Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4+ T cells

BACKGROUND & AIMS: Mice that have a truncated mutation of the common cytokine receptor gamma chain (CR gamma -/Y) are known to spontaneously develop colitis. To identify the pathologic elements responsible for triggering this localized inflammatory disease, we elucidated and characterized aberrant T cells and their enteropathogenic cytokines in CR gamma -/Y mice with colitis. METHODS: The histologic appearance, cell population, T-cell receptor V beta usage, and cytokine production of lamina propria lymphocytes were assessed. CR gamma -/Y mice were treated with anti-interleukin (IL)-6 receptor monoclonal antibody to evaluate its ability to control colitis, and splenic CD4 + T cells from the same mouse model were adoptively transferred into SCID mice to see if they spurred the appearance of colitis. RESULTS: We found marked thickening of the large intestine, an increase in crypt depth, and infiltration of the colonic lamina propria and submucosa with mononuclear cells in the euthymic CR gamma -/Y mice, but not in the athymic CR gamma -/Y mice, starting at the age of 8 weeks. Colonic CD4 + T cells with high expressions of antiapoptotic Bcl-x and Bcl-2 were found to use selected subsets (V beta 14) of T-cell receptor and to exclusively produce IL-6. Treatment of CR gamma -/Y mice with anti-IL-6 receptor monoclonal antibody prevented the formation of colitis via the induction of apoptosis in IL-6-producing CD4 + T cells. Adoptive transfer of pathologic CD4 + T cells induced colitis in the recipient SCID mice. CONCLUSIONS: Colonic IL-6-producing thymus-derived CD4 + T cells are responsible for the development of colitis in CR gamma -/Y mice.     

Acid rereflux: a review,emphasizing detection by impedance,manometry, and scintigraphy,and the impact on acid clearing pathophysiology as well as interpreting the pH record

Acid clearing, the interval while intraesophageal pH is <4 after a traditional acid reflux event (RE), is a potential blind spot during pH monitoring, when reflux of acidified gastric contents may occur undetected by the pH probe. This is termed acid rereflux. Acid rereflux comprised 61% (169/262) of acid REs in recumbent postprandial patients with severe GERD in two reports using simultaneous pH monitoring and manometry as well as multichannel intraluminal impedance (MII) in one, and scintigraphy in the other. Acid rereflux events often recurred with short intervals between them. The pH probe alone was insufficient to detect most acid rereflux REs, since expanding pH criteria for an acid RE (>1 unit fall while pH < 4) detected only 35% of acid rereflux REs. When a variety of patients and study conditions was examined, simultaneous manometry–pH monitoring found more frequent acid rereflux in the following situations: (1) patients with vs those without esophagitis; (2) recumbent vs upright posture, and (3) postprandial vs preprandial. Of pathophysiologic importance, acid rereflux in the blind spot is the most common cause of prolonged daytime acid REs in GERD patients. Of clinical importance, the 24-hr pH parameter % acid exposure should be relied upon most in interpreting the 24-hr pH record, because those parameters that relate to RE frequency may be inaccurate due to acid rereflux REs that are not counted. Furthermore, identifying as many REs as possible gives a more reliable indication of the severity of antireflux barrier incompetence, as well as more REs to correlate with patients symptoms that should improve sensitivity of the symptom index. Ambulatory simultaneous pH monitoring and MII will allow these and other roles for acid rereflux to be assessed during the patients normal day.     

Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week dosing period in elderly patients with advanced non-small cell lung cancer

Background

S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established.

A novel therapeutic approach for LPIN1 mutation–associated rhabdomyolysis—The Austrian experience

Introduction: Lipin 1 gene (LPIN1) mutations lead to cellular energy deficiency and cause up to 50% of the rhabdomyolysis episodes seen in pediatric patients. These episodes are associated with poor prognosis, as treatment options have been limited. We propose a novel therapeutic strategy based on prevention and early treatment of catabolism. Methods: Five patients were diagnosed with LPIN1 mutations. They were instructed to maintain high caloric intake in situations possibly leading to catabolism such as viral infections or excessive physical activity. When an episode of rhabdomyolysis occurred, patients were treated with intravenous high‐concentration glucose at first symptoms. Results: The therapeutic strategies described limited the number of rhabdomyolyis episodes, and the duration of episodes was reduced from 7–10 days, as reported in the literature, to 5 days. Conclusion: In this small series, patients with LPIN1 mutations appear to have benefited from prevention and early treatment of catabolism. Muscle Nerve 52:437–439, 2015     

Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but also neuronal degeneration and cognitive impairment

Chronic cerebral hypoperfusion (CCH) induces cognitive impairment, but the compensative mechanism of cerebral blood flow (CBF) is not fully understood. The present study mainly investigated dynamic changes in CBF, angiogenesis, and cellular pathology in the cortex, the striatum, and the cerebellum, and also studied cognitive impairment of rats induced by bilateral common carotid artery occlusion (BCCAO). Magnetic resonance imaging (MRI) techniques, immunochemistry, and Morris water maze were employed to the study. The CBF of the cortex, striatum, and cerebellum dramatically decreased after right common carotid artery occlusion (RCCAO), and remained lower level at 2 weeks after BCCAO. It returned to the sham level from 3 to 6 weeks companied by the dilation of vertebral arteries after BCCAO. The number of microvessels declined at 2, 3, and 4 weeks but increased at 6 weeks after BCCAO. Neuronal degeneration occurred in the cortex and striatum from 2 to 6 weeks, but the number of glial cells dramatically increased at 4 weeks after BCCAO. Cognitive impairment of ischemic rats was directly related to ischemic duration. Our results suggest that CCH induces a compensative mechanism attempting to maintain optimal CBF to the brain. However, this limited compensation cannot prevent neuronal loss and cognitive impairment after permanent ischemia.     

山西某市城区中小学生常见病患病情况调查

目的：：掌握山西省长治市城区中小学生常见病患病情况,为进一步开展健康教育和疾病防治提供依据。方法：对32477名在校学生进行常见病检查,并对结果进行分析。结果：体检对象视力不良、龋齿、扁桃体肿大、沙眼、营养不良、肥胖检出率分别为47.47%、6.41%、9.25%、1.21%、1.28%和12.71%。其中视力不良检出率最高,其它依次是肥胖、扁桃体肿大、龋齿、营养不良、沙眼。男生沙眼和肥胖的检出率高于女生(P <0.05),而女生视力不良、龋齿、营养不良的检出率高于男生(P <0.05)。初中生视力不良、龋齿和肥胖检出率高于小学生(P <0.05),营养不良和扁桃体肿大检出率低于小学生(P <0.05)。结论：常见病对中小学生健康的影响不容忽视,应加强对中小学生6种常见病的监测、及时治疗和预防,以提高学生健康水平。     

腹腔镜胆总管探查术对肝功能损害患者的影响

目的比较腹腔镜胆总管探查术和开腹胆总管探查术对术前有肝功能损害患者的肝功能及机体应激反应的影响。方法选择42例择期行胆总管探查术的患者,随机分为2组:腹腔镜胆总管探查组(L组,21例)和开腹胆总管探查组(O组,21例),分别于手术前、术后1 d、术后3 d和术后5 d空腹抽取静脉血,测定血清TBIL、ALT、C一反应蛋白(CRP)和降钙素原(PCT)的浓度。结果术后1天、3天、5天2组患者的TBIL、ALT均较术前下降(P0.05),术后5天2组患者的TBIL、ALT血清浓度比较差异有显著性(P0.01,P0.05);术后1天、3天两组比较差异无显著性(P0.05);术后1 d、3 d、5d两组患者的CRP均高于术前,和术前相比差异均有显著性(P0.05),且两组之间比较差异均有显著性(P0.05),CRP于术后第3d达到峰值。术后1 d、3 d两组患者的PCT均高于术前(P0.05),且两组之间比较差异有显著性(P0.05),两组患者的PCT于术后1 d达到峰值;术后5 d开腹组仍高于术前(P0.05),腹腔镜组与术前相比较差异无显著性(P0.05),但两组之间比较差异有显著性(P0.01)。结论对于术前有肝功能损害的患者,腹腔镜与开腹胆总管探查术术后均可改善患者的肝功能,但腹腔镜组恢复更快,且腹腔镜手术引起的机体应激和炎性反应较轻。