Measuring colonic transit time in chronic idiophatic constipation.

INTRODUCTION AND OBJECTIVES: Colonic transit time can define three types of delay: right colon (colonic inertial), left colon and recto sigmoid. The aim of this study is to compare clinic characteristics and manometric results among the different groups with segmental colonic transit disorder. PATIENTS AND METHODS: 61 subjects were included in our study (5 men and 56 women) with and average age of 47.5 years (range: 17-84 years). We carried our a study of segmental and total colonic transit time, with the use of radio-opaque markers and sequential abdominal X-rays. We considered that transit time was prolonged when it was longer than 72 hours, and segmental transit time, when right colon was longer than 22 hours, left colon 37.2 hours and recto-sigmoid 37.2 hours. We included different clinic data: age, sex, place of residence stool frequency, abdominal pain, painful evacuation, incomplete evacuation, evacuation desire, dietary fibre intake, use of laxatives. We practised anorectal manometry in 20 patients. RESULTS: The average total colonic transit time was 38.2 hours in normal transit and 103 hours with disorder. The frequency in the three colonic segments, when there was a long total colonic transit time, was: 40% in the left colon, 33% in the recto-sigmoid and 27% in the right colon. We analysed the clinical characteristics of these three groups, finding more frequency of painful evacuation and defecation desire and lower dietary fibre intake in recto sigmoid. The most important abnormality in anorectal manometry was the hiposensitivity in the anorectal area, that only appeared in subjects with long segmental transit time in the right colon (colonic inertia), statistically significant. CONCLUSIONS: The measurement of colonic transit time with radio-opaque markers is a simple technique that allows for the objective detection of the different groups of patients with chronic idiopathic constipation. The exact typification of the abnormality is important for the individualization of each treatment.     

Remote Monitoring of Implantable Cardioverter Defibrillators versus Quarterly Device Interrogations in Clinic: Results from a Randomized Pilot Clinical Trial

ICD: Remote Monitoring Versus Clinic Interrogations . Introduction: Remote monitoring is increasingly becoming the new standard of care for implantable cardioverter defibrillator (ICD) follow‐up. We sought to determine whether remote monitoring of ICDs improves patient outcomes compared with quarterly device interrogations in clinic. Methods and Results: In this single‐center pilot clinical trial, adult patients with an ICD were randomly assigned to remote monitoring versus quarterly device interrogations in clinic. The primary endpoint was a composite of cardiovascular hospitalization, emergency room visit for a cardiac cause, and unscheduled visit to the electrophysiology clinic for a device‐related issue at 1 year. We also examined health‐related quality of life, costs, and patient satisfaction with their ICD care. Of 151 patients enrolled in this trial, 76 were randomized to remote monitoring and 75 to quarterly device interrogations in clinic. There was no significant difference in the primary endpoint (32% in the remote monitoring arm vs 34% in the control arm; P = 0.8), mortality, or cost between the 2 arms. Quality of life and patient satisfaction were significantly better in the control arm than in the remote monitoring arm at 6 months (83 [25th, 75th percentiles 70, 90] vs 75 [50, 85]; P = 0.002 and 88 [75, 100] vs 75 [75, 88]; P = 0.03, respectively), but not at 12 months. Conclusion: We showed no significant reduction in cardiac‐related resource utilization with remote monitoring of ICDs. However, given the small number of patients in our study, the real clinical and health economics impact of remote monitoring needs to be verified by a large, multicenter, randomized clinical trial. (J Cardiovasc Electrophysiol, Vol. 21, pp. 545‐550, May 2010)     

Responsiveness to thyroid hormone and to ambient temperature underlies differences between brown adipose tissue and skeletal muscle thermogenesis in a mouse model of diet-induced obesity

Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism.     

Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34(+) progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity.     

Third-line rescue therapy with levofloxacin after two H. pylori treatment failures

AIM: Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin fails in a considerable number of cases. A rescue therapy still fails in more than 20% of the cases. Our aim was to evaluate the efficacy and tolerability of a third-line levofloxacin-based regimen in patients with two consecutive Helicobacter pylori eradication failures. METHODS: Design: Prospective multicenter study. Patients: In whom a first treatment with omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed. Intervention: A third eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. Outcome: Eradication was confirmed with 13C-urea breath test 4-8 wk after therapy. RESULTS: One-hundred patients were initially included, and nine were lost for follow-up. All patients but five took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 66% (95% CI = 56-75%) and 60% (50-70%). Adverse effects were reported in 25% of the patients, mainly including metallic taste (8%), nausea (8%), myalgia/arthralgia (5%), and diarrhea (4%); none of them were severe. CONCLUSION: Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, and tetracycline.     

一氧化氮代谢物的测定及其与病毒性肝炎若干相关因素的分析

测定了423例各型肝炎、肝炎后肝硬化患者一氧化氮代谢物NO2-／NO3-的值，并与42例正常人作对照，结果肝硬化组NO2-/NO3-值高于对照组及其他各型肝炎组（P＜0．01）。肝硬化NO2-／NO3-的升高与血浆白蛋白（ALB）呈负相关，与腹水量呈正相关，与门脉宽度呈正相关．而与TBA、SB、ALT、AST、凝血酶原活动度等无相关性。提示一氧化氮可能在高动力循环、腹水生成、白蛋白合成方面起重要作用。     

雷帕霉素-替罗非班复合药物涂层支架的血液及组织相容性

目的:观察雷帕霉素-替罗非班复合药物涂层支架置入后再狭窄、血栓、生化指标和重要器官组织病理学变化情况,评估其血液及组织相容性。方法:实验于2005-03/11在解放军第四军医大学实验外科实验室完成。以聚合高分子材料为药物载体,采用微喷法制备雷帕霉素支架及雷帕霉素-替罗非班复合药物涂层支架。实验分组:8只小型猪按随机数字表法分为两组,复合药物组和雷帕霉素组,每组4只。复合药物组应用雷帕霉素-替罗非班复合药物涂层支架,雷帕霉素组应用雷帕霉素支架。再狭窄模型采用国际公认的小型猪冠状动脉过度扩张再狭窄模型。每只猪于冠状动脉中成功置入上述支架各2枚。术后两组小型猪服用硫酸氯吡格雷75mg/d抗血小板治疗,雷帕霉素组服用3个月,复合药物组服用1个月。实验评估:①观察术后动物行为状态。②支架置入术前、术后2,7d,4,12周分析全血细胞计数、生化指标。③麻醉后处死动物,取出支架置入段血管,行组织病理学观察,计算管腔面积丢失率。管腔面积丢失率(%)=(支架围绕面积-管腔面积)/支架围绕面积×100%。④取肺、肝、肾组织及支架血管段供血的心室壁行组织学观察。结果:8只小型猪均进入结果分析。①术后动物行为学观察:两组术前、术中及术后3个月造影时,动物心率、血压、体质量的变化差异无显著性意义,术后也无明显行为异常及饮食、排尿便异常。②血细胞计数和生化检测结果:复合药物组、雷帕霉素组术后2d白细胞计数均高于术前[分别为(13.1±2.8)×109,(7.2±2.1)×109L-1;(12.5±3.3)×109,(6.3±2.2)×109L-1],差异有显著性意义(t=3.37,3.08,P<0.05);其余各时段两组外周全血红细胞、白细胞、血小板计数差异无显著性意义(P>0.05)。γ-血清谷丙转氨酶、谷氨酰转肽酶及肌酐、尿素氮未见明显改变(P>0.05)。③血管组织病理学检测:两组血管均未见附壁血栓。复合药物组血管腔面积、新生内膜面积高于雷帕霉素组[分别为(4.96±0.35),(4.89±0.46)mm2;(1.12±0.10),(1.05±0.09)mm2],管腔面积丢失率低于雷帕霉素组[(19±9)%,(21±7)%],差异均无显著性意义(P>0.05)。④重要脏器大体形态及病理学检查:证实细胞形态结构正常,无炎性细胞浸泡、出血和坏死。结论:雷帕霉素-替罗非班复合药物涂层支架置入小型猪冠状动脉后3个月的血液相容性及组织相容性良好,并可减少术后抗血小板药物的全身用药量。     

Menstrual tension-type headache: evidence for its existence

OBJECTIVE: To determine whether menstrual tension-type headache is a real disorder. BACKGROUND: An appendix was included in the second edition of the International Classification of Headache Disorders by the International Headache Society. Diagnostic criteria are proposed in this appendix for 2 types of menstrual migraine: pure menstrual migraine without aura and menstrually related migraine without aura. References to menstrual tension-type headache do not appear in this classification. METHODS: In a neurological outpatient clinic 165 patients were identified in whom headache was related to menstruation and the criteria of the International Classification of Headache Disorders for menstrual migraine adapted to menstrual tension-type headache were applied. RESULTS: Twenty-one patients met the criteria of menstrual tension-type headache, 6 for pure menstrual tension-type headache, and 15 for menstrually related tension-type headache. CONCLUSION: Menstrual tension-type headache is a real condition that should be recognized in the International Classification of Headache Disorders.     

Lactobacillus fermentum, a probiotic capable to release glutathione, prevents colonic inflammation in the TNBS model of rat colitis

Background and aims Inflammatory bowel disease is associated with intestinal oxidative stress. In the present study we test the preventative effect of Lactobacillus fermentum, a probiotic that produces per se glutathione, in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis.Methods Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0.25 ml of 50% ethanol. L. fermentum was administered orally (5×10⁸ CFU suspended in 0.5 ml of skim milk) to a group of rats for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated both histologically and biochemically, and the colonic luminal contents were used for bacterial studies as well as for short chain fatty acid (SCFA) production.Results L. fermentum treatment resulted in an amelioration of the inflammatory response in colitic rats as evidenced histologically and by a significant reduction of colonic MPO activity (P<0.05). The probiotic partially counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, probiotic-treated colitic rats showed significant lower colonic tumour necrosis factor (TNF)α levels (P<0.01) and inducible nitric oxide synthase (iNOS) expression when compared to non-treated rats. Finally, the probiotic induced growth of Lactobacilli species and production of SCFA in colonic contents in comparison with control colitic rats.Conclusion Administration of the probiotic L. fermentum facilitates the recovery of the inflamed tissue in the TNBS model of rat colitis, an effect associated with increased levels of glutathione as well as with amelioration of the production of some of the mediators involved in the inflammatory response of the intestine, such as TNFα and NO.