Student and faculty assumptions about the nature of uncertainty in medicine and medical education

Clinical reasoning involves an element of uncertainty. Teaching clinical reasoning involves understanding how students view uncertainty as well as how medical problems are solved. This study uses Perry's model of intellectual development to explore changes in how medical students, residents, and instructors think about the nature of knowledge. A total of 31 medical students, residents, and instructors completed the Widick and Knefelkamp Measure of Intellectual Development revised to focus specifically on uncertainty in medicine. Consistent with Perry's theory, scores reflected increasing degrees of acceptance of the role of uncertainty in medicine with increasing experience. Based on these results, it is concluded that to improve the effectiveness of teaching problem solving in medicine, faculty must challenge the assumptions held by medical students about the certainty of medical knowledge while teaching the process of clinical diagnosis.     

The vertical position of the patella estimated by four radiographic measurements

The methods of Insall and Salvati, Blackburne and Peel, Caton and Laurin of assessing the vertical position of the patella, were applied on 200 normal knees. The indices for Insall and Salvati's, and Blackburne and Peel's methods were 1.07 +/- 0.25 and 0.78 +/- 0.19 respectively, independent of sex and flexion of the knee. The measurements for Caton's index were 0.95 +/- 0.24 and 0.88 +/- 0.22 at kneeflexions of 45 degrees and 90 degrees. Laurin's method was insufficient as it showed 50% of the patellas to be high riding. The different methods were compared. The technique of Insall and Salvati was a reliable and applicable method, and is therefore recommended for routine use.     

Resolution and binding site determination of D,L-thyronine by high-performance liquid chromatography using immobilized albumin as chiral stationary phase. Determination of the optical purity of thyroxine in tablets

Human and bovine serum albumin bound to silica or aminopropyl silica were used as chiral stationary phases (CSPs). D,L-Thyronine, D,L-tryptophan, N-benzoyl-D,L-phenylalanine, D,L-warfarin and D,L-benzoin could be resolved on these CSPs using a mobile phase of 0.05 M phosphate buffer, pH 7.0. The capacity factor of D-thyronine was higher than that of L-thyronine. The resolution of D,L-thyronine was completely lost by the presence of bilirubin in the mobile phase, but only little affected by caprylate. By contrast, the resolution of D,L-tryptophan was not affected by bilirubin, but lost by the presence of caprylate. These results are consistent with binding of D-thyronine to the bilirubin binding site and L-tryptophan to the caprylate binding site in albumin, respectively, and suggests that such "displacement chromatography" can be used for the determination of binding sites. The optical purity of D-thyroxine in tablets was determined indirectly after de-iodination by catalytic hydrogenation.     

Computerized scintigraphic technique for the evaluation of adult respiratory distress syndrome: initial clinical trials

Eleven patients with suspected adult respiratory distress syndrome (ARDS) and five control patients were studied using a computerized gamma imaging and analysis technique and 99mTc-labeled human serum albumin. The heart and right lung were imaged, lung:heart ratio was plotted vs. time, and a linear regression was fitted to the data points displayed. The slope of this fit was termed the "slope index." An index value of 2 standard deviations greater than the control mean was considered positive. Radiographs from the six positive studies revealed typical diffuse air-space disease. Radiographs from two of the five negative studies demonstrated air-space consolidation. Both of these patients had elevated pulmonary capillary wedge pressure, cardiomegaly, and clinical course consistent with cardiogenic pulmonary edema. These preliminary data demonstrated a good correlation between positive slope index and clinical ARDS.     

Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction

Failure to secrete adequate amounts of insulin in response to increasing concentrations of glucose is an important feature of type 2 diabetes. The mechanism for loss of glucose responsiveness is unknown. Uncoupling protein 2 (UCP2), by virtue of its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated insulin secretion. Of interest, it has recently been shown that superoxide, when added to isolated mitochondria, activates UCP2-mediated proton leak. Since obesity and chronic hyperglycemia increase mitochondrial superoxide production, as well as UCP2 expression in pancreatic beta cells, a superoxide-UCP2 pathway could contribute importantly to obesity- and hyperglycemia-induced beta cell dysfunction. This study demonstrates that endogenously produced mitochondrial superoxide activates UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose-stimulated insulin secretion. Furthermore, hyperglycemia- and obesity-induced loss of glucose responsiveness is prevented by reduction of mitochondrial superoxide production or gene knockout of UCP2. Importantly, reduction of superoxide has no beneficial effect in the absence of UCP2, and superoxide levels are increased further in the absence of UCP2, demonstrating that the adverse effects of superoxide on beta cell glucose sensing are caused by activation of UCP2. Therefore, superoxide-mediated activation of UCP2 could play an important role in the pathogenesis of beta cell dysfunction and type 2 diabetes.     

Allelic loss of chromosome 2p21-16.3 is associated with reduced survival in sporadic colorectal cancer

BACKGROUND: Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers. METHODS: The association between allelic loss and survival was analysed by univariate and multivariate tests to identify independent variables of survival. RESULTS: Loss of chromosome 2p21-16.3 reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic significance was evident in patients with Dukes' A + B as well as Dukes' C tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis, tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1 or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21-16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were independent variables of survival. Loss of 2p21-16.3 was, moreover, associated with increased loss of the other tumour suppressor loci (P = 0.012). CONCLUSIONS: The results show that loss of 2p21-16.3 is an independent indicator of survival in patients with colorectal cancer.