The role of delayed head CT in evaluation of elderly blunt head trauma victims taking antithrombotic therapy.

INTRODUCTION: Increasing active longevity has created an increasing surge of elderly trauma patients. The majority of these patients suffer blunt trauma and many are taking antithrombotic agents. The literature is mixed regarding the utility of routine repeat head CT in patients taking antithrombotic medications with a GCS of 15 and initial negative head CT. We hypothesized that scheduled delayed CT head 12 h after admission (D-CTH) in elderly blunt trauma victims would not identify clinically significant new hemorrhages or change management. METHODS: A retrospective chart review using our institutional trauma registry of patients ≥65 years sustaining blunt head injuries from 2010 to 2012 was performed. By hospital protocol, all such patients on antithrombotic therapy receive a routine D-CTH. All of these patients were included. Demographics, injuries, medications, laboratory values, LOS, mental status, and management were analyzed. RESULTS: Of the 234 patients meeting inclusion criteria, 8 initially were identified as having D-ICH. Upon further review, five patients had the same findings on both initial and delayed CT scans and one patient was determined to actually have had a hemorrhage stroke. Ultimately, only two patients (0.85%, 95% CI 0.1-3.1%) had new ICH discovered on D-CTH. None of the patients on warfarin demonstrated any new injury on D-CTH (95% CI ≤ 4.6%). Only one patient taking aspirin as a sole agent had a delayed injury on D-CTH (1.1%, 95% CI 0-4.2%). The remaining patient was taking a combination of aspirin and clopidogrel representing 2.2% of 45 patients on combination therapy (95% CI 0.1-11.8%). Only two patients taking a direct thrombin inhibitor (dabigatran) met inclusion criteria and neither endured a bleed (95% CI ≤ 77.6%). Further analysis revealed no cases with clinical changes or surgical intervention for new ICH on delayed imaging. No inference could be made to predict which patients would suffer D-ICH. CONCLUSIONS: D-CTH in elderly trauma patients taking antithrombotic agents shows no statistically significant or clinical benefit for diagnosing delayed intracranial hemorrhage after minor head injury. In those with delayed imaging showing new ICH, management was not significantly altered. Not enough data were available to predict which patients would develop D-ICH, even if asymptomatic.

[Von-Hippel-Lindau gene mutation types. Association of gene expression signatures in clear cell renal cell carcinoma]. / Von-Hippel-Lindau-Gen-Mutationstypen. Assoziation mit Genexpressionssignaturen in klarzelligen Nierenzellkarzinomen.

AIMS: The von-Hippel-Lindau (VHL) tumor suppressor is a multifunctional protein. VHL mutations are common in sporadic clear cell renal cell carcinoma (ccRCC). Different mutation types may specifically alter pVHL functions, which have significant impact on gene expression and, consequently, on the disease outcome. The aim of this study was to identify gene expression signatures that correlate with specific VHL gene mutation types in RCC. METHODS: Total RNA and genomic DNA were extracted from 94 frozen clear cell (ccRCC) and 21 papillary RCC (pRCC) specimens from the tumor biobank of Zurich University Hospital. Transcriptome analysis was performed using Affymetrix HG U133A gene chips. All ccRCC tumors were subjected to VHL gene mutation analysis. RESULTS: By applying significance analysis of microarrays genes were identified, which were differentially regulated among the tumor subgroups. Hierarchical clustering based on the expression profile of the most differentially regulated genes resulted in a significant stratification between the two RCC populations. A total of 186 differentially expressed genes were identified by comparing the gene expression profiles of ccRCC with VHL loss-of-function mutations and ccRCC with no gene alterations. CONCLUSIONS: The results clearly argue for a significant influence of VHL mutations on gene expression profiles in RCC.

cDNA cloning and physical mapping of porcine 3 beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4 isomerase.

The 3 beta-hydroxysteroid dehydrogenase/Delta 5-Delta 4-isomerase (3 beta-HSD) enzymes are essential for the biosynthesis of steroid hormones. The 3 beta-HSD gene family has been reported to encode for different isoenzymes which function either as dehydrogenase/isomerase or as reductase. The 3 beta-HSD enzymes are involved in the formation of the pheromone androstenone (5 alpha-androst-16-ene-3-one) which contributes to the unpleasant odour present in the meat of uncastrated boars. An reverse-transcription-polymerase chain reaction (RT-PCR) probe from porcine testicular tissue of a 3 beta-HSD enzyme was used to screen a porcine adipose tissue cDNA library. Both strands of the positive clones were sequenced and the putative coding sequence of 1122 nucleotides encodes 374 amino acids. Comparison of the putative open reading frame with the bovine and the human type I homologues revealed 85.6 and 79.3% identity, respectively. Fluorescence in situ hybridization (FISH) was performed with a labelled PAC clone containing the gene of interest. The 3 beta-HSD gene was mapped to the porcine chromosome 4q16-4q21 which is in accordance with the comparative gene map.

Differential expression of alpha-tubulin mRNA in rat cerebellum as revealed by in situ hybridization.

Nucleotide sequence analysis of two rat alpha-tubulin cDNA clones showed a marked divergence in their 3'-untranslated regions. However, each of the alpha-tubulin isotypes shows a high interspecies homology in this region, when compared with an isotubulin sequence from human and Chinese hamster. In situ hybridization of rat cerebellum with alpha-tubulin cDNA revealed differential expression in various cell layers. The mitotically active cells in the external granular layer show the highest level of alpha-tubulin mRNA, while lower levels are observed in the migrating cells in the molecular layer and in the differentiating cells in the internal granular layer. Very low levels of the mRNA are observed in the prenatally differentiated Purkinje cells.

Regulation of three beta-tubulin mRNAs during rat brain development.

The nucleotide sequence of a complete rat brain beta-tubulin T beta 15 has been determined from three overlapping cDNA clones. The overall length of the T beta 15 sequence is 1589 bp and shows between 84.5% and 88.6% homology within the coding region as compared with chick and human beta-tubulin sequences. On the other hand, the 3'-non-coding region is highly divergent. Comparison of the derived amino acid sequences from different species demonstrates that the amino acid changes are not randomly distributed, but rather there are several conserved and two highly variable regions common to beta-tubulin polypeptides from various sources. The T beta 15 sequence encodes a dominant neuronal 1.8-kb beta-tubulin mRNA species. Two other minor beta-tubulin mRNA species of 2.6 and 2.9 kb are present in rat brain. By using two synthetic oligonucleotide probes complementary to the carboxyl-terminal divergent region and to the amino-terminal conserved region, we have shown that the three mRNAs are distinct species, which are developmentally regulated. The level of the 1.8-kb mRNA species increases till the age of 12 days thereafter its level decreases. The 2.9-kb mRNA is an early neuronal mRNA species, while the 2.6-kb mRNA is a late neuronal species which is detected at 30 days of rat brain development. The data illustrate that there is a differential expression of the beta-tubulin multigene family during rat brain development which may suggest different functions for the various beta-tubulin isotopes.

Life events and illness: a three year prospective study.

In an investigation of the relation between life events (stressors) and illness, 87 medical students reported on a prospective basis their health and life events history over a three year period. There were a few positive findings, e.g. that subjects who reported more life events during the period also reported more illnesses during that period. Overall, however, the study showed a lack of statistically significant association between life events and illness.

The role of stress as a precipitating factor of psychiatric illness.

Fifty-six psychiatric patients were interviewed to obtain a record of life events preceding admission to hospital, using a modified version of the Schedule of Recent Experiences. Two control groups were studied for comparison: medical and surgical in-patients and a "normal" population studied independently by Myers. Psychiatric patients reported a significantly larger number of events than the medical-surgical patients, who, in turn, reported significantly more events than the "normal" population. There were no significant differences in the specific life event histories between groups.