Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.     

CD44-stimulated human B cells express transcripts specifically involved in immunomodulation and inflammation as analyzed by DNA microarrays

A number of studies have implicated a role for the cell surface glycoprotein CD44 in several biologic events, such as lymphopoiesis, homing, lymphocyte activation, and apoptosis. We have earlier reported that signaling via CD44 on naive B cells in addition to B-cell receptor (BCR) and CD40 engagement generated a germinal center-like phenotype. To further characterize the global role of CD44 in B differentiation, we examined the expression profile of human B cells cultured in vitro in the presence or absence of CD44 ligation, together with anti-immunoglobulin (anti-Ig) and anti-CD40 antibodies. The data sets derived from DNA microarrays were analyzed using a novel statistical analysis scheme created to retrieve the most likely expression pattern of CD44 ligation. Our results show that genes such as interleukin-6 (IL-6), IL-1alpha, and beta(2)-adrenergic receptor (beta(2)-AR) were specifically up-regulated by CD44 ligation, suggesting a novel role for CD44 in immunoregulation and inflammation.     

How to Increase Reach and Adherence of Web-Based Interventions: A Design Research Viewpoint

Nowadays, technology is increasingly used to increase people’s well-being. For example, many mobile and Web-based apps have been developed that can support people to become mentally fit or to manage their daily diet. However, analyses of current Web-based interventions show that many systems are only used by a specific group of users (eg, women, highly educated), and that even they often do not persist and drop out as the intervention unfolds. In this paper, we assess the impact of design features of Web-based interventions on reach and adherence and conclude that the power that design can have has not been used to its full potential. We propose looking at design research as a source of inspiration for new (to the field) design approaches. The paper goes on to specify and discuss three of these approaches: personalization, ambient information, and use of metaphors. Central to our viewpoint is the role of positive affect triggered by well-designed persuasive features to boost adherence and well-being. Finally, we discuss the future of persuasive eHealth interventions and suggest avenues for follow-up research.     

微核实验评价自制烤瓷合金的生物相容性

目的：通过微核实验检测自制Ni-Cr-Ti烤瓷合金对小鼠的致畸作用,评价其生物相容性. 方法：实验于2006-04/08在中国医科大学中心实验室完成.①实验分组：选择N1H纯系小鼠80只,按随机数字表法分为8组,每组10只：Ni-Cr-Ti合金组（剂量分别为0.02,0.002,0.000 2 mL/kg）、纯钛浸提液组（剂量分别为0.02,0.002,0.000 2 mL/kg）,阴性对照组（生理盐水）,阳性对照组（注射用环磷酰胺,75 mg/kg）.②实验方法：按50 mL/kg口服同剂量的浸提液,各组均于一次给药后24 h,麻醉后处死小鼠,取小鼠骨髓细胞.③实验评估：光镜下计数1 000个嗜多染红细胞的微核细胞数,并计数嗜多染红细胞与正红细胞的比值,即P/N比值.比值≥1,属于正常,比值＜1,则可能受试物对骨髓细胞产生毒性. 结果：Ni-Cr-Ti合金组、纯钛浸提液组每1 000个嗜多染红细胞的微核细胞数与阴性对照组比较,差异无显著性意义（P＞0.05）,即Ni-Cr-Ti合金、纯钛浸提液对骨髓细胞无毒性.阳性对照组每1 000个嗜多染红细胞的微核细胞数高于Ni-Cr-Ti合金组、纯钛浸提液组,差异有显著性意义（P＜0.01）,对骨髓有毒性作用.Ni-Cr-Ti合金组、纯钛浸提液组P/N比值均≥1. 结论：自制Ni-Cr-Ti合金对小鼠无致畸作用,有较良好的生物相容性.     

Anti-Jka, -C, and -E in a single patient, initially demonstrable only by the manual hexadimethrine bromide (Polybrene) test, with incompatibilities confirmed by 51Cr-labeled red cell studies

Published reports have confirmed the superior sensitivity of the manual hexadimethrine bromide (Polybrene) test (MPT) for demonstrating many alloantibodies in vitro; however, the clinical significance of alloantibodies demonstrable exclusively by MPT has not been shown conclusively. A patient with macroglobulinemia experienced chills, fever, hemoglobinemia, and hemoglobinuria following the transfusion of 1 unit of red cells (RBCs) shown to be compatible by the low-ionic-strength antiglobulin (LIS-AG) method. Serologic investigation was negative. Intravascular hemolysis occurred with a second "compatible" unit. Serologic studies were again negative by LIS-AG and ficin-AG methods, but revealed anti-Jka by MPT. Both donors were Jk(a+b-), and 51Cr studies of the second donor's RBCs revealed a t1/2 of less than 30 minutes, with marked intravascular hemolysis. A LIS-AG-compatible Jk(a-) unit was transfused uneventfully, but with no rise in hematocrit. MPT next revealed anti-C; subsequent 51Cr studies with the Jk(a-), Cc donor's RBCs showed a 51Cr t1/2 of 100 minutes with slight intravascular lysis. Four transfusions of Jk(a-), C- blood were uneventful, but 5 days later the patient's hemoglobin declined. The following day, anti-E was demonstrable exclusively by MPT. 51Cr-labeled Jk(a-), C-, E- RBCs had normal 24-hour survival. The patient's hemoglobin rose to 11 g per dl following transfusions of Jk(a-), C-, E- RBCs, and he was discharged. In vitro studies employing the patient's purified IgM paraprotein revealed no interference with alloantibody binding or detection.     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

A one‐year school‐based diet/exercise intervention improves non‐traditional disease biomarkers in Mexican‐American children

School‐based interventions are an effective way to treat childhood obesity. The purpose of the present study was to biologically validate an established school‐based intervention designed to reduce standardised body mass index (zBMI) over a period of 12 months. This intervention focused on a subset of Mexican‐American children who were participating in a larger clinical weight loss study. Plasma samples were analysed from self‐identified Mexican‐American children (12–14 years) who were randomised to either a school‐based intervention (IN, n = 152) or self‐help control (CN, n = 69). Treatment was 4 days week^?1 of exercise (45 min day^?1) and 1 day week^?1 of nutritional counselling for 6 months. Fasting (>8 h) blood samples were collected at baseline, 6 months (end of active intervention) and 12 months (6 months after the end of the active intervention). Plasma resistin, adiponectin and leptin concentration were measured using a multiplex assay. Separate linear mixed models and a P < 0.05 were used to test for significance. Significant group × time interactions were found for resistin (P < 0.0001), adiponectin (P = 0.001) and leptin (P = 0.013). For resistin, IN was 12% lower at 6 months than CN. Adiponectin concentration in IN was greater at 6 months (26%) and 12 months (8%) than CN. Leptin concentration was 22% lower for IN at 12 months than CN. We have previously reported that our school‐based intervention reduced zBMI and now reported alterations in biologically relevant disease biomarkers. Some of the observed changes were only present at the end of the active intervention (resistin), while others persisted until 12 months (leptin and adiponectin). These changes underscore the effectiveness of our school‐based intervention at not only improving zBMI but also at reducing disease risk.     

Correcting post‐keratoplasty anisometropia with the implantable collamer phakic intraocular lens

Background: We evaluate the Visian Implantable Collamer Lens (Staar, Monrovia, CA, USA) phakic intraocular lens for treating post‐keratoplasty anisometropia. Methods: Case series of three eyes (2 phakic and 1 pseudophakic). Results: The mean age was 47.3 years (range 30–73 years), with a minimum of 3‐month follow up. The mean preoperative spherical equivalent was ?8.75 ± 5.17 D (?4.00 to ?14.25 D) improving to ?0.29 ± 1.21 D postoperatively (range 0.75 to ?1.625 D). Mean logMAR uncorrected visual acuity improved from 1.66 ± 0.60 (6/240) preoperatively to 0.41 ± 0.52 (6/15²). Mean logMAR best spectacle‐corrected visual acuity improved from 0.32 ± 0.15 (6/12) preoperatively to 0.10 ± 0.11 (6/7.5). Anisometropia improved from a difference of 6.37 ± 2.59 D preoperatively to 2.09 ± 1.37 D postoperatively, and there were no complications. Conclusion: Our technique for this clinical indication shows that the Visian Implantable Collamer Lens is a safe and effective alternative for treating post‐keratoplasty anisometropia.