Biomedical subjects
Publications and source records attributed to T Fletcher.
A case of carnitine palmityl transferase deficiency in skeletal muscle is described. The usual symptoms associated with this disease (recurrent muscle cramps or pain and pigmenturia) were observed but sudden exposure to cold precipitate rhabdomyolysis in this patient.
Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit).
Explore the source record for details and available documents.
An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.
Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: The aim of this study is to validate a questionnaire intended to assess retrospective occupational exposure to pesticides in a case control study of workers exposed to pesticides and congenital malformations. METHODS: Occupational data were gathered through personal interviews to 56 agricultural workers and this information was compared to: 1) personal interviews with the workers' foremen, 2) direct observation of working places and 3) another questionnaire self-administered previously by the workers as a part of the "Training Program for Pesticide Applicators". RESULTS: Accuracy and reliability indices are high for variables such as the crops where the interviewees have been working, the time period of the treatments with pesticides and the use of personal protection during treatments (sensitivity ranges between 0.81 and 1 and Kappa index ranges between 0.65 and 0.80). However, for variables such as the duration of the treatments and the pesticides used, sensitivity values range between 0.32 and 0.50. CONCLUSIONS: The results suggest that the questionnaire is a valid tool for measuring some items but in order to improve the quality of the exposure assessment the questionnaire was modified, including a question about size of treated areas (as a proxy variable for duration of treatments) and prompt lists were developed to make easier recall by the workers of specific pesticides used in treatments.
We conducted a survey of managed care plan (MCP) patients who presented to the emergency department (ED) but were denied insurance authorization during a 3-month period. Patients were identified by triage or registration records, contacted by telephone after their visit, and surveyed regarding their satisfaction with the ED and MCP, follow-up care, and future behavior. We surveyed 72 (73.4%) of 98 subjects who were denied authorization. Forty-nine (68.1%) were redirected to a clinic or primary physician, 14 (19.4%) to an urgent care or other ED, and 9 (12.5%) were given no follow-up. Fifty-five respondents (76.4%) stated they had followed-up as directed, but 34 (47.2%) felt the delay had a negative impact. Thirty-nine (54.2%) were dissatisfied with their MCP. If their problems were to recur, 27 (37.5%) stated they would go to a clinic or call their MCP, but 34 (47.2%) would return to the ED. Many patients who are denied authorization are dissatisfied with their MCP and will return to the ED in the future, despite previous denials.
OBJECTIVES: Many studies of air pollution and health are carried out over several geographical areas, and sometimes over several countries. This paper explores three approaches to analysis in such studies: a non hierarchical model, a two-stage analysis, and multilevel modelling. Illustrations are given using a preliminary subset of data from the CESAR study. DESIGN: The Central European Study on Air pollution and Respiratory Health (CESAR) was conducted in 25 areas within six Central European countries, enrolling 20,271 schoolchildren. Pollution averages were calculated for each area. Associations between pollution and health outcomes were estimated under different models. MAIN RESULTS: A regression analysis of log FVC (forced vital capacity) on PM10, ignoring the geographical hierarchy, estimated a significant mean drop in FVC (adjusted for confounders) of 2.2% (95% CI 0.5% to 1.3%), p=0.007, from the area with the lowest PM10 to that with the highest. A multilevel model (mlm), using data for all children, but with random effects at area and country level, estimated a drop of 2.8% (-0.6% to 6.1%), p=0.110. A two-stage analysis (mean log FVC, adjusted for confounders, was estimated for each area using regression, and these means then regressed on PM10) estimated a drop of 2.6% (-0.5% to 5.5%), p=0.101. Simulation exercises showed the non hierarchical method to be very inadequate in the context of the CESAR study, with only half of all 95% confidence intervals for the estimated PM10 slope containing the true value (i.e., that used to create the simulated data). The two-stage and multilevel modelling methods gave results which were substantially better, though both underperformed slightly. All three methods appeared to give unbiased slope estimates. CONCLUSIONS: Acknowledgement of hierarchical structures is essential in statistical inference--standard errors can be substantially incorrect when they are ignored. Multilevel, random-effects models correctly address hierarchical structures, though having few units at higher levels can cause problems in convergence, especially where complex modelling is required. Two-stage analyses, acknowledging hierarchy, provide simple alternatives to random-effects models.