Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets

Endometrial carcinoma (EnCa) is the most common invasive gynaecologic carcinoma. Over 85% of EnCa are classified as endometrioid, expressing steroid hormone receptors and mostly involving pathological prestages. Human endogenous retroviruses (ERV) are chromosomally integrated genes, account for about 8% of the human genome and are implicated in the etiology of carcinomas. The majority of ERV envelope (env) coding genes are either not present or not consistently represented between common gene expression microarrays. The aim of this study was to analyse the absolute gene expression of all known 21 ERV env genes including 19 codogenic and two env genes with premature stop codons in EnCa, endometrium as well as in hyperplasia and polyps. For EnCa seven env genes had high expression with >200 mol/ng cDNA (e.g. envH1-3, Syncytin-1, envT), two middle >50 mol/ng cDNA (envFc2, erv-3) and 12 low <50 mol/ng cDNA (e.g. Syncytin-2, envV2). Regarding tumor parameters, Syncytin-1 and Syncytin-2 were significantly over-expressed in advanced stage pT2 compared to pT1b. In less differentiated EnCa Syncytin-1, erv-3, envT and envFc2 were significantly over-expressed. Syncytin-1, Syncytin-2 and erv-3 were specific to glandular epithelial cells of polyps, hyperplasia and EnCa using immunohistochemistry. An analysis of 10 patient-matched EnCa with endometrium revealed that the ERV-W 5'' long terminal repeat regulating Syncytin-1 was hypomethylated, including the ERE and CRE overlapping MeCP2 sites. Functional analyses showed that 10 env genes were regulated by methylation in EnCa using the RL95-2 cell line. In conclusion, over-expressed env genes could serve as indicators for pathological pre-stages and EnCa.     

Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience

Abstract Hohlreider, Matthias, Stephanie Thaler, Walter Wuertl, Wolfgang Voelckel, Hanno Ulmer, Hermann Brugger, and Peter Mair. Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience. High Alt. Med. Biol. 9:229-234, 2008.-The planning and execution of avalanche rescue missions to search for totally buried avalanche victims are mostly based on personal experience and preference, as evidence-based information from literature is almost completely missing. Hence, the aim of this study was to identify major factors determining the survival probability of totally buried victims during avalanche rescue missions carried out by organized rescue teams (Austrian Mountain Rescue Service, Tyrol). During the 12-year period studied, 109 totally buried persons (56 off-piste, 53 backcountry), were rescued or recovered; 18.3% survived to hospital discharge. Median depth of burial was 1.25 m; median duration of burial was 85 min. The majority (61.6%) of the rescue missions were conducted under considerably dangerous avalanche conditions. The probability of survival was highest when located visually and lowest for those located by avalanche transceiver; survival did not significantly differ between those found by rescue dogs and those located with avalanche probes. Multivariate analysis revealed short duration of burial and off-piste terrain to be the two independent predictors of survival. Whenever companion rescue fails, snow burial in an avalanche is associated with extraordinarily high mortality. Searching the avalanche debris with probe lines seems to be equally effective as compared to searching with rescue dogs. The potential hazard for rescuers during avalanche rescue missions comes mainly from self-triggered avalanches, hence thorough mission planning and critical risk-benefit assessment are of utmost importance for risk reduction.     

A new technique for establishing dry weight in hemodialysis patients via whole body bioimpedance

BACKGROUND: Quantitative techniques are necessary to achieve dry weight (DW) in patients with kidney failure. Bioimpedance spectroscopy (BIS) is a non-invasive method that determines the volume of body fluid compartments. The current work evaluates the use of BIS data in hemodialysis patients for the prediction of DW. METHODS: A new technique has been devised for the estimation of DW that involves the intersection of two slopes, slope normovolemia (SNV) and slope hypervolemia (SHV). These slopes characterize the variation in extracellular water (ECW) with body weight (BW) in the states of normovolemia and hypervolemia, respectively. SNV was established via measurements of ECW and BW in 30 healthy subjects. In a longitudinal study in new hemodialysis patients, successive reduction of post-dialysis weight (PDW) was attempted until clinical signs of normovolemia were presented. Measurements of ECW and BW that were acquired at the beginning of each treatment were used to determine SHV. RESULTS: SNV was found to be 0.239 L/kg and 0.214 L/kg for male and female healthy subjects, respectively. A significant DeltaPDW predicted by the new method (-4.98 kg) was highly correlated to the DeltaPDW achieved in the study (-5.85 kg, R = 0.839). Blood pressure was reduced (P < 0.001) and an 86% decrease in antihypertensive agents was achieved. CONCLUSION: The method of intersecting slopes (SHV with SNV) via BIS is a new method for the prediction DW. This approach will offer considerable improvement for the routine management of DW in the dialysis setting.     

Early postoperative results of surgery for rectal carcinoma as a function of the distance of the tumor from the anal verge: results of a multicenter prospective evaluation

BACKGROUND: The problems associated with rectal surgery are frequently discussed with no reference being made to the distance of the tumor from the anal verge. This study examined the effect of the location of the tumor on early postoperative results. PATIENTS AND METHODS: This was a multicenter study involving 75 German hospitals and 3756 patients, of whom 1463 had rectal carcinoma. On the basis of the location of the tumor (distance from the anal verge), four groups were distinguished: <4, 4-7.9, 8-11.9, and 12-16 cm. RESULTS: Resection and abdominoperineal resection rates and the incidence of postoperative complications depended on the location of the tumor. Significantly higher resection rates and fewer specific complications, and a significant reduction in overall postoperative morbidity were found with tumor locations more than 8 cm from the anal verge. The highest anastomotic leak rate was observed with anastomoses less than 7 cm from the anal verge. The logistic regression showed that the distance of the tumor from the anal verge is an independent variable for the development of an anastomotic leak. CONCLUSIONS: Early results are greatly affected by the location of the rectal carcinoma. This applies to both abdominoperineal resection rates and specific postoperative complications, such as anastomotic leak rate and operation morbidity in general.     

Results of long-term follow-up after curative resection of Dukes A colorectal cancer

Patients with Dukes A (UICC I) colorectal cancer have a good prognosis after curative resection. It is not known, however, if the outcome is significantly different for UICC Ia and Ib patients or if patients with reduced risks of recurrences can be identified early after surgery. This is of interest, as it would permit a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program. To study these questions, a prospective follow-up database, including 1375 patients after curative resection of colorectal cancer, was analyzed. A total of 296 patients with Dukes A colorectal cancer with a median follow-up of 44 months were studied. Perioperative and follow-up mortality rates were 3% and 14%, respectively. Recurrent disease developed in 10% of Dukes A patients after a disease-free interval of 16 months. Significantly more patients suffering from pT2 (UICC Ib) cancer had recurrent disease than patients with pT1 (UICC Ia) cancer (13% vs. 4%; p <0.05). Preoperative CEA levels in patients with recurrent disease were significantly higher than in long-term disease-free patients (5.3 +/- 1.8 vs. 3.5 +/- 0.6 ng/ml; p <0.05). Curative resection of recurrent disease was achieved in 38% of the patients with recurrences (4% of all patients). Survival analysis showed significantly better survival in patients with Dukes A cancer than in those at higher tumor stages (log rank, <0.0001), and only 39% of all Dukes A patients who died during follow-up had recurrent disease. Dukes A (UICC Ia and Ib) colorectal cancer was diagnosed in 22% of our patients treated for cure, and long-term survival was 86%. There were significantly fewer cases of recurrent disease after curative resection of UICC Ia (pT1N0M0) cancer, so we propose a novel, less intensive follow-up regimen for these patients, leading to a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program.     

Do ultrasound renal resistance indices reflect systemic rather than renal vascular damage in chronic kidney disease?

BACKGROUND: In patients suffering from chronic kidney disease (CKD), ultrasound renal resistance indices predict progression of kidney disease and death. Although ultrasound resistance indices were initially considered to directly reflect intrarenal vascular resistance, they are complex composite parameters that are influenced by various vascular factors. We hypothesized that renal resistance indices reflect systemic vascular disease rather than local renal damage in patients with CKD. METHODS: In 140 patients suffering from CKD not receiving renal replacement therapy, intrarenal resistance indices were measured in interlobar arteries. For assessment of systemic atherosclerotic disease, common carotid intima-media thickness (IMT) and ankle-brachial blood pressure index were determined. Categories of risk for coronary heart diseases were defined by Framingham risk scoring. RESULTS: Increased renal resistance indices were associated with high Framingham risk scores and with the presence of atherosclerotic disease. In addition, ultrasound renal resistance indices progressively increased with the stage of renal function impairment, and patients suffering from diabetic nephropathy had higher resistance indices than patients suffering from other renal diseases. In a multivariate linear regression analysis, IMT, Framingham risk score, renal function, presence of diabetic nephropathy and pulse pressure independently predicted resistance indices. However, when additionally adjusting for age, IMT and Framingham risk score were no longer independent predictors of resistance indices. CONCLUSIONS: In patients suffering from CKD, intrarenal resistance indices are independently associated with cardiovascular risk score and systemic vascular disease as well as with aetiology and stage of CKD. This may explain their strong association with both impaired renal outcome and death.     

The use of chest computed tomography versus chest X-ray in patients with major blunt trauma

INTRODUCTION: Computed tomography (CT) scans are often used in the evaluation of patients with blunt trauma. This study identifies the clinical features associated with further diagnostic information obtained on a CT chest scan compared with a standard chest X-ray in patients sustaining blunt trauma to the chest. METHODS: A 2-year retrospective survey of 141 patients who attended a Level 1 trauma centre for blunt trauma and had a chest CT scan and a chest X-ray as part of an initial assessment was undertaken. Data extracted from the medical record included vital signs, laboratory findings, interventions and the type and severity of injury. RESULTS: The CT chest scan is significantly more likely to provide further diagnostic information for the management of blunt trauma compared to a chest X-ray in patients with chest wall tenderness (OR=6.73, 95% CI=2.56, 17.70, p<0.001), reduced air-entry (OR=4.48, 95% CI=1.33, 15.02, p=0.015) and/or abnormal respiratory effort (OR=4.05, 95% CI=1.28, 12.66, p=0.017). CT scan was significantly more effective than routine chest X-ray in detecting lung contusions, pneumothoraces, mediastinal haematomas, as well as fractured ribs, scapulas, sternums and vertebrae. CONCLUSION: In alert patients without evidence of chest wall tenderness, reduced air-entry or abnormal respiratory effort, selective use of CT chest scanning as a screening tool could be adopted. This is supported by the fact that most chest injuries can be treated with simple observation. Intubated patients, in most instances, should receive a routine CT chest scan in their first assessment.