School of Clinical Medicine

Permanent URI for this communityhttps://hdl.handle.net/10413/6700

Browse

Now showing 1 - 20 of 335

Conditions associated with levels of allergens and fungal aerosols in selected homes of selected primary school children in Durban.
(2007) Jafta, Nkosana.
This indoor environment study formed part of the South Durban Health Study (SDHS) that investigated the health effects of exposure to ambient air pollution. Homes of children from seven communities corresponding schools were recruited to participate. This study was designed to determine characteristics in the homes that are associated with higher or lower levels of allergens and fungal aerosols. Homes were inspected using a field tested walkthrough checklist to collect data on home characteristics associated to adverse health effects. The characteristics include dampness, visible mould, type of flooring, type of bedding, type of heating systems, and building type and age. Dust samples for allergen analysis were collected from the bedding and the floor of the sleep area used by the children. Air samples from all rooms in the house were collected on malt extract agar, the media used for identifying and quantifying airborne fungal aerosols. More than 70% of the homes were single units standing on their own, 20% were attached houses (flats or apartments) and the rest (10%) were informal houses. Construction material of the homes comprised of bricks (93%), wood (5%) and other material (2%) such as corrugated iron of which 94% were formally constructed. Dampness signs were observed in 51% of the homes and visible mould growth 13% of them. In all them, at least one characteristic that is hypothetically associated to elevated house dust mite allergens was found. Levels of mould (Asp f 1) allergen and house dust mite (Der p 1 and Der f 1) allergen were comparable to levels found in other parts of the world. Asp f 1 allergen levels ranged between 0.32-1.379g/g and Der p 1 and Der f 1 allergen levels ranged from undetectable to 49.61 and from undetectable to 39.319g/g of dust respectively. Some home characteristics from walkthrough checklist were associated with Asp f 1, Der p1 and Der f 1 allergen levels when simple regression analysis was performed. Asp f 1 was significantly associated with single family home [OR= 0.004 (95%CI 0.004–0.35)] and polyester filled pillows [OR= 0.07 (95%CI 0.01– 0.61)] in logistic regression models. Der p 1 allergen was associated with observed extent of roof dampness [OR= 0.33 (95%CI 0.13–0.81)]. Fungal aerosol mixture consisted of Cladosporium spp. as the predominant genus together with other genera such as Aspergillus, Penicillium and Fusarium were, to a lesser extent, identified in the samples from the homes. Mean concentration of total indoor fungal aerosol of indoor and outdoor were 1108 CFU/m3 and 1298 CFU/m3 respectively. Individual genera of fungi in the childrens sleep area had mean levels of 783 CFU/ m3, 30CFU/ m3, 64CFU/ m3, 48CFU/ m3 and 43 CFU m3 for Cladosporium spp., Aspergillus spp., Penicillium, spp., Fusarium spp. and Rhizopus spp. respectively. Simple regression showed some conditions in the homes to be predictors of higher levels of total fungal aerosols. In a linear regression models, total outdoor fungal levels were a protective effect on total indoor fungal levels [C= 0.542 (95%CI 0.437–0.647)] whilst homes with hard floors had about 25 CFU/m3 [C= 5.235 (95%CI 0.557–9.913)] in the homes were significantly associated. This study showed the need to adapt observational instrument/ checklist/ questionnaire to suit the environment or the study area of interest. As other studies and findings indicated, the best way to assess exposure to biological pollutants indoors needs a combination of two or more methods, i.e. direct and indirect methods.
Does blood cardioplegia solution cause deterioration in clinical pulmonary function following coronary artery bypass graft surgery?
(2006) Farlane, Tamara Cindy.; Kleinloog, Robert.; Robbs, John Vivian.
Pulmonary dysfunction following cardiopulmonary bypass surgery is a widely explored complication and a multitude of factors have been implicated, including but not limited to: operative trauma; the cardiopulmonary bypass circuit; cardioplegia; the type of donor grafts utilised; anaesthesia and fluid administered. There is a paucity of information regarding the effect of cardioplegia on the lungs. No studies have previously investigated whether allowing cold-blood cardioplegic solution to enter the lung parenchyma, during the period of cardioplegia delivery, has an effect on the clinical outcome of lung function following cardiopulmonary bypass surgery. For this reason an original study was done to determine the effect of preventing cardioplegia from entering the lungs, by evacuating overflow of cardioplegia not drained via the atriocaval cannula, by using a pulmonary artery vent. A total of 403 patients admitted to undergo full cardiopulmonary bypass were screened and 142 patients who fitted the criteria for inclusion and provided informed consent took part in this prospective double blind randomised clinical trial. The control group underwent routine cardiopulmonary bypass grafting. The study group had the intervention of a pulmonary artery vent sutured in position at the time the heart was cannulated for bypass. During cardioplegia delivery the cardioplegia was removed via the atriocaval cannula in the control group (A) and via the atriocaval cannula and the pulmonary artery vent in the study group (B). Aside from this difference, the two groups were managed identically intra- and post-operatively. Outcomes which were compared included eight time measures of arterial blood gases; electrolytes and shunt fraction; bedside lung spirometry measures over five time periods; radiographic measures of atelectasis and effusion over three time points; as well as physiotherapy and hospitalisation requirements. Numerous other potentially extraneous variables were measured and compared in order to monitor homogeneity of the study samples. The consistency of the results within each group throughout the study provides strong evidence that the measurements taken were accurate. The use of standardised equipment and vigilant adherence to the protocol ensured no extraneous deviation. The internal validity of this study was therefore good and accurate. The findings of the study however brought into question a previously accepted belief that the pulmonary artery vent prevents the overflow of cardioplegia, not drained from the right atrium, from entering the lungs. There was no literature or previous studies to confirm or dispute this accepted ‘observation’ by cardiac surgeons that the cardioplegia does enter the lung parenchyma. To therefore validate the findings of the study a further four original studies were designed and initiated. The objective of these studies was to establish the efficacy of the pulmonary artery vent and to determine whether cardioplegia indeed circulates through the lung parenchyma or merely accumulates and ‘pools’. Technetium (Tc-99m), a radio labelled isotope was added to the cold blood cardioplegia solution prior to delivery in order to determine this. In the four sub-studies it was confirmed that the pulmonary artery vent is 90-100% effective in retrieving any cardioplegic solution not drained by the atriocaval cannulae, thus confirming the effectiveness of the pulmonary artery vent in preventing cold blood cardioplegic solution from entering the lungs. The findings of the main study confirmed that respiratory impairment after uncomplicated cardiopulmonary bypass, even in low risk patients, is relatively common, as within each group there was a significant change in outcome measures over time. Inter-group comparisons however showed these changes were not significant, with both groups deteriorating by the same degree post-operatively, therefore establishing that these changes were independent of the intervention of the pulmonary artery vent. In the control group, the cold blood cardioplegia solution that did not drain from the atriocaval cannula entered the lungs and circulated the lung parenchyma during cardiopulmonary bypass. The study group made certain that none, or very little, of the cold blood cardioplegia solution entered the lungs. The main findings of this study are therefore that pulmonary function and gas exchange, although markedly reduced following cardiac surgery, are not affected by placement and suctioning via a pulmonary artery vent during the time of cardioplegia delivery intraoperatively. Furthermore, these studies strongly suggest that cold blood cardioplegia solution is innocuous to the lungs
Spot urine protein to creatinine ratio testing : new techniques for detecting proteinurra in pre-eclampsia.
(2008) Gangaram, Rajesh.
Background: The most commonly employed screening method for proteinuria is a semi- quantitative dipstick urinalysis, but it has been shown to be inaccurate in pregnancy. New developments in the assessment of proteinuria have included the use of urinary albumin measurements. The Clinitek Microalbumin Reagent Strip (Bayer Healthcare LLC, USA) is a semi-quantitative dipstick test. It is used to measure the spot urinary microalbumin to creatinine ratio that is read using the Clinitek 50 portable urine chemistry analyzer. Aims We embarked on a pilot study to validate the Clinitek 50 system by determining the accuracy of spot urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks (Makromed) compared to the laboratory urinary microalbumin to creatinine ratio quantification to detect significant proteinuria in normotensive and hypertensive antenatal attendees. The accuracy of spot urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks were then compared to a 24 hour urinary protein (gold standard) to detect significant proteinuria in hypertensive disorders of pregnancy. We then determined the role of proteinuria as assessed by the diagnostic accuracy of both the 24 hour urinary protein (gold standard) and the spot urinary microalbumin to creatinine ratio dipstick, in pregnancy outcomes of these participants. Methods This was a prospective study conducted at hospitals serving the Durban Metropolitan region in South Africa. To validate the urinary microalbumin to creatinine ratio dipstick, fifteen normotensive healthy pregnant women and 11 women with new onset hypertension in pregnancy were recruited .Each women had a spot midstream urine, which was assessed for proteinuria using a semi-quantitative visual dipstick (Makromed) and analysed using the semi-quantitative urinary microalbumin to creatinine ratio dipsticks (Clinitek® Microalbumin) read on the Clinitek® 50 urine chemistry analyser. A result of 1 + on visual dipsticks and a spot urinary microalbumin to creatinine ratio UAC of > 300mg/g (33.9mg/mmol) was considered as positive for significant proteinuria. The results were compared to the laboratory quantitative measurement of the urinary microalbumin to creatinine ratio. The study group comprised 163 women presenting with newly diagnosed hypertension during pregnancy after 20 weeks of gestation, being recruited from antenatal clinics. Each participant had a spot urine sample that was tested by trained midwives for proteinuria using a semi-quantitative visual dipstick (Makromed). Participants were admitted to the ward where a spot midstream urine sample was collected and analysed using the semi-quantitative urinary microalbumin to creatinine ratio dipsticks. A 24 hour quantitative urinary protein analysis was completed. The results of the urinary microalbumin to creatinine ratio dipsticks and conventional visual dipsticks were compared to the 24 hour urinary protein (gold standard) to detect significant proteinuria. A urinary microalbumin to creatinine ratio of < 300mg/g (nil and trace on visual urine dipsticks) was considered to be a negative result. A urinary microalbumin to creatinine ratio 300 mg/g (1+ to 4+ on visual urine dipsticks) was considered to be a positive result. Urinary protein 0.3 g/24 hours was considered significant proteinuria. The outcomes of pregnancy in 2 sub-categories viz. those with and without significant proteinuria were compared using the 24 hr urinary protein measurement. A secondary analysis of outcomes of pregnancy was performed by subcategorizing the participants according to the diagnostic accuracy of the urinary microalbumin to creatinine ratio dipsticks. In the 26 patients enrolled in the initial study , the visual dipstick had a sensitivity of 25% ( 95% CI [0.04-0.64] ) and specificity of 89% ( 95% CI [0.64 -0.98]).The urinary microalbumin to creatinine ratio dipsticks had a sensitivity of 88% ( 95% CI [0.47-0.99]), specificity of 89% (95% CI [0.64-0.98]), negative predictive value (NPV) of 94% (95% CI [0.69-1.00]) and positive predictive value (PPV) of 78% (95% CI [0.40-0.96]). In the 163 patients subsequently enrolled the visual dipstick had a sensitivity of 51 % ( 95% CI [0.41-0.61]) and specificity of 91% (95% CI [0.81-0.96]) .The PPV and NPV was 89 %( 95% CI [0.77-0.95]) and 58% (95% CI [0.48-0.67]) respectively. The urinary microalbumin to creatinine ratio dipsticks had a sensitivity of 63% (95% CI [0.52-0.72]) and specificity of 81 % (95% CI [0.70-0.89]). The PPV was 82% (95% CI [0.71-0.90]) and NPV was 62% (95% CI [0.51-0.71]). Our results show that in hypertensive pregnant women, significant proteinuria determined by the quantitative 24 hour urinary protein is associated with delivery at an earlier gestational age, increased induction of labour and lower birthweights compared to the non-proteinuric hypertensives (gestational hypertension). There is also a trend towards an increased maternal morbidity and perinatal mortality. When the groups were classified into pre-eclampsia and gestational hypertension using the diagnostic accuracy of the urinary microalbumin to creatinine ratio dipsticks, there were no differences in the clinical outcomes between the false negatives and true negatives except a trend towards a higher caesarean section rate in the false negatives. Conclusion The urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system provides a semi – quantitative result of the urinary microalbumin to creatinine ratio that has good sensitivity and specificity. Furthermore, the urinary microalbumin to creatinine ratio dipstick has a good negative predictive value and a result of < 300mg/g rules out significant proteinuria and avoids unnecessary investigations in pregnancy. Both the visual dipstick (Makromed) and the urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system are not accurate when compared to the total 24 hour urinary protein. Differences between the urinary microalbumin to creatinine ratio and 24 hour total urinary protein may be due to the variation in the albumin fraction of the total urinary protein of pre-eclampsia, technical problems with imprecision of the assay technique and clinical causes of false positives and negatives. The improved sensitivity of the automated urinary microalbumin to creatinine ratio dipstick over the visual dipstick suggests it may be a suitable substitute for the visual dipstick in clinical practice Hypertension in pregnancy associated with significant proteinuria is associated with greater adverse maternal and fetal outcome. Outcome of pregnancy is similar when a classification of gestational hypertension is made based either on the 24 hour urinary protein or the urinary microalbumin to creatinine ratio dipstick read on the Clinitek 50 system. The urinary microalbumin to creatinine ratio dipstick is a good screening test to rule out significant proteinuria. It has the potential to improve accuracy of screening for proteinuria and enhancing safety by preventing incorrect diagnosis and unnecessary investigation. Further research is required to determine its full impact and cost effectiveness in the clinical setting.
Cannabis use in psychiatry inpatients.
(2008) Talatala, Mvuyiso.; Nair, Margaret Gemma.; Mkize, Dan Lamla.
Background: Cannabis among patients admitted in psychiatric units is higher than the general population and this has been shown in various countries where studies on cannabis use have been undertaken. Such an observation has been made by psychiatrists in South Africa and the association between cannabis use and psychotic presentation among these patients has also been observed. Cannabis use by patients with severe or chronic medical illnesses to ameliorate the symptoms of such illnesses has been documented in the literature. A study to explore use of cannabis among psychiatric inpatients as well as medical patients was undertaken. Purpose: The purpose of this study was to firstly determine the prevalence of cannabis use in psychiatric patients admitted to an acute admissions unit in King Edward VIII Hospital and to correlate it with the psychiatric diagnosis. Secondly, it was to compare the cannabis use in psychiatric patients admitted to an acute admissions unit to patients admitted in a medical ward at King Edward VIII Hospital. Thirdly, to assess self reporting of cannabis use by psychiatric and medical patients. Methods: A case control study was conducted at King Edward VIII Hospital, Durban, where cannabis use among 64 subjects included in the study admitted in a psychiatric ward was compared with a control group of 63 control subjects admitted in a medical ward. Both groups were tested for urinary cannabinoids and a questionnaire was filled. The questionnaire contained demographic details as well as a question on use of substances including cannabis. Results: 17 subjects (26.6%) in the study group tested positive for urinary cannabinoids and 2 subjects (3.2%) in the control group tested positive. Cannabis use was significantly higher among males when compared to females in both the study group and the control group. Only 7 subjects in the study group reported cannabis use and out of those 7 subjects, 4 subjects tested positive for urinary cannabinoids. The commonest diagnosis among the study group subjects were the psychotic disorders and schizophrenia being the most common psychotic disorder. Conclusion: Cannabis use is significantly higher among psychiatric patients as compared to medical patients and it is probably higher than in the general population. Self reporting of cannabis use among psychiatric patients is low and unreliable and psychiatrists treating these patients must continue to use objective measures such as objective testing as well as collateral information to determine such use. In this study most subjects who tested positive for urine cannabis were likely to have a psychotic disorder and tended to be of younger age groups. The low prevalence of cannabis use in the control group makes it unlikely that there was a significant number of subjects in this group who were using cannabis for medicinal purposes.
Evaluation of haematological parameters and immune markers in HIV-infected and non-infected pre-eclamptic Black women.
(2007) Naidoo, Kalendri.; Moodley, Jagidesa.
This study focuses on women with both pre-eclampsia and Human Immunodeficiency Virus (HIV). Pre-eclampsia is a pregnancy-specific syndrome that occurs after 20 weeks gestation. Thrombocytopenia is the most common haematological abnormality in pre-eclampsia. Further, studies suggest that the immunological mechanism plays some role in the aetiology of pre-eclampsia. The immunological hallmark of HIV infection is a progressive decline in the number of CD4 T lymphocytes and significant haematological abnormalities are also common in HIV-infected individuals i.e. anaemia, thrombocytopenia and leukopenia. The study population comprised of two groups i.e., pre-eclamptic HIV-positive African women and preeclamptic HIV-negative African women as the control group. Samples were analysed for haematological parameters (full blood count) and immunological markers (flow cytometry). There was no statistical significance in the following parameters: RBC, Hb, haematocrit, MCV, MCH, MCHC, platelets, MPV, WBC, lymphocytes, neutrophils, eosinophils, monocytes, basophils and CD8. There was a statistical difference in the CD3 and CD4 counts between both the groups. However, the CD3 and CD4 counts were within the normal range in the HIV-negative pre-eclamptic group and even though CD3 decreased, it was still within the normal range in the HIV-positive pre-eclamptic group, with CD4 decreasing below the normal range in the HIV-positive pre-eclamptic group. This suggests that immune mechanisms involving CD estimations do not play a role in pre-eclampsia since the decrease in the counts can be solely attributed to HIV infection. Results obtained in this study do not show any severe haematological or immunological abnormalities when women have both pre-eclampsia and HIV infection.
Nephrotic syndrome in African and Indian children in South Africa.
(1981) Adhikari, Miriam.
There are comprehensive accounts of the nephrotic syndrome in childhood in temperate countries. Many of the important features of this disease have been known for close on to two decades. The causal link between malaria and nephrosis in tropical Africa has also been recognised and documented for a similar length of time. Very little was known of the nephrotic syndrome in the sub-tropical zones of Africa where malaria is not endemic. Anecdotal evidence in South Africa suggested that African children with this disease appeared to have steroid resistant nephrosis and a more protracted clinical course than expected from prevailing accounts in the literature and that Indian South African children generally responded to steroids. This thesis is the result of detailed investigations in to this disease in African and Indian children in Durban, South Africa. 2. Preliminary Study A preliminary study was undertaken in which 53 (12 African and 41 Indian) children with the nephrotic syndrome defined by clinical and biochemical criteria 1 ii were studied. Renal biopsies were not available on these patients. The results revealed that two thirds of the African children were over 5 years of age and 50% were males. Of the Indian children 50% were under 5 years of age and 50% were males. Nine African children were treated with steroids and 8 did not respond whereas 31 of the 39 Indian children treated clearly responded to steroid therapy. In addition 5 Indian patients were treated with cyclophosphamide and 3 responded. On follow-up 7 of the African children had persistent proteinuria, 2 experienced remissions and 3 were lost to follow-up. All the Indian patients experienced remissions. The differences between the 2 groups of nephrotic patients were quite striking and therefore a more detailed prospective study of this problem was undertaken. 3. Prospective Study of Primary Nephrotic Syndrome One hundred and seventy children of whom 104 were African and 66 Indian with primary nephrotic syndrome were studied. In both racial groups the male sex dominated, Indian children tended to present iii at a younger age group whereas African children presented at two peak ages, 5 years and between 5 - 10 years. 3.1 Histological Differences The histological types found on light microscopic examination of renal tissue were distinctly different between the African and the Indian children. The majority (85.6%) of the African children had 'obvious' glomerular lesions, the commonest being extramembranous nephropathy (29.8%). Although the proliferative group was the single largest group (40%) none of the subgroups exceeded the extramembranous type in their number. Minimal change accounted for only 14.4% of the African children with nephrotic syndrome. The majority of Indian children (72.7%) had minimal change on light microscopy, 9.1% focal glomerulosclerosis and 12.1% had proliferative changes. 3.2 Immunofluorescence Immunofluorescent studies also indicated differences between the two groups of patients. Generally, heavier deposits of immunoglobulins iv and complement components were identified on renal biopsy specimens of African children. This occurred even in MCNS where most African children had heavy IgG, light IgM, IgA and complement components whereas only a few of the Indian children had light IgM deposits. Similar differences were observed in diffuse mesangial proliferative glomerulonephritis and focal glomerulosclerosis where the numbers of patients were comparable. 3.3 Presenting Features Clinical features at presentation in the two groups were different, as expected from the nature of the histological findings in each group. In the African children (all histological groups) haematuria occurred in 35.5%, hypertension 16.3% and renal failure in 2.9%. The clinical features in the Indian children were not too different from MCNS elsewhere. Haematuria occurred in a small percentage (3%) of MCNS but was more frequent (10.7%) in other groups. Hypertension and renal failure occurred infrequently in histological categories other than MCNS where they did not occur at all. 3.4 Course and Outcome In view of the above it was not unexpected to find that the clinical course and outcome in the two groups were quite dissimilar. African patients in certain of the histological groups fared reasonably well, but none of the groups had the excellent prognosis of Indian MCNS. 3.4.1 Minimal Change One third of the African MCNS patients remitted and this was unrelated to steroids. The remainder who were followed for a reasonable duration of time remained proteinuric. None developed signs of serious renal impairment (azotaemia, hypertension). Indian MCNS experienced an excellent prognosis with 97.8% achieving remission and 81.6% being steroid sensitive. One third of these patients had a single episode of nephrosis while frequent relapses occurred in 28.2%. 3.4.2 Extramembranous Nephropathy Patients with extramembranous nephropathy, the largest group in the African patients, experienced hypertension more often (20%) vi and remission less often (30%) than do children in temperate climates. The clinical presentation, course and outcome in the majority of these patients were similar to adults with extramembranous nephropathy. 3.4.3 Proliferative Glomerulonephritis The patients in the proliferative group had a variable outcome depending on the subgroup to which they belonged. In diffuse mesangial proliferation, African patients had a higher incidence of hypertension and fewer remissions and fared less well than Indian patients. The diffuse endocapillary glomerulonephritis, membranoproliferative and focal proliferative nephritis groups of patients suffered severe disease with a failure to remit and progression to death. In the diffuse exudative group, remissions occurred or proteinuria persisted but severe relapse and death did not occur. The worst prognosis was in the focal proliferative group with the highest incidence of persistent relapse. 3.4.4 Focal Glomerular Sclerosis Focal glomerular sclerosis was an unusual vii histological diagnosis in the African child (3.9%) with a poorer prognosis (persistent proteinuria or death) when compared to Indian children in whom one third remitted and the rest had persistent proteinuria. 3.4.5 Tropical Nephropathies It is difficult to comment on the course of the tropical nephropathy (not related to malaria) and tropical extramembranous groups as the numbers are small. However, in tropical extramembranous, none remitted (all African children) and in tropical nephropathy one Indian child remitted but one of 2 African children died and the other had persistent proteinuria. 3.5 Response to Therapy Perhaps the most important practical aspect of the nephrotic syndrome in the African child was the response to steroid therapy. Thirty two African children were given steroid therapy. Thirty (93.7%) did not respond. Five children deteriorated or died during steroid therapy. Very few patients (4) were given cyclophosphamide and none responded. viii Generally intravenous albumen, diuretics and a high protein diet were not very effective in those patients with severe, clinical disease but were of benefit in milder disease. Indian children taken as a whole, responded well to steroid therapy. Seventy-eight percent of the whole group responded to steroids and 21.4% developed cushingoid features. Of the 19 Indian children (all MCNS) treated with cyclophosphamide 63.2% responded of whom about a quarter got toxic side effects (alopecia, darkened nails and leucopenia). Chlorambucil therapy in 4 children (all MCNS) was successful in all. 3.6 Complications Serious infections (septicaemia, peritonitis, urinary tract infection, meningitis, arthritis, osteitis, measles, chicken pox) occurred in 8.7% of the African patients. Eighteen percent had less severe infections. Just over a quarter of the Indian children suffered severe infections. The majority of these patients were MCNS and about 50% were on steroids or cyclophosphamide at the ix time of their infection. Renal biopsy complications were minor, these being abdominal pain and tenderness or transient haematuria. A few patients developed renal haematomas which were detected or monitored by ultrasonography. The single serious complication was the development of a renal abscess at the biopsy site requiring partial nephrectomy. 3.7 Mortality The overall mortality was 5.8%. Seven of the 10 deaths were African children in the Proliferative Group and 3 of the 10 deaths were Indian children. 4. Secondary Nephrotic Syndrome The secondary nephrotics formed an interesting group of patients. Of the 22 patients classified as secondary nephrotics 11 (50%) were related to streptococcal infection either as rapidly progressive glomerulonephritis or transient NS following APSGN. HBsAg was detected in the blood of 8.6% of the African patients. However the HB sAg carrier rate in this age group is 7.4%.The incidence in these patients probably reflects the high incidence in this population group. Collagen vascular disease occurred in 2 patients, both Indian. 5. Conclusions and Recommendations The results of this study demonstrates the strikingly different incidences of the various histological categories in the two race groups studied with a less favourable prognosis and fewer remission rates being achieved in African children. Indian children had more serious infections more often than African children. Steroid and immunosuppressive agents were of no value and probably hazardous in the African child. Some patients deteriorated on these drugs. Indian children who had an excellent response to these drugs were however at significant risk of developing serious infections. Why African children in Durban develop obvious glomerular lesions has not been established. Known or possible aetiological agents such as malaria, schistosomiasis, streptococcal infections and collagen diseases have been excluded. The answer to the above question may in fact lie in genetic predisposition,host factors and environmental influences, either singly or in combination, predisposing to the development of obvious x i glomerular lesions. These require more intensive investigation and judging from the yield of similar studies in other areas of the world expectations have to be guarded.
The association of various HLA-A, -B and -DR loci with membranous glomerulonephritis, IgA nephropathy, and focal segmental glomerulosclerosis in KwaZulu-Natal renal patients.
(2007) Allen, Veronica.; Assounga, Alain Guy Honore.
This KwaZulu-Natal (KZN) based study investigates hypertension, glomerulonephritides and the rarity of IgA Nephropathy (IgAN) in Africans in association with the Human Leukocyte Antigen (HLA). A retrospective hypertensive study found a positive association with HLA-B40 (P c<0.05) and HLA-B15 (Pc<0.02) in Indians and Africans respectively. No association was found in Whites. A prospective study showed glomerulonephritides to be positively associated with HLA-A33 in Indians (Pc 0.049). No associations were found with glomerulonephritides in Africans and Whites. Combined Race groups show no HLA associations. HLA-A30; HLA-A34; HLA-A29; HLA-B42; HLA-B58; HLA-B70 and HLA-DR11 were extremely significantly higher in Africans compared to Indians and Whites (all P<0.0001). In conclusion, HLA-B40 and I 1LA-B15 are possible disease susceptibility markers in Indian and African hypertensives; HLA-A33 is a possible disease susceptibility marker for glomerulonephritides in Indians and alleles in linkage might be responsible for the rarity of IgAN in Africans but further studies need to be employed.
Profile of mortality amongst women with gestational trophoblastic disease (GTD) infected with the human immunodeficiency virus (HIV) in relation to HIV non-infected women.
(2008) Budhram, Samantha.; Moodley, Mathew.
OBJECTIVES: To determine if women with Human Immunodeficiency Virus infection with severe degrees of immunosuppression are more predisposed to mortality from Gestational Trophoblastic Disease compared with HIV-infected women with less severe degrees of immunosuppression and Human Immunodefiency Virus (HIV) non-infected women. DESIGN: Retrospective review of case records. METHOD: A retrospective review was performed on all patients with Gestational Trophoblastic from 2003 to July 2007. A chart review was conducted and information captured on a data sheet. This retrospective audit was performed at the combined gynaecology oncology clinic of Inkosi Albert Luthuli Central Hospital. All information was kept confidential and was strictly for the purposes of the audit. STATISTICS: Factors associated with mortality were tested using Fisher's exact test. Odds ratios were reported as a measure of the strength of association. Breslow-Day's test for homogeneity in odds ratios was used to compare mortality in HIV-infected and HIV non-infected women. The analysis was done using Stata 9. i RESULTS: A total of 78 patients with Gestational Trophoblastic Disease were reviewed. There were 53 patients with invasive molar pregnancy and 25 patients with choriocarcinoma. The HIV sero-prevalence was 31%. There were 15 deaths (19%). There were 8 HIV-infected (33%o) and 7 HIV non-infected (13%) women who demised. Of the 8 patients with CD4 counts less than 200 cells/ uL, 7 patients demised. There were no mortalities amongst patients with CD4 counts more than 200 cells/uL. Of the 15 deaths, 5 HIV-infected patients and 5 HIV non-infected patients received chemotherapy. There were 5 patients admitted in very poor general condition precluding the administration of chemotherapy. Amongst the 10 patients who received chemotherapy and demised, the causes of death included widespread disease, multiorgan failure and toxicity due to chemotherapy. CONCLUSION: The overall survival of all patients managed with Gestational Trophoblastic Disease was 82% in keeping with the expected high survival reported elsewhere. The majority of patients who demised were admitted in poor general condition and had abnormal blood profiles. Despite resuscitation, these patients failed to improve precluding the administration of chemotherapy which is the mainstay of treatment. Although the numbers are small, there is clear evidence that if patients are HIV-infected with CD4 counts 200 cells/uL despite transient grade 2 myelotoxicity.
Human immunodeficiency virus-1 infection and the acquired immunodeficiency syndrome in African children : natural history from birth to early childhood.
(1999) Bobat, Raziya Ahmed.; Coovadia, Hoosen Mahomed.
Background: in 1987, the first child with HIV-1 infection was identified in the paediatric wards at King Edward VIII Hospital in Durban. This made paediatricians aware that the epidemic had spread to the children of KwaZulu/Natal. Although information on transmission and natural history was becoming available from developed countries, little was known about the disease in developing countries. It was important to determine transmission rates and disease patterns in the local population, in order to appropriately counsel women, and for management of infected infants. In addition, with resources for laboratory diagnoses being limited in developing countries, much emphasis had to be placed on clinical findings for identification of infected children. In 1989, a retrospective analysis was made of the HIV-infected children seen over a 2-year period, between 1987 and 1989. Nine such children were identified and their clinical and biochemical features were described. It was concluded that HIV infected children presented with an identifiable pattern of signs, fairly similar to that described for children in industrialised countries. With these findings, a prospective study was undertaken, to determine the vertical transmission rate, the factors affecting this rate, and natural history of vertically transmitted I-IIV-1 infection. ix KwaZulu/Natal, being at the epicentre of the epidemic in South Africa, was a natural site for the study. Patients and Methods: a trained research worker was placed in the antenatal clinic at King Edward VIII Hospital for the specific purpose of educating, counselling, and testing of all women attending the clinic. Women attending the clinic for the first time in the index pregnancy were offered HIV testing if informed consent was obtained. Blood for HIV serology was drawn at the same time as sampling for the obligatory syphilis serology. The acceptance rate for sampling was > 95%. The majority of the women attending the clinic were black, and first attendance was generally late, into the third trimester. The same research worker was responsible for post-test counselling which was offered to all the women, not only those who tested positive. This research worker was also responsible for obtaining maternal consent for entering the newborn infant into the study. All newborn infants were seen within 48 hours of birth. At this time they were examined, growth parameters were recorded, and initial blood samples taken. These infants were then followed-up at 1 month, 2 months, 3 months, then at 3-month intervals up to 18 months, then at 6-month intervals. At each visit, a thorough clinical examination was performed, growth measurements taken, and development assessed. Record was made of any interim illness and visits to health centres, and of hospital admissions. Method of feeding was note& and details on immunisation obtained from the child's immunisation card. The children received all the x routine childhood immunisations according to the national regimen, based on WHO recommendations. Mothers were asked to bring the child to the follow up clinic for any problem, so that episodes of illness would not be missed. The women were reimbursed for transport costs to encourage follow up visits. Calculation of transmission rate and classification of infection status were made according to the recommendations of the Ghent workshop. Children were regarded as infected if they were antibody positive at 18 months or had an HIV related death. They were classified as uninfectd if the antibody test was negative at 9 months of age. Those infants who were lost to follow up before the age of nine months whilst still antibody positive and those whose cause of death could not be determined, were classified as indeterminate. The diagnosis of AIDS was based on the WHO criteria. Blood samples were taken at birth, at age one and three months, then at three month intervals to 18 months; thereafter at six month intervals. Sera were tested for HIV1 antibodies by a commercial enzyme-linked immunosorbent assay,ELISA. Samples that tested positive were confirmed by two tests, a Roche Elisa and by an immunoflourescent assay (IFA). A sample was regarded as being positive if both the second ELISA as well as the IFA or the Western Blot tested positive. xi Results: between October 1990 and March 1993, 234 infants and their 229 mothers were entered into the study. Those who did not attend a single follow up after birth were excluded from the study. The final cohort comprised 181 infants, of whom 48 were classified as infected ( including 17 deaths); 93 not infected, and 40 as indeterminate ( including 8 deaths). Maternal Data: about 60% of the mothers were under 30 years of age and were multiparous; 18% tested positive for syphilis serology; 22.9% were anaemic during pregnancy, and 37% were delivered by caesarean section. Most women lived in urban areas, and 16% chose to bottle-feed exclusively. Vertical Transmission Rate and Factors affecting this Rate: the median vertical transmission rate was 34%, (95% confidence intervals, CI 26%-42%). This figure is similar to that found in most parts of Africa, but much higher than those for Europe and USA. The maternal factors found to be associated with an increased risk of transmission were vaginal deliveries and a low haemoglobin level during pregnancy. Breastfeeding, Transmission, and Outcome: breastfeeding was found to have an increased risk of transmission, by 15 % (CI 1.8-31.8). On assessing growth and morbidity, it was noted that breastfed infants were not protected against such common childhood infections as pneumonia and diarrhoea, and that failure to thrive occurred with equal frequency in both those breastfed as well as those receiving artificial feeds. Newborn Data: when comparing newborn data between those infants who were subsequently found to be infected with those who were uninfected, it was found that there were no major differences between these groups with regard to growth parameters and neonatal complications. However, those infants with rapidly progressive disease (those who died within 24 months), were noted to have lower mean birth weights and lengths, a higher frequency of low birth weights, and tended to have more neonatal problems. Clinical Manifestations: the first differences between the infected and the uninfected infants generally manifested from about 3 months of age. HIV infected children were identifiable by higher frequencies of thrush, lymphadenopathy, skin rash, and hepatosplenomegaly in the early stages, and later on with a higher tendency to neurological and developmental abnormalities, as well as of diarrhoea. Pneumonia was found with equal frequencies in both the infected and uninfected children. The HIV infected child could be distinguished fairly early in life by the combination of the manifestations described above. Progression to AIDS: AIDS was diagnosed in 44% of all the infected children during the study period. Ninety five percent of these children were identified by 12 months of life, showing a rapid progression of the disease Longitudinal Growth: when longitudinal growth parameters were analysed in this cohort, it was found that HIV infected children were stunted from as early as 3 months of age, and remained below the international standards into early childhood. Infected children were also found to be malnourished (i.e. weight for age below international means), from an early age, and this persisted throughout early childhood. Of note, the uninfected childrens' weights, although comparable to international means initially, dropped after the first year of life. However, both groups did not have significant wasting, when compared to international means. Mortality: there were 25 known deaths during the study period. Of these, 17 were classified as HIV-related, and 8 as indeterminate. The mean age at death was 10.1 months, with 83% of all the HIV-related deaths occurring within the first year of life. The commonest diagnoses at the ti me of death were diarrhoea, pneumonia, and failure to thrive; also, thrush was common, as were neurological abnormalities.
Host allergic response variation in children with measles infection.
(1977) Coovadia, Hoosen Mahomed.; Smythe, P. M.
In many infections some patients recover while others die or are permanently disabled. These extremes in clinical outcome may be determined as much by the capacity of the host to eliminate the infecting agent as by the antigenic load on the individual. Children with measles who do not recover may succumb to acute complications (mainly respiratory) or chronic disease (respiratory and neurological) may develop. Analysis of immunological function antedating any of these final events would assist in understanding their pathogenesis and possibly aid in management. In order to achieve t h i s , immunological responsiveness was at f i r st studied in 24 children with acute measles and compared with that in 20 children with established chronic post measles chest disease investigated 6 - 1 6 weeks after appearance of the rash. The immunosuppressive effects of acute measles were extensive. Total white cells were reduced and this reduction was accounted for entirely by lymphopenia which was equally expressed among the major lymphocyte sub-populations studied; the function of T cells, assessed by radioisotope incorporation into phytohaemaggiutinin-transformed lymphocytes and by delayed skin hypersensitivity to dinitrochlorobenzene, was depressed. Serum IgA was reduced in acute measles patients. In contrast there was a relative sparing of the measured indices of immunity in patients with chronic post measles chest disease, with the major defect being an impaired delayed hypersensitivity reaction to dinitrochlorobenzene. There were minor alterations in complement components in both groups of patients with the evidence suggesting minimal utilisation of the alternative pathway in acute measles and classical pathway in chronic patients. High levels of heterophile antibodies to sheep red blood cells were detected in patients with chronic chest disease. (11) The results suggested that the conditions for chronicity of pulmonary disease in measles were unlikely to be determined by persistent abnormalities in the immunopathological factors enumerated, most of which were normal in chronic patients. It was not possible to interpret the findings of defective delayed hypersensitivity and complement components in patients with chronic chest disease as being either the cause or the effect of chronicity. The latter findings would have to be compared with results in children who had recovered from measles studied six weeks after onset of rash. An attempt was made to resolve this problem. Twenty-two children with measles were studied in the acute stage of the rash and six weeks later and results compared with matched controls. The above findings in acute measles were confirmed: the total lymphocyte count and major lymphocyte sub-populations were significantly below control values. At six weeks the B cell and Null cell counts were s t i ll significantly diminished. The function of T cells assessed by radioisotope uptake by phytohaemagglutinin-stimulated lymphocytes and by delayed skin hypersensitivity reaction to dinitrochlorobenzene was impaired during the acute stage and this persisted for six weeks. No important abnormalities were detected in serum immunoglobulins and complement components. Partial reversal of immunological suppression caused by measles was therefore demonstrated at 6 weeks after the appearance of rash. Demonstration of a persistently defective delayed hypersensitivity in those who recovered made i t unlikely that this anergy was important in the development of chronicity. Complement abnormalities were similarly unrelated to progression to chronic lung damage. ( Children who recovered, when studied at six weeks, appeared to be worse o f f immunologically than those with established chronic chest disease following measles. Children with chronic chest disease were studied 6 - 1 6 weeks after onset of rash, by which time the partial reversal of immune deficiency, noted at 6 weeks, would be complete. Among the group of children studied during the acute rash of measles there were five who subsequently died and one who progressed to chronic chest disease. Results in these six children were compared with those in six age-matched children who recovered from measles within a week. In the children who subsequently died or developed chronic pneumonia, immunosuppression was more pronounced during the acute rash ( i . e ., 3 - 2 0 days before death) than in the children who recovered. The absolute total lymphocyte count (T and B cells) was s i g n i f i c a n t ly lower in those who died or developed chronicity. Mean serum C, was also lower in this group. There were no significant differences between the two groups for total white c e l l s , neutrophils, Null c e l l s, cells with both T and B cell markers, other complement factors, serum immunoglobulins and phytohaemagglutinin stimulation of lymphocytes. The total lymphocyte count in a further nineteen patients with measles who had died, studied retrospectively, was s i g n i f i c a n t l y lower than that in twenty-seven patients with measles who recovered. Children whose outcome was poor generally had absolute lymphocyte 3 counts below 2000 cells/mm whereas those who recovered had values above this level. (iv) Therefore children who w i l l die or develop chronic chest disease can be often distinguished, within two days of the appearance of the rash, from those who w i l l recover. In order to test the v a l i d i t y of this conclusion based on results obtained from a small sample the study was extended so as to increase the number of patients with measles who had severe lymphopenia (< 2000 cells/mm3). Seventy seven per cent of 30 children who had severe lymphopenia within 2 days of appearance of rash f a i l e d to recover: 30% died from pulmonary complications within a few days to two months of the onset of the exanthem while 47% developed chronic lung damage. This was s i g n i f i c a n t ly worse than the outcome in 30 children with lymphocyte counts above 2000 3 cells/mm , of whom 67% recovered, 33% developed chronic chest disease and none died. Persistence of severe lymphopenia (which was due to reduction 3 in both T and B cells) in those with i n i t i a l counts below 2000 cells/mm , for at least fifteen days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in those with i n i t i a l severe lymphopenia was slower and less complete 42 days from the appearance of the rash in children who subsequently died or progressed to chronicity than in those who recovered. All patients who died f a i l ed to produce an adequate or sustained antibody response to measles. The results of these studies suggest that long term pulmonary and possibly neurological sequelae of measles are probably due to a transient widespread immunoparesis during early measles with persistent defects in specific immunity to measles and probably other viruses, whereas recovery is due to less severe effects of shorter duration. (v) In order to answer the question why some children do badly and others well after measles, studies on the HLA frequencies and measles antigen load have been undertaken in children with severe lymphopenia. Results of viral load are inconclusive and those of HLA suggest a trend towards histocompatibility linked genetic susceptibility to the development of severe lymphopenia in measles associated with HLA AW32. The therapeutic implication of these studies is that children with measles who are at risk for death and chronic disease can be identified early in the disease and intervention at this stage may reverse the severe immunosuppression which leads to rapid demise or modify the immunopathological changes progressing relentlessly in some cases to permanent lung and brain damage and occasionally to death.
Dyskinesia : An analysis of abnormal involuntary movement types among white psychiatric inmates of Town Hill Hospital, Pietermaritzburg.
(1985) Dunn, John Anthony.; Wessels, Wessel Hendrik.
An overview of the varied clinico-neurological features of dyskinesias in general is presented, and literature an the epidemiology af tardive dyskinesia since the introduction of antipsychotic drugs in 1950, reviewed. Furthermore reasons for the wide variations in previously published prevalence figures have been critically highlighted, and suggestions based upon the current state of clinical and experimental knowledge put forward concerning the pathogenesis of drug induced movement disorders. The type and prevalence of abnormal or purposeless involuntary movements has been surveyed among a large sample of long term White patients resident in Town Hill Hospital for a period of not less than 4 years, mast af whom were either currently receiving or had received neuroleptic medication. This sample comprised 190 men and 98 women whose ages ranged from the third to the ninth decade. Patients manifesting abnormal movements were grouped into 5 general diagnostic categories for analysis viz. schisophrenic disorders, affective disorders, organic brain disorders and syndromes, defective mental development and discrete neurological disorder. The movements were clinically classified in terms cf the areas of the body involved and semi quantitatively measured according to a standardised duration rating scale procedure. Involuntary movements were noted to be present in a total o-f 83 patients examined, most o-f which were adjudged to correspond to the syndrome currently termed 'tardive dyskinesia'. Subtype analysis o-f movement distribution indicated that 277. of cases manifested classical oro-facial dyskinesia while 527. showed body dyskinesia o-f the type designated ' pseudaakathisia'; the balance o-f the patients presented combinations o-f the two types. Schizophrenic disorders constituted the commonest diagnostic category in the dyskinesia group up to the fifth decade. Functionally obtrusive involuntary movements were observed in only some 77. of the patients with dyskinesia. Prevalence overall was equal between the sexes, and no correlations were discerned between age, sex, diagnosis or dyskinesia subtype of cases and the rating scores obtained. Prevalence rates obtained by this survey are favourably low by comparison with many results of overseas investigators, and are similar in this respect to figures reported in the very few prevalence studies carried out to date in South African institutions.
Exploring racial differences in disease stage and risk profile at presentation, and its influence on outcome in men with prostate cancer in KwaZulu-Natal.
(2009) Govender, Poovandren Soobiah.; Abdel-Goad, Ehab Helmy.; Esterhuizen, Tonya.
Introduction Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second leading cause of male cancer death in the Western world. In the United States of America (USA), African American men (AAM) have among the highest rates of PCa in the world. They develop the disease 1.5 times more frequently than European American men (EAM) of the same age .The mortality rate is approximately two to three times higher for AAM compared to EAM. There is a dearth of literature exploring the incidence and treatment outcomes of this disease based on racial profiling in a South African population. This study aims to evaluate racial disparities with a focus on patients with PCa managed in the public health care sector in the province of Kwazulu Natal (KZN). Patients and methods The study was a retrospective analysis of patients with PCa treated at Inkosi Albert Luthuli Central Hospital and Addington Hospital, which are both based in the Durban Metropolitan area in the province of KZN. Data extracted from the folders of patients with PCa who presented between March 2003 and December 2007 were collated onto a data capture form and analysed. Patient data were analysed according to the following categories: „h Patient demographics; „h Patient follow-up period; „h Disease risk profile; „h Response to treatment; „h Compliance on treatment. SPSS version 15.0 was used to analyse the data. Within each disease category, the response variables were analysed by race group using non-parametric Kruskal-Wallis tests. Multiple comparisons were made using pairwise Mann-Whitney tests and Bonferroni adjusted significance levels according to the number of multiple comparisons made. In order to control for other confounding factors such as age, serum PSA levels and compliance, Cox proportional hazards models were used. Hazard ratios and 95% confidence intervals were also reported. Results In KZN, the majority of the population is classified as blacks (82.9%). The Indian population group makes up 9.0% of the provincial population while white and coloured people make up 6.1% and 2.0% of the provincial population respectively. In this study population, Blacks made up 57.7% and whites made up 27.5%, followed by 11.4% of Indians and 3.4% of coloureds. The racial frequency distribution of the study population demonstrated that whites had a higher incidence of PCa when analysing their demographic profile in the province. Blacks had the highest median total serum prostate specific antigen (PSA) levels on presentation. When compared to that of the white study population, this was found to be statistically significant (p < 0.001). There was a significant association between stage of disease and race (p = 0.001). In the black group, a greater proportion had metastatic rather than localised or locally advanced disease, and in the white group the converse was seen, whereas in the Indian and coloured groups an almost equal proportion had localised or locally advanced disease versus metastatic disease. A crude analysis of progression free survival (PFS) data in patients with metastatic disease demonstrated that PFS was significantly (p = 0.003) longer for whites compared to blacks. Cox regression analysis did not confirm the influence of race on disease progression but this was confounded by incomplete data. Discussion The high incidence of whites in our study population relative to their racial distribution in the province may be explained by better educational and awareness levels of PCa and better access to healthcare facilities in this race group as compared to blacks. The data demonstrating a more advanced stage of disease presentation and higher median PSA levels in the black population may be reflective of an informational void on screening and awareness of PCa and/or a more aggressive disease course in this population group. The hypothesis that the black population may have a more aggressive disease course is given further credence by the crude analysis data suggesting a longer PFS for whites when compared to blacks. Conclusions This study invites further exploration of racial trends in PCa incidence, risk profile and outcomes amongst the diverse population groups of SA.
A psychiatric study of Zulu male certified patients, comparing those who had been exposed to extreme civil unrest before admission, with those who had not been so exposed : with special emphasis on post-traumatic stress disorder.
(1991) Brayshaw, Bertram Maclear.; Lasich, Angelo.
No abstract available.
Aids for the early diagnosis of tuberculous meningitis (TBM)
(1985) Ramkissoon, Arthi.; Coovadia, Hoosen Mahomed.
Mortality and morbidity rates associated with tuberculous meningitis (TBM) are substantial. The average duration of the untreated disease from onset to death is about 17 days. The prognosis of TBM is known to correlate with the stage of the disease at the time of diagnosis and commencement of chemotherapy. Early diagnosis improves the chances of recovery without neurological sequelae. Early diagnosis is a problem because the presenting symptoms are non-specific and the onset of the disease is typically insidious. To date no single test is available that is totally reliable and specific for TBM. I have attempted to develop a reliable and easily applicable test for the diagnosis of TBM. In fulfilling this objective, the work undertaken may be divided into three major sections:- 1. Detection of soluble Mycobacterium tuberculosis antigens in the cerebrospinal fluid (CSF) of patients with TBM and in control groups by using Mycobacterium bovis BCG antigens. The technique used was that of inhibition enzyme-linked immunosorbent assay (ELISA). The principle of this technique is illustrated in Fig. 5. 2. Detection of soluble M. tuberculosis antigens in the CSF of tuberculous and control groups of patients by using antibodies raised against M.bovis BCG. The technique used was that of the double antibody sandwich ELISA. An outline of this ELISA is given in Fig. 6. 3. Correlation of chloride levels in the blood and CSF of patients with tuberculous and other forms of meningitis. It has been established that the SERUM/CSF ratio of bromide tends towards unity in patients with TBM because the permeability of the blood-brain barrier is impaired. Since both bromide and chloride are chemically similar (both being halides), it was thought that a similar pattern may exist for BLOOD/CSF chloride ratios; and this was investigated. The method used for the INHIBITION ELISA had to be standardized before the samples could be tested. This involved investigating the acceptability of various microtitre plates; determination of the optimal working dilutions for the coating solution and conjugate; and determination of optimal conditions for the various incubation periods, both in terms of time and temperature. A total of 70 specimens was tested. These consisted of 25 normal CSF controls; 25 pleural and ascitic fluid samples; 10 TBM samples, and 10 bacterial meningitis CSF samples. It was found that a distinction existed between the absorbance values obtained from positive TBM CSF samples (Mean 0,658 + 0,043) and that from normal CSF samples (Mean 1,089 + 0,224). The mean absorbance of the culture-positive bacterial CSF's also differed significantly from the other 2 groups (Tables VII; IX). Some overlap occurred amongst the absorbance values of bacterial culture positive CSF's (Range 0,975-0,879) and normal CSF's (Range 1,486-0,934). The mean absorbance value for bacterial positive CSF samples (0,920 _+ 0,029) differed significantly (p <0,01) from those of normal CSF (1,089 + 0,224) and TBM CSF's (0,658 + 0,043). The difference between the mean values obtained with tuberculous and non-tuberculous groups of pleural and ascitic fluid was also significant (p < 0,01). The method used for the DOUBLE ANTIBODY SANDWICH ELISA was that of Sada et al. (1983). Before the samples could be tested, the method had to be standardized and similar investigations to those for the INHIBITION ELISA were performed. In addition, antibodies raised against M.bovis BCG were conjugated to alkaline phosphatase since no commercial preparation was available. Unfortunately no distinction was recorded between negative and positive test specimens, even on repetition of the entire procedure. Measurement of chloride was done by a fully automated procedure using the BECKMAN ASTRA-8. A total of 149 samples were tested. Of these 10 were tuberculous, 34 were viral, and the remainder were bacterial meningitis. No pattern was established that could differentiate TBM from viral or bacterial meningitis. The results obtained are tabulated in Table III and illustrated in Figures 9, 10, and 11. In summarizing, the use of the INHIBITION ELISA technique for the accurate diagnosis of TBM seems promising. However, its validity in the clinical situation will have to be assessed further and with greater numbers of specimens before it can be adopted as a diagnostic procedure for TBM. OBJECTIVE. To determine 1. The ability and reliability of the INHIBITION ELISA1 technique to detect mycobacterial antigens in pleural, ascitic, and cerebrospinal fluids. 2. The accuracy and reproducibility of the double antibody sandwich ELISA in the detection of mycobacterial antigens in CSF of patients with tuberculous meningitis (TBM). 3. Whether a correlation exists between blood and CSF chloride levels in patients with tuberculous and other forms of meningitis.
The role of the kallikrein-kinin system in prostate and breast tumourigenesis and tumour-associated angiogenesis..
(2007) Wright, Jaclyn.; Naidoo, Strinivasen.; Botha, Julia Hilary.
This thesis consists of three main parts. An introduction to diode-pumped solid-state lasers, thermal modelling of solid-state lasers and rate-equation modelling of solid-state lasers. The first part explains the basic components and operation principles of a typical diode-end-pumped solid-state laser. The stimulated emission process, solid-state laser gain media, various pump geometries and a basic end-pumped laser resonator configuration are among the topics that are explained. Since thermal effects are one of the main limiting factors in the power-scaling of diode-pumped solid-state lasers, the second part of this thesis describes numerical and analytical thermal models that determine the thermal lens and thermally induced stresses in a laser crystal. As a first step, a time-independent numerical thermal model which calculates the three-dimensional temperature distribution in the laser crystal is implemented. In order to calculate the time dependent thermally induced stresses in a laser crystal, a coupled thermal-stress finite element analysis model was implemented. Even though some steady-state analytical solutions for simple crystal geometries do exist, the finite element analysis approach was taken so that the time dependent thermally induced stresses could be calculated for birefringent crystals of various geometries. In order to validate the numerical results, they are compared to experimental data and analytical solutions where possible. In the last part, the population dynamics inside the laser gain medium are described and modelled with a quasi-three-level rate-equation model. A comprehensive spatially resolved rate-equation model is developed and discussed. In order to simplify the implementation of the rate-equation model as a computer simulation, the spatial dependence of the laser parameters is ignored so that the model reduces to a singleelement plane-wave model. The simplified rate-equation model is implemented and solved numerically. The model is applied to a four-level CW and Q-switched Nd:YLF laser as well as a quasi-three-level QCW Tm:GdV04 laser. The models' predictions are thoroughly verified with experimental results and also with analytical solutions where possible.
Cardiovascular evaluation of hypertensive disorders of pregnancy by echocardiography.
(2004) Desai, Dushyant K.; Moodley, Jagidesa.; Naidoo, Datshana Prakesh.
Background: Preliminary observations suggest that aberrations in maternal central hemodynamics and uterine artery Doppler velocimetry reflect the severity of hypertensive disorders of pregnancy. In addition, the precise changes of cardiac output in normal pregnancy, particularly in the third trimester, have remained controversial. Aims and Objective: To measure concomitantly Doppler echocardiographic maternal central hemodynamics and uterine artery Doppler velocimetry and evaluate their association with adverse feto-neonatal outcome in hypertensive pregnant women. To evaluate cardiac output longitudinally in the latter half of pregnancy in normal healthy women. Design and Setting: Prospective study conducted at the Obstetric Unit, King Edward VIII Hospital, Durban, South Africa. Study sample: forty (40) pregnant hypertensives without any prior therapy and a further group of pre-eclamptic women (n=22) treated with stat dose sodium gardinal and alpha-methyldopa were studied. Results: i) A trend to a higher cardiac output was seen in the hypertensives compared to the normotensives. Hypertensive women were of larger stature; there was no difference in cardiac index. Fetal birthweight correlated poorly with cardiac index in pre-eclamptic women (r =0.21). A better correlation was seen with uterine artery resistance index (r = - 0.65) and systemic vascular resistance index (r = -0.49). Critical values for cardiac index and systemic vascular resistance index to predict poor adverse feto-neonatal outcome with good predictive values were not identified. ii) Pre-eclamptics treated with stat dose of sodium gardinal and/or methyldopa prior to echocardiography had a significantly lower systemic vascular resistance index and uterine artery resistance index compared to the untreated group. The lower systemic vascular resistance index in this treated cohort occurred from a combination of non-significant lower blood pressure and higher cardiac index. iii) Compared to normotensive women, untreated pre-eclamptics had a significantly lower heart rate (p< 0.001), a higher stroke index (p=0.018) and no difference in resultant cardiac index (p=0.452). iv) In gestational apoteinuric hypertensives presenting after 34 weeks gestation, maternal hemodynamics and uterine artery resistance index did not help define a higher risk group. v) In chronic hypertensives pregnancies, left ventricular hypertrophy correlated with severity of blood pressure. Higher risk chronic hypertensives were better selected by proteinuria than maternal central hemodynamics or uterine artery resistance index. vi) In normal pregnancy, maternal cardiac output peaked in early to mid third trimester and was maintained till term. Significant correlations were observed among maternal cardiac output, maternal body surface area and fetal birth weight. Discussion: i) This study shows that cardiac index and systemic vascular resistance index measured in the latter part of the second and third trimesters in hypertensive pregnant women were not associated with adverse fetal outcome. Large variations in cardiac index values were observed that restricted detection of satisfactory critical values for cardiac index and systemic vascular resistance index to predict adverse outcome. ii) An improved correlation of uterine artery resistance index with maternal hemodynamics and fetal birthweight in pre-eclampsia supports the hypothesis that poor placentation does not allow for a normal increase in uterine blood flow. iii) The poor correlation between uterine artery resistance index and maternal central hemodynamics, does not support the hypothesis that elevated cardiac output in hypertensive pregnancies (hyperdynamic disease model) occurs as a compensatory response to maintain adequate perfusion in a utero-placental bed with high resistance that did not decrease.
Effects of a prostaglandin precursor, gamma-linolenic acid (GLA), on malignant cells in vitro and in vivo.
(1985) Ramchurren, Nirasha.; Botha, Julia Hilary.; Robinson, K. M.
Recent studies have shown that the proliferation of various human and murine tumour lines can be inhibited by the addition of gamma-linolenic acid (GLA) to the culture medium. These findings are consistent with the proposal put forward by Horrobin (1980) that malignant cells lack the enzyme/ A 6 desaturase; which is responsible for the conversion of linoleic acid (LA) to GLA. Since GLA is a prostaglandin (PG) precursor/ inadequate conversion of LA to GLA would result in decreased production of PGs/ particularly PGEi/ which has been shown to have an inhibitory effect on cell growth. Provision of GLA to enzyme deficient malignant cells should therefore bypass this blockade/ increase PGET synthesis and thus "normalise malignant cells". This study was performed to examine further the effects of exogenous GLA on growth of malignant cells in vitro and in vivo. Cells of the continuous murine sarcoma (M52B) line and primary cultures of non malignant fibroblasts were used to investigate effects of GLA in vitro. Cultures were exposed to either single or multiple doses of a range of concentrations of GLA. Radioimmunoassay (RIA) was performed to compare the amounts of PGE and PGF released into the medium by GLA treated and control M52B cultures and thus determine whether the addition of GLA in vitro significantly affected production of these PGs. Athymic BALB/c mice and immunocompetent BALB/c and Biozze mice as well as mice of the "Onderstepoort Strain" were used in various in vivo studies. Tumours were induced by the subcutaneous inoculation of approximately 1 x 106 cells of either the M52B line (into immunocompetent and athymic mice) or human breast carcinoma (NUB 1) line (into athymic mice). Take rates and latent periods were recorded. GLA treatment was initiated after tumours were established. In one study the fatty acid in hydrogenated coconut oil (HCO), which contains no PG precursors/ was administered parenterally (100 ug/ml/day) to Biozze mice. Control mice were either untreated or injected with HCO only. In another study, BALB/c mice and mice of the "Onderstepoort Strain" had their diet supplemented with GLA (in the form of EPO) to an extent of 3.5%. Control mice consumed either standard laboratory chow only or, chow supplemented with either 35% sunflower seed oil (SSO) or 35% HCO/ neither of which contain GLA. All diets were supplied ad libitum. Tumour sizes were measured every 48 hours and at the end of each experiment at which time tumours were excised and examined histologically. GLA was found to produce inhibitory and toxic effects on growth of both M52B cells and non malignant fibroblasts in vitro/ although the effect in the latter was observed only with high concentrations of the fatty acid. The inhibition of malignant cell growth was concentration dependant and was positively related to the duration of exposure to the fatty acid. Prior to death/ cells treated with GLA accumulated vii paranuclear granules which were shown histochemically to be lipid in nature. Electron microscopy confirmed the presence of large lipid deposits. Cultured M52B cells treated with GLA also released more PGE and PGF into the medium than did cells not exposed to the fatty acid. However, analysis of results using the Mann Whitney U test showed these differences to be statistically non significant for both PGE and PGF on two tailed tests. In contrast to the inhibition of M52B cell growth observed in vitro, growth of solid M52B sarcomas and NUB 1 carcinoma xenografts in athymic mice was apparently unaffected by administration of dietary GLA. Analysis of data using an unpaired student's t-test showed that the differences in tumour volumes between control and treated groups were not statistically significant either before or at the end of the experiment. While the inhibition of malignant cell growth caused by GLA in vitro was consistent with Horrobin's proposal that malignant cells may lack this PG precursor, whether or not these actions are mediated by the PGs remains obscure. Although an increase in PGE production by M52B cells was observed following GLA treatment, besides this increase being statistically non significant, it was not possible to determine whether this was due to PGE, (as suggested by Horrobin) or PGE2. It is possible that the effect produced in vitro was due to some factor other than raised PGE production, for example a non-specific fat-overload effect or a change in cell membrane fluidity. The lack of effect of GLA on tumour growth in vivo may have been due to inadequate delivery of the fatty acid to the tumour site. However, whatever the mechanism of action of GLA in vitro/ since oral GLA was supplemented to the maximum tolerated extent and produced no effect in immunodeficient mice inyiyo, it would seem that in a similar clinical situation oral doses which would be practical may be ineffective.
Assisted respiration in the treatment of neonatal tetanus.
(1967) Thambiran, A. K.
Dyslipidaemic pancreatitis : clinical assessment and analysis of disease severity and outcomes.
(2006) Anderson, Frank.
Introduction: The relationship between pancreatitis and dyslipidaemia is unclear and has never been studied in a South African context. Patients and methods: A prospective evaluation of all admissions with acute pancreatitis to a regional hospital general surgical service was performed to ascertain its relationship to dyslipidaemia. Aetiology was determined by history and ultrasound assessment. Disease severity was assessed using a modified Imrie score and an organ failure score. Body mass index was calculated. A lipid profile was obtained. Abnormal profiles were repeated. Secondary causes of dyslipidaemia were noted. A comparison of the demographic profile, aetiology, disease severity scores, complications and deaths were made in relationship to the lipid profiles. Results: From June 2001 to May 2005, there were 230 admissions, of whom 31% were women and 69% men. The median age was 38 years(range 13- 73). The pancreatitis was associated with alcohol in 146(63%), gallstones in 42(19%) and idiopathic in 27(12%). The amylase was significantly higher with a gallstone aetiology (p
The clinical natural history of snakebite victims in Southern Africa.
(2000) Blaylock, Roger.; Robbs, John Vivian.
The author wrote a dissertation for the Mmed Sc degree entitled The Clinical Natural History of Snakebite in Southern Africa, which dealt with the epidemiology of snakebite and the clinico-pathological events in snakebite victims. This thesis is a sequel on the management of snakebite victims. Publications on the overall management of snakebite in the Southern African region that include original scientific research are those of F.W. Fitzsimons (1912), F.W. Fitzsimons (1929) (assisted by V.F.M. Fitzsimons), P.A. Christensen (1955, 1966, 1969) and Christensen & Anderson (1967). Subsequent books, pamphlets and journal articles have rehashed this knowledge or advocated methods of treatment developed in other countries. An example of the latter is the pressure immobilisation prehospital measure advocated for snakebites in Australia (Sutherland et aL, 1979, 1981, 1995), which I regard as benefiting less than 1% of snakebite victims here and being deleterious in most cases. In view of the paucity of research done in Southern African in recent years, many questions remain unanswered, and some strongly held views are without logical or scientific foundation. Most of these questions arose prior to the writing of this thesis, and others arose when the data were analysed. The following are some questions on the management of snakebite that have still have to be addressed. Is vaccination against snakebite possible and practical? Are folk and traditional remedies advantageous or deleterious? How commonly are they used? Immobilisation of the bitten part and the patient is an internationally recognised aid measure, but is this relevant to the Southern African situation? Tourniquet use in the case of necrotising venoms is considered to aggravate or precipitate necrosis. Does immediate active movement following a bite ameliorate or prevent necrosis without increasing mortality? The majority of clinicians recommend antibiotic prophylaxis, but is this necessary for all snakebites, against which bacteria should antibiotics be administered, and what is the source of these bacteria? Should antivenom be administered to all snakebite victims: for species-specific bites, only if envenomation is present, for severe envenomation, or not at all? Acute adverse reactions to South African manufactured snakebite antivenom has been variously recorded as less than 1% (Visser & Chapman 1978) up to 76% (Moran et al., 1998). What is the truth? Is syndromic management of snakebite efficacious or is it essential to identify the particular snake species? Is the present liberal use of fasciotomy necessary? Is there an optimum time to debride necrotic areas and is surgery necessary at all? Is paresis or paralysis due to neurotoxic envenomation always the result of a post-synaptic block? Would such a block respond to neostigmine or prostigmine in a similar way to post-synaptic anaesthetic muscle relaxants? Is heparin of value when procoagulant toxins induce a consumption coagulopathy? Do fibrinstabilising agents or fibrinolytics have a role? Does the management of pregnant snakebite patients differ from that of non-pregnant patients? Is snake venom teratogenic? Does snake venom ophthalmia frequently lead to blindness? Are steroids, NSAIDs and antihistaminics, which are commonly used in the management of snakebite, of proven value? This thesis attempts to answer these questions and more, and comprises six sections. The first section deals with pre-hospital management, the second with infection which may occur at the bite site wound, the third with SAIMR snakebite antivenom, the fourth with the three envenomation syndromes, the fifth with snakebite in pregnancy, venom ophthalmia and other treatment modalities, and the sixth section includes a summary, appendix and references. Unless otherwise stated, the materials and methods of each chapter are based on 336 snakebite victims admitted to Eshowe Hospital, KwaZulu-Natal, from January 1990 - July 1993 and other victims treated by the author, the data of which have been prospectively maintained. This has been an ongoing process up to the present time.

Browse

Browsing School of Clinical Medicine by Date Accessioned