Quality of life after open versus laparoscopic preperitoneal mesh repair for unilateral inguinal hernias.

Background: Both the open transinguinal preperitoneal repair (TIPP) and the laparoscopic total extraperitoneal mesh repair (TEP) show excellent outcomes. Direct comparative data between these 2 preperitoneal techniques is lacking. The aim of this study was to assess postoperative outcomes and quality of life (QoL) for these open and laparoscopic preperitoneal repair techniques.

Comparison of methods to estimate the affected body surface area and the dosage of topical treatments in psoriasis and atopic dermatitis: the advantage of a picture-based tool.

Background: The accurate determination of the dosage of topical treatments is important given its repercussions on patient adherence and therapeutic efficacy. Up till now, the fingertip unit calculated by the rule of hands is considered the gold standard, although its use is associated with several drawbacks.

Objective: To compare different methods to estimate the affected body surface area (BSA) and dosage of topical treatments in atopic dermatitis and psoriasis and investigate its reliability, user-friendliness and timing.

Depletion of Kupffer cells modulates ethanol-induced hepatocyte DNA synthesis in C57Bl/6 mice.

Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is one means of KC activation.

Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients.

Bortezomib induced peripheral neuropathy is a dose-limiting side effect and a major concern in the treatment of multiple myeloma. To identify genetic risk factors associated with the development of this side effect in bortezomib treated multiple myeloma patients, a pharmacogenetic association study was performed using a discovery set (IFM 2005-01; n = 238) and a validation set (HOVON65/GMMG-HD4 and a Czech dataset; n = 231). After multiplicity correction, none of the 2,149 single nucleotide polymorphisms tested revealed any significant association with bortezomib induced peripheral neuropathy.

Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma.

Purpose: To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN).

Patients And Methods: We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the association of TrPN with 3,404 SNPs.

Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial.

Background: Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity in patients with multiple myeloma, often requiring adjustment of treatment and affecting quality of life. We investigated the molecular profiles of early-onset (within one treatment cycle) versus late-onset (after two or three treatment cycles) bortezomib-induced peripheral neuropathy and compared them with those of vincristine-induced peripheral neuropathy during the induction phase of a prospective phase 3 trial.

Methods: In the induction phase of the HOVON-65/GMMG-HD4 trial, patients (aged 18-65 years) with newly diagnosed Salmon and Durie stage 2 or 3 multiple myeloma were randomly assigned to three cycles of bortezomib-based or vincristine-based induction treatment.

Kupffer cells participate in 2-butoxyethanol-induced liver hemangiosarcomas.

2-Butoxyethanol increases hemangiosarcomas selectively in male mouse liver after chronic inhalation through mechanisms that have not fully been elucidated. Hemolysis, a primary toxic effect associated with 2-butoxyethanol exposure in rodents, increased hemosiderin (iron) deposition in Kupffer cells in the liver. These findings, along with the induction of hepatic neoplastic lesions, led to our hypothesis that the induction hemangiosarcomas by 2-butoxyethanol is due to the activation of Kupffer cells, subsequent to hemolysis, that results in the induction of DNA synthesis in target cells (endothelial cells); allowing for the selective proliferation of preneoplastic target cells and/or the promotion of new initiated cells.

Micro-RNA-15a and micro-RNA-16 expression and chromosome 13 deletions in multiple myeloma.

We have used copy number variation (CNV) analysis with SNP mapping arrays for miRNA-15a and miRNA-16-1 expression analysis in patients with multiple myeloma (MM) with or without deletion of chromosome 13q14. MiRNA-15a and miRNA-16 display a range of expression patterns in MM patients, independent of the chromosome 13 status. These findings suggest that genes other than miR-15a and miR-16 may explain the prognostic significance of 13q14 deletions.

Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping.

A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)-based single nucleotide polymorphism (SNP) chip containing 3404 SNPs.

Mechanisms of 2-butoxyethanol-induced hemangiosarcomas.

Chronic exposure to 2-butoxyethanol increased liver hemangiosarcomas in male mice. The mechanism for the selective induction of hemangiosarcomas by 2-butoxyethanol is unknown but has been suggested to occur through non-DNA-reactive mechanisms. The occurrence of liver hemangiosarcomas in male mice has been linked to oxidative damage subsequent to RBC hemolysis and iron deposition and activation of macrophages (Kupffer cells) in the liver, events that exhibit a threshold in both animals and humans.

Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples.

In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine kinase 3 (FLT3) gene predict poor prognosis. We determined FLT3 internal tandem duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse samples from 80 pediatric and adult AML patients. One D835 point mutation was found in an initial pediatric AML sample.

Differential immune effects mediated by Toll-like receptors stimulation in precursor B-cell acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and, although current therapy is widely effective, relapse remains a significant clinical problem for which new treatment strategies are required. The ligation of Toll-like receptors (TLR) on antigen-presenting cells stimulates the generation of strong T-cell helper type 1 (Th1) adaptive immune responses. Although TLR9 ligation has been shown to enhance immunogenicity of a number of leukaemia cell types, there have been few reports of the effects mediated through other TLR.