Checking random assignment with claims data.
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Biomedical subjects
Publications and source records attributed to R Tate.
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OBJECTIVE: The 5 alpha-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5 alpha-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5 alpha-reductase activity of the gland in men with BPH treated with the drug for 3 months. DESIGN AND PATIENTS: Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months. MEASUREMENTS: Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5 alpha-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels. RESULTS: There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT (P = 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5 alpha-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5 alpha-reductase activity of the gland and tissue DHT concentrations. CONCLUSIONS: Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5 alpha-reductase responsible for the accumulation of DHT in the gland.
By its inability to grow on sulfate as the sole sulfur source, a mutant strain (CTNUX8) of Rhizobium etli carrying Tn5 was isolated and characterized. Sequence analysis showed that Tn5 is inserted into a cysG (siroheme synthetase)-homologous gene. By RNase protection assays, it was established that the cysG-like gene had a basal level of expression in thiosulfate- or cysteine-grown cells, which was induced when sulfate or methionine was used. Unlike its wild-type parent (strain CE3), the mutant strain, CTNUX8, was also unable to grow on nitrate as the sole nitrogen source and was unable to induce a high level of nitrite reductase. Despite its pleiotropic phenotype, strain CTNUX8 was able to induce pink, effective (N2-fixing) nodules on the roots of Phaseolus vulgaris plants. However, mixed inoculation experiments showed that strain CTNUX8 is significantly different from the wild type in its ability to nodulate. Our data support the notion that sulfate (or sulfite) is the sulfur source of R. etli in the rhizosphere, while cysteine, methionine, or glutathione is supplied by the root cells to bacteria growing inside the plant.
A review of workers' compensation board (WCB) claims in Manitoba, Canada identified an estimated 382 upper limb repetitive strain injury (RSI) claims or 9.3% of all upper limb WCB claims accepted in 1991. Tendonitis and carpal tunnel syndrome (CTS) were the most frequent diagnoses (27.5% and 19.3%, respectively). Rates of RSI were not significantly different by gender and age. RSI claimants had been experiencing symptoms for an average of 8 months prior to filing a compensation claim. While clerical occupations accounted for 13.6% of all upper limb RSI claims, the rates for RSIs in these occupations were low (0.67/1,000 workers), in contrast to occupations with the highest RSI rates: food, beverage, and related processing occupations (14.68/1,000 workers) and fabricating, assembling, and repairing of metal products (9.32/1,000). The highest risk industries were meat and poultry processing-related (23.48/1,000) and the manufacturing of airplanes (9.06/1,000). RSI claims were significantly more costly (+5,569 vs. +2,480, p < 0.0001) and required more time loss (71.4 vs. 33.6 d, p < 0.0001) than similar musculoskeletal non-RSI claims. Similarly, RSI claimants were less likely to return to the same job (67.3% vs. 81.0%, p < 0.0001) than non-RSI claimants. It was concluded that the cost and severity of RSI claims militate for intensified preventive measures.
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The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.
This study evaluated a two-year multidisciplinary early intervention pilot programme for back-injured nurses employed at a large teaching hospital, using a pre- versus post-programme analysis. The purpose was to ascertain whether this programme could reduce the incidence, morbidity, time lost and cost due to back injuries in the 250 nurses employed on ten targeted high-risk wards. Injuries in the remaining 1395 nurses employed on the other 45 wards were monitored concurrently for comparison. The programme consisted of prompt assessment, treatment and rehabilitation through modified work. Evaluative data were gathered by one research nurse on standardized forms at the time of injury, weekly until return to work, and at a six-month follow-up. Time lost and cost data for up to one-year post-injury were derived from workers' compensation statements. Compared to the two years prior to introduction of the programme, the rates of back injuries and lost-time back injuries decreased by 23% and 43%, respectively, on the targeted wards, while these increased on the control wards. Combined expenditure was 32% lower per injury and 34% lower per lost-time injury for those in the targeted group who consented to take part in the programme compared to their counterparts on the control wards, as the increased assessment and treatment costs per case attributable to the programme were more than offset by the savings in lower compensation (wage loss) costs. This programme thus reduced the incidence and time lost due to back injuries and was cost-beneficial.
Two years of prospective data on 416 back injuries were gathered at a 1100-bed acute and tertiary care hospital to assist target prevention efforts. The rate of injury among 1645 nurses was found to be highest for those working on orthopaedic, medicine, neurology, spinal and surgery wards, indicating priorities for prevention. In fact, 51% of the orthopaedic nurses sustained at least one back injury during the two-year period. Gender did not significantly affect the risk of back injury; however, injuries were slightly more common in nurses with less seniority and younger nurses were found to be at significantly increased risk of back injury. Almost 63% of the back injuries which occurred in nurses working 8 h shifts on the high-risk wards occurred during the first two hours of the shift. Lifting and transferring patients with assistance were the two most common mechanisms for back injury (22.6% and 23.3%, respectively). In total, injured nurses attributed 52.3% of their injuries to inadequate training; inadequate staffing was given as the primary reason for 13.8% of the injuries. The results suggest that training in the indications for and use of mechanical devices for lifting/transferring patients requires intensification, and a 'warm-up' period should also be considered in the face of injuries occurring early in the shift if work activities cannot be evenly planned.
Persons with disabilities occasionally report that dentists are reluctant to provide them with either dental care or necessary services. There is very little information about the kinds of services that Canadian dentists provide to disabled people. To answer this question, a mail survey, following Dillman's Total Design Method, was undertaken in Manitoba. Questionnaires were mailed to all dentists licensed to practise in Manitoba in 1990. A total of 342 surveys were returned, representing a 62 per cent response rate. In all, 259 (76 per cent) of respondents reported regularly providing dental care to disabled people of all ages who were afflicted by a broad range of disabling conditions. The private dental office was the primary location in which this dental care was provided, but 65 dentists (25 per cent) reported providing dental care in hospitals or other institutions such as nursing homes. Forty per cent of the dentists who reported treating disabled people were willing to accept referrals of new patients with disabilities. Dentists reported providing a full range of dental services to disabled people, and using similar modes of pain control for both disabled and non-disabled patients. The primary mechanism of payment was social assistance programs. Dentists reported that they received adequate compensation (defined as their usual and customary fee) in only 50 per cent of the cases in which they provided dental care to disabled patients. However, 27 per cent of the respondents reported always receiving their customary fee, and 52 per cent indicated that they would be willing to attend continuing education courses offered in the area of special patient care.(ABSTRACT TRUNCATED AT 250 WORDS)
This study examined mortality to December 31, 1989 in a cohort of 2,222 males employed between 1947 and 1975 at a transformer manufacturing plant in Canada, where there had been extensive use of transformer fluid, some containing polychlorinated biphenyls (PCBs). A combined cohort list of 2,222 names was independently obtained from plant management and union officials. Mortality of 1,939 workers with known birthdates was ascertained by record linkage with the Canadian Mortality Data-base. Standardized mortality ratios (SMRs) for different criteria for acceptance of the death certificate link and for cohort membership (based on work history) ranged from .71-1.05. There was no significant increase in overall cancer deaths. The only significant site-specific increased mortality was pancreatic cancer (11 deaths), with SMRs ranging from 2.92-7.64 and higher mortality risk in those who entered the cohort prior to 1960. All but one of these deaths had a latency period of at least 10 years, and greatest SMRs were found in departments with the greatest exposure to transformer fluid. Several previous studies have found excess pancreatic cancers in association with oil exposures and electrical equipment manufacturing. The need to further investigate pancreatic cancer in transformer manufacturing and related exposures is evident.
To evaluate the hypothesis that testicular descent is mediated by the action of high local concentrations of dihydrotestosterone in the gubernaculum, testis, or epididymis, we obtained tissues from 30 male pig fetuses between 63 and 101 days of gestation. We assayed the 5 alpha-reductase activity in homogenates of pooled tissue by following the conversion of (3H)testosterone to (3H)dihydrotestosterone. The 5 alpha-reductase activity in the urethra and prostate increased prior to and during, but decreased after, the period of testicular descent. The 5 alpha-reductase activity in the gubernaculum remained constant throughout gestation and was not significantly higher than the background activity found in umbilical cord, testis plus epididymis, striated thigh muscle and heat inactivated samples of prostate and urethra. Prior to testicular descent, the 5 alpha-reductase activity was approximately 60 to 300 times higher in the urethra than in the gubernaculum, and approximately 20 to 55 times higher in the prostate than in the gubernaculum. These findings indicate that local conversion of testosterone to dihydrotestosterone in the gubernaculum or epididymis does not play a role in the mediation of testicular descent in the pig fetus.
Nursing caries is a specific form of rampant dental caries affecting the majority of preschool aboriginal children who live in the Province of Manitoba, Canada. Since the majority of these individuals live in remote regions of the province access to dental treatment is difficult, resulting in long delays in the provision of treatment and, most likely, significant morbidity associated with dental pain and oral infection. Travel to distant centres for treatment under general anesthesia by pediatric dentists has become the usual method by which treatment is provided to the majority of affected children. We believed that this was an expensive method of providing these necessary services and our purpose was to document all costs associated with the treatment of nursing caries in this population. We analyzed the records of 884 children who were treated for nursing caries between 1980 and 1988 in Manitoba and collected data for costs in the following categories: travel, lodging, medical, dental, hospital and nursing. Our results show that the remote band groups had significantly higher costs (P < 0.001) than groups which were located closer to treatment centres. The costs which accounted primarily for this significant difference were travel and medical costs associated with hospitalization and the administration of general anesthesia. Our results support the need for the redeployment of resources on the basis of regional need and the development of community-based preventive programs and treatment programs which will significantly reduce the incidence of nursing caries in preschool Canadian aboriginal children.
This paper re-examines the association between menopause and depression using data from a study in which 477 women were interviewed 6 times over a 3-year period. Menopause is examined as one of a series of factors which may increase the risk of depression for women in middle age, such as children leaving home, the death and illness of family members, the stresses of daily living, health and the onset of chronic disease. Rather than hormonal changes, it seems to be her health coupled with the shifts and stresses of family life in a woman's menopausal years which may trigger her depression.
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A comparison was conducted of the immunogenicity of two yeast recombinant vaccines with different doses [10 micrograms Recombivax-HB (Merck Sharpe & Dohme Ltd) vs. 20 micrograms Engerix-B (Smith Kline Biologicals)]. This was conducted as a randomized, blinded study in healthy preclinical medical students, negative for hepatitis B markers. The geometric mean titres (GMT) showed a wide individual variability for both vaccines, and approximately a two- to threefold greater GMT of anti-HBs in recipients of the 20 micrograms vaccine. However, the 95% confidence interval showed an overlap of the means of the GMT for both vaccine groups, and in this study there was no significant difference in immunogenicity of these two vaccines. At 6-7 months after completion of immunization, antibody levels fell to one-third of the levels of one month post-immunization. A case report of an allergic urticarial reaction to one of the recombinant vaccines is presented.
From June 1986 to March 1990, a prospective seroprevalence survey and questionnaire of individuals at risk for HIV infection was conducted with volunteers in Winnipeg. Of 610 individuals enrolled, 146 were injected drug users (IDU). Fifteen IDU were in a methadone treatment program and all were seronegative. Three of 131 remaining IDU were HIV-1 seropositive (2.3%), a rate similar to 2.2% positive (20+ of 927) in diagnostic specimens from IDU tested in the province. Demographics and behaviour of 131 IDU were compared with 335 individuals, of whom 112 were gay/bisexual [24 of whom also had sexually transmitted diseases (STD)] and 223 heterosexuals who had STD. Males enrolled were significantly older than females. Multivariate analysis showed that factors independently associated with IDU were: a younger age, less education, mental health counselling, unemployment, and a history of jaundice or hepatitis. Drugs most commonly used were Ritalin/Talwin, cocaine, and heroin. Over 90% of individuals admitted to sharing needles. In spite of the low seroprevalence of HIV-1 infections, these individuals are important for the potential spread of HIV because of multiple means of acquiring and transmitting HIV and a high rate of needle sharing.
Canadian and American analysts commonly find that a small proportion of the elderly is responsible for a large share of health care expenditures. Data on a representative cohort in Manitoba indicate that the longer the time frame studied, the less health care usage concentrates in a single small group of elderly people. Over the sixteen-year period treated, the average older person's risks of using hospital and nursing home services is nevertheless notably higher than reported to date; yet, one-half of the elderly make relatively minimal demands on the health care system. The results reinforce calls for targeting the needs of intensive consumers of health care services and highlight the variability of cumulative usage patterns among older Manitobans.
The careers of graduates who had taken the BSc (Medicine) (BScMed) program at the University of Manitoba, Winnipeg, between 1950 and 1975 were compared with those of matched classmate controls to determine whether the program had any influence on the research careers of the graduates. More BScMed graduates than control subjects chose an academic career (49% v. 21%), achieved specialty certification (83% v. 65%), and obtained grants (51% v. 18%) and personal awards (37% v. 18%). The BScMed graduates also had significantly more publications than the control subjects. Although part of the difference between the two groups may be explained by the tendency of students who were more inclined toward an academic career to enter the BScMed program, it was evident that the program has a substantial effect on promoting the development of clinical investigators.