Well leg compartment syndrome after pelvic and perineal surgery in the lithotomy position

Objective: Lower limb compartment syndrome after prolonged surgical procedures performed in the lithotomy position is a rare but potentially devastating complication. It is recognised after urological, colorectal, and gynaecological procedures. Sixteen cases of compartment syndrome after urological surgery have been reported. The objective of this study was to estimate the incidence of this complication in urological practice and identify risk factors for its development. Design: A postal survey of UK consultant urologists was conducted. Results: Replies were received from 261 consultants. In total there were 65 cases of compartment syndrome. Compartment syndrome occurred after radical cystectomy and urinary diversion in 51 cases and was rare in procedures lasting less than four hours. The incidence of compartment syndrome after cystectomy was estimated at around 1 in 500 cases. Risk factors for its development included perioperative blood loss, peripheral vascular disease, and obesity. Conclusions: Compartment syndrome after use of the lithotomy position may be more common than is generally appreciated and has been underreported in the past. All staff should be aware of this serious complication and adopt strategies for its avoidance.     

The test-retest reliability of a standardized neurocognitive and neurophysiological test battery: "neuromarker"

NeuroMarker combines EEG and ERP measures with neurocognitive tests in a fully computerized and standardized testing system. It is designed for use across the lifespan and has a large normative database of over 1,000 subjects. This study was a preliminary evaluation of "NeuroMarker" in subjects spanning four decades. Twenty-one healthy subjects (12-57 years) were tested at baseline and four weeks later. From the "Neuromarker" battery, the authors analyzed EEG data (eyes open and closed) and ERPs elicited during auditory oddball (N100, P200, N200, P300) and working memory (P150, P300) tasks. Concomitant neuropsychological data, acquired using a touch-screen system, comprised measures of sensori-motor, attention, verbal, executive, and memory function. Test-retest data were examined using analyses of variance and correlational procedures (corrected for multiple comparisons), with parallel analyses of age. EEG data did not differ across sessions, and showed high test-retest reliability (.71-.95), particularly for theta and delta (>.85). ERP components also showed sound reliability, particularly for sites where components are maximal: fronto-central N100 (.76-.77), centro-parietal P300 (.78-.81) to oddball targets, N100 and P200 (.74-.86) to oddball non-targets, and P150 amplitude and latency (.84-.93) to working memory stimuli. Neuropsychological tests showed a similarly sound level of consistency (on average, .70), with the most consistent tests tapping simple motor function, estimated intelligence, switching of attention (Part 2), verbal interference response time and memory intrusions (.71-.89). Age and sex did not have a differential impact on reliability for EEG, ERP, or neuropsychology measures. These findings provide preliminary evidence that the "NeuroMarker" battery is reliable for test-retest assessments. The results suggest that the standardized approach has utility for providing sensitive clinical and treatment evaluations across age groups.     

Transmigration across a lung epithelial monolayer delays apoptosis of polymorphonuclear leukocytes

BACKGROUND: Suppression of polymorphonuclear leukocyte (PMNL) apoptosis may cause or exaggerate acute lung injury that is associated with the acute respiratory distress syndrome. We hypothesized that transepithelial migration would modulate PMNL apoptosis. METHOD: PMNLs that were freshly purified from normal volunteers were allowed to migrate across transwell membranes alone or coated with monolayers of human lung epithelial cells in response to chemoattractants (interleukin-8, formyl-methionylleucylphenylalanine and leukotriene B(4)). We assessed for migration efficiency, apoptosis, and functional activity of the PMNLs. Changes in the expression of genes modulating PMNL apoptosis were examined with messenger RNA and protein analyses. RESULTS: Transepithelial migration caused a significant decrease in the percentage of apoptotic PMNLs (interleukin-8; from 31% to 16% at 8 hours; P<.01). This apoptotic delay was sustained to at least 20 hours that was associated with prolongation of PMNL functional activity and independent of chemoattractant-type. Gene and protein expression levels of the antiapoptotic proteins Mcl-1 and 14-3-3 zeta were either augmented or preserved by interleukin-8 treatment alone and after transepithelial migration. CONCLUSION: Our data reveal, for the first time, the important role of transepithelial migration in the modulation of PMNL apoptosis and may provide insights into possible novel targets for the regulation of PMNL apoptosis during lung inflammation and injury.     

Promoter Hypermethylation Frequency and BRAF Mutations Distinguish Hereditary Non-Polyposis Colon Cancer from Sporadic MSI-H Colon Cancer

BACKGROUND: Colorectal cancers resulting from defective DNA mismatch repair can occur in both hereditary non-polyposis colon cancer (HNPCC) and in the sporadic setting. They are characterised by a high level of microsatellite instability (MSI-H) and superficially resemble each other in that they are frequently located in the proximal colon and share features such as circumscribed tumour margins and tumour-infiltrating lymphocytes. However, significant differences can be demonstrated at the molecular level including widespread promoter hypermethylation and BRAF -activating mutations which occur significantly less often in HNPCC. AIMS: In this study, we sought to determine whether the presence of widespread promoter hypermethylation and BRAF mutations would exclude HNPCC. MATERIALS AND METHODS: We investigated the methylation status of four methylated in tumour markers (MINTs 1,2,12 and 31), and the promoter regions of 5 genes hMLH1, HPP1, MGMT, p16INK4A and p14ARF, in 21 sporadic MSI-H colorectal cancers and compared these with 18 cancers from HNPCC patients. The methylation status of CpG islands were determined by either methylation specific PCR (MSP) or combined bisulfite restricton analysis (COBRA). In addition we considered the BRAF mutation status of 18 HNPCC tumours and 19 sporadic MSI-H cancers which had been previously determined by RFLP analysis and confirmatory sequencing. RESULTS: Methylation of the promoter regions in target genes occurred less frequently within the HNPCC tumours (27% of analyses), compared with the sporadic MSI-H tumours (59% of analyses) (P < 0.001). Methylation of MINTs 1, 2, 12 and 31 occurred in 4% of analyses for HNPCC tumours contrasted with 73% for sporadic MSI-H tumours (P < 0.001). BRAF mutations were detected in 74% of sporadic tumours but none of the HNPCC cancers tested. CONCLUSIONS: The total number of genes and MINTs methylated in HNPCC was lower than in MSI-H colorectal tumours. No HNPCC tumour showed evidence of widespread promoter hypermethylation or BRAF mutation suggesting this feature could be used as a discriminator between familial and sporadic cases.