匹维溴铵对肠易激综合征患者回盲部肥大细胞脱粒的影响

目的评价匹维溴胺对腹泻型肠易激综合征(ir-ritable bowel syndrome,IBS)的临床疗效以及对回盲部肥大细胞脱粒的影响,探讨其治疗腹泻型IBS的可能机制。方法应用匹维溴胺治疗符合入选标准的IBS患者48例,观察其对腹泻型患者的疗效,并以便秘型患者作对照,同时检测治疗前后IBS患者回盲部脱颗粒肥大细胞的数目变化。结果匹维溴胺治疗腹泻型IBS疗效明显,治疗前后腹泻型IBS患者脱颗粒肥大细胞数目有显著变化。结论匹维溴胺治疗腹泻型IBS有效,可能与抑制了肥大细胞的脱粒有关。     

肠易激综合征精神心理因素、肠黏膜肥大细胞及5-羟色胺的变化

目的:探讨精神心理因素、肠黏膜肥大细胞(MC)及5-羟色胺(5-HT)变化在肠易激综合征(IBS)发病机制中的作用.方法:应用汉密尔顿焦虑量表(HAMA)和汉密尔顿抑郁量表(HAMD)分别对27例IBS患者和27例对照者进行精神心理因素评分.应用免疫组化法检测回盲部肠黏膜MC含量.应用高效液相电化学检测法测定回盲部肠黏膜5-HT含量.应用直线相关分析焦虑抑郁评分、回盲部肠黏膜MC数目和脱颗粒比率、5-HT浓度之间的关系.结果:IBS组焦虑抑郁评分HAMA(18.26±6.23)和HAMD(20.93±6.96)总分均明显高于对照组(9.15±4.91,9.89±5.31),差异有显著性(P＜0.05).IBS组回盲部肠黏膜MC数目、MC脱颗粒比率便秘型(22.1±6.5/HP,35.4%±7.1%)和腹泻型(28.4±7.3/HP和42.3%±10.1%)明显高于对照组(15.6±6.9/HP和24.8%±7.2%),差异有显著性(P＜0.05),其中腹泻型较便秘型明显升高(P＜0.05).IBS组回盲部肠黏膜5-HT浓度便秘型和腹泻型明显高于对照组(2669±920,2628±906 ng/g vs 1893±984 ng/g,P＜0.05),其中便秘型和腹泻型相比无显著性差异(P＞0.05).IBS患者焦虑抑郁评分与回盲部肠黏膜MC数目、MC脱颗粒比率呈正相关性(rHAMA=0.784,0.842,rHAMD=0.711,0.860,P＜0.01),与回盲部肠黏膜5-HT浓度无明显相关性(P＞0.05).IBS患者回盲部肠黏膜5-HT浓度与MC数目、MC脱颗粒比率之间无明显相关性(P＞0.05).结论:IBS精神心理因素异常,回盲部肠黏膜MC含量及活化比例增高,5-HT浓度增高.精神心理因素异常与肠黏膜MC含量增加及肠黏膜MC的脱颗粒有关.     

中西医结合治疗腹泻型肠易激综合征60例

[目的]观察中医药联合匹维溴胺(商品名:得舒特)治疗腹泻型肠易激综合征(IBS)的疗效.[方法]将118例腹泻型IBS患者随机分为2组,治疗组60例,给予中药疏肝健脾剂配合匹维溴胺50 mg口服,每日3次;对照组58例,给予口服匹维溴胺50 mg,每日3次.[结果]治疗4周后,治疗组总有效率96.8%,对组照80.2%,2组比较差异有统计学意义(P＜0.05).[结论]中医药联合匹维溴胺治疗腹泻型IBS有较好的疗效.     

黄术灌肠液对腹泻型肠易激综合征大鼠肥大细胞与P物质的影响

目的:评价黄术灌肠液对腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome,D-IBS)大鼠回盲部肥大细胞数量以及血清和回盲部肠组织匀浆P物质含量的影响.方法:将36只♀SD大鼠随机分成4组,分别是正常对照组、模型对照组、治疗组(黄术灌肠液组和匹维溴铵组),每组9只,采用乙酸灌肠加束缚应激法建立D-IBS大鼠模型,采用甲苯胺蓝改良染色法观察各组大鼠回盲部肥大细胞数目的变化,采用ELISA法检测血清和回盲部肠组织匀浆P物质的含量.结果:与正常对照组比较,模型对照组大鼠回盲部肥大细胞数目显著增多(3.07±0.56vs1.47±0.26;t=7.787,P<0.01),血清和回盲部肠组织匀浆P物质含量均显著升高(600.38±175.25vs181.12±40.03,194.01±35.54vs60.01±9.33;t=6.997,t=10.943,均P<0.01);与模型对照组比较,黄术灌肠液组大鼠回盲部肥大细胞数目、血清P物质含量及回盲部肠组织匀浆P物质含量均显著减低(1.53±0.26vs3.07±0.56,237.86±19.75vs600.38±175.25,88.29±5.51vs194.01±35.54;均P<0.01);与匹维溴铵组比较,黄术灌肠液组大鼠回盲部肥大细胞数目及血清P物质含量均无显著差异(均P>0.05),回盲部肠组织匀浆P物质含量显著降低(88.29±5.51vs135.11±34.66;P<0.05).结论:黄术灌肠液能够减少D-IBS大鼠回盲部肥大细胞数目,降低血清及回盲部肠组织P物质含量,从而对D-IBS起到治疗作用.     

益气固肠方治疗腹泻型肠易激综合征的疗效观察及对结肠组织5-HT和肥大细胞脱颗粒情况的影响

[目的]观察益气固肠方治疗腹泻型肠易激综合征(irritable bowel syndrome,IBS)的疗效及其对结肠组织5-羟色胺(5-hydroxytryptamine,5-HT)和肥大细胞脱颗粒的影响。[方法]选取2016年3月~2017年6月我院中医科收治的腹泻型IBS患者118例,随机分为对照组与研究组各59例。对照组给予匹维溴铵片治疗,研究组给予益气固肠方治疗,2组治疗均持续4周。观察2组治疗前后中医症候积分、肠易激综合征患者生活质量问卷(irritable bowel syndrome quality of life,IBS-QOL)评分、结肠组织5-HT、肥大细胞数量及肥大细胞脱颗粒情况和治疗中的不良反应,评价2组临床疗效。[结果]治疗后,2组中医症候积分显著降低、IBS-QOL评分显著升高(P0.05),且研究组中医症候积分显著低于对照组、IBS-QOL评分显著高于对照组(P0.05);治疗后,2组结肠组织5-HT水平及肥大细胞数量、肥大细胞脱颗粒比例均显著降低(P0.05),且研究组显著低于对照组(P0.05);2组不良反应情况比较,差异无统计学意义(P0.05);研究组总有效率为96.61%,显著高于对照组81.36%(P0.05)。[结论]益气固肠方治疗腹泻型IBS疗效显著,且能降低结肠组织5-HT水平,减少肥大细胞脱颗粒。     

匹维溴胺联合谷维素治疗肠易激综合征疗效评议

目的探讨匹维溴胺联合谷维素治疗肠易激综合征（IBS）的临床疗效。方法选择36例IBS患者，随机分为对照组及治疗组各18例。对照组采用匹维溴胺治疗，50mg／次，3次／d；治疗组在此基础上服用谷维素，30mg／次，3次／d，疗程均为1个月。观察两组治疗前后的临床疗效、症状、体征。结果治疗组总有效率为94．44％，对照组总有效率为83．33％，治疗组与对照组比较，差异有显著性（P〈0．05）。治疗组对缓解腹痛、腹泻、便秘等症状优于对照组。结论匹维溴胺联合谷维素组可有效改善IBS患者的临床症状，提高疗效。     

肠道黏膜肥大细胞和降钙素基因相关肽在肠易激综合征中的表达

目的: 探讨肥大细胞和降钙素基因相关肽(CGRP)对肠易激综合征(irritable bowelsyndrome, IBS)发病机制的影响, 为今后从神经-内分泌-免疫网络方面分析研究IBS的发生机制提供理论依据.方法: 组织切片采用免疫组织化学的方法, 用兔抗人降钙素基因相关肽多克隆抗体, 测定染色阳性的CGRP, 用特殊染色的方法测定染色阳性的肥大细胞.结果: 四型IBS与对照组肠黏膜肥大细胞的数目相比在回盲部的分布不同( t = 11.8, 6.8, 2.5,12.2, P<0.05或0.01); 在乙状结肠部位只有腹泻型不同( t = 2.1, 0.01< P<0.05). IBS腹泻型患者回盲部、乙状结肠部肠黏膜中降钙素基因相关肽阳性神经肽纤维强度与对照组比较显著增强(11.13±1.3 vs 7.9±1.5, 9±2.1 vs 7.5±1.2, P<0.05或0.01). IBS回盲部黏膜中肥大细胞数和降钙素基因相关肽阳性神经肽纤维强度的表达呈正相关( r = 0.7, P<0.01).结论: 肥大细胞和降钙素基因相关肽对IBS的发病可能有一定程度的影响.     

健脾调肝温肾方对腹泻型肠易激综合征患者肠黏膜肥大细胞及5-HT的影响

[目的]观察健脾调肝温肾方治疗腹泻型肠易激综合征(D-IBS)的临床疗效,通过检测回盲部肠黏膜肥大细胞(MC)表达及5-HT浓度探讨健脾调肝温肾方治疗D-IBS的作用机制。[方法]选择80例D-IBS患者,随机分为中药治疗组与西药对照组各40例,选取健康体检肠镜检查者10例作为正常对照组,中药治疗组口服健脾调肝温肾方并随症加减,西药对照组口服匹维溴铵片。疗程为4周。应用腹痛视觉模拟评分及症状评分于治疗前及治疗后14d、28d观察并记录腹痛、排便次数及大便性状改变。钳取正常组及治疗前后患者回盲部肠黏膜,应用甲苯胺蓝染色法观察MC数量,应用双抗体夹心法测定5-HT浓度。[结果]治疗组腹痛视觉模拟评分、大便次数及大便性状评分治疗14d及28d均优于治疗前,差异有统计学意义(P0.01)。各症状评分治疗组均不同程度优于对照组(P0.05,P0.01)。中药治疗组与西药对照组治疗前肠黏膜MC数量明显增加,5-HT浓度增高(P0.01),应用健脾调肝温肾方及匹维溴铵治疗可以明显减少MC表达数目,降低5-HT浓度(P0.05,P0.01),其中健脾调肝温肾方治疗组优于匹维溴铵治疗组(P0.05)。[结论]健脾调肝温肾方可有效控制D-IBS患者的腹痛、腹泻症状,并随着疗程的延长中药的优势更明显。健脾调肝温肾方可能通过降低MC表达及活化,减少5-HT释放,调控神经介质和免疫细胞关系而改善IBS内脏高敏性,减轻或缓解临床症状。     

肠易激综合征患者内脏高敏感机制的实验研究

目的:研究肠易激综合征(IBS)患者肠黏膜肥大细胞 (MC)与神经肽免疫反应阳性纤维有无变化及其在IBS中的可能作用和临床意义。方法:黏膜标本取自19例正常人、22例腹泻型IBS患者和20例便秘型IBS患者的回肠末端、回盲部、升结肠、乙状结肠,应用特殊组化染色法(甲苯胺蓝改良染色法)和免疫组化染色法分别对MC和神经肽免疫反应纤维进行染色,并应用彩色病理图像分析软件及免疫组化分析软件进行分析。在回盲部和乙状结肠各加取2块黏膜标本,     

匹维溴铵治疗腹泻型肠易激综合征的临床观察

目的 观察匹维溴铵对腹泻型肠易综合征(IBS)的治疗效果.方法 95例腹泻型肠易激综合征患者接受匹维溴铵治疗2周,观察患者治疗前后腹痛、腹胀、腹泻、大便形态、生活质量改善以及药物副反应.结果 接受匹维溴铵治疗2周后,腹泻型lBS患者腹痛、腹胀和腹泻症状评分均较治疗前显著降低(P＜0.05),大便性状评分较治疗前下降(P＜0.05),生活质量评分较治疗前提高(P＜0.05).但在停药结束后4周上述指标评分较治疗前无明显差异(P＞0.05).结论 匹维溴铵可有效缓解腹泻型lBS患者的临床症状,但治疗疗程值得进一步研究.     

The Mitochondrial Permeability Transition: Role in Ischemia/Reperfusion Injury

The mitochondrial permeability transition (MPT) occurs when a non-specific pore opens in the inner mitochondrial membrane and converts the mitochondrion from an organelle whose ATP production sustains the normal function of the cell to an instrument of death. Conditions favouring the MPT including high [Ca2+], oxidative stress and adenine nucleotide depletion, all of which occur when a tissue is reperfused following a period of ischemia. Cyclosporin A (CsA) and low pH (<7.0) are potent inhibitors of the MPT. Methods have been devised to demonstrate directly that the MPT pores open upon reperfusion but not during ischemia. The mechanism of the MPT appears to involve binding of mitochondrial cyclophilin (CyP) to the adenine nucleotide translocase (ANT) followed by a calcium-mediated conformational change that converts the ANT into a non-specific pore. Understanding the molecular mechanism has assisted in devising strategies that can be used to protect tissues from damage caused by reperfusion injury. These might also be of benefit in the prevention of multiple organ failure for which reperfusion injury of the gut is thought to be the initial trigger. Protective regimes include the pretreatment of tissues prior to ischemia/reperfusion with CsA (binds to CyP), free radical scavengers that reduce oxidative stress (e.g., pyruvate and propofol) and agents that decrease pHi (e.g., pyruvate or amelioride derivatives). Reperfusion injury can produce both immediate cell death by necrosis or delayed apoptotic cell death and it appears that the mitochondria determine which route is taken. Prolonged opening leads to rapid cell death by necrosis, whilst transient opening leads to cytochrome c release and subsequent apoptosis hours or days later.     

The hypothalamic-pituitary-thyroid axis in critical illness

In severe illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. The observed decrease in serum concentration of both thyroid hormones and thyrotropin (TSH) are not compatible with a negative feedback loop and suggest a major change in setpoint regulation of the hypothalamic-pituitary-thyroid axis. This is supported by post mortem studies showing a decreased expression of thyrotropin-releasing hormone in the hypothalamic paraventricular nucleus of patients with a decreased serum T3 level. In critical illness, serum T3 may even become undetectable without giving rise to an elevated concentration of serum TSH. It is currently not clearly established whether this reflects an adaptation of the organism to illness or instead a potentially harmful condition leading to hypothyroidism at tissue level. There is thus a need for randomized clinical trials in critically ill patients to investigate whether they may benefit from a normalization of thyroid hormone concentration. Recent clinical studies in these patients involving the administration of hypothalamic peptides open up new ways of achieving this.     

Palliative management of refractory dyspnea in COPD

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics.     

Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice

Abstract

Dimethyl trisulfide (DMTS) is a natural organic trisulfide that has been patented as a promising antidotal candidate against cyanide (CN). The primary mode of action of DMTS is as a sulfur donor that enables the conversion of CN to thiocyanate. Recently, it was discovered that DMTS is capable of oxidizing hemoglobin (Hb) to methemoglobin (MetHb) in vitro. The goal of these experiments was to measure the extent of DMTS-induced MetHb formation in vivo. In these experiments, intramuscular (IM) injections of formulated DMTS were administered to mice. Following the IM injection, blood was drawn and analyzed for MetHb using a rapid spectrophotometric method. Methemoglobin levels peaked in a dose-dependent manner between 20 and 30?min., and then began dropping. The highest MetHb levels measured for the 50, 100, 200 and 250?mg/kg doses of DMTS were respectively 3.28, 6.12, 9.69, and 10.76% MetHb. These experiments provide the first experimental evidence that IM administered DMTS generates MetHb in vivo and provide additional evidence for the presence of a secondary therapeutic pathway for DMTS - CN scavenging by DMTS-generated MetHb.     

Relevance of Endocavitary Structures in Ablation Procedures for Ventricular Tachycardia

Endocavitary Structures and Ventricular Tachycardia Ablation. Background: Radiofrequency (RF) ablation for ventricular tachycardia (VT) has high failure rates. Whether endocavitary structures (ECS) such as the papillary muscles (PMs), moderator bands (MBs), or false tendons (FTs) impact VT ablation is unknown. Methods and Results: We retrospectively reviewed records of 190 consecutive patients presenting for VT ablation and identified 46 (24%) where ECS affected ablation. In 31 of 46 patients (67%), the ECS created difficulty with catheter manipulation (n = 20), interpretation of pace map data (n = 7), or with accurately defining a scar (n = 4). In 15 of 46 (33%), specific mapping and RF energy delivery targeting the ECS itself was necessary to eliminate the arrhythmia. Detailed electroanatomic mapping was performed in 11 of 15 (73%), noncontact mapping in 3 of 15 (20%), multielectrode catheter mapping in 1 of 15 (7%), and intracardiac ultrasound in 14 of 15 (93%) patients. The ablated ECS was a PM in 5 of 15, the MB in 7 of 15, and an FT in 3 of 15. The arrhythmogenic substrate on the ECS was a focus of automatic tachycardia in 9 of 15 and the slow zone responsible for reentrant arrhythmia in the remaining 6 of 15. Successful elimination of tachycardia without recurrence was obtained in all 15 cases. There was no evidence of valvular damage or disruption of the valvular apparatus. Conclusion: During VT ablation procedures, ECS should be considered for specific mapping and targeted ablation. Once recognized, these structures can be successfully targeted for ablation without valve damage. (J Cardiovasc Electrophysiol, Vol. 21, pp. 245–254, March 2010)     

Unchanged mortality in patients with acute cholangitis despite an increase in malignant etiologies – a 25-year epidemiological study

Background and aims: Acute cholangitis (AC) is a rare but serious condition, with an incidence of 7.0 per 10,000 people and mortality rates up to 10%. The aim of this study was to describe changes in obstruction etiology, comorbidities, clinical factors, and mortality among AC patients during a 25-year period.

Methods: Using a database of 11,563 consecutive ERCP-procedures performed from 1990–2015 at Odense University Hospital, we identified all AC cases during that period. Clinical and epidemiological data were collected from the database and the Danish Patient Registry. Association with 30-day mortality was investigated using multiple logistic regression analysis with adjustment for confounding factors.

Results: In total, 775 consecutive and individual cases of AC were included. Among cases, 42% (n?=?326) were of malignant etiology, with an increasing incidence over time (regression coefficient [95% CI]: 0.03 [0.01–0.04] per year; p?=?.01). Mean Charlson Comorbidity Index was 1.4, with an increase over time (regression coefficient [95% CI]: 0.04 [0.03–0.05] per year; p?<?.01). Malignant obstruction etiology was associated with 30-day mortality (OR [95% CI]: 1.11 [1.04–1.18]; p?<?.01). Overall 30-day mortality was 12% (n?=?91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time (OR [95% CI]: 1 [1–1.00]; p?=?.91 per year).

Conclusion: Significant increases in the incidence of malignant obstruction etiology and severity of comorbidities among AC patients were observed during the study period. Despite those findings, 30-day mortality remained unchanged, potentially reflecting a general improvement in the management of AC.     

脂蛋白(a)与动脉粥样硬化研究进展

脂蛋白(a)由低密度脂蛋白和载脂蛋白(a)组成.高血浆脂蛋白(a)水平是动脉粥样硬化和心血管疾病的独立危险因素.脂蛋白(a)不但能参与动脉粥样硬化斑块的形成,还能影响抗炎机制和血管壁中促凝与抗凝因子的平衡.血浆脂蛋白(a)水平的个体差异很大,主要受遗传因素控制.血浆脂蛋白(a)水平对药理和非药理因素都不敏感,临床上缺乏高效安全降低脂蛋白(a)水平的治疗方法.近年,科研工作者发现反义寡核苷酸链和人工合成的肽链等可以降低脂蛋白(a)水平,但用于临床治疗还需进一步研究.本文拟对近年来脂蛋白(a)与动脉粥样硬化研究的新进展进行综述.     

Expression of membrane-type matrix metalloproteinases in synovial tissue from patients with rheumatoid arthritis or osteoarthritis

We investigated the expression of membrane-type matrix metalloproteinase (MT-MMP) and matrix metalloproteinase (MMP) mRNAs in synovial tissue from patients with rheumatoid arthritis (RA, n = 5) or osteoarthritis (OA, n = 5) by Northern blot analysis. Northern analysis demonstrated strong expression of MT1-MMP, MT3-MMP, MMP-1, and MMP-3 and weak expression of MT2-MMP and MMP-8 in synovial tissue from patients with RA or OA. MT4-MMP was not detected. No significant difference was shown in the expression of MT-MMP mRNAs between RA and OA. Synovial tissue of RA or OA patients expressed MT-MMPs as well as MMPs. These results indicate that, in addition to MMPs, MT1-MMP, MT3-MMP, and probably MT2-MMP may play a role in the degradation of bone and cartilage matrix in RA and OA. Such information may provide a clue to the development of a novel therapeutic approach targeted on the prevention of joint destruction. Received: April 30, 2000 / Accepted: September 19, 2000     

Management of diabetes mellitus in dialysis patients: Obstacles and challenges

Background and aimsDiabetic kidney disease (DKD) is a major health issue that is associated with an increased risk of morbidity and mortality. The treatment of DKD is challenging given changes in blood glucose homeostasis, unclear accuracy of glucose metrics, and altered kinetics of the blood glucose-lowering medications. There is uncertainty surrounding the optimal glycemic target in this population although recent epidemiologic data suggest that HbA1c ranges of 6–8%, as well as 7–9%, are associated with increased survival rates among diabetic dialysis patients. Furthermore, the treatment of diabetes in patients maintained on dialysis is challenging, and many blood glucose-lowering medications are renally metabolized and excreted hence requiring dose adjustment or avoidance in dialysis patients.Methodology: PubMed, Google Scholar, and Medline were searched for all literature discussing the management of diabetes in dialysis patients.ResultsThe literature was discussed under many subheadings providing the latest evidence in the treatment of diabetes in dialysis patients.ConclusionThe management of diabetes in dialysis is very complex requiring a multi-disciplinary team involving endocrinologists and nephrologists to achieve targets and reduce morbidity and mortality.     

Mycobacterium tuberculosis infection in systemic lupus erythematosus patients

Aim of the work

To estimate prevalence of tuberculosis (TB) infection in systemic lupus erythematosus (SLE) patients; to study its relation to disease duration, activity, damage and treatment as well as to compare the performance of interferon gamma (IFN-γ) release assay and tuberculin skin test (TST) in detection of TB infection.