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Biomedical subjects

E K Smith

Publications and source records attributed to E K Smith.

At least 37 records · Page 2Linked to original sources

Modified essay questions: are they worth the effort?

The method chosen for important examinations strongly influences the nature of student learning. The Newcastle Medical School in Australia developed a 5-year problem-based curriculum and adopted the Modified Essay Question (MEQ) as the main written instrument for assessing students' problem-solving skills. Even with the best of intentions the MEQ has been abused by its over-use, as shown in this review of annual assessment for years 1, 3 and 5 of the course. Analysis of staff and students' dissatisfaction with this instrument showed some difficulties attributable to the nature of MEQ items. However, a number of problems also emerged as a result of subtle changes in the teaching staff's approach to learning and assessment. This paper concludes by acknowledging the strengths and limitations of the MEQ. It recommends ways in which the MEQ can be effective, as part of a balanced programme involving other suitable instruments.

Adolescent↗

Longevity of cold-exposed rats: a reevaluation of the "rate-of-living theory".

It has been postulated that increased energy expenditure results in shortened survival. To test this "rate-of-living theory" we examined the effect of raising energy expenditure by means of cold exposure on the longevity of rats. Male 6-mo-old SPF Long-Evans rats were gradually accustomed to immersion in cool water (23 degrees C). After 3 mo they were standing in the cool water for 4 h/day, 5 days/wk. They were maintained on this program until age 32 mo. The cold exposure resulted in a 44% increase in food intake (P less than 0.001). Despite their greater food intake, the cold-exposed rats' body weights were significantly lower than those of control animals from age 11 to 32 mo. The average age at death of the cold-exposed rats was 968 +/- 141 days compared with 923 +/- 159 days for the controls. The cold exposure appeared to protect against neoplasia, particularly sarcomas; only 24% of the necropsied cold-exposed rats had malignancies compared with 57% for the controls. The results of this study provide no support for the concept that increased energy expenditure decreases longevity.

Animals↗

Effect of voluntary exercise on longevity of rats.

The purpose of this study was to obtain information regarding the effects of exercise on longevity in rats. The exercise used was voluntary activity wheel running. The runners gradually decreased their running from approximately 4 to approximately 1 mile/day as they aged from 9 to 30 mo. The runners lived slightly but significantly longer than sedentary freely eating controls and sedentary pair-fed controls (1,012 +/- 138 vs. 923 +/- 160 and 928 +/- 186 days) but significantly less long than food-restricted paired-weight sedentary controls (1,113 +/- 150 days). Although the exercise improved survival, it did not result in an extension of life-span. In contrast, the food-restricted paired-weight sedentary rats showed a true increase in life-span. The paired-weight rats also had a significantly reduced incidence of malignancies compared with the other three groups. However, there was no significant difference between the runners and the freely eating or pair-fed sedentary controls in the cause of death. These results provide evidence that exercise improves survival but does not result in an extension of life-span in rats.

Animals↗

Polyclonal B cell hyperplasia associated with Epstein-Barr virus causing acute renal allograft failure.

Six weeks post cadaver renal transplantation, a patient developed a flu-like illness. Acute renal failure unresponsive to anti-rejection therapy occurred and he died four days later from Pneumocystis carinii pneumonia and Streptococcus viridans septicemia. Autopsy revealed a diffuse polymorphic polyclonal B cell infiltrate occupying most organs, including the allograft. Primary Epstein-Barr Virus (EBV) infection was established by 1) rising anti-EBV antibody titres; 2) the demonstration of EBV nuclear antigen in the infiltrate and 3) the presence of EBV specific DNA sequences in affected tissues. EBV associated polymorphic B cell hyperplasia can mimic rejection and result in acute allograft failure.

Antibodies, Viral↗

Direct solid-phase radioimmunoassay for screening 17 alpha-hydroxyprogesterone in whole-blood samples from newborns.

We describe a direct, solid-phase RIA for 17 alpha-hydroxyprogesterone (17-OH-P) that we are using to screen neonates for congenital adrenal hyperplasia. Phosphate buffer containing danazol and anti-17-OH-P is placed in tubes coated with antibody to IgG. The tubes also contain standards, controls, or blood samples on filter paper discs 3 mm in diameter. 125I-labeled 17-OH-P is added to each tube. The mixture is vortex-mixed and incubated overnight. The fluid and disc are removed, the radioactivity remaining in the tubes is counted, and the amount of 17-OH-P per disc is calculated by using a log-logit transformation of the standard curve. Results compare favorably with those by two extraction assays. Inter- and intra-assay CVs were less than 11% and less than 9%, respectively. Sensitivity was 2 pg per assay tube. There is no significant cross reactivity with structurally related steroids at their physiological concentrations. Analytical recovery of added 17-OH-P averaged 104%. 17-OH-P in whole blood spotted on filter paper is stable for at least six months.

17-alpha-Hydroxypregnenolone↗

Allergy to ethylene oxide in chronic hemodialysis patients.

Almost a decade ago, a single chronic hemodialysis patient in Hamilton, Ontario, Canada, who was experiencing recurrent acute reactions during hemodialysis was found to have become allergic to ethylene oxide gas (EO). This observation recently provided a stimulus to examine the possibility that others exhibiting acute allergic-type reactions during hemodialysis might be similarly sensitized. Serum was obtained from 27 reacting patients and tested in a radioallergosorbent test (RAST) for antibodies to EO. The test was positive for 22 of these sera. EO-related specificity of the antibodies was confirmed. However, EO sensitization was not found in other hemodialysis patients with isolated eosinophilia. In a survey of the current Hamilton chronic hemodialysis population for EO-related antibodies, 9% had a positive allergy skin test and 12% had a positive RAST. The sensitized individuals had no distinctive symptoms. The lesser sensitivity of the skin test contrasts with usual findings in allergic individuals; however, the use of histamine and codeine in chronic hemodialysis and peritoneal dialysis patients might well explain a reduced sensitivity of the EO-related allergy skin test. Chronic peritoneal dialysis could not be invoked as a source of sensitization. None of these patients had a positive skin test or RAST for EO-related antibodies that could be attributed to peritoneal dialysis.

Antibodies↗

Ethylene oxide allergy in a dialysis center: prevalence in hemodialysis and peritoneal dialysis populations.

Chronic hemodialysis (HD) and peritoneal dialysis (PD) patients in one dialysis center were examined for (EO)-related sensitization. Five of 56 (8.9%) HD patients and 0 of 30 PD patients skin tested with a conjugate of human serum albumin (HSA) and EO had positive skin prick tests. The sera of 13 of 107 (12.1%) HD patients including sera from 5 patients with negative skin tests were positive in an EO-HSA radioallergosorbent test (RAST). Sensitized patients in this population did not experience allergic-type reactions during hemodialysis. There were no positive EO-HSA RAST results which could be ascribed to PD. Non-specific cutaneous responsiveness of the renal failure patients was compared with that of normal adult subjects by the use of skin prick tests with codeine phosphate and histamine phosphate. A significantly reduced responsiveness is present in chronic renal failure patients which would be expected to lower the sensitivity of the diagnostic skin test by comparison with the RAST.

Adult↗

Regulation by calcium ions of glutamate receptor binding in hippocampal slices.

Hippocampal slices were incubated in a Krebs-bicarbonate buffer with various concentrations of calcium and [3H]glutamate receptor binding was measured in crude synaptic membranes derived from these slices. Increasing the calcium concentration from 0 to 2.5 mM resulted in a 2.2-fold increase in the maximal number of the Na-independent [3H]glutamate binding sites without changes in their affinity for [3H]glutamate. This effect was totally blocked by the addition of the protease inhibitor leupeptin (50 microM) to the slice incubation medium. No effect was observed on the Na-dependent [3H]glutamate binding nor on the Na-independent [ 3H ]glutamate binding measured in the presence of a concentration of calcium of 250 microM. Increasing the calcium concentration also resulted in an increased proteolytic activity which was inhibited by about 70% by the addition of leupeptin. Finally, increasing the calcium concentration induced the degradation of high-molecular weight proteins, the microtubule-associated proteins (MAPs) and the 220 000 dalton doublet protein corresponding to fodrin. Both effects were partially prevented by the addition of leupeptin in the slice incubation medium. These results indicate that the same calcium-dependent processes which were previously shown to regulate [ 3H ]glutamate receptor binding to hippocampal membranes occur in the hippocampal slice preparation, and they suggest a mechanism by which fluctuations in calcium levels can activate a calcium-dependent proteinase, the degradation of cytoskeletal-associated proteins and the unmasking of additional glutamate receptors. The participation of such processes in various forms of plasticity is discussed.

Animals↗

The regulation of pyruvate dehydrogenase activity in rat hippocampal slices: effect of dichloroacetate.

The effects of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on the phosphorylation of the alpha-subunit of pyruvate dehydrogenase and on the activity of pyruvate dehydrogenase (pyruvate:lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1, PDH) were investigated in rat hippocampal slices. Incubating hippocampal slices with increasing concentrations of DCA resulted in an increase in the active portion of PDH, without changes in the total PDH activity, as well as an increase in the in vitro phosphorylation of alpha-PDH. The effect of DCA on PDH activity was very rapid, being almost maximal after 5 min. These results indicate that DCA in the hippocampal slice preparation inhibits PDH kinase and consequently stimulates PDH activity by decreasing its endogenous state of phosphorylation. Moreover the time-course of the effect of DCA suggests that the turnover rate of the phosphate group carried by alpha-PDH is very rapid and can be manipulated by altering PDH kinase activity.

Acetates↗

Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents.

Random plasma somatomedin-C (SM-C) levels were measured in 143 children and adolescents with growth at or below the 5th percentile. 124 patients had short stature due to constitutional delay or genetic predisposition and 19 patients were growth hormone deficient (GHD). When analyzed according to bone age, mean somatomedin-C levels rose gradually with increasing bone age in non-GHD patients, while there was no change with increasing bone age in GHD patients. All patients with SM-C levels less than 0.05 U/ml underwent growth hormone testing to rule out GHD. This criterion resulted in 52% accuracy in identifying non-GHD patients and 100% accuracy in identifying GHD patients. Comparison of the SM-C test with the exercise GH screening test demonstrated the advantage of greater convenience for the SM-C test, and comparable cost effectiveness despite a lower specificity associated with the SM-C test. SM-C levels were not predictive of peak growth hormone response nor could they be used to differentiate constitutional delay of growth and maturation from genetic short stature.

Adolescent↗

Tuberculosis in dialysis patients.

In a retrospective study over a 13-year period, data from one of the largest dialysis units in Canada were reviewed. Seven cases of active tuberculosis were identified among a dialysis population of 433 patients. Although this was not a controlled study the data suggests a greater than 10 fold increase in incidence of tuberculosis among patients with end stage renal disease compared to the total population. The majority of patients were over 40 years of age; race and immigrant status appeared to be risk factors, and tuberculin skin tests in the main were unhelpful diagnostically. Symptoms and signs mimicked that of underlying chronic renal disease in most instances, and extrapulmonary disease occurred in 3 of 7 patients. Therapy proved safe and effective in all cases. In terms of the epidemiological and clinical indices the present study tends to support the observations of investigators in other countries.

Adult↗

Micromolar calcium stimulates proteolysis and glutamate binding in rat brain synaptic membranes.

Incubation of cortical synaptic membranes with low concentrations of calcium resulted in a decrease in the amount of a high-molecular-weight doublet protein and an increase in the sodium-independent binding of glutamate. Both effects were blocked by the thiol protease inhibitor leupeptin. These results suggest that calcium-induced proteolysis of membrane components regulates the number of glutamate receptors in neuronal membranes.

Animals↗

Detection of heterozygotes for congenital adrenal hyperplasia: 21-hydroxylase deficiency-a comparison of HLA typing and 17-OH progesterone response to ACTH infusion.

We have studied nine families in which at least one member has congenital adrenal hyperplasia, to compare the predictive value of HLA typing and the 17-hydroxy progesterone response to ACTH as methods for detection of heterozygotes. In each of six families, two children were affected and were HLA genotypically identical. None of the unaffected siblings were HLA identical with their affected siblings. When the 17-OHP response to ACTH and the HLA haplotypes of parents and unaffected siblings were compared, there was a 79% concordance for identification of heterozygotes. Two siblings were carriers according to HLA typing, but had normal 17-OHP responses consistent with the carrier state. Three individuals with recombinations involving the HLA region of chromosome number 6 were detected. Analysis of these recombinant individuals provided additional evidence suggesting that the 21-OH degrees gene is closely associated with the B-locus of HLA. When an affected individual has been identified, HLA typing is a direct and reliable method for determining the carrier state among family members.

Adrenal Hyperplasia, Congenital↗