Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues

We report that the disruption of bidirectional signaling between ephrin-B2 and EphB receptors impairs morphogenetic cell–cell septation and closure events during development of the embryonic midline. A novel role for reverse signaling is identified in tracheoesophageal foregut septation, as animals lacking the cytoplasmic domain of ephrin-B2 present with laryngotracheoesophageal cleft (LTEC), while both EphB2/EphB3 forward signaling and ephrin-B2 reverse signaling are shown to be required for midline fusion of the palate. In a third midline event, EphB2/EphB3 are shown to mediate ventral abdominal wall closure by acting principally as ligands to stimulate ephrin-B reverse signaling. Analysis of new ephrin-B2^6YFΔV and ephrin-B2^ΔV mutants that specifically ablate ephrin-B2 tyrosine phosphorylation- and/or PDZ domain-mediated signaling indicates there are at least two distinct phosphorylation-independent components of reverse signaling. These involve both PDZ domain interactions and a non-canonical SH2/PDZ-independent form of reverse signaling that may utilize associations with claudin family tetraspan molecules, as EphB2 and activated ephrin-B2 molecules are specifically co-localized with claudins in epithelia at the point of septation. Finally, the developmental phenotypes described here mirror common human midline birth defects found with the VACTERL association, suggesting a molecular link to bidirectional signaling through B-subclass Ephs and ephrins.     

Prevalence of drug-resistant microbes in sepsis cases of catheter and fistula based haemodialysis

BackgroundChronic stage renal disease is a severe disease of the kidney which affects people globally. According to the global burden of diseases in 2010, this disease has caused more deaths worldwide and due to the high death rate, the ESRD (end-stage renal disease) is now ranked up from 27th to 18th range in the list.MethodologyDialysis samples were collected from the Haripur city and surrounding areas. Samples were inoculated on different selective media for bacterial growth. In addition, different biochemical tests were also performed for identification, where as the resistance genes were identified through a polymerase chain reaction.ResultOut of the total 100 dialysis patient’s blood samples, only 17 showed the presence of gram-positive bacteria i.e., Staphylococcus aureus while two shown the presence of gram-negative bacteria i.e., Klebsiella pneumoniaeee and Pseudomonas aeruginosa. While in molecular identification two antibiotic resistance genes muc and mecA belong to the staphylococcus strain shown their presence.ConclusionA high infection rate has been observed in fistula-based hemodialysis (17(77.27%)) as compares to catheter-based hemodialysis (5(22.3%) with no significant difference of incidence between the groups (p > 0.05).     

犬获得性食管气管瘘模型建立及食管双瓣修补术实验研究

目的:1.建立犬食管气管瘘动物模型;2.观察食管壁双瓣修补气管缺损术局部组织病理学改变、愈合情况及该术式的治疗效果。方法:犬16只,随机分为2组,实验组(12只)建立犬食管气管瘘动物模型,行食管壁双瓣修补气管缺损术,对照组(4只)正常犬作为空白对照,术后支气管镜检查,术后1,2,8周处死动物,观察实验动物一般情况、修补局部的大体改变和组织病理学改变,测定气管狭窄指数。结果:成功建立了犬食管气管瘘动物模型;食管双瓣修补术后,实验组动物呛咳症状消失,均存活至预定时间,修补瓣和气管之间愈合良好,修补瓣血供良好,未出现气管狭窄情况,气管通畅度良好。结论:通过手术方式建立食管气管瘘模型方法可靠;食管双瓣修补术治疗TEF效果良好,值得进一步研究及推广。     

Digestibility of carbohydrates in growing pigs: a comparison between the t-cannula and the steered ileo-caecal valve cannula

We compared the determination of ileal and total tract digestibility of carbohydrates in five experimental diets using a double 5?×?5 Latin square design involving a total of 10 cannulated pigs; half of the pigs were equipped with a simple T-cannula and the other half with steered ileo-caecal valve (SICV)-cannula. The diets consisted of nitrogen-free mixture and soya bean meal, sunflower meal, peas or rape seed cake diluted to about 180?g/kg DM protein with the nitrogen-free mixture. There was no significant difference in the digestibility values using the two types of cannulas with regard to organic matter, sugars (sum of glucose, fructose and sucrose), α-galactosides (sum of raffinose, stachyose and verbascose), starch, cellulose, total non-cellulosic polysaccharides (NCP) and insoluble NCP constituents. The digestibility values for the NCP residues arabinose and galactose, however, were estimated higher but with a lower variability with the SICV-cannula compared with the T-cannula. The type of cannula did no influence the estimation of the total tract digestibility for any of the major dietary constituents, but the total tract digestibility was slightly more variable when the pigs were equipped with the SICV-cannula compared with the T-cannula. There was no difference in the ileal digestibility of sugars, α-galactosides, cellulose and the NCP arabinose and uronic acids residues among the experimental diets, while the ileal digestibility of starch and the remaining NCP sugar residues varied between diets. The total tract digestibility was complete for sugars, α-galactosides and starch, whereas the digestibility of the cell wall constituents varied in accordance with the polymeric composition of the cell walls. It was concluded that ileal digesta samples from SICV-cannula are more homogenous than those from the T-cannula. In cases where the precision of each determination is crucial, the SICV-cannula should be the option.     

Vacuum Effects over the Closing of Enterocutaneous Fistulae: A Mathematical Modeling Approach

Enterocutaneous fistulae are pathological communications between the intestinal lumen and the abdominal skin. Under surgery the mortality of this pathology is very high, therefore a vacuum applying system has been carried previously on attempting to close these fistulae. The objective of this article is the understanding of how these treatments might work through deterministic mathematical modelling. Four models are here proposed based on several assumptions involving: the conservation of the flow in the fistula, a low enough Reynolds number justifying a laminar flow, the use of Poiseuille law to model the movement of the fistulous liquid, as well as phenomenological equations including the fistula tissue and intermediate chamber compressibility. Interestingly, the four models show fistulae closing behaviour during experimental time (t<60 sec). To compare the models, both, simulations and pressure measurements, carried out on the vacuum connected to the patients, are performed. Time course of pressure are then simulated (from each model) and fitted to the experimental data. The model which best describes actual measurements shows exponential pumping flux kinetics. Applying this model, numerical relationship between the fistula compressibility and closure time is presented. The models here developed would contribute to clarify the treatment mechanism and, eventually, improve the fistulae treatment.     

自膨式食管金属加膜支架治疗恶性食管狭窄和气管食管瘘

目的：探讨自膨式食管金属加膜支架治疗恶性食管狭窄和气管食管瘘的疗效和并发症。方法：2004年1月至2009年6月对63例恶性食管狭窄和气管食管瘘患者实施食管支架置入,男45例,女28例;年龄45～81岁,平均69.3岁。支架为MTN型形状记忆钛镍合金食管加膜支架（南京微创医学科技有限公司生产）,支架植入均在DSA监视下操作完成。结果：63例均一次性放置成功,即刻口服造影通过顺利剂。结论：自膨式食管金属加膜支架是治疗恶性食管狭窄和气管食管瘘的有效方法。     

自膨式食管金属加膜支架治疗恶性食管狭窄和气管食管瘘

目的:探讨自膨式食管金属加膜支架治疗恶性食管狭窄和气管食管瘘的疗效和并发症。方法:2004年1月至2009年6月对63例恶性食管狭窄和气管食管瘘患者实施食管支架置入,男45例,女28例;年龄45～81岁,平均69.3岁。支架为MTN型形状记忆钛镍合金食管加膜支架(南京微创医学科技有限公司生产),支架植入均在DSA监视下操作完成。结果:63例均一次性放置成功,即刻口服造影通过顺利剂。结论:自膨式食管金属加膜支架是治疗恶性食管狭窄和气管食管瘘的有效方法。     

18 例维吾尔族膀胱阴道瘘临床分析

目的:探讨维吾尔族膀胱阴道瘘的病因、诊断及治疗措施。方法:对2006年6月～2011年6月新疆自治区人民医院泌尿外科经美兰试验和膀胱镜检查确诊的18例维吾尔族膀胱阴道瘘患者的病历资料进行回顾性的临床分析。17例患者行瘘修补术,其中12例(70.59%)经腹修补,5例(29.41%)经阴道修补。1例患者行双侧输尿管经皮造瘘术。结果:18例患者中,16例1次修补成功,1例2次修补后成功。术后随访1至12个月无复发。结论:阴道分娩难产在维吾尔族膀胱阴道瘘患者中最为多见,根据患者全身情况、瘘道大小及位置选择合适的手术路径,术前充分准备,术后严格管理,大大提高手术成功率。     

HLA-DRB1 * 03, but not the TNFA -308 promoter gene polymorphism, confers protection against fistulising Crohn’s disease

 Crohn’s disease (CD) appears in forms so diverse that it has been hypothesized CD might be a syndrome, with different pathogenic mechanisms leading to the various clinical phenotypes. This may plausibly explain the conflicting and inconclusive results with regard to HLA associations in unselected groups of patients. The power of these association studies may increase when disease heterogeneity is taken into account. As fistulising CD has been proposed as a separate subgroup of patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in 35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A striking decrease in the frequency of the DRB1 ^* 03 allele was found in those patients with peri-anal fistulas when compared with a panel of 2400 healthy controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1 ^* 03 allele is in strong linkage disequilibrium with a polymorphism at position –308 in the promoter region of the gene encoding TNFα (TNFA-308 ^* 2). We investigated whether this allele frequency was decreased as well. Surprisingly, the CF of TNFA-308 ^* 2 was 29%, not different from the CF of 98 HC (34%; P = 0.7; OR = 0.8). This study is the first showing a significant negative association between DRB1 ^* 03 and a particular subgroup of CD patients. Thus, patient selection may largely determine the outcome of genetic association studies in CD, as we previously observed no association with this allele in an unselected population of CD patients. As DRB1 ^* 03 frequency, but not the closely linked TNFA-308 ^* 2, was decreased, this suggests recombination between the DRB1 and TNFA loci in this group of patients, and may help to define the biological basis of fistula formation. Received: 29 September 1997 / Revised: 3 December 1997     

先天性耳前瘘管二次手术68 例治疗体会

目的:探讨先天性耳前瘘管术后复发原因,以及二次手术临床治疗的效果。方法:回顾性分析我院自2006年1月至2010年12月的共诊断收治的68例复发先天性耳前瘘管病例,观察其二次手术效果。结果:68例先天性耳前瘘管复发患者中,66例Ⅰ期愈合,治愈率97.06%。结论:再次手术是治疗先天性耳前瘘管术后复发的有效途径,完全切除残余的瘘管及上皮组织是防止再复发的关键。