Studies of sarcoplasmic reticulum function in rabbit and human left ventricular dysfunction

Heart Failure is a common clinical problem with high morbidity and mortality. While there are several pathological changes in cardiac failure, abnormalities of myocardial contraction at the cellular level are well documented. Myocyte Ca2+ handling which underlies excitation-contraction coupling is abnormal in heart failure and contributes to mechanical dysfunction. Changes in intracellular Ca2+ during contraction and relaxation are mediated by both sarcolemmal Ca2+ transport and sarcoplasmic reticulum (SR) Ca2+ release and re-uptake. Abnormalities of both sarcolemmal Ca2+ transport, and SR function have been described in heart failure and thus the pathophysiological mechanisms of abnormal handling and subsequent myocardial contraction need to be clarified. In this thesis, abnormalities of Ca2+ handling at the level of the whole myocyte are characterised in a coronary artery ligation model of heart failure in rabbit. Following this, a novel preparation for the specific study of SR function in permeabilised single, myocytes was developed. SR Ca2+ content was significantly reduced in myocytes from failing hearts compared to shams. Spontaneous SR Ca2+ release occurred less frequently in failure myocytes and with reduced amplitude than in myocytes from sham hearts. SR Ca2+ uptake was then directly measured in suspensions of single, permeabilised myocytes from failing rabbit hearts. SERCA 2A mediated SR Ca2+ uptake was significantly slower in failure cells than sham cells, and this difference was maintained in the presence of ruthenium red, a blocker of the SR Ca2+ release channel. Inhibitors of specific aspects of SR function were then used to model the changes in SR function seen in heart failure. Inhibition of SR Ca2+ uptake with thapsigargin in healthy permeabilised myocytes most closely modelled the heart failure phenotype. Inhibition of SR Ca2+ release at the ryanodine receptor with tetracaine, and stimulation of SR Ca2+ leak with ionomycin did not accurately model the changes in SR function seen in heart failure. The experimental techniques described in this thesis were then applied to human myocytes dissociated from small ventricular biopsies to ascertain whether similar protocols could be used in future studies to investigate SR function in human heart failure

Motion Tracking System in Surgical Training

Introduction: Simulation technology is evolving and becoming the focus of attention in surgical training. The development of this technology in assessing open surgical skills is far behind when compared to minimally invasive surgery (MIS) training. Surgical skills such as suturing and tying surgical knots are assessed by an observational tool. It is labour-intensive and time-consuming. Therefore, we explored the potential use of motion tracking system as a non-observational assessment tool for basic surgical skills

Laparoscopic Repair of Postoperative Perineal Hernia

Perineal hernias are infrequent complications following abdominoperineal operations. Various approaches have been described for repair of perineal hernias including open transabdominal, transperineal or combined abdominoperineal repairs. The use of laparoscopic transabdominal repair of perineal hernias is not well-described. We present a case report demonstrating the benefits of laparoscopic repair of perineal hernia following previous laparoscopic abdominoperineal resection (APR) using a nonabsorbable mesh to repair the defect. We have demonstrated that the use of laparoscopy with repair of the pelvic floor defect using a non absorbable synthetic mesh offers an excellent alternative with many potential advantages over open transabdominal and transperineal repairs

Adaptive space-meshing strategies for the numerical solution of parabolic partial differential equations in one space dimension

The effectiveness of adaptive space-meshing in the solution of one-dimensional parabolic partial differential equations (PDEs) is assessed. Present day PDE software typically involves discretisation in space (using Finite Differences or Finite Elements) to produce a system of ordinary differential equations (ODEs) which is then solved routinely using currently available high quality ODE integrators. Such approaches do not attempt to control the errors in the spatial discretisation and th e task of ensuring an effective spatial approxim ation and num erical grid are left entirely to the user. Numerical experiments with Burgers’ equation demonstrate the inadequacies of this approach and suggest the need foradaptive spatial m eshing as the problem evolves. The currently used adaptive m eshing techniques for parabolic problems are reviewed and two effective strategies are selected for study. Numerical experim ents dem onstrate their effectiveness in term s of reduced com putational overhead and increased accuracy. From these experiences possible future trends in adaptive meshing can be identified

Doctrinal Controversy and the Church Economy of Post-Chalcedon Palestine

The Fourth Ecumenical Council, held at Chalcedon in 451, began a period of extraordinary social and political crisis across the Eastern Mediterranean. In Palestine, as elsewhere, the centuries that followed were characterised by internecine conflict between local Christians, persisting until the collapse of Roman authority in the region during the reign of the emperor Heraclius. Since Edward Gibbon, historians have struggled to contextualise this debate, ostensibly an argument between proponents of rival, but also substantially identical, Christologies. This thesis considers what role socio-economic factors may have played in shaping contemporary accounts of the Council’s fraught reception. It asks whether this may have distorted our understanding of a defining Late Antique debate. Chalcedon’s reforms had wide-reaching consequences, not only for the Empire’s official Christological policy, but for the broader structure of the ‘Church economy,’ the systems through which Christian institutions were financed and maintained, referred to at length in the Council’s disciplinary canons. Its rulings held particular significance for Palestine in its status as the Christian ‘Holy Land.’ Here I explore this facet of Chalcedon’s legacy, whilst considering how the language of doctrinal controversy generated by the Council served to frame episodes of material competition between rival communities of clerics and monks. The thesis offers a new reading of the texts produced by key actors in these confrontations, many of which have been historically neglected. It follows in the wake of recent attempts to analyse other religious conflicts of this period in light of contemporary social or political conditions, or through reference to ‘networks’ of influence and patronage. I apply this methodology to the study of the Palestinian partisans in the antagonism which followed Chalcedon, whilst also drawing upon the archaeologically-grounded study of material culture which has influenced so many other areas of early medieval history.AHR

Gastrointestinal Foreign Bodies

Retained foreign bodies within the gastrointestinal tract (GIT) are common emergency presentations. The majority will pass spontaneously or be removed endoscopically, but a few selected cases may require emergency surgery for removal. This chapter reviews the management of foreign bodies within the GIT including both instances of foreign body ingestions and foreign body insertions. The scope of this chapter is not limited to evidence‐based data on selection of cases for conservative management but also includes data on endoscopic and surgical management

Laparoscopic Retrieval of a Peritoneal Mouse

A 67-year-old Caucasian male was referred by the urology service with a history of incomplete bowel emptying. He complained of tenesmus. MRI scan suggested a leiomyoma lying anterior to the rectum. He underwent examination under anaesthesia and attempted endorectal ultrasound and biopsy. However, the lesion seemed to migrate cranially and was impalpable. At laparoscopy, a mobile, unattached, 5.5 × 5 × 3.5, cream-coloured ‘egg was retrieved from the retrovesical space. Histology confirmed a hyalinised fibrocollagenous lesion lined with mesothelium. A comprehensive review of the literature is presented

Umbilical hernia rupture with evisceration of omentum from massive ascites: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of hernias is increased in patients with alcoholic liver disease with ascites. To the best of our knowledge, this is the first report of an acute rise in intra-abdominal pressure from straining for stool as the cause of a ruptured umbilical hernia.</p> <p>Case presentation</p> <p>An 81-year-old Caucasian man with a history of alcoholic liver disease presented to our emergency department with an erythematous umbilical hernia and clear, yellow discharge from the umbilicus. On straining for stool, after initial clinical assessment, our patient noted a gush of fluid and evisceration of omentum from the umbilical hernia. An urgent laparotomy was performed with excision of the umbilicus and devitalized omentum.</p> <p>Conclusion</p> <p>We report the case of a patient with a history of alcoholic liver disease with ascites. Ascites causes a chronic increase in intra-abdominal pressure. A sudden increase in intra-abdominal pressure, such as coughing, vomiting, gastroscopy or, as in this case, straining for stool can cause rupture of an umbilical hernia. The presence of discoloration, ulceration or a rapid increase in size of the umbilical hernia signals impending rupture and should prompt the physician to reduce the intra-abdominal pressure.</p

Radiocephalic and brachiocephalic arteriovenous fistula outcomes in the elderly

BackgroundA recent meta-analysis has suggested that patients aged >65 have worse outcomes with radiocephalic arteriovenous fistulas (RCAVFs) compared with brachiocephalic arteriovenous fistulas (BCAVFs). We hypothesized that outcomes in patients aged ≥80—a rapidly expanding cohort within this elderly group—might be skewing the results, and that age >65 may not be a contraindication to RCAVF formation. This study examined the effect of age group (<65, 65 to 79, ≥80) on functional outcomes (use; primary and secondary functional patency) in RCVAFs and BCAVFs.MethodsWe identified the outcomes of all patients undergoing a first surgical access procedure for a RCAVF or BCVAF between January 1, 2000, and December 31, 2005. We examined the effect of age and other factors including sex, diabetes mellitus, hypertension, late referral (<3 months before dialysis), dialysis before surgical access, preoperative duplex ultrasound imaging, and ethnicity on non-AVF use and primary and secondary functional AVF patency. Logistic regression and Cox proportional hazards regression models were used.ResultsFrom a total of 658 patients, 361 had a RCAVF, and 297 had a BCAVF. Their median age was 68.5 years (interquartile range [IQR], 54.4 to 76.5 years), and 288 (43.8%) were aged <65 years, 274 (41.6%) were 65 to 79, and 96 (14.6%) were ≥80. Age did not influence the site of the first surgical access (P = .874). Only 85.7% of patients actually progressed to hemodialysis, and the RCAVF or BCAVF in 45.7% of those was never used for dialysis. Female sex (hazard ratio [HR], 2.24; 95% confidence interval [CI] 1.387 to 3.643; P = .001) was the only factor associated with an increase risk of RCAVF nonuse, whereas diabetes (HR, 2.095; 95% CI, 1.261 to 3.482; P = .004) was the only factor associated with an increase risk of BCAVF nonuse. The respective primary patency rates at 1 and 2 years for RCAVFs were 46.0% and 27.1% for patients <65, 47.0% and 36.0% for those 65 to 79, and 45.7% and 38.1% for those ≥80. Only female sex (HR, 1.679; 95% CI, 1.261 to 2.236; P = .001) and prior hemodialysis (HR, 1.363; 95% CI, 1.0.29 to 1.804; P = .031) were associated with loss of patency of RCAVFs. The primary functional patency rates for BCAVFs at 1 and 2 years were 39.3% and 31.0% for those <65 years; 53.30% and 37.5% for those 65 to 79, and 46.3% and 42.6% for those ≥80. No factors analyzed were associated with loss of primary functional patency of BCAVFs.ConclusionsAge did not affect usability, primary or secondary patency of either RCAVFs or BCAVFs. Although patient selection is important, even patients ≥80 years who are considered suitable for surgical placement of access should not be denied a RCAVF solely because of age