Biomedical subjects
Publications and source records attributed to G McFarlane.
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We documented available information concerning incident cases of gastric cancer in part of Kenya's Eastern Province between 1991 and 1993. By reviewing the records of all major health facilities in the area, 200 cases of gastric carcinoma were found giving an annual average crude incidence rate of 7.01 per 100 000 males and 3.7 for females (world age-standardised rates, 14.3 for males and 7.1 for females). There is likely to be underascertainment of cases especially among those aged over 65 years. Previous incidence estimates for the same area of Kenya were reviewed and a 10-fold increase in the recorded indirectly standardised incidence rate between the periods 1965-70 and 1991-93 was noted but this may be due to improved diagnostic facilities. The recent rates in this part of Kenya are comparable to Eastern European rates and similar to those recorded in other highland regions of Africa.
STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury. BACKGROUND: Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues. METHODS: A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews. RESULTS: Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly. CONCLUSIONS: In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.
A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC(50) = 0.29 microM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC(50) = 0.14 microM)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED(50) = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC(50) = 0.10 microM) which shows excellent in vivo efficacy (ED(50) = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4-(1, 1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED(20) = 100 mg/kg; selectivity: MAP ED(20)/bladder ED(50) = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI.
Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for infection and progression to AIDS led us to examine a potential role of this gene in AIDS lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-delta32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi's sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a decreased response of B cells to the mitogenic activity of RANTES.
BACKGROUND: Combination antiretroviral therapy including protease inhibitors (combo+PI) is effective in suppressing systemic viral load in HIV infection, but its impact on HIV-associated cognitive impairment is unclear. OBJECTIVE: To determine whether psychomotor speed, a sensitive measure of impairment in HIV dementia, improves with combo+PI compared with other antiretroviral treatments. METHODS: A total of 411 HIV-seropositive (HIV+) homosexual men (with longitudinal neuropsychological testing) in the Multicenter AIDS Cohort Study and, in a separate analysis, 282 HIV+ homosexual men with psychomotor slowing at baseline were classified by treatment into four groups: antiretroviral naive (no antiretroviral medication treatment), monotherapy, combination antiretroviral therapy without protease inhibitors (combo-noPI), and combo+PI. We compared longitudinal performance on three tests of psychomotor speed: the Grooved Pegboard (GP) (nondominant and dominant hands), Trail Making Test B, and the Symbol Digit Modalities Test (SDMT). RESULTS: Relative to antiretroviral-naïve and monotherapy participants, on the GP nondominant hand test, combo+PI participants with abnormal baseline neuropsychological testing showed improved performance (difference = +0.63 standard deviation [SD], p = 0.02). For the SDMT, both combo+PI participants (difference = +0.26 SD, p = 0.03) and combo-noPI participants (difference = +0.29 SD, p = 0.01) with abnormal baseline neuropsychological testing improved compared with antiretroviral-naïve and monotherapy groups. CONCLUSION: Combo+PI and combo-noPI are associated with improved psychomotor speed performance in HIV+ homosexual men with abnormal neuropsychological testing.
CONTEXT: Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. OBJECTIVE: To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters). DESIGN: Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model. SETTING: The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh, Pa). PARTICIPANTS: A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population. MAIN OUTCOME MEASURES: Time from seroconversion to development of AIDS and to death and change in CD4 cell count. RESULTS: A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01 ) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. CONCLUSIONS: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.
Although several studies describe the prevalence of coronary artery disease in patients with abdominal aortic aneurysms (AAA), the opposite relationship is virtually unexplored. It is the purpose of this study to determine the prevalence of AAA in patients with severe coronary artery disease undergoing bypass grafting (CABG). Patients scheduled for elective CABG underwent aortic ultrasound (US) preoperatively. A control group of patients without cardiovascular disease also underwent US. An AAA was defined as a maximal diameter > or =3.0 cm. US was performed on 192 CABG patients and 140 controls. The overall prevalence (previously repaired AAA and new cases) of AAA in CABG patients was 18.2%. The prevalence of new cases of AAA was 13.0% compared to 1.4% in controls (p = 0.0001). Ten patients had an AAA greater than 5.0 cm in size (5.2%). Logistic regression identified age > or =65 years and smoking as significant risk factors for AAA in the CABG population. The higher prevalence of AAA in CABG patients was confirmed by a case-control analysis of 73 age-matched patients. This study provides the first convincing evidence that the prevalence of AAA is higher in patients undergoing CABG than in the control population in Vermont. Consideration should be given to screening patients for AAA who are undergoing CABG, particularly older, smoking males.
STUDY DESIGN: Back-injured workers with high disability risk scores on a predictive questionnaire participated in a randomized, controlled trial of physician notification, with outcomes follow-up 3 months after injury. OBJECTIVES: To test whether physician intervention improves return to work and self-assessment outcomes for people at relatively high risk for disability. SUMMARY OF BACKGROUND DATA: Only a small number of back-injured workers suffer significant disability. Quick identification of these people would facilitate more efficient targeting and trials of interventions. Controlling variations in practice through practice guidelines has been recommended as a promising strategy for improving care and reducing disability. METHODS: Workers filing back injury reports responded to a disability prediction questionnaire. Those with high risk scores were randomly assigned to control or intervention groups. Patient-designated physicians in the intervention group received two letters identifying the patient's risk and making recommendations for care, including the Agency for Health Care Policy and Research's algorithms for acute low back pain. Predictive accuracy of the questionnaire and efficacy of physician intervention were evaluated on the basis of work status and self-assessments 3 months after injury. RESULTS: Of the 268 workers completing the questionnaire portion of the study, 32 (12%) were out of work because of back pain 3 months after injury. The questionnaire's predictive accuracy included maximum kappa of 0.277 and a receiver operating curve area of 0.78. Fifty-three people completed the physician intervention trial. The intervention had no significant impact on return to work, self-assessed pain, or satisfaction with health care. CONCLUSIONS: Stratification of back-injured people according to disability risk can can increase intervention efficiency by identifying those who require treatment and sparing those who do not. The apparent failure of risk notification and practice guidelines to reduce disability in this study may be improved by different application methods in the future.
UNLABELLED: Research has shown that diagnostic quality images for most teleradiology applications requires a sophisticated telemedicine system and access to a large amount of bandwidth. While the ideal standards have been set by those involved in evaluating teleradiology, these standards are impractical for many small rural health centers which deliver routine trauma care. While there is no disagreement about the ultimate need for this level of teleradiology support, the purpose of this research was to determine whether Orthopedists would be able to read plain radiographs of orthopedic trauma injuries using a desktop teleradiology system in support of rural trauma care. METHOD: Two radiology residents and two orthopedic residents viewed forty radiographs, twenty through a desktop teleradiology system and twenty in person. Diagnostic findings and certainty of diagnosis were recorded. FINDINGS: There was no statistically significant difference between modalities in orthopedic residents' ability to correctly diagnose orthopedic trauma injuries. Further, for those instances when the diagnosis was imprecise, the residents were aware of their inability to make an accurate diagnosis. CONCLUSION: Although the study was relatively limited and further research needs to be done, the use of desktop teleradiology in support of rural orthopedic trauma consultation is a promising alternative to the more expensive forms of telemedicine technology.
Educators at The Toronto Hospital took an innovative approach to providing education and support to nursing staff prior to, during, and after the implementation of computerized nursing documentation. The education strategy included a combination of formal classroom training, inservices on the unit, a self-learning package and an electronic scavenger hunt. Resources such as Clinical Teachers, Clinical Nurse Specialists and Information Systems Analysts and Educators who provided support during the implementation phase received additional education to prepare for their role on the nursing units. Nurses were provided intensive twenty-four hour support for a period of four weeks, and a documentation checklist helped monitor the progress of individual nurses during the implementation. This strategy was designed to maximize consistent support and to minimize cost.
Abnormalities in glucose tolerance in nondiabetic patients and rapid alteration in non-insulin-dependent diabetics have been reported with antihypertensive drugs such as beta-blockers or thiazide diuretics. Such deleterious effects on a cardiovascular risk factor could limit the long-term benefit of an antihypertensive treatment. Indapamide is a nonthiazide antihypertensive agent that appears to respect the glucose tolerance in hypertensive patients. The present study was conducted to assess the effects of indapamide 2.5 mg in 10 hypertensive non-insulin-dependent diabetic patients treated for a one-year period. Glucose tolerance was evaluated using a 50-g oral glucose test, with measurements of plasma glucose and insulin before and after treatment. At the end of the one-year treatment, both systolic and diastolic blood pressure were significantly reduced, whereas there was no significant alteration in either plasma glucose or plasma insulin levels. Thus, indapamide appears as an effective antihypertensive agent in the diabetic patient, with no adverse effects on the glucose tolerance.
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Despite better control of diabetic patients with morbidity and mortality from heart disease is significantly higher than in non-diabetics. While this may be a result of premature atherosclerosis or primary diabetic cardiopathy, the possibility of oral hypoglycemic agents have adverse cardiac effects must be considered. Using nuclear angiography the effect of the acute administration of 1 g tolbutamide on left ventricular ejection fraction (EF) in a group of 10 Type-1 diabetics was investigated. There was no difference in the response of the EF when compared to the response in 10 diabetic controls given i.v. saline. While i.v. tolbutamide may have adverse cardiac effects when administered to animals or in vitro this does not necessarily apply to human diabetics.
Four dynamic tests of cardiac function were compared in a group of 13 long-standing insulin-dependent diabetics who had no clinical evidence of cardio-respiratory disease. One patient developed abnormal features during 24 hour ambulatory electrocardiograms while all 13 patients had normal exercise electrocardiograms. The change in left ventricular ejection fraction during dynamic supine exercise as measured by gated blood-pool scintigraphy was not significantly different from control subjects (p less than 0.1) while during cold stimulation testing the change in left ventricular ejection fraction in the diabetics was highly significantly different from the control subjects (p less than 0.01). Five of the patients had one or more abnormal tests of autonomic function. The cold stimulation test may be a sensitive index of cardiac dysfunction in diabetics but as the mechanism is unclear alternative explanations are possible. While the etiology of heart disease in such patients is uncertain it is likely to be multifactorial and this test may prove useful in investigating the natural history and pathogenesis of cardiac disease in diabetics.
Ten hypertensive non-insulin-dependent diabetic patients were treated with the antihypertensive drug indapamide to assess its effect on glucose tolerance over 1 year. Both systolic and diastolic blood pressures fell significantly (p less than 0.001) over the first month of treatment, and no change in plasma glucose or plasma insulin levels during an oral glucose tolerance test occurred at any time. Indapamide is an effective antihypertensive drug and, in contrast to thiazide diuretics, has no adverse effect on glucose tolerance in non-insulin-dependent diabetic patients.