High prevalence of fatigue in inflammatory bowel disease: A case control study.

Background And Aims: Many outpatients with Inflammatory Bowel Disease (IBD) complain about fatigue, even in a quiescent disease. The aim of this study is to examine prevalence of fatigue in IBD outpatients and define possible determinants of fatigue.

Methods: A case-control study was conducted in consecutive IBD outpatients, with Lynchsyndrome gene carriers (Lynch) as a control group.

The microenvironment in follicular lymphoma.

It has become increasingly clear that proliferation and survival in FL is not only driven by genetic changes, but also and possibly even predominantly by the close interaction with the immune microenvironment and stromal cells. Based on in vitro studies and experimental models and supported by immunohistochemical studies in biopsy specimens of FL patients, classes of CD4+ T-cell populations including follicular helper T cells and regulatory T cells are now identified as major players to regulate the delicate balance of effector populations into a supportive microenvironment. These insights may thoroughly change the therapeutic approaches in FL and translate into programs that combine direct cytotoxic and indirect immunomodulatory aspects.

Dielectrophoresis-based cellular microarray chip for anticancer drug screening in perfusion microenvironments.

We present a dielectrophoresis (DEP)-based cellular microarray chip for cell-based anticancer drug screening in perfusion microenvironments. Human breast cancer cells, MCF7, were seeded into the chip and patterned via DEP forces onto the planar interdigitated ring electrode (PIRE) arrays. Roughly, only one third of the cell amount was required for the chip compared to that for a 96-well plate control.

Delineation of chondroid lipoma: an immunohistochemical and molecular biological analysis.

Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics.

Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium.

The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols.

Serum beta-HCG and CA-125 as tumor markers in a patient with osteosarcoma: case report.

Background: Elevated beta-HCG serum levels are usually an indication of pregnancy or pregnancy-related disorders, but beta-HCG can also be elevated in testis and germ cell tumors. HCG expression by osteosarcoma is a rare phenomenon, with a few documented cases. CA-125 is commonly used to monitor disease progression and treatment response in ovarian cancer.

Determining equilibrium constants for dimerization reactions from molecular dynamics simulations.

With today's available computer power, free energy calculations from equilibrium molecular dynamics simulations "via counting" become feasible for an increasing number of reactions. An example is the dimerization reaction of transmembrane alpha-helices. If an extended simulation of the two helices covers sufficiently many dimerization and dissociation events, their binding free energy is readily derived from the fraction of time during which the two helices are observed in dimeric form.

Prognostic relevance of immunohistochemical subclassification of diffuse large B-cell lymphoma in two prospective phase III clinical trials.

Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large B-cell lymphoma (DLBCL) subtypes.

Patients And Methods: We have analyzed tumor samples from patients treated in 2 prospective multicenter phase III trials, ie HOVON 25 (patients≥65 years, n=153) and HOVON 26 (patients<65 years, n=144) using whole sections (WS) or tissue microarray (TMA).

Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2.

Objective: Autophagy has recently been shown to modulate the production of pro-inflammatory cytokine production and to contribute to antigen processing and presentation through the major histocompatibility complex. Genetic variation in the autophagy gene ATG16L1 has been recently implicated in Crohn's disease pathogenesis. The mechanisms underlying this association are not yet known, although experimental models suggest an inhibitory effect of autophagy on interleukin 1β (IL-1β) responses.

Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient.

Objectives: Maraviroc is the first licensed chemokine co-receptor 5 (CCR5) co-receptor antagonist in clinical practice. It is currently being used in patients harbouring exclusively CCR5-tropic virus. The objective of the study was to investigate the impact of maraviroc on viruses with different co-receptor preferences in a patient with a dual/mixed (D/M) infection.

Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture.

Malignant transformation of perianal and enterocutaneous fistulas is rare: results of 17 years of follow-up from The Netherlands.

Objective: Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perianal and enterocutaneous fistulas in both CD patients and non-CD patients from nine large, mostly tertiary referral, hospitals in The Netherlands.

Differential Toll-like receptor recognition and induction of cytokine profile by Bifidobacterium breve and Lactobacillus strains of probiotics.

The use of probiotics as a food supplement has gained tremendous interest in the last few years as beneficial effects were reported in gut homeostasis and nutrient absorption but also in immunocompromised patients, supporting protection from colonization or infection with pathogenic bacteria or fungi. As a treatment approach for inflammatory bowel diseases, a suitable probiotic strain would ideally be one with a low immunogenic potential. Insight into the immunogenicities and types of T-cell responses induced by potentially probiotic strains allows a more rational selection of a particular strain.

Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients.

Multiple osteochondromas (MO) is a hereditary skeletal disorder characterized by the presence of cartilage capped bony outgrowths at bone surface. Causative mutations in EXT1 or EXT2 genes have been described in 85-90 % of MO cases. However, in about 10-15 % of the MO cases, genomic alterations can not be detected, implying the potential role of other alterations.

Effect of childbirth on the course of Crohn's disease; results from a retrospective cohort study in the Netherlands.

Background: Pregnant women with Crohn's disease needs proper counselling about the effect of pregnancy and childbirth on their disease. However, Literature about the effect of childbirth on Crohn's disease is limited. This study examined the effect of childbirth on the course of Crohn's disease and especially perianal Crohn's disease.

Opening the archives for state of the art tumour genetic research: sample processing for array-CGH using decalcified, formalin-fixed, paraffin-embedded tissue-derived DNA samples.

Background: Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these intrinsic hurdles for bone tumour research.

Appropriate infliximab infusion dosage and monitoring: results of a panel meeting of rheumatologists, dermatologists and gastroenterologists.

What Is Already Known About This Subject: Infliximab is an effective treatment for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis and national and international guidelines have been developed for each indication.

What This Study Adds: This study is the first study which compared current international, national and local guidelines from the medical specialties involved in the treatment with infliximab on the following topics: indication, dosage, synergy and monitoring of vital signs.

Aims: Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis.

The molecular background of aggressive B cell lymphomas as a basis for targeted therapy.

In contrast to classifications for the majority of solid tumours, non-Hodgkin's lymphomas have been defined on the basis of their genetic alterations for many years, providing a biologically highly relevant classification. However, for aggressive B cell lymphomas, which unfortunately is the most prevalent group of lymphomas in adults, the stratification is less optimal. Gene expression profiling, analyses of chromosomal alterations and functional assays have been instrumental in dissecting these tumours to support the distinction of essentially different diseases, such as diffuse large B cell lymphoma and Burkitt's lymphoma, and now start to identify the dominant driving oncogenetic pathways that may serve as rational therapeutic targets in this essentially heterogeneous group.

The functional -765G→C polymorphism of the COX-2 gene may reduce the risk of developing crohn's disease.

Background: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.

Aim: The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms -1195 A→G and -765G→C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population.

Chronic yersiniosis due to defects in the TLR5 and NOD2 recognition pathways.

Infection with Yersinia enterocolitica leads to a self-limiting disease, but in a small number of cases a protracted course can develop. The host genetic factors contributing to the advancement of the disease to the chronic phase are not known. We describe a patient suffering from an abdominal inflammatory mass due to chronic yersiniosis.

[Guideline 'Diagnosis and treatment of inflammatory bowel disease in adults'. I. Diagnosis and treatment].

The Dutch national practice guideline 'Diagnosis and treatment of inflammatory bowel diseases (IBD) in adults' describes the multidisciplinary approach for adult patients with (suspected) IBD, recommended following analysis of the literature according to the principles of evidence based guideline development. The symptoms on first presentation of a patient with IBD are mainly connected with the localisation and severity of the disease and less with the resulting diagnosis 'Crohn's disease' or 'ulcerative colitis'. There is no test by which the diseases can be distinguished with certainty.

Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of NI-0401 (a fully human anti-CD3 monoclonal antibody) in patients with moderate to severe active Crohn's disease.

Background: NI-0401 is a fully human monoclonal antibody, which binds to the CD3 subunit of the T-cell receptor, causing modulation of T-cell activity. We investigated the safety and the ability to modulate the TCR-CD3 complex of NI-0401 in patients with active Crohn's disease (CD).

Methods: A double-blind, placebo-controlled, randomized, multicenter, dose-escalating trial was conducted in CD patients age 18-70 years, a Crohn's Disease Activity Index (CDAI) of 220-450, and detectable levels of C-reactive protein.

Microalbuminuria is not a valuable marker for relapse in Crohn's disease.

Background: Previous reports correlated microalbuminuria with disease activity in patients with Crohn's disease (CD). The aim of the present study is to determine the value of microalbuminuria as a marker for relapses in quiescent CD.

Methods: In a 1-year prospective maintenance trial with oral budesonide in patients with CD in remission, microalbuminuria was measured at randomization, after 2, 6 and 12 months, plus at the time of a relapse.

Misclassification of dysplasia in patients with inflammatory bowel disease: consequences for progression rates to advanced neoplasia.

Background: The natural behavior of flat low-grade (LGD) and indefinite dysplasia (IND) in patients with inflammatory bowel disease (IBD) remains uncertain and seems to be dependent on the interpretation of the pathologist. We studied the progression rate of flat LGD and IND to advanced neoplasia (high-grade dysplasia [HGD] or colorectal cancer [CRC]) before and after histopathological review by a panel of gastrointestinal expert pathologists.

Methods: A nationwide pathology database was used to identify IBD patients with dysplasia in six Dutch university medical centers between 1990 and 2006.