Prognostic Value of Colonic Tissue and Blood Eosinophils in Ulcerative Colitis.

BACKGROUND It has been suggested that eosinophils may be a prognostic marker of disease outcome in ulcerative colitis (UC), but conflicting data exist. The objective was to investigate the extent of mucosal eosinophils and peripheral blood eosinophil count in newly diagnosed UC patients and to investigate its predictive value in short- and long-term disease outcomes. METHODS The degree of eosinophilia in baseline colonic biopsies and blood of newly diagnosed UC patients was retrospectively analyzed. It was investigated if tissue and blood eosinophilia could be a marker of a severe phenotype of UC, defined as the need for corticosteroids or immunomodulators in the first year or treatment with therapeutic monoclonal antibodies or colectomy during follow-up. Time to therapeutic monoclonal antibodies and time to colectomy were also evaluated as outcomes. RESULTS There were 103 UC patients (median age 26 years) included. Median tissue peak eosinophil count (PEC) was 70.0 and median peripheral blood eosinophil count was 0.3 × 109/L at diagnosis. Tissue PEC (r = -0.161, P = .104) and blood eosinophil count (r = 0.022, P = .877) were not correlated with the severity of histologic inflammation. Logistic regression analyses did not identify PEC and blood eosinophil count as predictors of more severe disease outcomes. Tissue PEC and peripheral blood eosinophil count did not predict the time the initiation of therapeutic monoclonal antibodies or colectomy. CONCLUSION Baseline tissue or peripheral blood eosinophils are not markers of disease activity and cannot be used as a predictor of severe disease outcomes in both adults and children with UC

The influence of different floor-surf ace on starting to move a wheelchair

高齢者用車いすが在宅床面素材によってどのような影響を受けるのかを調べるため、特性の異なる車いす7台を用い、6種の床面で始動力を測定した。その結果、床面の種類、車いすの種類に有意な差を認めたため、さらに各床面で最も軽く、または重くなる車いすの構成要因を分析した。フローリンクとパイルカーペットでは、主輪空気圧を高めたものが軽く(p<0.01)なった。畳ではエアーキャスター付き車いすが軽く(p<0.01)、ソリットキャスターと主輪の空気圧を高めたものが最も重く(p<0.01)なった。畳にカーベットを敷いた床面では、ソリットキャスターと主輪の空気圧を高めたものが最も重く(p<0.01)なった。敷居や戸当段差では、81～252Nと他の床面に比べて全ての車いすが重く(p<0.01)なったが、その中でもエアーキャスターを装備する車いすは軽く(p<0.01)なった。このことから、床面の違いによって車いすの始動力は大きく影響を受け、硬い床面で軽く、柔らかな床面で始動力は重くなり、病院や施設で軽く動く車いすが在宅では同じ特性とならないことが明確となった。使用環境により車いすの構造や部品選択基準が異なることが示唆された。今回の研究により、住環境の床面条件に合わせた車いす構成要素の選択が重要であると考えられた。 / This study was conducted in order to examine the influence of different floor-surfaces on starting to move a wheelchair. The measurement performed in this study was the force required to move a wheelchair under six conditions of floor-surface, using seven types of wheelchair. Analysis of variance (ANOVA) was done among the different conditions and different types of wheelchair. As a result, significant differences were found depending on the conditions of floor-surfaces and the types of wheelchair. Therefore, we analyzed the composition factor of the wheelchair for which the force to move is the lowest, or the highest, on each floor-surface. ANOVA revealed, on flooring and pile carpet, the force to move a wheelchair with high pressure in its main tires was the lowest (p<0.01). On a tatami mat, that of the wheelchair with air casters was the lowest (p<0.01), while that of the wheelchair with solid casters and the one with high-pressure main tires was the highest (p<0.0l). On a carpeted tatami mat, that of the wheelchair with solid casters and the one with high-pressure main tires was also the highest (p<0.0l). At threshold and doorsill, the force was high (81-252N) compared with the other floor-surfaces and all wheelchairs, although that of the wheelchair with air casters was lower than others (p<0. 01). The differences of floor-surface have a great influence on the force required to move a wheelchair; it is higher on soft floor-surfaces and lower on hard floor-surfaces. It became obvious that wheelchairs which move easily at hospitals and facilities did not show the same characteristic at the home. The results of this study suggest that the structure and choice of parts for a wheelchair should be considered in relation to the environment where it will be used, with particular attention to floor-surface materials

Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I

Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease. 10 adult patients with refractory Crohn's disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1-2×10(6) cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients' Crohn's disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn's disease endoscopic index of severity. MSCs isolated from patients with Crohn's disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn's disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening. Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn's disease. No serious adverse events were detected during bone marrow harvesting and administratio

Lower Expression of TLR2 and SOCS-3 Is Associated with Schistosoma haematobium Infection and with Lower Risk for Allergic Reactivity in Children Living in a Rural Area in Ghana

Inflammatory diseases such as atopic disorders are a major health problem in the Western world, but their prevalence is also increasing in developing countries, especially in urban centres. There is increasing evidence that exposure to a rural environment with high burden of compounds derived from parasites and microorganisms is associated with protection from atopic disorders. Since urbanisation is progressing at a rapid pace, particularly in less-developed nations, there is a need to understand the molecular processes that control the progress towards the development of allergic diseases in developing countries. In this study we have examined a population of school children living in a rural area of Ghana, where helminth (worm) infections are prevalent and associated with protection from skin reactivity to house dust mite. Blood samples were collected from these children and analysed for the expression levels of several genes involved in the development of a pro allergic immune system. The results point at a potential molecular link that might explain the negative association between schistosome infections and allergies

Rational and clinical development of the anti-MAdCAM monoclonal antibody for the treatment of IBD

Introduction: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in gut-associated lymphoid tissue is upregulated in patients with inflammatory bowel disease (IBD). Blocking adhesion molecules and thereby inhibiting migration of lymphocytes into sites of inflammation in the gut is an attractive new treatment target in drug development for IBD. Areas covered: This review discusses the preclinical and clinical experience on SHP647 (previously called PF-00547659 and PF-00547,659), a fully human IgG2K monoclonal antibody that binds to MAdCAM-1 to selectively reduce lymphocyte homing to the intestinal tract. Expert opinion: Blocking endothelial adhesion molecule MAdCAM−1 could represent an attractive target for the treatment of IBD. In the next years, the results from the phase III studies as well as data to support therapeutic drug monitoring based on drug levels to guide and optimize individual therapy will become available. Furthermore, much effort is put in the development of clinical prediction models to predict which drug is optimal for an individual patient

In vivo Biodistribution of Stem Cells Using Molecular Nuclear Medicine Imaging

Studies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results. Major questions in this research field have been raised as to how and in which numbers stem cells home to target tissues after administration, whether the cells engraft and differentiate, and what their long-term fate is. To answer these questions, reliable in vivo tracking techniques are essential. In vivo molecular imaging techniques using magnetic resonance imaging, bioluminescence, and scintigraphy have been applied for this purpose in experimental studies. The aim of this review is to discuss various radiolabeling techniques for early stem cell tracking, the need for validation of viability and performance of the cells after labeling, and the routes of administration in experimental animal models. In addition, we evaluate current problems and directions related to stem cell tracking using radiolabels, including a possible role for their clinical implementation. © 2010 Wiley-Liss, Inc

In vivo Biodistribution of Stem Cells Using Molecular Nuclear Medicine Imaging

Studies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results. Major questions in this research field have been raised as to how and in which numbers stem cells home to target tissues after administration, whether the cells engraft and differentiate, and what their long-term fate is. To answer these questions, reliable in vivo tracking techniques are essential. In vivo molecular imaging techniques using magnetic resonance imaging, bioluminescence, and scintigraphy have been applied for this purpose in experimental studies. The aim of this review is to discuss various radiolabeling techniques for early stem cell tracking, the need for validation of viability and performance of the cells after labeling, and the routes of administration in experimental animal models. In addition, we evaluate current problems and directions related to stem cell tracking using radiolabels, including a possible role for their clinical implementation. J. Cell. Physiol. 226: 1444-1452, 2011. (C) 2010 Wiley-Liss, Inc

Letter: tricky reactions to switch back from subcutaneous to intravenous vedolizumab in inflammatory bowel disease patients—authors' reply

Cellular mechanisms in basic and clinical gastroenterology and hepatolog