Outcomes after thoracic endovascular aortic repair (TEVAR) in patients with traumatic thoracic aortic injuries (TTAI) - a single center retrospective reviewChinyepi, Nkhabe 01 February 2019 (has links)
Background: Blunt and penetrating traumatic thoracic aortic injuries constitute surgical emergencies that are attended with high mortality rates. Most patients do not survive long enough, post injury, to reach a hospital. On-site mortality rates may approach approximately 85%. Two main treatment options for blunt thoracic aortic injuries (BTAI) are open surgery and thoracic endovascular repair (TEVAR). Penetrating thoracic aortic injuries (PTAI) have a higher mortality than blunt trauma, with patients often only reaching the hospital in extremis. Most will require early intervention. Currently TEVAR is rapidly evolving as the standard of care for thoracic aortic injuries (TAI) at many centres, primarily due to the emerging evidence of lower mortality and morbidity trends in comparison to open surgery (1–4). Methods: From December 2006 to December 2016, 34 patients (30 blunt trauma, 4 penetrating trauma) with traumatic aortic injuries (grades I-IV) were treated with thoracic aortic stent-grafts in the Groote Schuur Hospital Vascular Unit, Cape Town. We assessed the technical and clinical outcomes following TEVAR in these patients. Results: The 30- day mortality rate was 5.8%, corresponding to 2 deaths both associated with the index trauma-related fatal strokes. The overall mortality rate was 11.8% (4/34): three deaths were due to major strokes and one death was related to pulmonary complications. Conclusion: TEVAR after TAI is associated with significantly lower procedural and postoperative mortality. The 30 day and overall mortality after TEVAR in our unit is comparable to international standards. Even though there is a paucity of literature on PTAI, TEVAR has low peri-procedural adverse events and is safe in selected patients.
Surveillance colonoscopy for Lynch syndrome in the Northern Cape: Does direct contact improve compliance?Coccia, Anna Claudia 31 January 2019 (has links)
Introduction The Annual Northern Cape Colonoscopy Outreach program provides surveillance colonoscopy to high–risk individuals known with Lynch Syndrome along the west coast and in the Northern Cape Province of South Africa. There are currently over 100 known mutation positive individuals. Surveillance colonoscopies are performed annually in August/September, and are preceded a by a preparation visit approximately 6-8 weeks prior. The aim of the preparation trip has been to directly impart information, regarding preparation and importance of attendance, to individuals required to attend annual surveillance. During the preparation trip an attempt is made to reach all individuals scheduled for surveillance but due to the vastness of the Northern Cape inevitably every year some areas are not visited. It has been noted that over the past few years fewer than 25 % of the total participants obtained 100 % adherence to surveillance. Objectives The primary objective of this study is to determine whether there is a need for a yearly colonoscopy preparation visit to high–risk individuals in the Northern Cape. The study determines if direct interaction with patients prior to surveillance colonoscopy will significantly impact attendance and adequacy of bowel preparation. Methods Seventy-eight individuals known with a genetic mutation for Lynch syndrome were enrolled in this randomised crossover trial spanning two years of surveillance. The control group (Group A) of individuals had bowel preparation and instructions forwarded to their local clinics and distributed to them via clinic or hospital staff. The test group (Group B) of individuals were personally visited and provided with instructions and bowel preparation by the research team. A measurement of attendance at surveillance colonoscopy as well as cleanliness of the colon was recorded. The study spanned two years of colonoscopy surveillance, July 2014 to September 2015, with a crossover of the control and test groups. Results The study cohort consisted of 28 (36%) male and 50 (64%) female participants with a median age of 39.5 years. Groups A and B consisted of 38 and 40 participants respectively. In September 2014 thirty-six (46.2%) participants presented for annual surveillance colonoscopy, 19 (50%) from the control group (Group A) and 17 (42.5%) from the intervention group (Group B). In 2015 there were 41 (53%) compliant individuals; this included 21 (55%) individuals receiving a preparatory direct contact visit (Group A), and 20 (50%) individuals from the 2015 control group B. Following exclusion of carry-over and period effect, the study intervention was found not to significantly impact attendance (p-value = 0.853). Superior attendance was noted in individuals with prior compliance to surveillance (p-value = 0.001). Conclusions Direct interaction with known Lynch syndrome individuals prior to annual surveillance colonoscopy has not shown to positively impact attendance. Interaction and counselling should focus on individuals identified to be defaulting surveillance.
Pillay, Santhoshan Thiagaraj
The Human Immunodeficiency Virus (HIV) epidemic still poses a problem with approximately 2 million new infections reported worldwide in 2014. New strategies are required to alleviate this burden. Our laboratory has previously shown that crude saliva and purified mucins from cervical plug mucin, saliva and breast milk inhibit HIV-1 infection in vitro. This project investigates purified mucins sourced from pig and horse mucus, as an alternative and abundant source of material for anti-HIV-1 research. Pig gastric and cervico-vaginal mucus was collected and stirred overnight in 6M guanidine hydrochloride with 10mM Na₂HPO4, 10mM EDTA, 1mM PMSF and 5mM NEM. Gastric and cervicovaginal mucus was purified by density gradient ultracentrifugations in CsCl at 105 000g for 48 hours, twice, and mucin rich fractions were separated by size exclusion column chromatography. Mucin-rich materials eluting in the void volume (V₀) were reduced with 10mM dithithreitol (DTT) or subjected to proteolysis with trypsin. Pig saliva was collected in 0.2M NaCl:0.02% sodium azide and horse saliva (due to its viscous nature) was collected and stirred overnight in 6M guanidine hydrochloride with 10mM Na₂HPO4, 10mM EDTA, 1mM PMSF and 5mM NEM. Pig and horse saliva samples underwent size exclusion column chromatography, where the V₀ fractions of both were purified with one density gradient ultracentrifugation and then dialysed and freeze dried, after which aliquots were treated with either DTT or trypsin. At every stage of purification, lyophilized aliquots of all mucin sources were tested on a luciferase based replication defective HIV neutralization assay on a CD4 expressing HeLa cell line. Luciferase expression quantified as relative light units by a luminometer was used to calculate percentage neutralization. Log dose response curves were constructed to extrapolate the half maximal inhibitory concentrations (IC₅₀) on GraphPad Prism. Samples were tested on an MTT cell toxicity assay. Pig gastric and cervicovaginal mucins were added to a simulated vaginal fluid to make gels (at a concentration of 30mg of mucin per ml of buffer). These gels were tested on the neutralization, MTT assays and the pig gastric mucin gel then underwent particle tracking and nanoparticle diffusion assays at varying pH. Pig gastric and cervicovaginal mucin showed good inhibition and low toxicity, with pig gastric mucin V₀ having the best IC₅₀ (1.668μg/ml). Pig and horse saliva showed inhibition but low cell viability. Pig gastric and cervicovaginal mucin gels exhibited good IC₅₀'s but pig gastric mucin had the best neutralization and lowest toxicity (PGM in Gel Solution 4 IC₅₀: 20.23μg/ml). HIV particle tracking and nanoparticle diffusion assays showed that the pig gastric mucin gel inhibited HIV-1 at low pH and existed as a soft gel. This project shows the efficacy of pig gastric mucin to possibly being a component of an anti-HIV-1 vaginal microbicide.
Immunohistochemical identification of mismatch repair gene deficit and its clinico-pathologic significance in young patients with colorectal cancerHameed, Muhammad Fayyaz January 2005 (has links)
Includes bibliographical references (leaves 43-52). / An immunohistochemical technique is used in this study to detect mismatch repair deficit in young patients with colorectal cancers. Ninety three patients who were 45 years of age or younger at the time of diagnosis of colorectal cancer were studied.
28 April 2020
Scaffold based delivery of RNA interference (RNAi) molecules such as free small interfering RNA (siRNA) and microRNA has recently begun to be employed towards treatment of diseases such as cancer, bone regeneration, muscular dystrophy and cardiovascular disease. Effective translation from bench side to clinical use of RNAi has been limited in part because upon systemic delivery the RNAi molecules are degraded by RNases and flushed by excretory organs causing an inefficient duration of gene silencing effect at target tissues. These challenges can potentially be minimised by delivering RNAi molecules via non-viral nanoparticle carriers encapsulated in biocompatible, biodegradable and injectable scaffolds such as hydrogels. Various scaffolds have been shown to aid in sustained localised delivery of RNAi molecules and improve gene silencing. This research focused on optimising and establishing such an RNAi hydrogel-siRNA-nanoparticle (hydrogel-nanocomplex) system for targeted and sustained gene knockdown both in vitro and in vivo using dendrimer and lipid based nanoparticles in combination with synthetic polyethylene glycol (PEG) and natural fibrin hydrogel scaffolds. Four siRNA nanocarriers were investigated for siRNA delivery, that is, fourth generation dendrimer nanoparticles poly(amidoamine) (D) and its modified version (MD) with PEG and a lipid 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) molecule, commercial lipid based Lipofectamine® RNAiMax and Invivofectamine® 3.0 nanoparticles. D and MD achieved better RNase protection compared to lipid nanocomplexes though Invivofectamine® 3.0 nanocomplexes protected a small percentage of siRNA over 10 days. The MD nanoparticle displayed improved siRNA release and transfection efficacy compared to D but efficacy of the dendrimers was lower than the lipid particles. Four hydrogels that have not been investigated for RNAi were assessed for sustainability. Namely, hydrolytically and proteolytically degradable PEG-acrylate (PEGAC), proteolytically degradable PEG - vinyl sulfone (PEG-VS) hydrogels, unmodified fibrin and PEGylated fibrin hydrogel. The nanocomplex release rate in vitro from the various hydrogels showed minimal release from PEGylated hydrogels, burst release from unmodified fibrin and sustained release from PEGylated fibrin. Invivofectamine® 3.0 nanocomplexes retained efficacy optimally after release from PEGylated fibrin hence this hydrogel was utilised for downstream analysis. For in vivo sustained delivery to be effective, determination of hydrogel persistence in vivo was required. After injection in the mouse tibialis anterior (TA) muscle PEG-AC and PEGylated fibrin gels degraded within 2 days. The efficacy of the various nanocomplexes was assayed in a 3D assay that more closely resembled delivery in soft tissue. PEGylated fibrin containing nanocomplexes with cell death siRNA sequences was polymerised around a preformed PEGylated fibrin cell containing droplet. Invivofectamine® 3.0 nanocomplex consistently achieved the highest gene knockdown effect with no evidence of cytotoxicity whilst Lipofectamine® RNAiMax was ineffective. MD showed signs of cytotoxicity when delivered in a sustained fashion. Thus Invivofectamine® 3.0 nanocomplexes in PEGylated fibrin hydrogel were found to be the optimal gel-nanocomplex system to proceed to in vivo assessment. BALB/c GFP transgenic injected in their TA muscle with Invivofectamine® 3.0 nanocomplexes made with siRNA targeting GFP or myostatin (siGFP/siMSTN) in the presence or absence of PEGylated fibrin gel were analysed 7 days post treatment for siRNA retention and GFP and Mstn gene knockdown. Increased retention of siRNA after encapsulation in PEGylated fibrin was observed at 7 days. A non-significant reduction in GFP protein was seen for limbs injected with siGFP- fibrin after 7 days. A substantial and significant reduction in Mstn mRNA levels was elicited by delivery of siMstn–fibrin. Furthermore, only siMstn-fibrin resulted in significant increase in muscle mass. In this study, dendrimer based nanoparticles were found to effectively protect siRNA against RNases however lipid based nanocomplexes were the most efficacious at gene knockdown. The combination of Invivofectamine® 3.0 and PEGylated fibrin was shown to be the most effective in 3D assays and as an injectable controlled release scaffold into soft tissue suggesting that this approach has therapeutic potential.
23 July 2013
Health care spending in Canada has been increasing faster than the rate of gross domestic product (GDP). A disproportionate amount of the health care spending is allocated to care of older adults. Non-elective abdominal surgery is an expensive area of care for older adults. Despite this, the factors associated with cost in this patient population remain unclear. OBJECTIVES The primary objective of this study was to estimate the association between perioperative factors (age, American Society of Anesthetists (ASA) classification, operative severity (OS), frailty index (FI), complication severity) and health care costs among older adults undergoing non-elective abdominal surgery. The secondary objectives were: 1. to provide a comprehensive description of costs based on patient-level resource utilization; and 2. to examine the relationship between hospital costs and adverse events (non-fatal complication severity, mortality, and change in living arrangement). METHODS This study was an observational prospective cohort study. Over a 15 month period all patients 70 years or older who underwent non-elective abdominal surgery at the QEII Health Sciences Centre, Nova Scotia, were enrolled. Data were collected on patient demographics, investigations, treatments, and outcomes. Direct hospital health care costs (2012 $CAD) were calculated by tabulating patient-level resource use and assigning specific costs. The association between five perioperative factors and costs were analyzed using univariate non-parametric tests and multiple linear regression. The associations between adverse events and costs were assessed using univariate non-parametric tests and multiple linear regression. RESULTS During the study period, 212 patients who underwent abdominal surgery (median age 78 years (range 70-97)) were enrolled. The median costs of care were $9,166 (range $1,993-$104,403). The largest proportions of spending were non-procedural costs (65% [$2,176,875]) and intensive care costs (16% [$554,523]). The perioperative factors ASA classification (p=0.0010), OS (p<0.0001), FI (p=0.0002) and complication severity (p<0.0001) were all independently associated with health care costs, while age was not (p=0.5330). The following adverse events were independently associated with health care costs: non-fatal complication severity (p<0.0001), change in living arrangement (p=0.0002), and mortality (p=0.0337). Non-fatal complications had the strongest association with hospital costs (standardized β coefficient = 0.3931). CONCLUSION Four perioperative factors (ASA, OS, FI and complication severity) are associated with costs; therefore, representing a potential cost prediction model for this patient group. This study is important for health care administrators, identifying targets for cost reduction. Cost reduction strategies and research should concentrate on mitigating or preventing complications and high cost areas, such as non-procedural costs and intensive care, in order to achieve cost savings.
Introduction: The relationship between pancreatitis and dyslipidaemia is unclear and has never been studied in a South African context. Patients and methods: A prospective evaluation of all admissions with acute pancreatitis to a regional hospital general surgical service was performed to ascertain its relationship to dyslipidaemia. Aetiology was determined by history and ultrasound assessment. Disease severity was assessed using a modified Imrie score and an organ failure score. Body mass index was calculated. A lipid profile was obtained. Abnormal profiles were repeated. Secondary causes of dyslipidaemia were noted. A comparison of the demographic profile, aetiology, disease severity scores, complications and deaths were made in relationship to the lipid profiles. Results: From June 2001 to May 2005, there were 230 admissions, of whom 31% were women and 69% men. The median age was 38 years(range 13- 73). The pancreatitis was associated with alcohol in 146(63%), gallstones in 42(19%) and idiopathic in 27(12%). The amylase was significantly higher with a gallstone aetiology (p / Thesis (MMedSc)-University of KwaZulu-Natal, 2006.
Risk assessment for renal injury post aortic surgery using new and more sensitive markers of renal injury.Pillay, Woolagasen Ramalingham. January 2003 (has links)
Renal failure in patients undergoing Aortic surgery is associated with a poor outcome. The shortcomings of serum creatinine for measuring renal function are well documented. We examined the value of alternative markers in diagnosing and predicting renal damage in patients undergoing abdominal aortic surgery and those exposed to intravascular contrast media. Cystatin C lacks some of the reservations associated with serum creatinine when used as a marker of glomerular filtration rate. The protease inhibitor alpha-glutathione Stransferase (a-GST) is recovered in urine after injury to proximal tubular cells. Urine microalbumin is a marker of glomerular permeability. Together we used all four assays to detect and characterize the nature of renal injury after surgery and contrast exposure. Cystatin C had a marginally better sensitivity than serum creatinine at detecting baseline renal impairment. It also showed earlier changes in individual patients whose renal dysfunction deteriorated over time. The urinary markers showed an earlier significant rise after the onset of surgery when compared to serum markers, but only a-GST rose significantly after contrast exposure. Patients undergoing a supra-renal cross-clamp showed significantly higher a-GST levels (and not the other three markers) when compared to the infra-renal group. Cystatin C appears to have better sensitivity and specificity for predicting the need for dialysis in patients undergoing surgery. Peak serum creatinine and cystatin C after contrast exposure show good correlation with peak values after surgery. Cystatin C is equivalent to and may be better than serum creatinine in detecting preexisting and deteriorating renal impairment. Although the urinary assays are earlier markers of renal injury, their clinical significance needs to be determined. Elevation in creatinine and cystatin C after contrast exposure parallel those after surgical intervention and may be helpful in selecting out high-risk patients prior to surgery. / Thesis (M.Med.Sc.)-University of Natal, 2003.
Mulaudzi, Thanyani Victor.
Objective. To assess the influence of diabetes mellitus on early morbidity and mortality following open vascular surgical interventions. Methods. Clinical data on patients subjected to open vascular surgical procedures over a 5 year period at the Durban Metropolitan Vascular Service was culled from a prospectively maintained computerized database. They were divided according to the type of surgical procedure performed. These were open abdominal aortic surgery, peripheral bypass surgery, lower extremity major amputation and carotid endarterectomy. They were further subdivided into 2 groups, diabetic and non-diabetic. Results. 1104 charts were analysed. There were no significant differences in demographics and risk factors between the two groups. 273 patients had open abdominal aortic surgery. 217 (79%) were non-diabetic. diabetic patients had significantly higher incidence of myocardial infarction (p=0.00001) (6 of 6 patients), graft sepsis (p=0.000001) (7 of 7 patients) and mortality rate (p=0.0335) (5 of 10 patients). 337 patients had peripheral bypass procedures. 204 (60%) of these were non-diabetic. There was a high prevalence of smokers among non-diabetics and of hypertension among diabetics. Diabetic patients had a preponderance of graft infection (p=0.0015) (15 of 20 patients) and cardiovascular complications (p=0.0072) (7 of 8 patients). 230 patients had lower extremity major amputations, 81 (35%) were diabetic and 149 (65%) non-diabetic. Myocardial infarction and death (6 of 8 patients each) were significantly higher among diabetics (p =0.04). 264 patients had carotid endarterectomy, 170 (64%) being non-diabetic. The surgical outcome was similar between the two groups. Conclusions. This is retrospective study and as such it has some its limitations. Not all patients might have been included in the study and some of the information might have been lost. The numbers in this study are large and these limitations would appear not to have influenced the outcome of this study. This study has shown that diabetes mellitus had diverse influence on the early outcome following different vascular surgical procedures. Diabetes mellitus significantly increased the incidence of graft sepsis among those who had aorto-bifemoral bypass and peripheral bypass procedures. The incidence of peri-operative cardiovascular morbidity was significantly increased among diabetics who had peripheral bypass procedures, open abdominal aortic surgery and lower extremity major amputations. Diabetes mellitus had no influence on the surgical outcome following carotid endarterectomy. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.
Satyapal, Kapil Sewsaran.
In clinical anatomy, the renal venous system is relatively understudied compared to the arterial system. This investigation aims to clarify and update the variable patterns of the renal venous vasculature using cadaveric human (adult and foetal) and Chacma baboon (Papio ursinus) kidneys and to reflect on its clinical application, particularly in surgery and radiology. The study employed gross anatomical dissection and detailed morphometric and statistical analyses on resin cast and plastinated kidneys harvested from 211 adult, 20 foetal and 10 baboon cadavers. Radiological techniques were used to study intrarenal flow, renal veins and collateral pathways and renal vein valves. The gross anatomical description of the renal veins and its relations were confirmed and updated. Additional renal veins were observed much more frequently on the right side (31 %) than previously documented (15.4%). A practical classification system for the renal veins based on the number of primary tributaries, additional renal veins and anomalies is proposed. Detailed morphometric analyses of the various parameters of the renal veins corroborated and augmented previous anatomical studies. Contrary to standard anatomical textbooks, it was noted that the left renal vein is 2.5 times the length of its counterpart and that there are variable levels of entry of the renal veins into the IVC. Justification for the distal segment of the left renal vein to be termed the surgical trunk, and the proximal segment to be the homologue of the right renal vein is presented. Radiological investigations demonstrated a non-segmental and non-lobar intrarenal venous architecture, an absence of renal vein valves and extensive venous collaterals centering on the left renal vein. These collateral channels, present in the foetus, and persisting in the adult, may be operative and of clinical significance in pathological states. No sex differences and no race differences of note were recorded in this study. The Chacma baboon displayed similar intra-renal venous anatomy. The applied clinical anatomy of these findings with particular regard to renal surgery and uro-radiology is emphasised. / Thesis (M.D.)-University of Natal, 1993.
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