Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate

We tested the hypothesis that interaction between autoantigens and chemoattractant receptors may be an important step in the development of autoimmunity. The retinal autoantigens S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP) can induce autoimmune uveitis in rodent models. We evaluated the chemotactic activity of S-Ag and IRBP and found that both induced migration of human and mouse immature dendritic cells (iDCs) and lymphocytes, but not neutrophils, monocytes, or mature DCs. Cross-desensitization studies and single-receptor transfected cells revealed that subfamily of alpha chemokine receptors CXCR5 and CXCR3 mediated the chemotactic effect of IRBP, while only CXCR3 was required for the chemotactic response to S-Ag. Examination of the relationships between chemoattraction and the ability to elicit pathology at the protein or peptide levels in the mouse uveitis model revealed dissociation of the capacity to induce uveitis, lymphocyte proliferation, and chemoattraction. These studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5.     

Accreditation of processes in hepatology

The Spanish Association for the Study of the Liver decided in 2006 to develop a project to assess the quality of the professionals, processes and medical units dealing with the management of patients with liver diseases in Spain. The current article reports the criteria proposed to assess the quality and the accreditation of the processes in hepatology. The processes considered include most patients with liver diseases and the accreditation system designed is highly specific. This document, together with a previous one published in gastroenterología y hepatología concerning the accreditation of the professionals and a third document dealing with the accreditation of liver units that will be published soon, form the basis of the quality assessment of hepatology in our country.     

Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure

BACKGROUND: Nephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients. METHODS: Clinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients. RESULTS: All 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin-positive myofibroblasts. CONCLUSION: Nephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease.     

Serial changes in exercise capacity,quality of life and cardiopulmonary responses after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease

Background and Objectives

Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQL), exercise capacity and cardiopulmonary function. Pulmonary rehabilitation (PR) is beneficial to improve exercise capacity and HRQL. However, series changes of these parameters remain unclear.

Comorbid illness is an important determinant of health-related quality of life in patients with chronic hepatitis C

OBJECTIVES: Chronic hepatitis C (CHC) patients selected for entry into treatment trials have been reported to have impaired health-related quality of life (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC patients may have been underestimated because of the exclusion of patients with comorbid illness. The aim of this study was to assess HRQOL in an unselected group of CHC patients and to identify factors associated with impairment in HRQOL. METHODS: A total of 220 consecutive eligible CHC patients were enrolled from a hepatology clinic. HRQOL was assessed by the short form 36 (SF-36) and comorbid illnesses were assessed by an interview. RESULTS: CHC patients had significantly lower SF-36 scores in all subscales and in the summary scales when compared to those of the healthy general population in the United States (p < 0.001). Compared to CHC patients entering treatment trials, our patients had lower SF-36 scores on five subscales (p < 0.001). The presence of comorbid illness was the most important predictor of HRQOL in CHC patients. However, CHC alone resulted in significantly lower SF-36 scores in all subscales and summary scales (p < or = 0.003) compared to those of the healthy U.S. population. There was no correlation between SF-36 scores and history of i.v. drug use or dependence. alcohol dependence. and serum aminotransferase levels. CONCLUSIONS: We conclude that unselected CHC patients presenting for medical evaluation have a reduced HRQOL, which is lower than that reported for CHC patients entering treatment trials. CHC alone is associated with significant impairment in HRQOL, but the presence of comorbid illness leads to further diminution in HRQOL.     

Heterogeneous Helicobacter pylori isolates from H. pylori-infected couples in Taiwan

Helicobacter pylori strain diversity was investigated in 55 H. pylori seropositive couples in Taiwan in biopsy samples from the antrum and corpus. Two DNA typing methods were used to characterize 90 isolates from 25 couples. In only 1 of the 25 couples was the same strain colonized from both partners. Comparison of isolates from 2 sites in each of 40 patients showed that 9 pairs were distinct but might be related. Peptic ulcer occurred in 77.8% of these 9 patients compared with 29% of 31 patients with the same predominant strain in 2 biopsies (P=.025). Random amplified polymorphic DNA and sequence analyses of 2 closely related isolates from 1 patient support the hypothesis that development of genetic diversity of H. pylori results from horizontal genetic exchange during long-term colonization of mixed bacterial populations.     

The stochastic piston problem

We obtain analytical solutions for the perturbed shock paths induced by time-varying random motions of a piston moving inside an adiabatic tube of constant area. The variance of the shock location grows quadratically with time for early times and switches to linear growth for longer times. The analytical results are confirmed by stochastic numerical simulations, and deviations for large random piston motions are established.     

慢性乙型肝炎发病机制的超微形态学基础研究

为探讨慢性乙型肝炎（乙肝）肝细胞损伤机制的超微形态学基础，对５０例乙肝患者肝穿刺进行电观察，发现淋巴细胞浸入肝组织后，可以与肝细胞发生接触、质膜融合和胞质沟通。肝细胞和淋巴细胞之间可见电子致密物，这可能是淋巴细胞产生的多种因子。枯否细胞质膜与淋巴细胞质膜融合，浆细胞质膜可与淋巴细胞质膜融合，淋巴细胞之间胞质可互相沟通，提示了免疫细胞间以及免疫细胞与肝细胞间的一些关系，为研究乙肝的细胞免疫反应机制提     

The effect of different treatment strategies on left atrial size in patients with lone paroxysmal atrial fibrillation—a prospective cohort study

INTRODUCTION: The effect of different treatment strategies of atrial fibrillation on left atrial (LA) size has not been compared in lone paroxysmal atrial fibrillation. The objective of the present study was to evaluate the evolution of LA size over time in patients who underwent different treatment interventions. METHODS AND RESULTS: Two hundred forty patients with lone paroxysmal atrial fibrillation were assigned to four groups. The circumferential pulmonary vein ablation (CPVA) group (n = 60) was treated with CPVA, segmental pulmonary vein isolation (SPVI) group (n = 60) with SPVI, AMIO group (n = 60) with amiodarone alone, and AMIO + LO group (n = 60) with amiodarone plus losartan. LA diameter was measured with transthoracic echocardiogram at baseline, 3, 6, 9, and 12 months after the interventions. In the CPVA group, LA size at third, sixth, ninth, and 12th month had a significant decrease than that at baseline and in the other three groups. LA size in patients with atrial fibrillation recurrence in the four groups was significant higher than that in patients with no atrial fibrillation recurrence (P = 0.002-0.001). CONCLUSION: The results suggested that a shortened LA size is not consistent with improved sinus rhythm maintenance. Although maintenance of sinus rhythm is not the only factor in determining shrinking or enlargement of the left atrium, inhibiting or eliminating activity of the pulmonary vein is very important for paroxysmal atrial fibrillation. Atrial fibrillation recurrence is a main factor contributing to enlargement of the LA.