6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Predicting Friendship Quality in Autism Spectrum Disorders and Typical Development

The role played by social relationship variables (attachment security; mother–child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children’s descriptions of friendships (age 8–12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). Overall, half of the HFASD sample (54.45%) reported maternal attachment security, corroborating data from younger children with ASD. The hypothesized predictors and their interrelations had both direct and indirect effects on friendship for both groups of children, highlighting the importance of these factors in children’s friendship development and suggesting both compensatory and amplification mechanisms for friendship qualities. Practical and clinical implications are discussed for friendship support in both ASD and TYP

Array algorithms for H^2 and H^∞ estimation

Currently, the preferred method for implementing H^2 estimation algorithms is what is called the array form, and includes two main families: square-root array algorithms, that are typically more stable than conventional ones, and fast array algorithms, which, when the system is time-invariant, typically offer an order of magnitude reduction in the computational effort. Using our recent observation that H^∞ filtering coincides with Kalman filtering in Krein space, in this chapter we develop array algorithms for H^∞ filtering. These can be regarded as natural generalizations of their H^2 counterparts, and involve propagating the indefinite square roots of the quantities of interest. The H^∞ square-root and fast array algorithms both have the interesting feature that one does not need to explicitly check for the positivity conditions required for the existence of H^∞ filters. These conditions are built into the algorithms themselves so that an H^∞ estimator of the desired level exists if, and only if, the algorithms can be executed. However, since H^∞ square-root algorithms predominantly use J-unitary transformations, rather than the unitary transformations required in the H^2 case, further investigation is needed to determine the numerical behavior of such algorithms

Clinical significance of stromal apoptosis in colorectal cancer

BackgroundEpithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.MethodsTotal apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.ResultsEpithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (< or = median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05-3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (< or = median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17-2.35), 1.62 (1.15-2.29) and 1.69 (1.01-2.85), respectively.InterpretationStromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC

Psychosocial complaints are associated with venous access-device related complications in patients on home parenteral nutrition

Background: Complications related to venous access devices (VADs) remain the major drawback of home parenteral nutrition (HPN) support. In addition to technical issues, patients also experience psychosocial problems. The aim of this study is to present an overview of VAD-related complications in patients on long-term HPN and to assess whether these adversities are related to experienced psychosocial problems and quality of life (QOL).Methods: Information on VAD-related complications was collected from the medical charts of 110 adult HPN patients who were followed by the 2 major referral centers in the Netherlands. In addition, a survey was conducted in this group to characterize psychosocial problems and assess their association with technique-related complications; 75 patients (68%) responded.Results: At the time of survey, the majority of patients (76%) had developed 1 or more episodes of catheter-related sepsis at some point during their HPN treatment. The overall incidence of VAD-related blood stream infections (BSIs) was 3 per 1,000 venous access days. The incidence of VAD occlusions was 0.8 per 1,000 venous access days. During the observation period, there was a highly significant association between the incidence of VAD-related complications and the occurrence of psychosocial complaints (eg, depression, fatigue, social impairment, and decreased QOL).Conclusions: Psychosocial complaints are associated with previously experienced VAD-related complications in patients on HPN therapy. Although only an association, and not a causal relationship is demonstrated by these findings, our results underscore the need for preventive and therapeutic measures regarding both types of problems in these patients