36 results on '"Laker L"'
Search Results
2. The sequential effects of a multifactorial detergent based decellularization process on bovine pericardium
- Author
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Laker, L, primary, Dohmen, P M, additional, and Smit, F E, additional
- Published
- 2020
- Full Text
- View/download PDF
3. Impact of processing methods on bovine pericardial tissue integrity
- Author
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Botes, Lezelle, Smit, F. E., Dohmen, P. M., Laker, L., Botes, Lezelle, Smit, F. E., Dohmen, P. M., and Laker, L.
- Abstract
Introduction: The use of cardiac patches remains one of the main therapeutic solutions for surgical treatment. Cardiovascular patches are either synthetic or biological. Synthetic materials have become less popular over the years because they are rigid, have poor flexibility, are surgically difficult to handle, are prone to endocarditis and local inflammatory reactions that contributes to fibrosis and calcification, and have no regeneration potential. Autologous pericardium tends to retract, thicken, become aneurysmal and develop fibrosis once implanted. Therefore, xenogeneic transplanted tissue dominated by bovine pericardium has become an attractive alternative. Glutaraldehyde (GA)-fixation was introduced to overcome the aggressive recipient graft-specific rejection response, ensure sterility and to increase durability and mechanical stability. However, the residual GA toxicity and host immune responses seen in GA-preserved bovine pericardium causes degenerative processes that involves structural changes causing rigidity, shrinkage, calcium deposition and subsequent failure of the pericardial patch. Furthermore, GA limits host cell infiltration, remodeling and fails to remove or mask all animal specific antigens that contributes to chronic rejection. This resulted in several strategies to reduce the side-effects of GA-fixation and to provide alternatives to GA as a crosslinking agent but with mixed results. Therefore, nowadays basic research is focused to produce a scaffold with reduced antigenicity while maintaining structural integrity and create recellularization potential. Attempts to reduce antigenicity included decellularization (e.g., sodium dodecyl sulphate (SDS), Triton X-100 (TX), trypsin), enzymatic or gene knockout removal of epitopes, and solubilization-based antigen removal. The Frater Cardiovascular Research Centre developed a proprietary decellularization protocol. The aim of the study was to evaluate the potential application of this technology by
- Published
- 2020
4. PROLONGATION OF SEGMENTAL PANCREATIC ALLOGRAFTS WITH CYCLOSPORINE IN THE BABOON A PRELIMINARY REPORT
- Author
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DU TOIT, D. F., primary, HEYDENRYCH, J. J., additional, LOUW, G., additional, ZUURMOND, T., additional, ELS, D., additional, WOLFE-COOTE, S., additional, and LAKER, L., additional
- Published
- 1983
- Full Text
- View/download PDF
5. Segmental pancreatic allograft survival in primates treated with total-body or lymphoid irradiation and peroperative blood transfusions
- Author
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DU TOIT, D. F., primary, HEYDENRYCH, J. J., additional, SMIT, B., additional, ZUURMOND, T., additional, Louw, G., additional, LAKER, L., additional, ELS, D., additional, WOLFE-COOTE, S., additional, VAN DER MERWE, J. A., additional, and GROENEWALD, A. W., additional
- Published
- 1984
- Full Text
- View/download PDF
6. Segmental pancreatic allograft survival in primates treated with totalbody or lymphoid irradiation and peroperative blood transfusions
- Author
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TOIT, D. F. DU, HEYDENRYCH, J. J., SMIT, B., ZUURMOND, T., Louw, G., LAKER, L., ELS, D., WOLFE-COOTE, S., MERWE, J. A. VAN DER, and GROENEWALD, A. W.
- Published
- 1984
7. PROLONGATION OF SEGMENTAL PANCREATIC ALLOGRAFTS WITH CYCLOSPORINE IN THE BABOON A PRELIMINARY REPORT
- Author
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TOIT, D. F. DU, HEYDENRYCH, J. J., LOUW, G., ZUURMOND, T., ELS, D., WOLFE-COOTE, S., and LAKER, L.
- Published
- 1983
8. Synergy in a detergent combination results in superior decellularized bovine pericardial extracellular matrix scaffolds.
- Author
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Laker L, Dohmen PM, and Smit FE
- Subjects
- Animals, Cattle, Collagen drug effects, DNA chemistry, Deoxycholic Acid chemistry, Dogs, Drug Synergism, Elasticity, Octoxynol chemistry, Pericardium cytology, Sodium Dodecyl Sulfate chemistry, Tensile Strength, Tissue Engineering, Detergents pharmacology, Extracellular Matrix drug effects, Pericardium drug effects, Tissue Scaffolds chemistry
- Abstract
Decellularization involves removal of cellular material from tissue which results in a scaffold material consisting of only the extra cellular matrix (ECM). The effect of each individual decellularizing detergent on the final ECM scaffold and how that may differ from the combined use of these detergents is currently a gap in decellularization methodologies. This study evaluates the hypothesis that a synergistic effect exists when commonly used decellularization detergents are combined. This was evaluated with regard to decellularization efficiency, tissue strength, and collagen structure. Bovine pericardium was decellularized using a combination of 0.5% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate (SDC) and 1% TritonX-100, and compared to the use of each detergent individually. The combined detergent decellularization protocol showed effective decellularization (p = .004), with minimal effects on tissue strength (p = .21) and structure (p = .21). Use of detergents individually, resulted in detrimental effects on tissue structure and integrity or ineffective decellularization. This study shows a synergistic relationship between SDS, SDC and TritonX-100 when combined at specific concentrations. The use of detergents in combination instead of individually appears to be superior, as it results in less ECM damage and improved decellularization effectivity., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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- View/download PDF
9. Recovery of effective HIV-specific CD4+ T-cell activity following antiretroviral therapy in paediatric infection requires sustained suppression of viraemia.
- Author
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Adland E, Mori L, Laker L, Csala A, Muenchhoff M, Swordy A, Mori M, Matthews P, Tudor-Williams G, Jooste P, and Goulder P
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- CD8-Positive T-Lymphocytes immunology, Child, Child, Preschool, Female, Humans, Infant, Male, Viral Load, Anti-Retroviral Agents administration & dosage, CD4-Positive T-Lymphocytes immunology, HIV Infections drug therapy, HIV Infections immunology, Immune Reconstitution, Sustained Virologic Response
- Abstract
Background: The success of increasing access to antiretroviral therapy (ART) in paediatric HIV infection prompts the question of the potential for eradication of HIV infection in this age group. 'Shock-and-kill' HIV cure approaches, currently in development, may depend upon an effective antiviral T-cell response to eradicate virus-infected cells., Method: We here investigate the ability of HIV-infected children receiving ART from early childhood (median 24 months' age) to generate effective HIV-specific CD4 and CD8 T-cell immune responses that would facilitate future immune-based cure therapies., Results: Initial analysis of ART-naive HIV-infected children demonstrated that maintenance of normal-for-age absolute CD4 T-cell counts was strongly linked to high IL-2 production and polyfunctional HIV-specific CD4 T-cell responses (P < 0.0001 in each case). Low viral load was, similarly, strongly associated with markedly low IFN-γ and high IL-2 HIV-specific CD4 T-cell responses (P < 0.0001). In children receiving ART, establishment of this immune profile (high IL-2 and low IFN-γ HIV-specific T-cell production) was strongly related to the duration of viraemic suppression. Failure to suppress viraemia on ART, and even the successful suppression of viraemia interrupted by the occurrence of transient viraemia of more than 1000 HIV copies/ml, was associated with an immune profile of high IFN-γ and low IL-2 HIV-specific T-cell responses and low polyfunctionality., Conclusion: These data are consistent with recovery of functional CD4 T-cell responses in ART-treated children, in contrast to relative lack of CD4 T-cell function recovery described in ART-treated adults. However, the challenges of achieving long-term suppression of viraemia in ART-treated children through adolescence remain daunting.
- Published
- 2018
- Full Text
- View/download PDF
10. Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations.
- Author
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Malik A, Adland E, Laker L, Kløverpris H, Fardoos R, Roider J, Severinsen MC, Chen F, Riddell L, Edwards A, Buus S, Jooste P, Matthews PC, and Goulder PJR
- Subjects
- Adult, Africa South of the Sahara, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Young Adult, CD8-Positive T-Lymphocytes immunology, Cytomegalovirus immunology, Immunodominant Epitopes immunology
- Abstract
More than 90% of children in Africa are infected with cytomegalovirus (CMV) by the age of 12 months. However, the high-frequency, immunodominant CD8+ T-cell responses that control CMV infection have not been well studied in African populations. We therefore sought to define the immunodominant CMV-specific CD8+ T-cell responses within sub-Saharan African study subjects. Among 257 subjects, we determined the CD8+ T-cell responses to overlapping peptides spanning three of the most immunogenic CMV proteins, pp65, IE-1 and IE-2, using IFN-γ ELISpot assays. A bioinformatics tool was used to predict optimal epitopes within overlapping peptides whose recognition was statistically associated with expression of particular HLA class I molecules. Using this approach, we identified 16 predicted novel CMV-specific epitopes within CMV-pp65, IE-1 and IE-2. The immunodominant pp65-specific, IE-1, IE-2 responses were all either previously well characterised or were confirmed using peptide-MHC tetramers. The novel epitopes identified included an IE-2-specific epitope restricted by HLA*B*44:03 that induced high-frequency CD8+ T-cell responses (mean 3.4% of CD8+ T-cells) in 95% of HLA-B*44:03-positive subjects tested, in one individual accounting for 18.8% of all CD8+ T-cells. These predicted novel CMV-specific CD8+ T-cell epitopes identified in an African cohort will facilitate future analyses of immune responses in African populations where CMV infection is almost universal during infancy.
- Published
- 2017
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11. Tissue Engineered Small Vessel Conduits - The Anti-Thrombotic Effect of Re-Endothelialization of Decellularized Baboon Arteries: A Preliminary Experimental Study.
- Author
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Meiring M, Khemisi M, Laker L, Dohmen PM, and Smit FE
- Subjects
- Animals, Arteries growth & development, Blood Vessel Prosthesis veterinary, Endothelium, Vascular physiology, Extracellular Matrix physiology, Human Umbilical Vein Endothelial Cells physiology, Human Umbilical Vein Endothelial Cells transplantation, Humans, Papio, Perfusion, Platelet Activation, Preliminary Data, Thrombin pharmacology, Tissue Scaffolds, Arteries physiology, Tissue Engineering methods
- Abstract
BACKGROUND The use of decellularized biological scaffolds for the reconstruction of small-diameter vascular grafts remains a challenge in tissue engineering. Thrombogenicity is an important cause of obstruction in these vessels due to decellularization. Seeding of the decellularized vascular constructs with endothelial cells is therefore a prerequisite for the prevention of thrombosis. The aim of this study was to seed decellularized baboon arteries with endothelial cells and to compare the thrombogenicity to that of decellularized arteries after circulation of blood. MATERIAL AND METHODS Carotid, radial, and femoral arteries (12 arteries in total) were harvested from 2 Papio ursinus baboons. Ten arteries were decellularized. Normal morphology was confirmed in the control vessels. The effect of re-endothelialization was studied in the vessel scaffolds using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Decellularization resulted in vessel scaffolds with well-preserved extracellular matrix and intact basal membranes. Six of the decellularized vessel scaffolds were seeded with viable human umbilical vein endothelial cells (HUVEC). Luminal endothelialization was established after 7 days in a bioreactor and SEM confirmed confluency. Two control, 4 decellularized, and 6 decellularized re-endothelialized vessel scaffolds were studied in an in vitro flow chamber using baboon blood. RESULTS The decellularized arteries showed an absence of endothelial lining, and an intact basement membrane. The seeding process produced a complete endothelial layer on the surfaces of the arteries. After perfusion with whole blood, no thrombi were formed in the control arteries and re-endothelialized vessels. Widespread platelet activation and adhesion occurred in the decellularized vessels despite a relatively intact basal membrane. CONCLUSIONS This study supports the development of re-endothelialized tissue engineered small-vessel conduits.
- Published
- 2017
- Full Text
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12. Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.
- Author
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Mori M, Adland E, Paioni P, Swordy A, Mori L, Laker L, Muenchhoff M, Matthews PC, Tudor-Williams G, Lavandier N, van Zyl A, Hurst J, Walker BD, Ndung'u T, Prendergast A, Goulder P, and Jooste P
- Subjects
- Adolescent, CD4 Lymphocyte Count, Child, Child, Preschool, Cohort Studies, Female, HIV Infections epidemiology, HIV Infections pathology, Humans, Incidence, Infant, Infant, Newborn, Male, Severity of Illness Index, Sex Factors, South Africa epidemiology, Treatment Outcome, Viral Load drug effects, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy
- Abstract
The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex.
- Published
- 2015
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13. Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection.
- Author
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Adland E, Paioni P, Thobakgale C, Laker L, Mori L, Muenchhoff M, Csala A, Clapson M, Flynn J, Novelli V, Hurst J, Naidoo V, Shapiro R, Huang KH, Frater J, Prendergast A, Prado JG, Ndung'u T, Walker BD, Carrington M, Jooste P, and Goulder PJ
- Subjects
- Adult, Child, Cohort Studies, Disease Progression, Humans, Polymerase Chain Reaction, HIV Infections genetics, HIV-1 physiology, HLA Antigens genetics, Virus Replication genetics
- Abstract
HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.
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- 2015
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14. Takayasu's disease. A report of 3 cases.
- Author
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du Toit DF, Warren B, McCormich M, and Laker L
- Subjects
- Adult, Female, Humans, Prednisone therapeutic use, Aortic Arch Syndromes drug therapy, Takayasu Arteritis drug therapy
- Abstract
Three patients with Takayasu's disease are described. In 2 cases aortography demonstrated an occlusion of the great vessels at the origin of the arch of the aorta. In 1 patient there was concomitant aneurysmal dilatation of the brachiocephalic trunk. Common and internal carotid artery stenosis occurred in 1 patient and was associated with hemiplegia and blindness. All 3 patients had constitutional symptoms and signs of the disease as well as markedly elevated erythrocyte sedimentation rates; 2 patients had moderate clinical responses to steroid administration in the short term and 1 developed bilateral calf vein thrombosis, which responded satisfactorily to conservative management.
- Published
- 1985
15. Intraperitoneal transplantation of vascularized segmental pancreatic autografts without duct ligation in the primate.
- Author
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Du Toit DF, Heydenrych JJ, Louw G, Zuurmond T, Els D, Wolfe-Coote S, and Laker L
- Subjects
- Animals, Arteriovenous Shunt, Surgical, Blood Glucose analysis, Diabetes Mellitus, Experimental surgery, Female, Glucose Tolerance Test, Male, Pancreas ultrastructure, Pancreatitis etiology, Papio, Peritoneal Cavity, Potassium blood, Thrombophlebitis etiology, Transplantation, Autologous methods, Pancreas Transplantation
- Abstract
The aim of this study was to determine whether diabetes could be ameliorated in totally pancreatectomized baboons by heterotopic intraperitoneal autotransplantation of the tail of the pancreas with the duct unligated. Twenty-five baboons were made diabetic by total pancreatectomy. Six untreated pancreatectomized animals survived a median of 5 days with mean (+/- SE) plasma glucose levels of 18 +/- 1.37 mmol/L and mean (+/- SE) potassium (K) values of 0.36 +/- 0.02% before death. Successful autotransplantation of the tail of the pancreas rendered pancreatectomized baboons consistently normoglycemic. Intravenous glucose tolerance tests performed 6 weeks after transplantation in 12 autograft recipients showed glucose intolerance in 12 of 14 recipients, and K values were significantly reduced to 1.03 +/- 0.015% (P less than 0.05). The K value of 40 normal baboons was 2.18 +/- 0.15. Histologic examination of successfully transplanted autografts of 12 animals at 6 weeks showed islets with intact beta and alpha cells, atrophy of the exocrine pancreas, graft fibrosis, and a cellular infiltration of the mononuclear type. The addition of a distal arteriovenous fistula to the graft did not reduce the incidence of graft vessel thrombosis, and all five animals died of hemorrhagic pancreatitis and venous thrombosis within 24 hours of transplantation.
- Published
- 1983
16. Prolongation of intraperitoneal segmental pancreatic allografts in primates receiving cyclosporin A.
- Author
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Du Toit DF, Heydenrych JJ, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, and Davids H
- Subjects
- Animals, Cyclosporins blood, Female, Male, Papio, Peritoneum surgery, Transplantation Immunology drug effects, Transplantation, Homologous, Cyclosporins pharmacology, Graft Survival, Pancreas Transplantation
- Abstract
In this study the efficacy of the new immunosuppressive agent, cyclosporin A (CYA), was examined in a model of segmental, intraperitoneal pancreatic allotransplantation with free duct drainage in totally pancreatectomized, outbred Chacma baboons. CYA, in doses of 25 to 50 mg/kg/day administered to recipients of heterotopic segmental (tail) allografts, produced a slight but significant prolongation of graft survival. CYA (25 to 85 mg/kg/day), administered orally after pancreatic transplantation gave daily serum trough levels of CYA that ranged from 300 to 600 ng/ml. Mean serum trough levels on the first postoperative day in recipients of 50 mg/kg/day were 121.1 +/- 61.6 ng/ml. There was a wide variation in daily serum trough levels exhibited between primates on the same daily oral dose, and there was no correlation between absolute serum trough levels of CYA and rejection. It is postulated that adequate serum CYA levels were not achieved by the oral administration of the drug to ensure allograft survival beyond 60 days in pancreatectomized recipients. Adverse effects occurred frequently and included anorexia, diarrhea, and tremors and were in direct proportion to the quantity of CYA required to prolong graft survival. Free duct drainage into the abdominal cavity frequently resulted in pancreatic ascites, which necessitated paracentesis, indicating that this method of duct drainage has limited clinical application. Although heterotopic autotransplantation or allotransplantation of the tail of the pancreas in the baboon was capable of maintaining normoglycemia in pancreatectomized baboons, glucose intolerance, reduced K values, and hypoinsulinemia were consistent findings during glucose tolerance tests, suggesting that an insufficient islet cell mass had been transplanted.
- Published
- 1984
17. Buerger's disease. A case report and review of the literature.
- Author
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du Toit DF, Maritz J, Klompje J, Laker L, and Groenewald JH
- Subjects
- Adult, Amputation, Surgical, Fingers surgery, Gangrene, Humans, Leg surgery, Male, Recurrence, Smoking, Thumb surgery, Thromboangiitis Obliterans pathology, Thromboangiitis Obliterans surgery
- Abstract
A case of thrombo-angiitis obliterans (Buerger's disease) in a 30-year-old man is reported. Irremediable gangrene necessitated amputation of both legs, and distal amputation of the fingers and thumb of the right hand.
- Published
- 1984
18. Diabetes in pancreatectomized baboons: a model for pancreatic transplantation studies.
- Author
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Du Toit DF, Heydenrych JJ, Louw G, Zuurmond T, Laker L, Smit B, Els D, Weideman A, Davids H, and Wolfe-Coote S
- Subjects
- Animals, Blood Glucose analysis, Female, Glucose Tolerance Test, Insulin blood, Male, Pancreatectomy, Diabetes Mellitus, Experimental blood, Disease Models, Animal, Pancreas Transplantation, Papio
- Abstract
This study was designed to assess plasma glucose levels (PLG) and insulin release in totally pancreatectomized baboons when challenged with intravenous glucose administration (IVGTT). Ten animals (Papio ursinus) were used and duodenectomy was intentionally avoided. The PLG at death was 18.0 +/- mmol/L, and the mean K-value within 3 days after pancreatectomy was 0.4% +/- 0.2%, indicating a significant impairment of glucose disappearance from the blood when compared to the control animals (P less than 0.01). Plasma insulin levels before and after stimulation with glucose were below the lowest level of insulin assay sensitivity. We conclude that in the primate, as in the dog, surgical pancreatectomy produced a reliable diabetic model, which is uniformly lethal if left untreated.
- Published
- 1987
- Full Text
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19. The effect of corticosteroid therapy on lysosomal enzymes and protein and lipid metabolism in rabbit lung after administration of Freund's adjuvant.
- Author
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Engelbrecht FM, Blom M, Laker L, and Badenhorst E
- Subjects
- Acid Phosphatase metabolism, Animals, Bronchi cytology, Glucuronidase metabolism, Lipids biosynthesis, Methylprednisolone pharmacology, Methylprednisolone Acetate, Pneumonia chemically induced, Protein Biosynthesis, Pulmonary Alveoli cytology, Rabbits, Freund's Adjuvant adverse effects, Lung metabolism, Methylprednisolone analogs & derivatives, Pneumonia metabolism
- Abstract
The effect of corticosteroid therapy on the broncho-alveolar cell response, the changes in activity of some lysosomal enzymes and the protein and lipid biosynthesis rates in lung tissue of normal rabbits and of rabbits after induction of an acute inflammation by the intravenous injection of complete Freund's adjuvant (CFA) 0,2 ml/kg body weight was investigated. Three intramuscular injections of methylprednisolone acetate (Depo-Medrol) 1,2 mg/kg over a period of 8 days reduced the mean total broncho-alveolar free cell yields significantly. The percentages of lymphocytes and granulocytes were decreased. The increase in the macrophage percentage was associated with a significant increase in the acid phosphatase activity of the broncho-alveolar cells. The beta-glucuronidase activity, on the other hand, was lowered in alveolar cells and even significantly suppressed in lung tissue. Protein and lipid biosynthesis was significantly retarded in lung tissue 8 days after the start of therapy. Administration of a single dose of CFA 0,2 ml/kg evoked an acute lung inflammation and a significant increase in total alveolar free cell yields. The macrophage percentage was reduced and the lymphocyte numbers doubled, whereas the granulocyte percentage increased more than sevenfold. The change in the percentage distribution of granulocytes may be associated with the marked increase in beta-glucuronidase activity of the cells as well as of the lung tissue. In the inflammatory phase, protein biosynthesis was significantly increased but lipid synthesis was not affected. Corticosteroid therapy in animals treated with adjuvant reversed all the effects of CFA. It has very pronounced anti-inflammatory action and a catabolic effect on protein and lipid metabolism.
- Published
- 1982
20. Experimental vascularized segmental pancreatic and islet transplantation in the baboon.
- Author
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du Toit DF, Heydenrych JJ, Smit B, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, and van der Merwe EA
- Subjects
- Animals, Cyclosporins therapeutic use, Female, Immunosuppression Therapy, Male, Papio, Whole-Body Irradiation, Islets of Langerhans Transplantation, Pancreas Transplantation
- Published
- 1984
- Full Text
- View/download PDF
21. Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate.
- Author
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Du Toit DF, Heydenrych JJ, Smit B, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, and Du Toit LB
- Subjects
- Animals, Female, Lymphoid Tissue radiation effects, Male, Pancreas physiology, Pancreatic Function Tests, Papio, Particle Accelerators, Whole-Body Irradiation, Immunity radiation effects, Immunosuppression Therapy, Pancreas Transplantation, Transplantation Immunology
- Abstract
The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.
- Published
- 1986
- Full Text
- View/download PDF
22. Recurrent pancreatitis after partial ileal bypass for hyperlipidaemia. A case report.
- Author
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Du Toit DF, Knott-Craig C, and Laker L
- Subjects
- Acute Disease, Adult, Ethanol adverse effects, Humans, Hyperlipidemias complications, Male, Parenteral Nutrition, Total, Postoperative Complications, Recurrence, Hyperlipidemias surgery, Ileum surgery, Pancreatitis etiology
- Abstract
The case of a 28-year-old man with alcohol-induced bouts of recurrent acute pancreatitis after a partial ileal bypass performed for hyperlipidaemia is presented. Serial computed tomography proved valuable for assessing the resolution of the pancreatic mass. Peripheral parenteral hyperalimentation for 6 weeks had a beneficial effect on the course of the pancreatitis and proved to be useful for nutritional support.
- Published
- 1985
23. [Infection of artificial vascular prostheses. Case reports].
- Author
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du Toit DF and Laker L
- Subjects
- Aged, Humans, Male, Middle Aged, Polyethylene Terephthalates, Polytetrafluoroethylene, Postoperative Complications, Blood Vessel Prosthesis, Staphylococcal Infections etiology
- Abstract
Four patients with prosthetic graft infection are presented. In 3 patients infection occurred in a Dacron aortobifemoral graft. In all 4 patients the infection originated at the femoral anastomoses. In 2 patients the entire aortofemoral graft was removed; one patient died of septicaemia and the other required an above-knee amputation. In 1 patient partial removal of the graft limb proved successful after a femorofemoral bypass using an autogenous venous graft. Above-knee amputation was performed in a further patient after removal of an infected axillofemoral graft. Staphylococcus was consistently isolated from the infected grafts in all the patients.
- Published
- 1985
24. Hydatid cyst of the pancreatic tail. A case report.
- Author
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du Toit DF, Loxton AJ, Laker L, and Dreyer JF
- Subjects
- Aged, Calcinosis, Echinococcosis diagnostic imaging, Female, Humans, Pancreatic Cyst diagnostic imaging, Radiography, Ultrasonography, Echinococcosis surgery, Pancreatic Cyst surgery
- Abstract
A case of calcified hydatid cyst of the pancreatic tail is presented. The ultrasonographic and computed tomographic features of the lesion suggested the presence of a cystadenoma or a calcified hydatid cyst. Computed tomography proved the most useful investigation and accurately localized the lesion. A distal pancreatectomy and splenectomy were performed because on the basis of the results of pre-operative investigations and macroscopic operative findings, carcinoma of the pancreatic tail could not be ruled out with certainty. The patient made an uneventful recovery.
- Published
- 1984
25. [The role of transluminal angioplasty in vascular surgery].
- Author
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du Toit DF and Laker L
- Subjects
- Humans, Angioplasty, Balloon, Vascular Surgical Procedures
- Published
- 1984
26. Extracranial internal carotid artery aneurysm. A case report.
- Author
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du Toit DF, van Zyl JA, Laker L, and Groenewald JH
- Subjects
- Adult, Carotid Artery, Internal surgery, Humans, Male, Aneurysm surgery, Carotid Artery Diseases surgery
- Abstract
A patient with an asymptomatic, right-sided internal carotid artery aneurysm is reported. The entity was accurately located and diagnosed pre-operatively by utilizing a duplex ultrasonographic scanner. Treatment comprised aneurysmectomy and restoration of arterial continuity by autogenous venous grafting. The patient recovered without the occurrence of any sequelae.
- Published
- 1984
27. Hepatic abscess in a patient with polycystic liver disease. A case report.
- Author
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du Toit DF, van Schalkwyk P, and Laker L
- Subjects
- Adult, Female, Humans, Cysts complications, Liver Abscess complications, Liver Diseases complications, Polycystic Kidney Diseases complications
- Abstract
A patient with a liver abscess and underlying polycystic renal and liver disease is described. The liver abscess was diagnosed on the clinical findings and accurately localized by ultrasonography. Tube drainage and antibiotic administration resulted in a rapid recovery. The polycystic liver disease, which was previously undiagnosed and asymptomatic, was an unexpected finding at laparotomy.
- Published
- 1985
28. Bleeding from varicose vein--still potentially fatal. A case report.
- Author
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du Toit DF, Knott-Craig C, and Laker L
- Subjects
- Female, Humans, Middle Aged, Hemorrhage etiology, Varicose Ulcer complications
- Abstract
A 57-year-old woman was admitted to hospital with spontaneous profuse haemorrhage from a small acute varicose ulcer of the left leg. She was in shock, semicomatose and anaemic because of blood loss. The haemorrhage was easily controlled by elevating the leg, applying compression bandages and administering a blood transfusion. The patient made an uneventful recovery.
- Published
- 1985
29. Deep-vein thrombosis in pregnancy. A case report.
- Author
-
du Toit DF, McCormich M, and Laker L
- Subjects
- Adult, Female, Humans, Pregnancy, Thrombophlebitis diagnosis, Heparin therapeutic use, Pregnancy Complications, Cardiovascular drug therapy, Thrombophlebitis drug therapy
- Abstract
The incidence of thrombo-embolic complications in pregnancy varies between 2 and 5 per 1000 deliveries. Deep-vein thrombosis (DVT) is classically associated with pulmonary embolism and chronic venous insufficiency, which are leading causes of maternal morbidity and mortality. An accurate diagnosis of iliofemoral or calf vein thrombosis should be confirmed by either Doppler ultrasonography, impedance plethysmography or ascending phlebography. Full-dose continuous intravenous heparin for 5-10 days is the established method of therapy for acute DVT and pulmonary embolism occurring during pregnancy or in the puerperium. Thereafter, long-term treatment with self-administered subcutaneous injections of heparin in low doses is feasible and effective. During pregnancy, coumarin administration results in embryopathy as it readily crosses the placenta; it should be avoided until after delivery. In view of its safety and effectiveness, low-dosage intravenous heparin or heparin by subcutaneous injection seems to be the anticoagulant of choice for the expectant mother.
- Published
- 1985
30. Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report.
- Author
-
du Toit DF, Heydenrych JJ, Smit B, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, and van der Merwe EA
- Subjects
- Animals, Blood Glucose analysis, Blood Transfusion, Combined Modality Therapy, Cyclosporins blood, Female, Glucose Tolerance Test, Immunosuppression Therapy methods, Lymphoid Tissue radiation effects, Male, Pancreas pathology, Pancreatectomy, Papio, Time Factors, Cyclosporins therapeutic use, Graft Survival drug effects, Graft Survival radiation effects, Pancreas Transplantation, Whole-Body Irradiation adverse effects
- Abstract
The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 X 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 X 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 X 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 X 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients. Some immunosuppressive regimens gave modest graft survival, none resulted in indefinite graft survival, and there was considerable toxicity with many of the regimens. Although CS administration alone or in combination with irradiation resulted in modest pancreatic allograft survival in this model, the place of CS combined with TBI or TLI or other chemical immunosuppressive agents remains to be defined.
- Published
- 1985
31. Organ allotransplantation since the advent of cyclosporin.
- Author
-
Du Toit DF, Heydenrych JJ, and Laker L
- Subjects
- Azathioprine therapeutic use, Bone Marrow Transplantation, Heart Transplantation, Humans, Islets of Langerhans Transplantation, Kidney Transplantation, Liver Transplantation, Cyclosporins therapeutic use, Immunosuppression Therapy, Transplantation, Homologous
- Abstract
Successful long-term organ transplantation has been made possible by the use of conventional immunosuppression. In contrast with transplantation of other organs, transplantation of the kidney has become an accepted successful form of therapy, 80% of patients being fully rehabilitated. However, complications of therapy are frequent and severe and include bone necrosis, cataract formation, infections and stunted growth in children. The discovery of the immunosuppressive properties of cyclosporin A (CYA) by Borel in 1976 offered new hope to recipients of hepatic, cardiac, pancreatic and heart-lung transplants, since rejection frequently resulted in death. Although the use of CYA has led to significant accomplishments, subsequent studies have documented deleterious side-effects including nephrotoxicity, hepatotoxicity, hirsutism, gingival hyperplasia, tremors and tumours. Yet despite the side-effects, CYA has proved to be a promising immunosuppressive agent for use in human organ transplantation and is at present being evaluated in transplant centres throughout the world.
- Published
- 1985
32. Gangrene of the hand and forearm after inadvertent intra-arterial injection of pyrazole. A case report.
- Author
-
Du Toit DF, Sunshine M, Knott-Craig C, and Laker L
- Subjects
- Adult, Humans, Injections, Intra-Arterial adverse effects, Male, Pyrazoles administration & dosage, Forearm, Gangrene chemically induced, Hand, Pyrazoles adverse effects
- Abstract
A case of gangrene of the hand following inadvertent intra-arterial injection of a pyrazole derivative (Tomanol) is presented. Gangrene of the hand and superficial sloughing of the distal arm necessitated a forearm amputation. Because of the serious sequelae, precautions must be taken to avoid inadvertent intra-arterial injections and due consideration must be given to the anatomical variation of the brachial artery and its branches in the cubital fossa.
- Published
- 1985
33. The effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study.
- Author
-
Du Toit DF, Heydenrych JJ, Smit B, Zuurmond T, Louw G, Laker L, Els D, Weideman A, Wolfe-Coote S, and Du Toit LB
- Subjects
- Animals, Bone Marrow pathology, Bone Marrow radiation effects, Female, Glucose Tolerance Test, Immunoenzyme Techniques, Insulin metabolism, Male, Necrosis pathology, Pancreas metabolism, Pancreas pathology, Pancreatectomy, Papio, Radiation Dosage, Radiation Injuries, Experimental metabolism, Whole-Body Irradiation, Pancreas radiation effects, Radiation Injuries, Experimental pathology
- Abstract
In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.
- Published
- 1987
- Full Text
- View/download PDF
34. Early postoperative pancreatic endocrine function after segmental and pancreaticoduodenal allotransplantation in nonimmunosuppressed primates.
- Author
-
Du Toit DF, Heydenrych JJ, Smit B, Louw G, Zuurmond T, Laker L, Els D, Weideman A, Wolfe-Coote S, and Du Toit L
- Subjects
- Animals, Blood Glucose analysis, Glucagon metabolism, Glucose Tolerance Test, Insulin metabolism, Insulin Secretion, Methods, Pancreatectomy, Papio, Postoperative Period, Transplantation, Homologous, Duodenum transplantation, Immunosuppression Therapy, Islets of Langerhans metabolism, Pancreas Transplantation
- Abstract
In this study we evaluated the short-term hormonal effects of segmental and whole pancreatic allotransplantation on the glucose intolerance produced by hemipancreatectomy in the primate. In hemipancreatectomized animals without grafts the K-values were reduced to 0.6 +/- 0.05, plasma insulin increased from 27.5 +/- 2.5 to 63.5 +/- 6.3 microU/ml, and glucagon levels declined from 252 +/- 29.9 to 216.5 +/- 33.0 pg/ml. Hemipancreatectomized segmental allograft recipients rendered K-values of 0.79 +/- 0.05, plasma insulin increased from 19.98 +/- 3.43 to 66.0 +/- 17.03 microU/ml, and glucagon release declined from 395.6 +/- 63.0 to 226.2 +/- 37.6 pg/ml during IVGTT postoperatively. Hemipancreatectomized, pancreaticoduodenal allograft recipients rendered K-values of 0.82 +/- 0.1, results not significantly different from hemipancreatectomized or segmental allograft recipients. Plasma insulin increased from 29.5 +/- 4.0 to 186.0 +/- 25.0 microU/ml, and glucagon release declined from 1,087.0 +/- 31.6 to 656.0 +/- 12.7 pg/ml. In summary, segmental pancreatic allotransplantation could not, in the short-term, restore the reduced K-values and hypoinsulinaemia in hemipancreatectomized primates to that of normal, unstressed controls. Although K-values of hemipancreatectomized recipients were not significantly improved, whole pancreas transplantation resulted in improved insulin release and hyperglucagonaemia during IVGTT when compared to segmental allograft recipients. The unexpected findings of hypoinsulinaemia and hyperglucagonaemia in both transplant groups may only reflect a function of the stressed state of the animals in the immediate postoperative phase.
- Published
- 1987
- Full Text
- View/download PDF
35. Intrahepatic gallstones. A case report.
- Author
-
du Toit DF, Retief A, Laker L, Warren B, and van Zyl JA
- Subjects
- Acute Disease, Adult, Bile Duct Diseases complications, Bile Duct Diseases surgery, Cholecystitis complications, Cholelithiasis complications, Female, Gallstones complications, Humans, Bile Ducts, Intrahepatic, Cholelithiasis surgery, Gallstones surgery
- Abstract
A Coloured woman was admitted to hospital with a 3-day history of acute right upper abdominal pain, nausea and vomiting. Acute cholecystitis was confirmed by biliary imaging using technetium-99m. An acutely inflamed gallbladder and two pigment stones in the common bile duct were removed. There were numerous retained gallstones in biliary radicles of the right hepatic duct; attempts to dislodge these by saline flushing failed. An extended choledochotomy with further exploration of the intrahepatic radicles also failed to remove the incarcerated stones. Biliary enteric drainage was achieved by choledochoduodenostomy and short-term postoperative progress was uneventful.
- Published
- 1985
36. Syphilitic aortitis. A case report.
- Author
-
du Toit DF, McCormich M, and Laker L
- Subjects
- Humans, Male, Middle Aged, Arteriosclerosis complications, Syphilis, Cardiovascular complications
- Abstract
A case of syphilitic aortitis with total occlusion of the infrarenal aorta without aneurysmal dilatation is presented. Incapacitating claudication of both legs together with pain at rest necessitated an aortobifemoral bypass operation, which resulted in complete relief of symptoms. Histological examination of the aorta showed atherosclerosis together with characteristic perivascular lymphocytic infiltration of the aortic vasa vasorum.
- Published
- 1985
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