Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Enteral stenting versus gastrojejunostomy for palliation of malignant gastric outlet obstruction

Background and aims

Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes.

Patients and methods

This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy.

Results

120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p < 0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p = 0.79). Chemotherapy [adjusted hazard ratio (HR) 3 > 0.57, p = 0.04] and radiation therapy (adjusted HR 0.35, p = 0.03) were associated with significantly longer duration of oral intake after ES or GJ.

Conclusion

ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.     

Endoscopic stenting for benign upper gastrointestinal strictures and leaks

Background

Self-expandable metal stents (SEMS) and self-expandable plastic stents (SEPS) maybe used for the treatment of benign upper gastrointestinal (GI) leaks and strictures. This study reviewed our experience with stent insertions in patients with benign upper GI conditions.

Methods

Patients who underwent stent placement for benign upper GI strictures and leaks between March 2007 and April 2011 at a tertiary referral academic center were studied using an endoscopic database and electronic patient records. The technical success, complications, and clinical improvement after stent removal were compared according to type of stent. The outcomes measured were clinical response, adverse events, and predictors of stent migration.

Results

Thirty-eight patients (50 % male, mean age = 54 years, range = 12–82) underwent 121 endoscopic procedures. Twenty patients had stents placed for strictures, and 18 had stents placed for leaks. Stent placement was technically successful in all patients. The average duration of stent placement was 54 days (range = 18–118). Clinical improvement immediately after stent placement was seen in 29 of the 38 patients (76.3 %). Immediate post-procedure adverse events occurred in 8 patients. Late adverse events were seen in 18 patients. Evidence of stent migration occurred in 16 patients and was seen in 42 of the 118 successfully placed stents (35.5 %). Migration was more frequent with fully covered SEMS (p = 0.002). After stent removal, 27 patients were evaluable for long-term success (median follow-up time of 283 days, IQR 38–762). Resolution of strictures or leaks was seen in 11 patients (40.7 %). Predictors for long-term success included increasing age and if the stent did not cross the GE junction.

Conclusions

Placement of SEPS and SEMS for benign refractory strictures and fistulas has modest long-term clinical efficacy and is limited by a significant migration rate. Stent migration is common and frequent with fully covered SEMS compared to other types of stents, regardless of indication or location.     

乐脉颗粒促进鸡胚绒毛尿囊膜血管的生成

目的:乐脉颗粒在缺血性心脑血管病的治疗中具有较好的效果,其是否通过促进血管生成而发挥作用还不清楚。观察乐脉颗粒对鸡胚绒毛尿囊膜血管生成的影响。方法:实验于2005-03/08在江西省重点实验室南昌大学第二附属医院分子中心完成。①实验材料:新西兰大白兔8只,体质量2～2.5kg;新鲜白皮种蛋70只,质量50～60g。②实验方法:种蛋在(37.5±0.5)℃条件下孵育,种蛋受精率90%以上。第7天开窗暴露鸡胚绒毛尿囊膜建立鸡胚绒毛尿囊膜模型。将60枚存活鸡胚随机分为生理盐水组、正常血清组、乐脉血清组、内膜损伤血清组、内膜损伤乐脉治疗组以及血管内皮生长因子(20mg/L)组,每组10枚鸡胚。新西兰大白兔腹主动脉用球囊导管损伤建立血管内膜损伤模型,乐脉血清组及内膜损伤乐脉治疗组给予乐脉颗粒25mg/(kg·d)喂饲,各组7d后取血清。第8天,在鸡胚绒毛尿囊膜上放一直径为5mm的滤膜作为载体,分别加样5μL,1次/d,连续3d,③实验评估:第11天取鸡胚绒毛尿囊膜,数码相机拍照后平铺于载玻片上,计数载体周围血管数目及滤膜周围0.5cm范围内的血管分支点数并进行比较。结果:纳入大白兔8只,存活鸡胚60枚,均进入结果分析,无脱落。与正常血清组相比较,乐脉血清组鸡胚绒毛尿囊膜周围血管总数明显增多,血管以载体为中心呈辐辏状生长,差异具有显著性意义(P<0.05);与正常血清组相比较,内膜损伤血清组血清载体周围血管数量明显增多,差异具有极显著性意义(P<0.01);与内膜损伤乐脉治疗组相比较,血管总数差异无显著性。结论:①兔乐脉颗粒血清能够明显促进鸡胚绒毛尿囊膜上血管生成。②血管内膜损伤7d后的血清能够促进鸡胚绒毛尿囊膜上血管生成。     

激光小角光散射仪测定右旋糖酐分子量

激光小角光散射仪(LALLS)由于采用了激光光源,具有光强度高、单色性强、准直性好等特点,可以在微量样品池及很低浓度的溶液中进行小角度(3°～7°)散射光强的测量,溶质的瑞利系数与其分子量有如下关系:     

雪灵芝对二乙基亚硝胺诱导大鼠肝癌组织细胞的抑制作用

目的：验证雪灵芝是否具有抑制大鼠肝癌的功效。方法：实验于2003—09/2004—08在广西疾病预防控制中心SPF级动物实验室完成。选用健康成年SD大鼠160只。按体质量分层随机分为5组：空白对照组、模型组、雪灵芝高剂量组、雪灵芝中剂量组和雪灵芝低剂量组，每组32只。雪灵芝高、中、低剂量组大鼠分别灌胃2．500，1．250，0．625mL/kg雪灵芝溶液，阴性对照组和模型组灌胃等量蒸馏水，1次／d，连续60d。第61天开始雪灵芝高、中、低剂量组和模型组灌胃二乙基亚硝胺溶液，对照组灌胃等量的生理盐水。于停止灌胃90d后各组处死一半受试大鼠（雌雄各半），检测血常规及血清主要生化指标，观察各脏器大体形态改变、脏器的癌变程度。1周后给剩余大鼠灌胃雪灵芝溶液（不含二乙基亚硝胺）。7周后处死余下的一半雄性大鼠，进行相同操作。8周后处死余下的全部大鼠，操作及检测方法同前。结果：纳入的160只SD大鼠，145只进入结果分析，15只脱落。①病理切片检查结果：除阴性对照组，其他各组大鼠肝组织均发生癌变或癌前病变。雪灵芝高、中、低剂量组的癌前病变发生率与模型组相近（P〉0．05）；癌变的发生率均低于模型组，差异有显著性意义（P〈0．05，0．01）。②大体标本检查结果：阴性对照组大鼠肝脏的大体标本均无异常改变，其他各组大鼠的肝脏有些可见表面粗糙等病理改变。模型组大体标本病理改变的阳性率高于雪灵芝高、中、低剂量组，差异有显著性意义（P〈0．05）。肉眼观模型组癌变发生率高于其他各组。③其他脏器检查结果：模型组2只大鼠有肝癌肺转移。结论：以较大剂量的二乙基亚硝胺连续灌胃30d可以复制大鼠肝癌模型；雪灵芝对二乙基亚硝胺诱导的大鼠肝癌具有预防和抑制的作用。     

Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons

BACKGROUND: Recently, a short-course treatment using 60 daily doses of rifampin and pyrazinamide was recommended for latent tuberculosis (TB) infection (LTBI). STUDY OBJECTIVES: To determine the acceptability, tolerability, and completion of treatment. DESIGN: Observational cohort study. SETTING: Five county jails and TB outreach clinics for homeless populations in three cities. PATIENTS: Study staff enrolled 1,211 patients (844 inmates and 367 homeless persons). INTERVENTIONS: Sites used 60 daily doses of rifampin and pyrazinamide, an approved treatment regimen for LTBI. MEASUREMENTS: Types and frequency of drug-related adverse events and outcomes of treatment. RESULTS: Prior to treatment, 25 of 1,178 patients (2.1%) had a serum aminotransferase measurement at least 2.5 times the upper limit of normal. Patients who reported excess alcohol use in the past 12 months were more likely than other patients to have an elevated pretreatment serum aminotransferase level (odds ratio, 2.1; 95% confidence interval, 1.1 to 6.1; p = 0.03). Treatment was stopped in 66 of 162 patients (13.4%) who had a drug-related adverse event. Among 715 patients who had serum aminotransferase measured during treatment, 43 patients (6.0%) had an elevation > 5 times the upper limits of normal, including one patient who died of liver failure attributed to treatment. In multivariate analyses, increasing age, an abnormal baseline aspartate aminotransferase level, and unemployment within the past 24 months were independent risk factors for hepatotoxicity. Completion rates were similar in jail inmates (47.5%) and homeless persons (43.6%). CONCLUSIONS: This study detected the first treatment-associated fatality with the rifampin and pyrazinamide regimen, prompting surveillance that detected unacceptable levels of hepatotoxicity and retraction of recommendations for its routine use. Completion rates for LTBI treatment using a short-course regimen exceeds historical rates using isoniazid. Efforts to identify an effective short-course treatment for LTBI should be given a high priority.     

Comparison of phenolphthalein and phenolphthalein glucuronide on net water transport in rat ileum and colon

Phenolphthalein is an odorless, tasteless compound, poorly soluble in water, but readily soluble in alcohol or ether. Although its laxative activity was discovered in 1902, the mechanism of action remains unclear. Phenolphthalein has been found to be an ineffective laxative in both jaundiced patients and in experimental animals with ligated common bile ducts. In contrast to the poor solubility of phenolphthalein, phenolphthalein glucuronide is highly water-soluble. In addition, phenolphthalein glucuronide is found in bile following oral phenolphthalein administration, suggesting an enterohepatic circulation. We compared the effect of phenolphthalein and phenolphthalein glucuronide on net water absorption of the ileum and colon of Sprague-Dawley rats using a single-pass perfusion technique. Perfusion of phenolphthalein (10 mg/dl in 154 mM NaCl with 0.5% ethanol and 0.1 g/l gum arabic) resulted in significantly reduced water absorption in both the ileum and colon (66% and 64%, respectively, P less than 0.05). In contrast, phenolphthalein glucuronide did not have a significant effect on net water flux compared to control perfusion in either the ileum or colon. In the ileum only 77 +/- 3% and colon 71 +/- 1.2% of the phenolphthalein infused was recovered, suggesting that much of the infused phenolphthalein was absorbed. In contrast there was no evidence of absorption of phenolphthalein glucuronide, as 98.9 +/- 1.2% was recovered from ileal and colon perfusions. Phenolphthalein glucuronide is not the active form of phenolphthalein, although it may be an effective laxative after deconjugation by colonic bacteria.