Microvessel quantification in primary colorectal carcinoma: an immunohistochemical study.

The vascularisation of human primary colorectal carcinomas was studied immunohistochemically using the endothelial cell markers CD31 and factor VIII-related antigen. Tumour sections were systematically scanned at a magnification of x 100 to find areas of intense neovascularisation. Microvessel counts within these vascular 'hotspots' were performed at magnification x 250. Regions in which tumour cords were surrounded by a collagen IV-positive basement membrane were compared with those in which this was absent and with normal mucosa. CD31 appeared to be a more sensitive marker for endothelial cells than factor VIII-related antigen (mean 185 +/- 59 and 120 +/- 38 microvessels mm-2). Within individual tumour sections microvessel counts in vascular hotspots with highest vessel density correlated significantly with microvessel counts in vascular hotspots with second highest vessel density (P < 0.01). Microvessel counts in tumour areas where collagen IV-positive basement membrane were absent exceeded those in areas where it was present (factor of 1.7) and those in normal mucosa (factor of 1.6). The differences in vessel density between individual tumours and the low variability in vessel density within individual tumours using this quantification technique allow us to investigate the prognostic value of vessel density in areas of intense neovascularisation in human primary colorectal carcinomas

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Inflammation subsequent to mild iron excess differentially alters regional brain iron metabolism, oxidation and neuroinflammation status in mice

Iron dyshomeostasis and neuroinflammation, characteristic features of the aged brain, and exacerbated in neurodegenerative disease, may induce oxidative stress-mediated neurodegeneration. In this study, the effects of potential priming with mild systemic iron injections on subsequent lipopolysaccharide (LPS)-induced inflammation in adult C57Bl/6J mice were examined. After cognitive testing, regional brain tissues were dissected for iron (metal) measurements by total reflection X-ray fluorescence and synchrotron radiation X-Ray fluorescence-based elemental mapping; and iron regulatory, ferroptosis-related, and glia-specific protein analysis, and lipid peroxidation by western blotting. Microglial morphology and astrogliosis were assessed by immunohistochemistry. Iron only treatment enhanced cognitive performance on the novel object location task compared with iron priming and subsequent LPS-induced inflammation. LPS-induced inflammation, with or without iron treatment, attenuated hippocampal heme oxygenase-1 and augmented 4-hydroxynonenal levels. Conversely, in the cortex, elevated ferritin light chain and xCT (light chain of System Xc−) were observed in response to LPS-induced inflammation, without and with iron-priming. Increased microglial branch/process lengths and astrocyte immunoreactivity were also increased by combined iron and LPS in both the hippocampus and cortex. Here, we demonstrate iron priming and subsequent LPS-induced inflammation led to iron dyshomeostasis, compromised antioxidant function, increased lipid peroxidation and altered neuroinflammatory state in a brain region-dependent manner

The role of open abdomen in non-trauma patient : WSES Consensus Paper

The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients. In addition to utilization recommendations, questions with insufficient evidence urgently requiring future study were identified.Peer reviewe

First‐time application of droplet digital PCR for methylation testing of the 11p15.5 imprinting regions

Abstract Background Beckwith‐Wiedemann syndrome and Silver‐Russel syndrome are two imprinting disorders caused by opposite molecular alterations in 11p15.5. With the current diagnostic tests, their molecular diagnosis is challenging due to molecular heterogeneity and mosaic occurrence of the most frequent alterations. As the determination of precise (epi)genotype of patients is relevant as the basis for a personalized treatment, different approaches are needed to increase the sensitivity of diagnostic testing of imprinting disorders. Methods We established methylation‐specific droplet digital PCR approaches (MS‐ddPCR) for the two imprinting centers in 11p15.5, and analyzed patients with paternal uniparental disomy of chromosome 11p15.5 (upd(11)pat) and other imprinting defects in the region. The results were compared to those from MS‐MLPA (multiplex ligation‐dependent probe amplification) and MS‐pyrosequencing. Results MS‐ddPCR confirmed the molecular alterations in all patients and the results matched well with MS‐MLPA. The results of MS‐pyrosequencing varied between different runs, whereas MS‐ddPCR results were reproducible. Conclusion We show for the first time that MS‐ddPCR is a reliable and easy applicable method for determination of MS‐associated changes in imprinting disorders. It is therefore an additional tool for multimethod diagnostics of imprinting disorders suitable to improve the diagnostic yield