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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    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.