School of Clinical Medicine (ETDs)

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    Surgical aortopulmonary shunts - a thirty-seven year experience in a South African tertiary institution
    (University of the Witwatersrand, Johannesburg, 2019-11) Dladla-Mukansi, Nontobeko Charity; Cilliers, Antoinette; Mammen, Vijay; Vanderdonk, Kathy
    Introduction: The surgical aortopulmonary shunt is a valuable palliative procedure in the management of congenital heart diseases. There is a paucity of data regarding aortopulmonary shunts in the developing world, including South Africa. Objectives: The primary objective was to describe the demographic, clinical and echocardiographic characteristics of children between ages 0 and 14 years that underwent surgical aortopulmonary shunts. The secondary objectives were to describe trends in aortopulmonary shunt designs, outcomes in terms of morbidity and mortality, progression to definitive surgery and to assess patency of shunts. Material and Methods: A retrospective clinical audit of patient files who underwent an aortopulmonary shunt between 01 January 1980 to 30 December 2016 was undertaken at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, Johannesburg. The study period was divided into 3 stages and for descriptive purposes as follows: 1980-1991 refers to period 1, 1992-2003 refers to period 2 and 2004-2016 refers to period 3. Results: A total of 177 aortopulmonary shunts were done over the 37-year study period. Of these 177 patients, 165 (93.2%) patient files were available. Fifty-six percent of the patients included in the study were male. The majority of patients were from the Gauteng Province (76.8%). The four most common diagnoses across the entire study period were tricuspid atresia (26.0%), pulmonary atresia with VSD (23.7%), tetralogy of Fallot (23.2%) and complex cardiac lesions (16.9%), with no particular trend in the proportion of these diagnoses presenting across this study period. There was no statistical difference between period 1 and 2 (p-value a=0,328) and between period 1 and 3 (p-value b=0,548). The total number of all surgeries done over the entire study period was 2145, of which 8.3% were aortopulmonary shunts. Period 1 had the highest percentage [35 (10.9%)] of aortopulmonary shunts compared to the total number of surgeries performed. There was a decline in the number of aortopulmonary shunts performed over the study periods 1-3. With no statistical difference across periods as shown in table 1 with p-value a and b. Of the different types of aortopulmonary shunts, most patients [157 (88.7%)] had a modified Blalock-Taussig shunt (BTS). The remainder of the shunts included 3 (1.7%) classic BTS, 12 (6.8%) central shunts and 5 (2.8%) unknown BTS. The percentage of modified BTS done increased from 80% in period 1 to 87.3% in period 2 and to 95.2% in period 3. Period 1 had the most complications (28.6%) compared to 11.4% in period 2 and 19.1% in period 3. Sepsis as a complication following surgery increased over the study period from 2.9% in period 1 to 3.8% and 7.9% in periods 2 and 3 respectively. Early mortality was 17.1%, 26.6% and 25.4% from periods 1-3 respectively. Late mortality declined from 17.0% in period 1 to 11.4% and 0% in periods 2 and 3 respectively. Only 37 (20.9%) patients were documented to have further surgery after the initial aortopulmonary shunt. Across all three study periods, no blocked shunts were documented. Conclusions: This study describes the characteristics and outcomes of aortopulmonary shunts over a 37-year period in a tertiary care resource limited low to middle income country setting. The commonest cardiac lesions for which aortopulmonary shunts are performed are tricuspid atresia, pulmonary atresia with VSD, tetralogy of Fallot and other complex cyanotic cardiac lesions. The frequency of aortopulmonary shunts compared to total surgeries has corrective surgery for these cardiac lesions. The modified BTS is the most frequently performed aortopulmonary shunt used for palliative surgery in our setting, which is a similar trend in developed countries. The morbidity and mortality in this study is higher than developed countries, with sepsis being the most common complication. Attention to infection control practises need to be emphasized peri- and post-operatively in our hospitals.
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    Liver cancer epidemiology and risk factors in South Africa
    (2019) Mak, Daniel Wei-Hong
    Primary liver cancer (LC) in South Africa (SA) is a public health concern; it is currently the seventh leading cause of death among SA men and women after colon cancer according to GLOBOCAN 2018. Despite this, publications of this disease remains scarce, if not absent. Accordingly, trend analysis for LC incidence (from 1993-2012) and mortality (from 1999-2015) rates demonstrated an overall decrease in SA, and these trends varied between different sex-, age- and population-subgroups. Specifically, rates markedly increased in the middle-aged black African women in the recent years. LC risk was highest in black African men in their early 30s, and survival from this malignancy provided a dismal outlook as most patients were only diagnosed during autopsy rather than during hospital and/or clinic consultations. Barring this, these findings demonstrate the utility of mortality data in supplementing the cancer registries for cancer that progress quickly. Liver cancer has several types, each originate from various type of cells that becomes cancerous. Hepatocellular carcinoma (HCC) accounts for the majority of liver cancers and originates from hepatocellular cells. The study of 150 HCC patients and 438 non-HCC cancer controls showed that risk factors that were significantly associated with HCC include: rural birthplace, male sex and living in an urban area for <14 years, Hepatitis B virus (HBV) DNA levels (>2000-≥200,000 IU/ml) and antibodies against hepatitis C virus (anti-HCV) positivity. Interestingly, human immunodeficiency virus (HIV) infection alone did not confer any risk in developing HCC, nor did it synergistically interact with HBV infection. Comparably, lifestyle-related risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were not associated with HCC risk. Phylogenetic analyses of the HBV isolates from the HCC patients and non-HCC controls demonstrated that HBV subgenotypes included A1 (90.7%), A2 (2.3%) and A3 (7%). Core promoter mutations (T1753V, A1762T and G1764A), preS deletions, ps2F22L, and preS2 start codon mutations were associated with HCC development, and the combination of which may potentially assist in the development of more targeted screening in high-risk groups. In view of these findings, this work provides much needed analysis of LC trends in SA and provides a critical assessment of current control strategies, or gaps, in the prevention of and interventions for LC in SA. Moreover, this work pays particular attention to the consolidation of what is an overview of LC in SA by reporting various aspects: incidence, mortality, demographics, viral and non-viral risk factors and a combination of HBV mutations as biomarkers.
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    The demographic profile, substance use, competence to stand trial and criminal responsibility among “ Observation Patients” admitted for forensic psychiatric evaluation at Sterkfontein Hospital, Gauteng, South Africa.
    (2011-10-19) Pillay, Anben
    A review of the literature indicates that young males, who are unemployed with low levels of education, predominate in populations of pre-trial criminal offenders suspected of having a psychiatric illness, also known as “Observation Patients” according to the Criminal Procedures Act of 1977 in South Africa. Other contributory factors include a history of mental illness and non-compliance on psychiatric medication, a previous forensic history, co-morbid substance abuse and being intoxicated at the time of the offence. Dual diagnosis is considered a key contributor to criminal behaviour in this group of patients. The review of the literature also shows a significant proportion of co-morbid intellectual disability among offenders found to be psychiatrically ill at the time of the criminal event. A previous study conducted 20 years earlier, in 1986 at the Sterkfontein Forensic Psychiatric Unit by Vorster (1986) showed that the typical profile was a single, unemployed, poorly educated male in his twenties, usually with a history of psychiatric treatment. This typical profile confirmed the evidence in the literatures at the time of the study.
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    The role of increased gastrointestinal alcohol production in patients with the metabolic syndrome: Implications for the pathogenesis of non-alcoholic fatty liver disease
    (University of the Witwatersrand, Johannesburg, 2006) Menezes, Colin Nigel; Immelman, Ronnie; Raal, Derick
    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with hepatic histology that resembles alcoholic liver disease. It is a frequent cause of chronic liver disease and is attracting increasing scientific attention worldwide. I explored the possibility that increased gastrointestinal alcohol production may have a role as a “second hit” in the pathogenesis of NAFLD in study subjects with the metabolic syndrome. In an attempt to investigate this hypothesis, this study looked at blood, urine and breath levels of alcohol in patients with the metabolic syndrome versus matched age and ethnic group healthy controls. Of the twenty study subjects, 80% had dyslipidaemia, 60% had hypertension and 70% had type 2 diabetes mellitus. Their mean BMI was 35.1±8.2 kg/m² (mean ± SD, P < 0.0001 versus controls). The serum aminotransferases were significantly elevated in the study subjects, their ALT levels being 57.4±44.79 U/L versus 17.4±4.60 U/L in the controls (95% CI 18.02 – 61.42, P < 0.001), and their AST levels 52.5±36.21 U/L versus 23.4±4.86 U/L in the controls (95% CI 11.99 – 46.20, P < 0.01). Seventy five percent of the study group had sonar features suggestive of fatty liver disease. Two adipocytokines, adiponectin and leptin, mediators of insulin resistance, an important factor in the development and progression of NAFLD, were also measured. Adiponectin levels were significantly lower (6875 ng/L versus 15475 ng/L; median value, P < 0.01), and leptin concentration levels significantly higher (13.56 ng/L versus 3.05 ng/L; median value, P < 0.05) in the study subjects than in the control group. Alcohol was detected in 60% of the study subjects, of which 35% tested positive for ethanol, 55% tested positive for methanol, and 30% tested positive for both ethanol and methanol. This was a statistically significant result, as none of the control group tested positive for any of the alcohols. The ethanol concentration in the study subjects’ blood was 7.14±3.28 mg% (mean ± SD), in their urine 3.71± 12.87 mg% (mean ± SD) whilst none was detected in their breath. The methanol concentration in the study subjects’ blood was 16.17±17.95 mg% (mean ± SD), in their urine 6.8± 13.58 mg% (mean ± SD) while their breath level was 2.05±3.19 mg (mean ± SD). This study therefore suggests that endogenous alcohol production may be indeed be involved in the pathogenesis of NAFLD in subjects with the metabolic syndrome. Not only ethanol but also methanol was detected in the subjects tested. endogenous alcohol may therefore be responsible for the ‘second hit’ theory in the pathogenesis of NAFLD, and it is likely that formaldehyde, the metabolite of methanol may be a more potent toxin of the patocyte injury as opposed to acetaldehyde, the metabolite of ethanol. The most likely source of the alcohol is from intestinal bacterial flora. These findings provide further insight into the pathogenesis of NALFD, suggesting other therapeutic alternatives such as the use of antibiotics and probiotics as a potential treatment strategy for NAFLD.