Doctoral Degrees (General Internal Medicine)

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Browsing Doctoral Degrees (General Internal Medicine) by browse.metadata.advisor "Jacobs, Peter"

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    A historical perspective of allogeneic and autologous immunohaematopoietic stem cell transplantation in South Africa and a study of the non-haematologic consequences
    (Stellenbosch : Stellenbosch University, 2015-03) Wood, Lucille; Jacobs, Peter; Irusen, Elvis; Abayomi, Akin; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. General Internal Medicine.
    ENGLISH ABSTRACT: HISTORICAL PERSPECTIVE Stem cell therapy was commenced after using rabbits as research models. Once this process was successful, the first human transplant was done in 1974. Certain prerequisites were necessary and these were achieved - a protected environment, an apheresis unit, protocols and accreditation with International Registries. Initially, unmanipulated bone marrow and peripheral blood stem cells were used together with immunosuppressive drugs followed by the use of Cyclosporin A then the addition of ex vivo Campath®. AUDIT OF ACUTE ASSOCIATIONS (468 subjects in initial cohort) NEPHROLOGY Creatinine was used as an indication of renal function. Of the 76 available for analysis, 47% had acute kidney injury. Dialysis had a poor outcome as reported in the literature. Renal complications occurred frequently mostly due to infection. CARDIOLOGY A total of 119 individuals were available for analysis. Echocardiograms and electrocardiograms were part of pre-transplant assessment. Left ventricular systolic dysfunction predicted for increasing post transplant problems. Cardiac complications occurred at a lower frequency than other post-transplants side-effects consistent with the published data. DERMATOLOGY Cases were evaluated on a daily basis and referred to a dermatologist when necessary. To confirm Graft-Versus-Host Disease (GVHD), a skin biopsy was done to differentiate it from drug hypersensitivity or viral infections. The exposure to ex vivo Campath® significantly improved outcome by reducing the incidence and severity of GVHD. Quality of life was enhanced with substantial cost saving. GASTROENTEROLOGY Foregut symptoms occurred in 90% of patients. Nutritional problems were encountered. Altered liver functions were relatively common attributable to drugs, sepsis and conditioning regimens. Liver biopsies were not performed in this series and endoscopy performed only when necessary. A STUDY ON LATE COMPLICATIONS (55 subjects) RESPIRATORY Spirometry and diffusing capacity were done in this cohort. All the lung function studies were within the predicted normal range apart from some marginal reduction in diffusing capacity. In none of these patients did late consequences such as Bronchiolitis Obliterans Organising Pneumonia and Late Onset Non-Infectious Pulmonary complications occur. Cytomegalovirus reactivation was common but early intervention prevented serious complications. IMMUNOLOGY An in vitro functional study was done. Both the innate and adaptive systems were evaluated. Taken into consideration were the type of transplant, age from transplant, diagnosis and conditioning. The granulocyte Burst-test was done for the innate profile. Reduced activity was shown in all the subgroups. It appears as if the innate response of the granulocytic cells never recovered due to reduced granulocytic function in vitro. The adaptive responses were evaluated in vitro and only the autografts showed better CD4+ and CD8+ cytokine production. No major differences were seen in other groups. Normal cytokine production by CD4+ and CD8+ T cells were present when these were activated in vitro to produce regulatory cytokines, implying that their lymphoid component was intact post-transplant. BONE DISEASE Here both the Dual energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT) were used to evaluate bone mineral density. There was a discrepancy present between the two modalities. DXA showed no osteoporosis but QCT 22%. Biomarkers were normal in all. There was no history of fracture and no objective evidence of vertebral fractures using vertebral fracture assessment. Although QCT was used for the study, DXA remains the gold standard in South Africa. CONCLUSION This doctoral provided information on the non-haematological consequences in South Africa with the use of Campath® ex vivo.