ABSTRACT In the modern era, the most common post-operative complications following cardiopulmonary bypass (CPB) are neurocognitive deficits (NCD) and atrial fibrillation (AF). Both morbidities have been linked to inflammation resulting from surgery, anesthesia and CPB. Microemboli, inadequate oxygen delivery and the inflammatory response consequent to blood contacting artificial components of the CPB circuit have all been linked to postoperative NCD and to a lesser extent post-operative AF. The artificial components of the CPB circuit consist of stainless steel, polyvinylchloride (PVC), polycarbonate and other carbon-based plastics. In order to attenuate the negative sequelae of blood-circuit contact related inflammatory response, industry developed the biocompatible circuit (BCC) coating for the disposable CPB circuits. Four such coatings were studied and compared to an uncoated control group in a total of 101 patients undergoing routine CPB-assisted cardiac surgical procedures. Soluble adhesion molecule (SAM) activation was studied at different time points and common clinical outcomes such as white blood cell activation, serum renal function parameters urea and creatinine, postoperative bleeding, transfusion requirements, intensive care and hospital length of stay, CPB pump volume balances, changes in weight, postoperative serum lactate and glucose and the development of AF postoperatively, were compared. Additionally, postoperative neurocognitive testing was performed using a simple bedside neurocognitive test called the antisaccadic eye movement test. The patients in all groups were tested for comparison preoperatively and 72 hr postoperatively. Results: The mandate of BCC coating development and manufacture is to attenuate the well-documented and demonstrated inflammatory response consequent to the contact of blood with artificial CPB surfaces. The studied BCCs significantly decreased platelet transfusions in females. In addition, the BCCs decreased the concentrations of 2 SAMs when measured 6 hours after surgery and CPB. The difference in SAM expression seen between the coated and uncoated groups at 6 hr was no longer apparent at 72 hr. Very little difference was noted between the four BCC groups. Patients who developed AF postoperatively seemed predisposed to do so as the serum levels of soluble vascular cell adhesion molecule was significantly higher at baseline and remained so at 6 and 72 hr. The decreased platelet transfusions in females resulting from BCC use is a highly significant finding within this high-risk group of patients. As most platelet transfusions occur soon after the patient is disconnected from CPB, the short-term decrease in SAM activation can be linked to this improved clinical finding. The studied BCC coatings have achieved limited success in their intended mandate to attenuate inflammatory response in terms of improved clinical and laboratory desired outcomes.

No description available.

Please read the abstract in the dissertation. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Clinical Epidemiology / unrestricted

Listeria monocytogenes is the etiological agent of listeriosis in humans and ruminants causing bacteremia, central nervous system (CNS) infections, abortion, and gastroenteritis among other clinical outcomes. Recent studies have integrated whole genome sequence (WGS), epidemiology data, and host susceptibility to provide evidence for variation in virulence among strains, as a small number of hypervirulent clones have been found linked to a high proportion of human and ruminant invasive listeriosis cases, however, still little is known about variation in virulence across different L. monocytogenes subgroups. To assess and compare the genetic diversity of clinical listeriosis isolates from ruminants in the Upper Great Plains states, we used multilocus sequence typing (MLST) and found that the variation in virulence potential varies among clonal complex (CC), which is reflected in the epidemiology of L. monocytogenes. Based on these results, we evaluated the strains’ virulence potential in Galleria mellonella through larvae survival, LD50, and cytotoxicity, and monitored health index scores and bacterial concentrations post-infection as quantifiable indicators of virulence and immunogenicity. Our findings suggest that strains belonging to CC14, as well as isolates from MN infections are hypervirulent in G. mellonella, as they need a lower bacterial concentration to cause disease and produce a low-level infection that could help in evading the host immune response. We also identify genomic elements associated with strains causing three different clinical outcomes: bacteremia, central nervous system infections, and maternal-neonatal infections. By analyzing 232 whole genome sequences from invasive listeriosis cases, we identified orthologous genes of phage phiX174, transfer RNAs and type I restrictionmodification (RM) system genes along with SNPs in loci associated with environmental adaptation such as rpoB and the phosphotransferase system (PTS) associated with one or more clinical outcomes. Novel genetic variants may be associated with a particular virulence phenotype, as it is likely that strains causing the same clinical outcome share unique genetic elements. Variation in virulence among L. monocytogenes subgroups may confer an increased ability to cross host barriers or higher adaptability to food processing environments, thus the investigation of strainspecific genetic features can impact the design of prevention and management plans for listeriosis.

Background: Chronic Kidney Disease (CKD) can be described as the loss of the kidney function over time. Symptoms usually develop slowly and it may not appear in early stages. Lab tests can confirm a CKD diagnosis. The approximate number of incidents per year is more than 200,000 cases and approximately 30 million people are living with CKD today in the United States. This long-standing disease ultimately leads to renal failure at the end. At this present time, there are no known cures for CKD and the only treatment available is dialysis. Objectives: The purpose of this study is to determine the association between CKD and further with Hemodialysis (HD) and medical condition such as cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications, and death. Methods: The study employed secondary data in a cross-sectional design. A sample of 106,969 was drawn from the population. The outcome variables were a diagnosis of CKD and/or CKD with HD. The predictor variables were cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death. Logistic regression was conducted to analyze the relationship between outcome variable and each independent variable. Variables with a p-value <0.05 were considered significant. Odds Ratio (OR) and 95% Confidence Intervals (CI) were reported and discussed. The statistical analysis was performed using SAS version 9.4. Results: Analysis shows that subjects with cardiac complications were 17% less likely to have CKD as compared to those who did not have cardiac complications (OR: 0.83, 95% CI: 0.78-0.88). CKD patients who had cardiac complications were 18% more likely to have HD than the subjects who did not have cardiac complications (OR: 1.18, 95% CI: 1.01-1.39). Patients with cardiogenic shock were 86% more likely to have CKD than the subjects who did not have cardiogenic shock (OR: 1.86, 95% CI: 1.82-1.91). CKD patients who had cardiogenic shock were also 18% more likely to have HD than the subjects who did not have cardiogenic shock (OR: 1.18, 95% CI: 1.11-1.25). Similar results have been reported if a patient had other conditions. Conclusion: Chronic kidney disease with hemodialysis is significantly associated by the other medical conditions such as cardiac complications cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death in the United States. Further studies are needed to confirm the results and to understand the prognosis.

No description available.

No description available.

acase@tulane.edu

[Truncated abstract] Articular cartilage has no vascular, neural, or lymphatic supply, and hence no intrinsic capacity to self-repair following injury. These physiological limitations, combined with the inability of local chondrocytes to contribute to the repair process, translate to poor structural and functional outcomes in these troublesome defects, and osteoarthritic deterioration with time. Subsequently, many surgical therapies have been trialed to stimulate cartilage repair, but none have produced reliable outcomes. Hence, cartilage repair research has been broadened, with many investigators now focused on cell-based treatment. Smith began a revolution of autologous cell research when in 1965 she isolated chondrocytes from articular cartilage and transplanted them into fresh cartilage nodules (Smith, 1965). Since, new technologies and improved techniques have seen autologous chondrocyte implantation (ACI) widely accepted for use in clinical orthopaedics (Bentley et al., 2003; Brittberg et al., 1994; Grande et al., 1989; Peterson et al., 2002). At present, matrix-induced autologous chondrocyte implantation (MACI) is the most surgically simple form of ACI, boasting clinical outcomes comparable to any technique on the market, and far less complications compared to the first generation of ACI - periosteal ACI (Bartlett et al., 2005; Behrens et al., 2006; Gigante et al., 2006; Henderson et al., 2004; Marlovits et al., 2005; Minas, 2001; Willers et al., 2007; Zheng et al., 2007). But whilst MACI has been adopted by the orthopaedic surgeon for articular cartilage repair, many of the molecular, histological, and clinical factors governing patient outcomes are still largely understudied. Firstly we assessed the bioactivity of fibrin sealant (FS - Tisseel®), a critical component of MACI, on the migration and proliferation of human articular chondrocytes in vitro. We also looked to elucidate the associated molecular mechanisms of thrombin, a key active ingredient in FS, by examining the expression and activation of proteaseactivated receptors (PARs), established thrombin receptors. All four PAR isoforms were detected in human chondrocytes, with PAR-1 being the major isoform expressed. '...' This thesis has demonstrated biological, histological, and clinical features of the MACI technique. Our in vitro has supported the use of fibrin sealant and collagen membrane as the major material components of MACI, illustrating improved chondrocyte proliferation, migration, and chondrogenic differentiation. We have evidenced that MACI stimulates successful production of hyaline-like cartilage by 6 months, while also showing that revised and clinically failed repair tissues are predominantly hyaline-like and fibrocartilage with inferior composition. Clinically, we have documented significant improvements in patient repair structure, function, symptoms, quality of life, and satisfaction, whilst concurrently confirming sentiment within the literature regarding the importance of exercise/ rehabilitation for maximising MACI outcome. In summary, the findings presented in this thesis suggest that MACI is a biologically sound and clinically efficacious cell-based treatment option for repairing articular cartilage defects.

No description available.