Browsing by Author "Jacobs, P."

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    AIDS defining lymphomas in the era of highly active antiretroviral therapy (HAART) - An African perspective
    (2007) Sissolak, G.; Abayomi, E. A.; Jacobs, P.
    The intermediate to high grade B-cell non-Hodgkin lymphomas are now one of three malignant AIDS defining conditions. The others being Kaposi's sarcoma and cervical carcinoma. While co-infection with oncogenic agents including the human herpes 8 or Epstein-Barr virus offer targets in preventive treatment strategies for these AIDS defining lymphomas (ADL), administration of highly active antiretroviral therapy leading to immune reconstitution permits use of standard or even high-dose cytotoxic drug regimens with curative intent. It is not certain whether this should be done concomitantly or sequentially. Additional benefit may derive from infusional or high-dose chemotherapy regimens depending on the histological subtype while use of monoclonal antibodies such as rituximab or immunohaematopoietic stem cell transplantation needs to be further evaluated within controlled studies. Socio-economic considerations have an impact especially in resource limited settings while availability of tools for appropriate geno-phenotypic diagnosis and immunological monitoring such as the CD4 cell count will play an important role in the risk stratification as well as disease management. While it is generally accepted that the impact of HAART has an overall benefit both in incidence and treatment outcome in ADL, the expanded access to HAART programs are falling short of all targets in Africa. Accordingly focus is given to some of these controversies, including epidemiology, pathogenesis, clinical features, therapeutic options and ethical considerations. © 2007 Elsevier Ltd. All rights reserved.
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    Haematology in 2010 - Part I
    (The Specialist Forum, 2010) Wood, L.; Jacobs, P.; Abayomi, E. A.
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    Haematopoitic and cardiovascular complications in patients infected with the human immunodeficiency virus
    (Resources in Cardiovascular Science, 2009) Sissolak, G.; Andrews, S.; Abayomi, E. A.; Jacobs, P.
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    Haemochromatosis : phenotype to genotype or man to molecules
    (Health and Medical Publishing Group (HMPG), 2013-06) Jacobs, P.; Wood, L.
    This is the third in our vignettes that are centred on everyday clinical presentations. Each emphasises practical aspects of team-based care that are applicable to general practitioners, specialists and paramedical professionals alike. Iron-overload syndromes, whether genetically or environmentally determined, increase morbidity and mortality. Familial haemochromatosis, as the prototype, may have a prolonged subclinical phase before presenting with dermatological, hepatic, pancreatic, cardiac, musculoskeletal or endocrine symptoms and signs. Improved understanding of iron metabolism, coupled with genetic testing, underlines current approaches to screening, diagnosis and proactive multidisciplinary management encompassing appropriate family studies. These changed circumstances strongly emphasise the need for much wider appreciation of hazards associated with accumulation of this trace metal above physiological limits and benefits of early, or pre-emptive, correction.
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    Immunohematopoietic stem cell transplantation in Cape Town: A ten-year outcome analysis in adults
    (2009) Wood, L.; Haveman, J.; Juritz, J.; Waldmann, H.; Hale, G.; Jacobs, P.
    BACKGROUND AND OBJECTIVES: Immunohematopoietic stem cell transplantation has curative potential in selected hematologic disorders. Stem cell transplantation was introduced into South Africa in 1970 as a structured experimental and clinical program. In this report, we summarize the demography and outcome by disease category, gender, and type of procedure in patients older than 18 years of age who were seen from April 1995 to December 2002. PATIENTS AND METHODS: This retrospective analysis included 247 individuals over 18 years of age for whom complete data were available. These patients received grafts mostly from peripheral blood with the appropriate stem cell population recovered by apheresis. RESULTS: Patient ages ranged from 20 to 65 years with a median age of 42 years. There were 101 females and 146 males. There were no withdrawals and 63% survived to the end of the study. At 96 months of follow-up, a stable plateau was reached for each disease category. Median survival was 3.3 years (n=6, 14.6%) for acute lymphoblastic anemia, 3.1 years (n=44, 18%) for acute myeloid leukemia, 2.8 years (n=47, 19%) for chronic granulocytic leukemia, 2.8 years (n=71, 29%) for lymphoma, 1.5 years (n=23, 9%) for myeloma, 1.43 years (n=10, 4%) for aplasia, and 1.4 years (n=38, 15%) for a miscellaneous group comprising less than 10 examples each. Multivariate analysis showed that only diagnosis and age had a significant impact on survival, but these two variables might be interrelated. There was no significant difference in outcome by source of graft. CONCLUSION: The results confirm that procedures carried out in a properly constituted and dedicated unit, which meets established criteria and strictly observes treatment protocols, generate results comparable to those in a First World referral center. Low rates of transplant-related mortality, rejection and graft-versus-host disease are confirmed, but the benefits cannot be extrapolated outside of academically oriented and supervised facilities.
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    Impact of the HIV epidemic and Anti-Retroviral Treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002-2009: Preliminary findings of the Tygerberg Lymphoma Study Group
    (2011) Abayomi, E. A.; Somers, A.; Grewal, R.; Sissolak, G.; Bassa, F.; Maartens, D.; Jacobs, P.; Stefan, C.; Ayers, L. W.
    The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and a roll-out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish the impact of HIV epidemic and the ARV roll-out treatment program on the incidence of HIV Related Lymphoma (HRL). Early data document that despite the ART roll out, cases of HRL are increasing in this geographical location, now accounting for 37% of all lymphomas seen in 2009 which is an increase from 5% in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B-cell lymphoma subtypes. The reasons for this observed increase in HRL are not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnoses are made has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reasons, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression. © 2011.
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    Isolation of a new human herpesvirus producing a lytic infection of helper (CD4) T-lymphocytes in peripheral blood lymphocyte cultures. Another cause of acquired immunodeficiency
    (Health & Medical Publishing Group, 1988-12) Becker, W. B.; Engelbrecht, S.; Becker, M. L. B.; Piek, C.; Robson, B. A.; Wood, L.; Jacobs, P.
    A new human helper (CD4) T-lymphotropic herpesvirus (HTLHV) was first isolated in February 1985 from the cultured peripheral blood lymphocytes (PBL) of a patient with the acquired immunodeficiency syndrome, and subsequently from the PBL of 1 patient with hairy cell leukaemia and 2 patients with lymphoproliferative disease associated with human T-lymphotropic virus type I infection. The viruses could be serially subcultured in umbilical cord PBL cultures in which they infected helper (CD4) T-lymphocytes producing multinucleate giant cells with intranuclear inclusions followed by cell lysis. Electron microscopy of infected cultures revealed that the isolates were herpesviruses. Specific DNA probing showed that the 4 isolates were related to one another but were distinct from cytomegalovirus, Epstein-Barr virus, Herpes-virus hominis types 1 and 2, and varicella-zoster virus. HTLHV lyses the same target cell as human immunodeficiency virus in PBL cultures suggesting that it may have a similar potential to cause acquired immune deficiency. The development of an unequivocally diagnostic serological test is a priority, so that the epidemiology and pathogenesis of HTLHV infection can be studied.
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    Use of novel proteosome inhibitors as a therapeutic strategy in lymphomas current experience and emerging concepts
    (2007) Abayomi, E. A.; Sissolak, G.; Jacobs, P.
    Precedent from preclinical experiments coupled with two pivotal phase 2 studies in myeloma has focused attention on a potential role for ubiquitin-proteasome pathway in modulating a number of events that occur commonly in the neoplastic process involving proteins in the regulation of cells cycling, growth and differentiation. This influence is vested in the proteasomes which are large complexes of proteolytic enzymes responsible for degradation of many of these intracellular messengers. Logically interest has centred on molecules having the capacity to influence, by degradation, such molecules and although a number of agents are in development bortezomib is the only one currently in clinical use. Velcade, formerly PS-341, is a novel dipeptide boronic acid capable of reversibly inhibiting the 26S proteasome through a range of activities. The latter are anti-proliferative and proapoptotic with the latter blocking nuclear transcription via NF-κ B in addition to down regulating adhesion and inhibiting angiogenesis. Additional changes are mediated in protein folding within the endoplasmic reticulum and contribute to cell death. These concepts are given focus by considering their introduction into treatment of lymphoreticular malignancy. © 2007.
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    V - Vitamins B12 and Folate - Part II - Diagnosis and treatment
    (The Specialist Forum, 2011) Van Wyk, J.; Grewal, R.; Wood, L.; Abayomi, E. A.; Jacobs, P.