively concluded that the vesicles, and their contents, form a barrier to water movement within these cells. X-ray microanalysis of unfixed thin sections shows that there is a concentration gradient of ions within these cells in aestivating animals which is not present in stimulated snails.Financial support from the National Research Council of Canada and the Atkinson Foundation. Toronto, is gratefully acknowledged. The work was performed during the sabbatical leave of one of us, using the facilities of the Department of Zoology and the Faculty of Medicine Electron Microscope Unit (supported, in part, by grant M.A. 4038 of the MRC of Canada), University of Toronto     

Ultrastructural Characteristics of Adult Rat Adrenocortical Cells Maintained in vitro With and Without ACTH

Bhattacharyya, T. K., Butler, D. G., Price, C. S. 1980. Ultrastructural characteristics of adult rat adrenocortical cells maintained in vitro with and without ACTH. (Ramsay Wright Zoological Laboratories, Department of Zoology, University of Toronto, and Division of Endocrinology, Toronto Western Hospital, and Department of Medicine, University of Toronto, Canada.) — Acta zool. (Stockh.) 61(1): 9–21. The ultrastructural morphology of adrenocortical cells of adult rats maintained in culture for four days with and without corticotropin (ACTH) was studied in comparison to freshly dissociated cells. Identification of cells belonging to zona glomerulosa, zona fasciculata, and zona reticularis was made on the characteristics of the mitochondria and smooth endoplasmic reticulum (SER), and was confirmed by comparison with cellular layers from intact adrenals. Without ACTH, glomerulosa and fasciculata cells showed disappearance of SER, atrophied Golgi apparatus (GA), and a striking proliferation of granular reticulum. Fascicular cells had a loss in mitochondrial matrix density and the mitochondrial cristae showed a tendency to convert to lamellar glomerulosa-type cristae. Zona reticularis cells were not strikingly altered. Maintenance with ACTH led to increased cell size and islet formation of cortical cells. Glomerulosa cells had normal appearance and fasciculata cells manifested a pronounced development of GA and SER, and a normal configuration of mitochondria. The effects of ACTH on glomerulosa cells suggest a trophic influence of ACTH on these cells in vitro. The alterations observed in fascicular cell mitochondria and SER can be explained in terms of known concepts of steroid biosynthesis and basically agree with the patterns of steroid synthesis observed in these cells previously (Price et al. 1975).     

Legal issues surrounding privately funded research cause furore in Toronto

Toronto physician Miriam Shuchman has spent the last 4 months tracking the research issues surrounding a controversial clinical trial conducted in Toronto. Much of the information appearing in this article was gathered while she was preparing a segment for the CBC Radio program Quirks and Quarks. Earlier, she had reported on similar issues in the US for the Annals of Internal Medicine.     

Seroprevalence of and risk factors for HIV-1 infection in injection drug users in Montreal and Toronto: a collaborative study.

OBJECTIVE: To determine the prevalence of antibodies to HIV-1 and risk factors for HIV-1 infection among injection drug users. DESIGN: Questionnaire survey. A venous blood sample was taken for HIV-1 antibody testing. SETTING: Montreal and Toronto. PARTICIPANTS: A total of 810 subjects who had used injection drugs in the previous 6 months recruited mainly from treatment centres and from the street in Montreal (425 subjects) and from treatment centres in Toronto (385 subjects) between September 1988 and September 1990. The overall participation rate was 82%. OUTCOME MEASURES: HIV-1 seropositivity, sociodemographic and behavioural risk factors for HIV-1 infection. RESULTS: The overall seroprevalence rate of HIV-1 infection was 4.8% (95% confidence limits [CL] 3.5 and 6.5). In Montreal the rate was 8.2% (95% CL 6.0 and 11.2), and in Toronto 1.0% (95% CL 0.4 and 2.6) (p < 0.001). Seropositive subjects were significantly older (p = 0.041) and were more likely to have a history of imprisonment (p = 0.006) than seronegative subjects. In univariate analysis seropositivity was associated with the following behaviours: more frequent cocaine use (p < 0.001), injecting drugs in "shooting galleries" (p = 0.002), sharing equipment with a person known to be HIV-1 seropositive (p = 0.006), "booting" fresh blood (p = 0.004), homosexual or bisexual orientation (p = 0.006), engaging in prostitution (p < 0.001) and, for men, number of male sexual partners in the previous 6 months (p = 0.007). In multivariate analysis the determinants of HIV-1 seropositivity were Montreal as the city of recruitment (odds ratio [OR] 6.7, 95% CL 2.32 and 19.42), engaging in prostitution (OR 2.13, 95% CL 1.01 and 4.75), a history of imprisonment (OR 3.51, 95% CL 1.33 and 9.29) and sharing equipment with a person known to be HIV-1 seropositive (OR 4.43, 95% CL 1.43 and 13.74). CONCLUSIONS: Our findings show that HIV-1 is circulating among injection drug users in Montreal and Toronto and that both drug use and sexual behaviours are implicated in the transmission of infection in the populations studied. Adapted preventive programs should be developed to prevent further spread of HIV-1 infection in this population.     

Effect of TRH (thyrotropin-releasing hormone) on the fine structure and replication of TSH and prolactin cells in the rat

Summary In intact male rats after TRH administration for 7 and 14 days, TSH cells showed similar morphological changes to those observed after thyroidectomy. These changes were paralleled by small numerical increases in TSH cell counts. After 34 days of TRH treatment, however, most of the TSH cells had a normal appearance and the number of TSH cells also had returned to normal. TRH treatment for 7, 14 and 34 days caused morphological changes in Prolactin cells similar to those obtained after a suckling stimulus. In the three groups these changes were also paralleled by small numerical increases in Prolactin cell counts. The cell replication after TRH for 7 and 14 days, as measured by incorporation of tritiated thymidine to obtain a labeling index, was slightly but significantly increased.This work was supported by grants MA-552 and MT-2701 from the Medical Research Council of Canada. The authors wish to thank Dr. D.A.J. Ives, Connaught Medical Research Laboratories, Toronto, for providing the TRH, and Mr. G. Penz for technical assistance.Fellow of the Medical Research Council of Canada.     

World AIDS Day 2007: AIDS at 26, are we there yet?

This Commentary reflects on the success of the XVI International Conference on AIDS, that was held in Toronto between August 13–18, 2006. Not only was the Conference judged to have been a scientific success, it will probably also be recognized over time as having had important political impact. It is vital that scientists and policy-makers continue to be able to interact at these meetings as part of global efforts to combat the HIV epidemic.     

Iodine Nutrition During Pregnancy in Toronto,Canada

ObjectiveTo evaluate the status of iodine nutrition among pregnant women presenting for routine antenatal care in Toronto, Canada, as determined by the median urine iodine concentration (UIC) of this population.MethodsA cross-sectional, observational study was conducted involving 142 pregnant women recruited from four low-risk antenatal outpatient clinics in Toronto, Canada. Subjects completed a questionnaire and provided a spot urine sample for the measurement of iodine concentration.ResultsMean maternal age was 33.8 ± 4.3 years. Mean gestational age was 29.3 ± 7.8 weeks. The median UIC was 221 μg/L (interquartile range, 142 to 397 μg/L). Six women (4.2%) had urine iodine levels <50 μg/L, and 36 women (25.4%) had levels between 50 and 150 μg/L.ConclusionThis cohort of primarily Caucasian, well-educated, and relatively affluent pregnant women in Toronto, Canada, are iodine sufficient, perhaps due to universal salt iodization and/or other dietary and lifestyle factors. (Endocr Pract. 2013;19:206-211)     

Red Cell Glucose-6-Phosphate Dehydrogenase Deficiency—A Newly Recognized Cause of Neonatal Jaundice and Kernicterus in Canada

Seven male newborns of Chinese, Greek and Italian origin presented with severe hemolytic jaundice due to red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. In five, the hemolysis was precipitated by inhalation of mothball vapours in the home. Kernicterus was evident upon admission in six infants and was fatal in four of these.G-6-PD deficiency should be suspected as a cause of jaundice in all full-term male infants of these ethnic groups. The diagnosis can be confirmed in any hospital by the methemoglobin reduction test. In areas similar to Toronto, Canada, where these high-risk ethnic groups prevail, the following measures are recommended: (1) detection of G-6-PD deficient newborns by screening cord bloods of all infants of these ethnic groups; (2) protection of affected infants from potentially hemolytic agents such as naphthalene, certain vitamin K preparations, and sulfonamides; and (3) observation of serum bilirubin levels to assess the need for exchange transfusion for hyperbilirubinemia.     

Malaria at the Hospital for Sick Children,Toronto.

The number of immigrants to Canada from countries where malaria is endemic increased sevenfold between 1964 and 1974. From January 1973 through July 1975, 15 cases of malaria were treated at the Hospital for Sick Children, Toronto. The only symptom common to all patients was fever, and it was not always cyclic. For any child with a fever of unknown cause who has been in a region where malaria is endemic within the previous 6 months, a blood smear should be examined for parasites. If the smear is negative even when stained with acridine orange, serologic testing should be performed. Acurrate species identification is important since therapy varies according to the causative organism.     

The olivieri case: Lessons for Australasia

The case of Dr. Nancy Olivieri, the Hospital for Sick Children, the University of Toronto, and Apotex Inc. vividly illustrates many of the issues central to contemporary health research and the safety of research participants. First, it exemplifies the financial and health stakes in such research. Second, it shows deficits in the ways in which research is governed. Finally, it was and remains relevant not only in Toronto but in communities across Canada and well beyond its borders because, absent appropriate policies, what happened in Toronto could have happened (and could well still happen) elsewhere. In Part One of this paper, we review the facts of the Olivieri case relevant to the issues we wish to highlight: first, the right of participants in a clinical trial to be informed of a risk that an investigator had identified during the course of the trial and the obligation of the investigator to inform participants (both her own and those of other investigators); and second, the obligation of institutions to protect and promote the well-being of research participants as well as academic freedom and research integrity, the obligations of research sponsors to inform participants, research regulators, and others about unforeseen risks, and the obligations of research regulators to ensure that participants are informed of unforeseen risks and to otherwise protect and promote research integrity. In Part Two, we relate these facts and issues to New Zealand and Australia. We also make detailed recommendations for changes to the various instruments used for the governance of research involving humans in Australasia.     

Trap-vaccinate-release and oral vaccination for rabies control in urban skunks, raccoons and foxes.

Two rabies control tactics, trap-vaccinate-release (T-V-R) and oral vaccination were used for the control of rabies in skunks (Mephitis mephitis), raccoons (Procyon lotor), and foxes (Vulpes vulpes) in metropolitan Toronto, Canada. Using T-V-R, a mean of 45% to 72% (95% confidence limits of 40% to 81%) of the skunks and a mean of 17% to 68% (95% confidence limits of 14% to 76%) of the raccoons in a 60 km2 area of Toronto were vaccinated against rabies between 1987 and 1991. The area has been free of skunk rabies from May 1989 to April 1992. Forty-five rabies cases were diagnosed during 1980 to 1986. In contrast, only three skunk cases have been reported since the vaccination program began in July 1987. The T-V-R area also remained rabies free during an epizootic of skunk rabies in metropolitan Toronto during 1991. Following distribution of rabies vaccine-baits throughout the ravines of metropolitan Toronto, June 1989 to December 1991, 46% to 80% of the Toronto fox population was immunized during 1989, 1990 and 1991. Only one case of fox rabies was reported in metropolitan Toronto since vaccination began, compared to 80 cases reported between 1982 and 1988. The area has been free of reported fox rabies from October 1990 to April 1992.     

Hydatid Disease in Toronto

Two case reports of Echinococcus granulosus disease are presented in detail, together with a survey of 35 cases of the disease encountered in Toronto hospitals since 1932; 32 of these have occurred since 1949. Only six of the 35 patients were born in and lived in Canada, and all of these came from Northern Ontario. The liver was involved in 20 of the 35 patients, and the lung in 16. In seven the lesions were multiple at the time of the first operation or several years later. The Casoni skin test was positive in 14 of 21 patients tested and the complement fixation test was positive in 13 of 16 subjects tested. Eosinophilia of 6% or more occurred in nine of the 26 patients on whom a differential white blood cell count was performed, and allergic manifestations were recorded in eight of the 35 subjects in the series.     

Immunological studies in a double blind randomized trial comparing intrapleural BCG against placebo in patients with resected stage I non-small cell lung cancer

Summary Immunological data were obtained during the course of a randomized trial comparing intrapleural BCG plus oral isoniazid (INH) with intrapleural saline plus oral placebo after resection of stage I non-small cell lung cancer. Immunological testing with a variety of assays was carried out with good standardization among six collaborating laboratories and with good reproducibility within each laboratory. Those patients with larger tumors tended to have higher initial white cell counts. The percentage of lymphocytes in the differential was greatest in those with non-squamous cancer histology. Otherwise, no associations were found between initial immunologic parameters and baseline variables. The main effect of BCG/INH therapy was to cause statistically significant increases in purified protein derivative (PPD) skin test induration and PPD in vitro blastogenesis compared with controls. Other skin tests and in vitro assays increased more in the saline/placebo control group, but these treatment differences were usually not statistically significant. Initial white count and neutrophil count elevations were found to be associated with increased risk of recurrence. Even after adjustment for treatment and tumor stage, initial neutrophil count elevation was associated with increased risk of recurrence. Surprisingly, a low 29° C T cell rosette index was associated with a decreased risk of recurrence, though the differences were minimal. Serial immunological tests were carried out to evaluate their potential for monitoring disease recurrence. White count elevations continued to be significantly associated with increased risk of recurrence, but more follow-up data are needed before other associations can be assessed.Members of the Lung Cancer Study Group include: E. C. Holmes** (Group Chairman), W. F. Coulson, K. P. Ramming, and T. H. Weisenburger from the University of California, Los Angeles; Z. Petrovich from Wadsworth Veterans Hospital, Los Angeles; R. T. Eagan**, R. E. Lee, W. S. Payne, R. E. Ritts, and L. Weiland from the Mayo Clinic, Rochester; C. F. Mountain**, H. T. Barkley, O. H. Frazier, K. Hermes, E. Hersh, and M. Valdivieso from the University of Texas System Cancer Center, MD Anderson Hospital, Houston; L. D. Hill**, M. D. Hafermann, and E. Morgan from the Mason Clinic, Seattle; P. W. Wright**, and K. E. Hellstrom from the Hutchinson Cancer Center, Seattle; C. Bagley, L. P. Johnson, H. Kellogg, and R. D. Pinkman from the Swedish Medical Center, Seattle; T. D. Ivey from University Hospital, Seattle; S. Hammar from Virginia Mason Hospital, Seattle; W. Nelems from St Paul's Hospital, Vancouver; R. Feld**, D. Bergsagel, T. C. Brown, J. Curtis, C. Keen, J. F. Pringle, I. Quirt, and L. Yeod from the Princess Margaret Hospital, Toronto; M. Blackstein and M. Goldberg from Mount Sinai Hospital, Toronto; F. G. Pearson**, D. W. Chamberlain, J. Cooper, W. Evans, and T. Todd from Toronto General Hospital, Toronto; M. Baker and R. Ginsberg from Toronto Western Hospital, Toronto; R. I. Mitchell from Wellesley Hospital, Toronto; R. K. Oldham**, J. T. Forbes, F. A. Greco, D. L. Page, R. Prager, R. L. Richardson, and S. L. Stroup from Vanderbilt University, Nashville; J. M. Lukeman** and S. M. Sajjad from the Pathology Reference Center of UT MD Anderson Hospital, Houston; P. Grifone, A. Lebeck, A. Sharpe, and T. Voss from the Operations Office, Silver Spring, Maryland; M. Gail and L. Rubinstein, Group Statisticians, W. McGuire, J. Allegra, G. Witman, Project Officers, from the National Cancer Institute, Bethesda, Maryland; and W. Heineman, J. Beach, L. Close, and B. Sharkey from Information Services, Bethesda, Maryland. Asterisks designate principal investigators