In an attempt to avoid the destructive process of bioprosthetic heart-valve calcification associa... more In an attempt to avoid the destructive process of bioprosthetic heart-valve calcification associated with the use of glutaraldehyde, valves are today prepared using low concentrations of the crosslinking reagent. In this review, we summarize our findings and those of others that confirm that the immunogenicity of such tissue is not sufficiently masked and that a defined humoral response is indeed mounted against a repertoire of antigens unrelated to those associated with vascularized and non-cross-linked xenograft organs. We demonstrate the need for increased cross-linking of tissue to satisfactorily mitigate that response; furthermore, we examine the impact of increased cross-link density on the macrophage as antigen presenting cell with respect to its involvement in both tissue erosion and pannus overgrowth. Finally we present evidence for a role of circulating antibodies in bioprosthesis calcification.
Twenty years ago, on 2 December 1967, the first human allogeneic heart transplantation was perfor... more Twenty years ago, on 2 December 1967, the first human allogeneic heart transplantation was performed at Groote Schuur Hospital, Cape Town [1]. This operation was based on experimental work by Lower, Stofer, and Shumway [2]. During these 20 years, several notable advances have taken place in this field at Groote Schuur Hospital and elsewhere. The technique of endomyocardial biopsy allowed a precise diagnosis of whether or not acute rejection was present [3]. In 1973, heterotopic heart transplantation was initiated by Barnard and Losman [4]. Since the early 1980s, results of cardiac transplantations have dramatically improved, mainly as a result of the introduction of cyclosporin A and more precise donor and recipient selection [5]. Hormonal therapy for organ donors was introduced in 1983 [6]. In addition, more sophisticated noninvasive monitoring of acute rejection is being undertaken - cytoimmunological monitoring of the peripheral blood and radionuclide scanning of the transplanted heart [7, 8].
Background and Objectives: The Western Cape public pediatric cardiac service is under-resourced. ... more Background and Objectives: The Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service. Methods: An uncontrolled retrospective pre-post study of all presenting patients over two, one-year periods; the pre-COVID-19 period (01/03/2019-29/02/2020) and the peri-COVID-19 period (01/03/2020-28/02/2021). Results: Admissions decreased by 39% (624 to 378) and cardiac surgeries decreased by 29% (293 to 208) in the peri-COVID-19 period, with an increase in urgent cases (PR:5.99, 95%CI:3.58-10.02, p < 0.001). Age at surgery was lower in the peri-COVID-19 period, 7.2 (2.4-20.4) vs. 10.8 (4.8-49.2) months (p < 0.05), likewise, age at surgery for transposition of the great arteries (TGA) was lower
RNA interference is a promising therapeutical approach presently hindered by delivery concerns su... more RNA interference is a promising therapeutical approach presently hindered by delivery concerns such as rapid RNA degradation and targeting of individual tissues. Injectable hydrogels are one potentially simple and direct route towards overcoming these barriers. Here we report on the utility of a combination of a mildly modified form of the clinically utilised fibrin hydrogel with Invivofectamine® 3.0, a lipid nonviral transfection vector, for local and sustained release. PEGylation of fibrin allowed for controlled release of small interfering RNA (siRNA)-lipopolyplexes for at least 10 days and greatly increased the stability of fibrin in vitro and in vivo. A 3D cell culture model and a release study showed transfection efficacy of siRNA-lipopolyplexes was retained for a minimum of 7 days. Injection in conjunction with PEGylated-fibrinogen significantly increased retention of siRNA-lipopolyplexes in mouse skeletal muscle and enhanced knockdown of myostatin mRNA that correlated with m...
changes in survival rate or cell proliferation. However, it clearly promoted the induction of cel... more changes in survival rate or cell proliferation. However, it clearly promoted the induction of cell hypertrophy. Conclusion In summary, these preliminary data suggest that SIK2 might modulate the hypertrophic response of cardiac tissue during pathological insults. Conflict of Interest No BS25
Background Tetralogy of Fallot (ToF) and coarctation of the aorta (CoA) each constitute approxima... more Background Tetralogy of Fallot (ToF) and coarctation of the aorta (CoA) each constitute approximately 7% of congenital heart disease (CHD) births worldwide. Compared to developed countries, developing countries have a disparate level of access to prompt diagnosis and treatment for these diseases. Computational fluid dynamics (CFD) approaches implemented on routinely available non-invasive imaging data may yield low-cost improvements to the management of these patients. Purpose The purpose of this research is to develop a patient-specific computational pipeline that allows the modelling of blood flow in diseased arteries of patients suffering from ToF and CoA. The project aims to prove the feasible use of broadly available imaging techniques - CT angiograms (CTA) and echocardiographs (echo) - for achieving this in low-to-middle income countries. The capability of the pipeline will be demonstrated through a qualitative study of the effects of different systemic to pulmonary shunt conf...
Despite early realization of the need to control inherent immunogenicity of bioprosthetic replace... more Despite early realization of the need to control inherent immunogenicity of bioprosthetic replacement heart valves and thereby mitigate the ensuing host response and its associated pathology, including dystrophic calcification, the problem remains unresolved to this day. Concerns over mechanical stiffness associated with prerequisite high cross-link density to effect abrogation of this response, together with the insinuated role of leaching glutaraldehyde monomer in subsequent dystrophic mineralization, have understandably introduced compromises. These have become so entrenched as a benchmark standard that residual immunogenicity of the extracellular matrix has seemingly been relegated to a very subordinate role. Instead, focus has shifted toward the removal of cellular compartment antigens renowned for their implication in the failure of vascularized organ xenotransplants. While decellularization certainly offers advantages, this review aims to refocus attention on the unresolved m...
Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR)... more Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification. Three sizes were developed from nickel-cobalt-chromium MP35N alloy tubes: Small/23 mm, Medium/26 mm and Large/29 mm. Crimp-diameters of valves with both bioprosthetic (sandwich-crosslinked decellularized pe...
Journal of Cardiothoracic and Vascular Anesthesia, 2022
OBJECTIVES Large data sets have been published on short- and long-term outcomes following bidirec... more OBJECTIVES Large data sets have been published on short- and long-term outcomes following bidirectional Glenn surgery (BDG), or partial cavopulmonary connection, in high-income countries. Data from low-income and middle-income countries are few and often limited to the immediate postoperative period. The primary outcome was any in-hospital postoperative complication, assessed according to predefined criteria, in children who underwent BDG surgery at Red Cross War Memorial Children's Hospital. DESIGN A retrospective cohort study. SETTING A tertiary teaching hospital. PARTICIPANTS The study authors identified 61 children (<18 years of age) who underwent BDG over 8 years. The median age of patients undergoing BDG was 2.5 years (interquartile range, 1.4-5.5 years). INTERVENTIONS BDG surgery. MEASUREMENTS AND MAIN RESULTS Thirty-five patients (57.4%) had a postoperative complication, with some patients (17 of 61, 27.9%) having more than 1 complication. The most frequent complications were infective (29.5%). Univariate analysis found that postoperative complications were associated with the use of nitric oxide (p = 0.004) and a longer duration of anesthesia (p = 0.045) and surgery (p = 0.004). Patients with complications spent longer in the pediatric intensive care unit (ICU) (p < 0.001) and in the hospital (p < 0.012). On multivariate analysis, a priori risk factors based on previous studies were not found to be statistically significant. A total of 37.3% of patients completed their single-ventricle palliation, and 30.5% of patients were lost to follow-up. CONCLUSIONS Important findings were the older age at which the BDG was performed compared to high-income countries, an acceptable mortality rate of 3.3%, infection being the most common complication, the association of a complication with increased ICU and hospital lengths of stay, and the high rate of patients lost to follow-up.
Thesis(M.Sc.) -- University of Stellenbosch, 1986.Full text to be digitised and attached to bibli... more Thesis(M.Sc.) -- University of Stellenbosch, 1986.Full text to be digitised and attached to bibliographic record
Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a den... more Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric c...
Journal of Tissue Engineering and Regenerative Medicine, 2020
Due to the abundance of lipoproteins in blood, it is challenging to characterize the biological f... more Due to the abundance of lipoproteins in blood, it is challenging to characterize the biological functions and components of blood‐derived extracellular vesicles. The aim of this study was to develop a multiple‐step purification protocol to separate serum exosomes from serum proteins and lipoproteins and assess their regenerative potential. Exosomes were isolated by concentrating them in human serum using ultracentrifugation (UC), followed sequentially by density gradient (DG) UC and size exclusion chromatography (SEC). Purity and characterization were assessed by western blots, Lipoprint®, enzyme‐linked immunosorbent assay, electron microscopy, mass spectrometry, and nanoparticle tracking analysis. Functionality was assessed by cell proliferation analysis and with an in vivo subcutaneous angiogenesis model. SEC alone isolated nano‐sized vesicles possessing vesicle markers TSG101 and CD9, but there was a substantial presence of apolipoprotein B, predominantly derived from very‐low‐ and intermediate‐density lipoprotein particles. This was reduced to an undetectable level using the combined UC DG SEC approach. Mass spectrometry identified 224 proteins in UC DG SEC isolates relative to the 135 from SEC, with considerable increases in exosome‐related proteins and reductions in lipoproteins. A consistent but limited increase in human dermal fibroblast proliferation and evidence of neovascularization enhancement were observed after exposure to UC DG SEC exosomes. An UC DG SEC purification protocol considerably improved the removal of lipoproteins during isolation of serum exosomes. The purified exosomes stimulated cell proliferation and potentially increased an in vivo angiogenic response. This multistep purification allows for more accurate identification of serum exosome functional activity and composition.
Frontiers in Bioengineering and Biotechnology, 2020
Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the ao... more Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the aorta (CoA) is one of the commoner CHD conditions, affecting around 1/1800 live births. CoA is considered a CHD of critical severity. Unfortunately, the prognosis for a child born in a low and lower-middle income country (LLMICs) with CoA is far worse than in a high-income country. Reduced diagnostic and interventional capacities of specialists in these regions lead to delayed diagnosis and treatment, which in turn lead to more cases presenting at an advanced stage. Computational fluid dynamics (CFD) is an important tool in this context since it can provide additional diagnostic data in the form of hemodynamic parameters. It also provides an in silico framework, both to test potential procedures and to assess the risk of further complications arising post-repair. Although this concept is already in practice in high income countries, the clinical infrastructure in LLMICs can be sparse, and access to advanced imaging modalities such as phase contrast magnetic resonance imaging (PC-MRI) is limited, if not impossible. In this study, a pipeline was developed in conjunction with clinicians at the Red Cross War Memorial Children's Hospital, Cape Town and was applied to perform a patient-specific CFD study of CoA. The pipeline uses data acquired from CT angiography and Doppler transthoracic echocardiography (both much more clinically available than MRI in LLMICs), while segmentation is conducted via SimVascular and simulation is realized using OpenFOAM. The reduction in cost through use of open-source software and the use of broadly available imaging modalities
The title compound 2, an electron-rich macrocyclic paracyclophane of the coronand type, known to ... more The title compound 2, an electron-rich macrocyclic paracyclophane of the coronand type, known to form a chargetransfer complex with paraquat, was found to encapsulate strontium cations and to bind to magnesium cations. X-ray analysis revealed that 2 forms a 2 : 1 (metal/substrate) complex with Sr(C104)2, in which the two benzene rings weakly overlap, whereas in the single crystals grown from Mg(C104)2, the metal cation prefers to lie outside the coronand (1 : 1 stoichiometry). In acetonitrile solution, cations were observed to trigger an hypsochromic shift of the UV absorption spectra, proportional to their size and charge density. The stoichiometries and binding constants were also determined by UV absorption titration in acetonitrile using the LETAGROP-SPEFO program for several monovalent and di
Objective: Constrictive external Nitinol meshes have been shown to suppress neointimal tissue for... more Objective: Constrictive external Nitinol meshes have been shown to suppress neointimal tissue formation and preserve endothelial integrity in vein grafts. As this mitigating effect increased with the degree of constriction, we investigated whether extreme constriction was possible without leading to detrimental luminal encroachment. Methods: A senescent non-human primate model (Chacma baboons/bilateral femoral interposition grafts) mimicking the clinical size-mismatch between vein grafts and runoff arteries was used. Control grafts were either untreated (group 1) or spray-coated with fibrin glue (group 2). Nitinol meshes constricting the lumen by <80% (group 3) were compared with longitudinally pleated meshes of identical circumference that constricted the lumen by >90% (group 4). Anastomotic size mismatch at implantation was expressed as quotient of cross-sectional area of runoff artery to vein graft (Q C). Results: At 6 months, all vein grafts without mesh support showed thick eccentric layers of neointimal tissue (group 1: 348 ؎ 130 m [Q C median at implant 0.19]; group 2: 318 ؎ 142 m [Q C median at implant 0.17]). Fibrin glue-spraying had no effect. In contrast, neointimal tissue was absent in all mesh-supported grafts (P < .007 in all cases) both at 6 weeks/6 months (group 3: 7.5 ؎ 8.8 m and 2.5 ؎ 4.4 m [Q C median at implant 1.47]; group 4: 1.3 ؎ 0.6 m and 3.8 ؎ 5.6 m [Q C median at implant 3.09]). Except for mild tissue buckling (fold height <356 m) in one group 3 graft, none of the mesh-constricted grafts showed wall folds. Endothelial coverage was only complete in the mesh-supported groups (100% in group 3 and 4 vs 85 ؎ 14%; P < .023 in group 1). Fibrin glue alone (52 ؎ 48%) did not preserve endothelialization of control grafts (P < .38). Conclusion: Extreme vein graft constriction using external Nitinol meshes is possible without detrimental tissue buckling. Although moderate constriction was found to be sufficient for mitigating diffuse intimal hyperplasia and endothelial detachment, extremer constriction may occasionally be required to eliminate luminal irregularities. (J Vasc Surg 2009; 49:1532-42.) Clinical Relevance: Neointimal proliferation holds a key to vein graft failure. Among the many factors contributing to the development of flow-limiting intimal hyperplasia, low shear stress and high circumferential wall stress play a key role. Constricting vein grafts with external meshes counters these forces through higher flow velocity and smaller diameters. Eliminating luminal irregularities additionally alleviates turbulences, a main trigger of focal stenoses. Being able to distinctly constrict vein grafts without creating folds protruding into the lumen will offer a clinical tool expected to distinctly improve the performance of vein grafts.
A significant reduction (p less than 0.0001) in plasma-free triiodothyronine (T3), which is known... more A significant reduction (p less than 0.0001) in plasma-free triiodothyronine (T3), which is known to have an inotropic effect, has been documented in patients undergoing open-heart procedures. To investigate the effect of this observation, 22 pigs underwent 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia during cardiopulmonary bypass (CPB) at 26 degrees C; the myocardium was protected by cardioplegic solution and cold saline solution at 30-minute intervals. After the pig was rewarmed to 37 degrees C, CPB was discontinued, and measurements of hemodynamic function were made 10 and 70 minutes later. Half of the pigs (Subgroup B) received 6 micrograms of T3 intravenously immediately after removal of the aortic cross-clamp; the remainder (Subgroup A) received no T3. After 2 hours of ischemia, untreated pigs showed significantly reduced myocardial function 10 minutes after discontinuation of CPB. By 70 minutes after the end of CPB, 2 of 5 untreated pigs (Subgroup A) had died of low cardiac output, but all 5 treated pigs (Subgroup B) survived. After 3 hours of ischemia, both groups showed some reduced function at 10 minutes, though the reduction was more marked in untreated animals. By 70 minutes, 4 of 6 untreated pigs had died of myocardial failure and all treated pigs remained alive (p less than 0.03). Surviving pigs in both groups still demonstrated some reduced function compared with values obtained before CPB. When all pigs are considered together, overall survival of those that did not receive T3 was significantly less than those that did (p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
In an attempt to avoid the destructive process of bioprosthetic heart-valve calcification associa... more In an attempt to avoid the destructive process of bioprosthetic heart-valve calcification associated with the use of glutaraldehyde, valves are today prepared using low concentrations of the crosslinking reagent. In this review, we summarize our findings and those of others that confirm that the immunogenicity of such tissue is not sufficiently masked and that a defined humoral response is indeed mounted against a repertoire of antigens unrelated to those associated with vascularized and non-cross-linked xenograft organs. We demonstrate the need for increased cross-linking of tissue to satisfactorily mitigate that response; furthermore, we examine the impact of increased cross-link density on the macrophage as antigen presenting cell with respect to its involvement in both tissue erosion and pannus overgrowth. Finally we present evidence for a role of circulating antibodies in bioprosthesis calcification.
Twenty years ago, on 2 December 1967, the first human allogeneic heart transplantation was perfor... more Twenty years ago, on 2 December 1967, the first human allogeneic heart transplantation was performed at Groote Schuur Hospital, Cape Town [1]. This operation was based on experimental work by Lower, Stofer, and Shumway [2]. During these 20 years, several notable advances have taken place in this field at Groote Schuur Hospital and elsewhere. The technique of endomyocardial biopsy allowed a precise diagnosis of whether or not acute rejection was present [3]. In 1973, heterotopic heart transplantation was initiated by Barnard and Losman [4]. Since the early 1980s, results of cardiac transplantations have dramatically improved, mainly as a result of the introduction of cyclosporin A and more precise donor and recipient selection [5]. Hormonal therapy for organ donors was introduced in 1983 [6]. In addition, more sophisticated noninvasive monitoring of acute rejection is being undertaken - cytoimmunological monitoring of the peripheral blood and radionuclide scanning of the transplanted heart [7, 8].
Background and Objectives: The Western Cape public pediatric cardiac service is under-resourced. ... more Background and Objectives: The Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service. Methods: An uncontrolled retrospective pre-post study of all presenting patients over two, one-year periods; the pre-COVID-19 period (01/03/2019-29/02/2020) and the peri-COVID-19 period (01/03/2020-28/02/2021). Results: Admissions decreased by 39% (624 to 378) and cardiac surgeries decreased by 29% (293 to 208) in the peri-COVID-19 period, with an increase in urgent cases (PR:5.99, 95%CI:3.58-10.02, p < 0.001). Age at surgery was lower in the peri-COVID-19 period, 7.2 (2.4-20.4) vs. 10.8 (4.8-49.2) months (p < 0.05), likewise, age at surgery for transposition of the great arteries (TGA) was lower
RNA interference is a promising therapeutical approach presently hindered by delivery concerns su... more RNA interference is a promising therapeutical approach presently hindered by delivery concerns such as rapid RNA degradation and targeting of individual tissues. Injectable hydrogels are one potentially simple and direct route towards overcoming these barriers. Here we report on the utility of a combination of a mildly modified form of the clinically utilised fibrin hydrogel with Invivofectamine® 3.0, a lipid nonviral transfection vector, for local and sustained release. PEGylation of fibrin allowed for controlled release of small interfering RNA (siRNA)-lipopolyplexes for at least 10 days and greatly increased the stability of fibrin in vitro and in vivo. A 3D cell culture model and a release study showed transfection efficacy of siRNA-lipopolyplexes was retained for a minimum of 7 days. Injection in conjunction with PEGylated-fibrinogen significantly increased retention of siRNA-lipopolyplexes in mouse skeletal muscle and enhanced knockdown of myostatin mRNA that correlated with m...
changes in survival rate or cell proliferation. However, it clearly promoted the induction of cel... more changes in survival rate or cell proliferation. However, it clearly promoted the induction of cell hypertrophy. Conclusion In summary, these preliminary data suggest that SIK2 might modulate the hypertrophic response of cardiac tissue during pathological insults. Conflict of Interest No BS25
Background Tetralogy of Fallot (ToF) and coarctation of the aorta (CoA) each constitute approxima... more Background Tetralogy of Fallot (ToF) and coarctation of the aorta (CoA) each constitute approximately 7% of congenital heart disease (CHD) births worldwide. Compared to developed countries, developing countries have a disparate level of access to prompt diagnosis and treatment for these diseases. Computational fluid dynamics (CFD) approaches implemented on routinely available non-invasive imaging data may yield low-cost improvements to the management of these patients. Purpose The purpose of this research is to develop a patient-specific computational pipeline that allows the modelling of blood flow in diseased arteries of patients suffering from ToF and CoA. The project aims to prove the feasible use of broadly available imaging techniques - CT angiograms (CTA) and echocardiographs (echo) - for achieving this in low-to-middle income countries. The capability of the pipeline will be demonstrated through a qualitative study of the effects of different systemic to pulmonary shunt conf...
Despite early realization of the need to control inherent immunogenicity of bioprosthetic replace... more Despite early realization of the need to control inherent immunogenicity of bioprosthetic replacement heart valves and thereby mitigate the ensuing host response and its associated pathology, including dystrophic calcification, the problem remains unresolved to this day. Concerns over mechanical stiffness associated with prerequisite high cross-link density to effect abrogation of this response, together with the insinuated role of leaching glutaraldehyde monomer in subsequent dystrophic mineralization, have understandably introduced compromises. These have become so entrenched as a benchmark standard that residual immunogenicity of the extracellular matrix has seemingly been relegated to a very subordinate role. Instead, focus has shifted toward the removal of cellular compartment antigens renowned for their implication in the failure of vascularized organ xenotransplants. While decellularization certainly offers advantages, this review aims to refocus attention on the unresolved m...
Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR)... more Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification. Three sizes were developed from nickel-cobalt-chromium MP35N alloy tubes: Small/23 mm, Medium/26 mm and Large/29 mm. Crimp-diameters of valves with both bioprosthetic (sandwich-crosslinked decellularized pe...
Journal of Cardiothoracic and Vascular Anesthesia, 2022
OBJECTIVES Large data sets have been published on short- and long-term outcomes following bidirec... more OBJECTIVES Large data sets have been published on short- and long-term outcomes following bidirectional Glenn surgery (BDG), or partial cavopulmonary connection, in high-income countries. Data from low-income and middle-income countries are few and often limited to the immediate postoperative period. The primary outcome was any in-hospital postoperative complication, assessed according to predefined criteria, in children who underwent BDG surgery at Red Cross War Memorial Children's Hospital. DESIGN A retrospective cohort study. SETTING A tertiary teaching hospital. PARTICIPANTS The study authors identified 61 children (<18 years of age) who underwent BDG over 8 years. The median age of patients undergoing BDG was 2.5 years (interquartile range, 1.4-5.5 years). INTERVENTIONS BDG surgery. MEASUREMENTS AND MAIN RESULTS Thirty-five patients (57.4%) had a postoperative complication, with some patients (17 of 61, 27.9%) having more than 1 complication. The most frequent complications were infective (29.5%). Univariate analysis found that postoperative complications were associated with the use of nitric oxide (p = 0.004) and a longer duration of anesthesia (p = 0.045) and surgery (p = 0.004). Patients with complications spent longer in the pediatric intensive care unit (ICU) (p < 0.001) and in the hospital (p < 0.012). On multivariate analysis, a priori risk factors based on previous studies were not found to be statistically significant. A total of 37.3% of patients completed their single-ventricle palliation, and 30.5% of patients were lost to follow-up. CONCLUSIONS Important findings were the older age at which the BDG was performed compared to high-income countries, an acceptable mortality rate of 3.3%, infection being the most common complication, the association of a complication with increased ICU and hospital lengths of stay, and the high rate of patients lost to follow-up.
Thesis(M.Sc.) -- University of Stellenbosch, 1986.Full text to be digitised and attached to bibli... more Thesis(M.Sc.) -- University of Stellenbosch, 1986.Full text to be digitised and attached to bibliographic record
Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a den... more Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric c...
Journal of Tissue Engineering and Regenerative Medicine, 2020
Due to the abundance of lipoproteins in blood, it is challenging to characterize the biological f... more Due to the abundance of lipoproteins in blood, it is challenging to characterize the biological functions and components of blood‐derived extracellular vesicles. The aim of this study was to develop a multiple‐step purification protocol to separate serum exosomes from serum proteins and lipoproteins and assess their regenerative potential. Exosomes were isolated by concentrating them in human serum using ultracentrifugation (UC), followed sequentially by density gradient (DG) UC and size exclusion chromatography (SEC). Purity and characterization were assessed by western blots, Lipoprint®, enzyme‐linked immunosorbent assay, electron microscopy, mass spectrometry, and nanoparticle tracking analysis. Functionality was assessed by cell proliferation analysis and with an in vivo subcutaneous angiogenesis model. SEC alone isolated nano‐sized vesicles possessing vesicle markers TSG101 and CD9, but there was a substantial presence of apolipoprotein B, predominantly derived from very‐low‐ and intermediate‐density lipoprotein particles. This was reduced to an undetectable level using the combined UC DG SEC approach. Mass spectrometry identified 224 proteins in UC DG SEC isolates relative to the 135 from SEC, with considerable increases in exosome‐related proteins and reductions in lipoproteins. A consistent but limited increase in human dermal fibroblast proliferation and evidence of neovascularization enhancement were observed after exposure to UC DG SEC exosomes. An UC DG SEC purification protocol considerably improved the removal of lipoproteins during isolation of serum exosomes. The purified exosomes stimulated cell proliferation and potentially increased an in vivo angiogenic response. This multistep purification allows for more accurate identification of serum exosome functional activity and composition.
Frontiers in Bioengineering and Biotechnology, 2020
Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the ao... more Congenital heart disease (CHD) is the most common birth defect globally and coarctation of the aorta (CoA) is one of the commoner CHD conditions, affecting around 1/1800 live births. CoA is considered a CHD of critical severity. Unfortunately, the prognosis for a child born in a low and lower-middle income country (LLMICs) with CoA is far worse than in a high-income country. Reduced diagnostic and interventional capacities of specialists in these regions lead to delayed diagnosis and treatment, which in turn lead to more cases presenting at an advanced stage. Computational fluid dynamics (CFD) is an important tool in this context since it can provide additional diagnostic data in the form of hemodynamic parameters. It also provides an in silico framework, both to test potential procedures and to assess the risk of further complications arising post-repair. Although this concept is already in practice in high income countries, the clinical infrastructure in LLMICs can be sparse, and access to advanced imaging modalities such as phase contrast magnetic resonance imaging (PC-MRI) is limited, if not impossible. In this study, a pipeline was developed in conjunction with clinicians at the Red Cross War Memorial Children's Hospital, Cape Town and was applied to perform a patient-specific CFD study of CoA. The pipeline uses data acquired from CT angiography and Doppler transthoracic echocardiography (both much more clinically available than MRI in LLMICs), while segmentation is conducted via SimVascular and simulation is realized using OpenFOAM. The reduction in cost through use of open-source software and the use of broadly available imaging modalities
The title compound 2, an electron-rich macrocyclic paracyclophane of the coronand type, known to ... more The title compound 2, an electron-rich macrocyclic paracyclophane of the coronand type, known to form a chargetransfer complex with paraquat, was found to encapsulate strontium cations and to bind to magnesium cations. X-ray analysis revealed that 2 forms a 2 : 1 (metal/substrate) complex with Sr(C104)2, in which the two benzene rings weakly overlap, whereas in the single crystals grown from Mg(C104)2, the metal cation prefers to lie outside the coronand (1 : 1 stoichiometry). In acetonitrile solution, cations were observed to trigger an hypsochromic shift of the UV absorption spectra, proportional to their size and charge density. The stoichiometries and binding constants were also determined by UV absorption titration in acetonitrile using the LETAGROP-SPEFO program for several monovalent and di
Objective: Constrictive external Nitinol meshes have been shown to suppress neointimal tissue for... more Objective: Constrictive external Nitinol meshes have been shown to suppress neointimal tissue formation and preserve endothelial integrity in vein grafts. As this mitigating effect increased with the degree of constriction, we investigated whether extreme constriction was possible without leading to detrimental luminal encroachment. Methods: A senescent non-human primate model (Chacma baboons/bilateral femoral interposition grafts) mimicking the clinical size-mismatch between vein grafts and runoff arteries was used. Control grafts were either untreated (group 1) or spray-coated with fibrin glue (group 2). Nitinol meshes constricting the lumen by <80% (group 3) were compared with longitudinally pleated meshes of identical circumference that constricted the lumen by >90% (group 4). Anastomotic size mismatch at implantation was expressed as quotient of cross-sectional area of runoff artery to vein graft (Q C). Results: At 6 months, all vein grafts without mesh support showed thick eccentric layers of neointimal tissue (group 1: 348 ؎ 130 m [Q C median at implant 0.19]; group 2: 318 ؎ 142 m [Q C median at implant 0.17]). Fibrin glue-spraying had no effect. In contrast, neointimal tissue was absent in all mesh-supported grafts (P < .007 in all cases) both at 6 weeks/6 months (group 3: 7.5 ؎ 8.8 m and 2.5 ؎ 4.4 m [Q C median at implant 1.47]; group 4: 1.3 ؎ 0.6 m and 3.8 ؎ 5.6 m [Q C median at implant 3.09]). Except for mild tissue buckling (fold height <356 m) in one group 3 graft, none of the mesh-constricted grafts showed wall folds. Endothelial coverage was only complete in the mesh-supported groups (100% in group 3 and 4 vs 85 ؎ 14%; P < .023 in group 1). Fibrin glue alone (52 ؎ 48%) did not preserve endothelialization of control grafts (P < .38). Conclusion: Extreme vein graft constriction using external Nitinol meshes is possible without detrimental tissue buckling. Although moderate constriction was found to be sufficient for mitigating diffuse intimal hyperplasia and endothelial detachment, extremer constriction may occasionally be required to eliminate luminal irregularities. (J Vasc Surg 2009; 49:1532-42.) Clinical Relevance: Neointimal proliferation holds a key to vein graft failure. Among the many factors contributing to the development of flow-limiting intimal hyperplasia, low shear stress and high circumferential wall stress play a key role. Constricting vein grafts with external meshes counters these forces through higher flow velocity and smaller diameters. Eliminating luminal irregularities additionally alleviates turbulences, a main trigger of focal stenoses. Being able to distinctly constrict vein grafts without creating folds protruding into the lumen will offer a clinical tool expected to distinctly improve the performance of vein grafts.
A significant reduction (p less than 0.0001) in plasma-free triiodothyronine (T3), which is known... more A significant reduction (p less than 0.0001) in plasma-free triiodothyronine (T3), which is known to have an inotropic effect, has been documented in patients undergoing open-heart procedures. To investigate the effect of this observation, 22 pigs underwent 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia during cardiopulmonary bypass (CPB) at 26 degrees C; the myocardium was protected by cardioplegic solution and cold saline solution at 30-minute intervals. After the pig was rewarmed to 37 degrees C, CPB was discontinued, and measurements of hemodynamic function were made 10 and 70 minutes later. Half of the pigs (Subgroup B) received 6 micrograms of T3 intravenously immediately after removal of the aortic cross-clamp; the remainder (Subgroup A) received no T3. After 2 hours of ischemia, untreated pigs showed significantly reduced myocardial function 10 minutes after discontinuation of CPB. By 70 minutes after the end of CPB, 2 of 5 untreated pigs (Subgroup A) had died of low cardiac output, but all 5 treated pigs (Subgroup B) survived. After 3 hours of ischemia, both groups showed some reduced function at 10 minutes, though the reduction was more marked in untreated animals. By 70 minutes, 4 of 6 untreated pigs had died of myocardial failure and all treated pigs remained alive (p less than 0.03). Surviving pigs in both groups still demonstrated some reduced function compared with values obtained before CPB. When all pigs are considered together, overall survival of those that did not receive T3 was significantly less than those that did (p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
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