Attempting to distinguish between endogenous and contaminating cytokeratins in a corneal proteomic study

Background  

The observation of cytokeratins (CK's) in mass spectrometry based studies raises the question of whether the identified CK is a true endogenous protein from the sample or simply represents a contaminant. This issue is especially important in proteomic studies of the corneal epithelium where several CK's have previously been reported to mark the stages of differentiation from corneal epithelial stem cell to the differentiated cell.     

Biphasic insulin aspart vs. human insulin in adolescents with type 1 diabetes on multiple daily insulin injections

The aim was to compare clinical efficacy and safety of two treatment regimens: biphasic insulin aspart (BIAsp) injected at all three meals plus neutral protamine Hagedorn (NPH) insulin at bedtime vs. a human insulin regimen, premixed human insulin at breakfast and soluble insulin at lunch and dinner and NPH at bedtime. A total of 167 adolescents (80 males and 87 females) with type 1 diabetes was included in the trial (multinational, randomized, open-label, and parallel group). Each subject received either of two treatment regimens for a 4-month period. BIAsp was injected immediately before main meals, human insulin products 30 min before meals, and NPH at night. Glycemic control was monitored by eight-point evaluations (after 6 and 16 wks) and hemoglobin A1c (HbA1c) (after 2, 6, and 16 wks). Safety evaluations included adverse events and incidence of hypoglycemic episodes. HbA1c (mean+/- SD) after 4 months on BIAsp (9.39+/- 0.14) was not significantly different from that with human insulin (9.30+/- 0.15). The average postprandial glucose increment in the BIAsp group was about half the increment in the human insulin group; the difference not statistically significant. The body mass index (BMI) increased in both groups, but significantly (p=0.005) less in the BIAsp group. However, in males on BIAsp, the BMI decreased compared with those on human insulin (p=0.007). No significant group differences were found for the rate of hypoglycemic episodes. We concluded that the BIAsp regimen was associated with similar glycemic control and similar incidence of hypoglycemic episodes as human insulin. However, the BIAsp regimen caused a significantly smaller increase in BMI, particularly in males, compared with the human insulin regimen.     

Management of acute adverse reactions to contrast media

When anaphylactoid and other severe adverse reactions to contrast media occur, prompt recognition and immediate treatment are essential. Simple guidelines for treatment have been requested by many radiologists, and therefore the Contrast Media Safety Committee has produced guidelines for treatment of acute adverse reactions to contrast media. The committee made an extensive review of the literature on treatment of adverse reactions to contrast media. Based on this, a report and guidelines were prepared. The resulting report was discussed at the 10th European Symposium on Urogenital Radiology in Uppsala. Sweden, September 2003. Guidelines for treatment of acute adverse reactions and a list of first-line drugs and equipment that should be available in the room where contrast medium is given are provided.The members of the Contrast Media Safety Committee of ESUR are H.S. Thomsen (Chairman, Denmark), S.K. Morcos (Secretary, United Kingdom), T. Almén (Sweden), P. Aspelin (Sweden), M.F. Bellin (France), H. Flaten (Amersham Health, Norway), J.Å. Jakobsen (Norway), G.P. Krestin (The Netherlands), A. Löwe (Schering, Germany), R. Oyen (Belgium), F. Stacul (Italy) and J.A.W. Webb (UK).     

Neural correlates of frustration

Psychological considerations suggest that the omission of rewards in humans comprises two effects: first, an allocentric effect triggering learning and behavioural changes potentially processed by dopaminergic neurons according to the prediction error theory; second, an egocentric effect representing the individual's emotional reaction, commonly called frustration. We investigated this second effect in the context of omission of monetary reward with functional magnetic resonance imaging. As expected, the contrast omission relative to receipt of reward led to a decrease in ventral striatal activation consistent with prediction error theory. Increased activation for this contrast was found in areas previously related to emotional pain: the right anterior insula and the right ventral prefrontal cortex. We interpreted this as a neural correlate of the egocentric effect.     

Progesterone Receptor Levels Independently Predict Survival in Endometrial Adenocarcinoma

Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas and those with eligible receptor measurements were analyzed with respect to correlations to cancer-specific survival in a multivariate analysis including histopathological characteristics. Median patient follow-up time was 67 months with 18 cancer deaths. The PR-DCC and ER-DCC values were dichotomized according to levels previously found by us to correspond to the best agreement between receptor status as determined by the DCC and ICA methods (130 fmol/mg cytosol protein for ER, 114 fmol/mg for PR). Using these thresholds, we found by multivariate analysis that “high” PR-DCC levels (>114 fmol/mg) correlated significantly (P= 0.004) with survival, independent of stage risk group (Ia + b vs Ic-IV). Patient age and histologic grade were prognostic factors in a univariate setting, but these parameters were eliminated in the multivariate model. While the PR-ICA scores also correlated significantly and independently with survival, the predictive effect of PR-ICA positivity alone could not be statistically evaluated due to the number of cases with eligible ICA values. However, we suggest that owing to a close correlation between DCC and ICA results, PR-ICA status may provide significant prognostic information when DCC measurements are not available.     

Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial

Open in a separate window OBJECTIVESCardiac surgery is associated with risk of cerebral injury and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) is suggested to be associated with cerebral injury. The ‘Perfusion Pressure Cerebral Infarcts’ (PPCI) trial randomized patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement to a MAP of 40–50 or 70–80 mmHg during CPB and found no difference in clinical or imaging outcomes between the groups. We here present PPCI trial predefined secondary end points, consisting of biomarkers of brain injury.METHODSBlood was collected from PPCI trial patients at baseline, 24 and 48 h after induction of anaesthesia and at discharge from the surgical ward. Blood was analysed for neuron-specific enolase, tau, neurofilament light and the glial marker glial fibrillary acidic protein. Linear mixed models were used to analyse differences in biomarker value changes from baseline between the 2 MAP allocation groups.RESULTSA total of 193 (98%) patients were included. We found no differences in biomarker levels over time from baseline to discharge between the 2 MAP allocation groups (P_NSE = 0.14, P_Tau = 0.46, P_NFL = 0.21, P_GFAP = 0.13) and the result did not change after adjustment for age, sex and type of surgery.CONCLUSIONSWe found no significant differences in levels of biomarkers of neurological injury in patients undergoing elective or subacute CABG and/or aortic valve replacement randomized to either a target MAP of 40–50 mmHg or a target MAP of 70–80 mmHg during CBP.     

Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors

BACKGROUND: To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors. PROCEDURE: We studied a consecutive sample of 133 patients (76 had received radiotherapy (RT)) who had a brain tumor diagnosed before the age of 15 years and were treated during the period January 1970 through February 1997 in the Eastern part of Denmark. Biologic effective dose of irradiation (BED) was assessed in 71 patients. One hundred twenty-seven patients were able to cooperate to WISC-R and WAIS-R. Multiple regression models were constructed to evaluate relationships between possible risk factors and cognitive outcome. RESULTS AND CONCLUSIONS: The mean intelligence (IQ) scores were substantially lower than the expected means of the general population. Younger age at diagnosis, tumor site in cerebral hemisphere, hydrocephalus treated with shunt, and treatment with RT were found to be significant predictors of lower cognitive functions. RT was the most important risk factor for impaired intellectual outcome. The mean observed full scale IQ was 97.1 (SD = 14.3) for the non-irradiated patients and 78.8 (SD = 14.3) for the irradiated patients (adjusted P < 0.001). Verbal IQ, but not performance and full scale IQ, had a significant negative correlation to BED to the tumor site (P < 0.05). These results can be used to identify subgroups of children who are at increased risk for cognitive deficits allowing early and goal-directed intervention.     

Chromosome 8q24 risk variants in hereditary and non-hereditary prostate cancer patients

BACKGROUND: Multiple variants in three regions at 8q24 are consistently found to be associated with prostate cancer (PCa) risk in population-based association studies. The role that these variants may play in familial prostate cancer risk has not been extensively investigated. METHODS: We evaluated 12 SNPs at three 8q24 regions using population-based association and family-based linkage and association methods in hereditary PCa (HPC) probands and their families, non-HPC patients, and unaffected screened controls, all recruited at Johns Hopkins Hospital. RESULTS: For multiple variants in Region 1 (e.g., rs1447295) and Region 2 (e.g., rs16901979), we found statistically significantly higher frequencies of previously identified risk alleles and genotypes in HPC probands than in unaffected controls. Furthermore, in Region 2 the risk alleles were statistically significantly more frequent in HPC probands than in non-HPC patients. Family-based transmission tests found risk alleles of SNPs in Region 2, but not in Regions 1 and 3, were significantly over-transmitted to affected men in these families. We found little evidence supporting PCa linkage at 8q24 in 168 HPC families, in part explained by the observation of multiple, different risk allele-containing haplotypes segregating in the vast majority of these families. CONCLUSIONS: Our study further supports the presence of PCa susceptibility loci at 8q24, particular at Region 2, and also provides evidence that these SNPs play an important role in familial prostate cancer. Large family-based studies are needed to confirm our novel findings.