Ischemia/reperfusion injury-mediated down-regulation of adenovirus-mediated gene expression in a rat heart transplantation model is inhibited by co-application of a TNFRp55-Ig chimeric construct

E1-deleted adenoviral vectors are efficient vectors for somatic gene therapy. Recently, we have shown that intratracheal application of an adenoviral reporter construct leads to significant reporter gene expression in rat lungs within 24 h. In contrast, reporter gene expression in syngeneic rat heart transplants after adenovirus-mediated gene transfer was delayed. Since the adenovirus cannot replicate, down-regulation of the hCMV-IE promoter controlled reporter gene expression in initially infected cells by cytokines, which are released as a result of ischemia/reperfusion injury, might be involved. In order to investigate the role of proinflammatory cytokines, eg TNF-alpha in affecting hCMV-IE promoter-driven reporter gene expression, transient blockade of TNF-alpha was achieved by local co-application of an Ad-construct encoding for a soluble TNFRp55-Ig chimeric molecule in a syngeneic rat heart transplantation model. Co-application of the reporter construct together with the TNFRp55-Ig chimeric molecule significantly increased the early reporter gene expression after transplantation. Moreover, infiltration of inflammatory cells (T cells, macrophages, NK cells) and production of TNF-alpha in the transplant was markedly reduced. Our results indicate that: (1) proinflammatory cytokines are involved in down-regulation of reporter gene expression in ischemia/reperfusion injured tissues; and (2) inhibition of TNF-alpha might be a useful tool to increase early gene expression in gene therapy protocols, particularly in transplantation. Gene Therapy (2000) 7, 1238-1243.     

Extensively drug‐resistant tuberculosis (XDR‐TB) among health care workers in South Africa

Objective To determine the clinical profile and outcomes of health care workers (HCWs) with extensively drug resistant tuberculosis (XDR‐TB) in the Eastern and Western Cape Provinces of South Africa. Method Retrospective case record review of 334 patients with XDR‐TB reported during the period 1996–2008 from Western and Eastern Cape Province, Cape Town, South Africa. Case records of HCWs with XDR‐TB were analysed for clinical and microbiological features, and treatment outcomes. Results From 334 case records of patients with XDR‐TB, 10 HCWs were identified. Eight of ten were HIV‐uninfected, and four of 10 had died of XDR‐TB despite treatment. All 10 HCWs had received an average of 2.4 courses of TB treatment before being diagnosed as XDR‐TB. Conclusions In the Eastern and Western Cape provinces of South Africa XDR‐TB affects HCWs, is diagnosed rather late, does not appear to be related to HIV status and carries a high mortality. There is an urgent need for the South African government to implement WHO infection control recommendations and make available rapid drug susceptibility testing for HCWs with suspected multidrug‐resistant (MDR)/XDR‐TB. Further studies to establish the actual risk and sources of infection (nosocomial or community) are required.     

Tooth autotransplantation with 3D-printed replicas as part of interdisciplinary management of children and adolescents: Two case reports

The management of missing teeth as a result of dental trauma or associated with hypodontia in children and adolescents presents as a clinical challenge for the dental team. One of the options that is regaining popularity is dental autotransplantation. To improve autotransplantation outcomes, careful interdisciplinary planning, surgical simulation using cone beam computed tomography images and three-dimensional-printed teeth replicas should be undertaken for presurgical preparation. This case report showcases two applications of autotransplantation, with emphasis on interdisciplinary management, presurgical preparation and postsurgical orthodontic and aesthetic management to deliver a good long-term, sustainable, biological outcome, as a part of a comprehensive rehabilitation treatment plan in children.     

Elective coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy.

The management of patients anticoagulated with warfarin and referred for coronary angiography presents a substantial challenge to the physician who must minimize risks of periprocedural hemorrhage and thromboembolism. The aim of this study was to evaluate the feasibility and safety of performing diagnostic coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Patients treated with warfarin were prospectively identified and enrolled in the study. Nineteen diagnostic cardiac catheterizations and six percutaneous coronary interventions were performed in 23 patients. The mean international normalized ratio was 2.4 +/- 0.5 (range, 1.8-3.5). Hemostasis was achieved with AngioSeal following 21 procedures and with Perclose following 4 procedures. No patient experienced a predefined endpoint. Specifically, no patient experienced procedure-related myocardial infarction, major or minor bleeding. We conclude that cardiac catheterization and percutaneous coronary intervention may be considered in the setting of uninterrupted warfarin therapy.     

Transvaginal cholecystectomy without laparoscopic support using prototype flexible endoscopic instruments in a porcine model

Background

Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. The next goal was to develop a natural orifice transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy without laparoscopic instruments using one flexible endoscope and flexible accessories. The aim of the study was to test the feasibility of the procedure in a survival porcine model.

Methods

Cholecystectomies were attempted in five 88–130-lb. pigs with a planned 2-week survival. Prototype flexible instruments (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access, dissection, and removal of the gallbladder via the transvaginal route.

Results

Cholecystectomy could be completed without abdominal incision using prototype instruments in four out of five pigs. The cystic duct could be exposed with a flexible hook knife and clips applied. The steerable trocar improved stability and the precision of the dissection. The critical view was established in all five pigs. Dissection of the gallbladder off the liver bed was imprecise resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At necropsy, all clips on the cystic duct were secure and no bile leak, bowel injury, or adhesions were present.

Conclusions

NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.     

Autonomic responses of paranoid, nonparanoid schizophrenic, and normal subjects to affective visual stimulation.

This investigation utilized a procedure designed to determine patterns of cognitive appraisal, and autonomic reactivity which characterize groups of normals, and paranoid and nonparanoid schizophrenics. Results indicated that both groups of schizophrenics evidenced electrodermal habituation and increased finger pulse constriction. Normals indicated that stress stimuli became less disturbing over trials and displayed both electrodermal and digital vasomotor habituation. Electrodermal habituation curves for paranoids and normals were similar, with nonparanoids evidencing slower habituation. Paranoids tended to under-rate or deny their emotional reactions.     

干、湿化学两检测系统4种生化分析仪检测结果的可比性评价

目的 通过对同一临床实验室两检测系统四种不同生化分析仪进行结果的检测,探讨不同生化分析仪之间检测结果是否具有可比性.方法 按照美国临床实验室标准化委员会(NCCLS)的EP9-A2文件要求,以OLYMPUS AU 5431全自动生化分析仪为比较方法(X),以OLYMPUS AU 5421全自动生化仪和强生VITROS ...