The district health system: a personal perspective from Zululand.
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Biomedical subjects
Publications and source records attributed to D Wilkinson.
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The global tuberculosis epidemic is being fuelled by dual infection with human immunodeficiency virus type I. Short-course chemotherapy is effective but usually fails for operational reasons. A community-based treatment programme of twice-weekly fully-supervised treatment is described in which 89% of surviving patients completed treatment under programme conditions. Half the patients were successfully supervised by non-health workers. New approaches are needed to combat the global tuberculosis epidemic.
This paper describes the application of radionuclide limb blood flow measurements in 60 patients presenting to the vascular surgeons with exercise-induced leg pain. All patients were considered to be diagnostic problems since either their symptoms were atypical for peripheral vascular disease, or they had normal peripheral pulses and/or a normal ankle/brachial pressure index. Thirty-one patients were ultimately shown to have peripheral vascular disease and underwent treatment. In all these cases the limb blood flow to one or both legs was below the normal range. Twenty-three patients were shown, by myelography, computed tomography or plain radiography, to have orthopaedic disease and in all cases their limb blood flow to both legs was within the normal range. In five patients, the limb blood flow was normal and the symptoms spontaneously resolved, no cause for the leg pain having been found (one patient refused angiography). Radionuclide limb blood flow is a simple and reliable diagnostic test which is superior to the assessment of peripheral pulses or their ankle to brachial pressure index in resolving diagnostic problems in vascular surgery.
BACKGROUND: Exercise-induced hypotension in patients with coronary artery disease (CAD) has been considered to be due to an inability to achieve an adequate increase in cardiac output to match the demands of exercise. We investigated 10 consecutive patients (9 men and 1 woman; age, 38 to 71 years; mean, 52 years) with angiographically documented CAD and exercise-induced hypotension (EIH) (BPPeak < BPRest). Ten approximately age- and sex-matched patients with documented CAD and normal exercise blood pressure response (NBP) served as control subjects. METHODS AND RESULTS: Nine patients with EIH and all 10 control subjects underwent forearm plethysmography and radionuclide ventriculography (RNV) during semierect cycle exercise. Forearm vascular resistance (FVR) fell by 35 +/- 21% in exercise-induced hypotension patients versus an increase of 78 +/- 65% in patients with an NBP response (P < .0001). Left ventricular ejection fraction increased by 5.1 +/- 7.5% in the group with EIH versus a fall of 4.1 +/- 6.2% in the control group (P = .004). Cardiac output at peak exercise (RNV) increased by 2.2 +/- 0.89-fold in the group with EIH versus 1.49 +/- 0.47-fold in the control group (P = .04). The tenth patient in the group with EIH underwent invasive hemodynamic evaluation during erect exercise. Systolic blood pressure fell (136/80Rest to 50/40Peak) and cardiac output (Fick) tripled, whereas calculated systemic vascular resistance decreased by a factor of 10. Successful angioplasty to an isolated circumflex lesion resulted in resolution of symptoms and abnormal hemodynamic responses during exercise. CONCLUSIONS: Abnormal vasodilation associated with a normal or even increased rather than decreased cardiac output response appears to be an important mechanism underlying EIH in some patients with CAD. In the present study, this appears to have been the dominant mechanism in 8 and contributory in 2 of the consecutive patients studied.
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Aspects of the epidemiology and clinical features of 81 consecutive patients admitted with snakebite to a rural hospital in Zululand are reviewed. Most bites occurred during the hot season, 40% in children under 10 years of age. Thirty per cent of bites occurred at night. Most bites showed features of local envenoming only, but systemic features (neurotoxicity and haemorrhage) were encountered. Snakebite caused significant morbidity and mortality. Thirty-one per cent of admissions needed surgery; almost 50% needed more than one operation. Five per cent, all children, died. The extent of local envenoming on admission proved to be a highly sensitive indicator of risk of worsening of local envenoming, and of the development of systemic signs. The analysis has allowed the development of rational guidelines on the management of snakebite in this hospital which, it is hoped, will reduce mortality rates, and has identified several areas warranting further research.
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The zinc finger gene Krox20 and many Hox homeobox genes are expressed in segment-restricted domains in the hindbrain. The restricted expression patterns appear before morphological segmentation, suggesting that these transcription factors may play an early role in the establishment and identity of rhombomeric segments. In this paper, we show that the HoxB2 (Hox2.8) gene is normally upregulated in rhombomeres (r) 3, 4, and 5, and we identify an enhancer region upstream of the gene that imposes r3/r5 expression in transgenic mice. This enhancer contains three Krox20-binding sites required in vitro for complex formation with Krox20 protein and in vivo for rhombomere-restricted expression. In transgenic mice, Krox20 expressed in ectopic domains can transactivate a reporter construct containing the HoxB2 r3/r5 enhancer. These data demonstrate that Krox20 is a part of the upstream transcriptional cascade that directly regulates HoxB2 expression during hindbrain segmentation.
Fingertip and venous blood lactate concentrations were determined pre-exercise and after 4-min bouts of treadmill running at 2.69, 3.13, 3.58 and 4.03 m s-1 in 14 normal healthy volunteers. A 1-min rest period intervened each exercise period, and was used for the simultaneous sampling of fingertip and venous blood. Compared to pre-exercise, fingertip and venous blood lactate (BLa) concentrations increased significantly (P < 0.05) in a progressive pattern with increasing exercise intensity. Fingertip BLa concentrations were significantly higher (P < 0.05) than venous blood prior to exercise and in response to all four running speeds. Treadmill speed, heart rate and oxygen consumption were significantly lower (P < 0.05) at a BLa concentration of 4 mM when estimated from fingertip blood as compared with venous blood. These results indicate that differences between fingertip and venous blood exist during treadmill exercise and should be considered when lactate determination is employed as a criterion to evaluate and predict performance and when used as a training guide to standardize exercise intensity.
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The effect of applying nitroglycerin or placebo ointment to the back of the hand before venipuncture and injection of propofol was investigated in 60 ASA physical status I unpremedicated women. Eighteen patients (67%) pretreated with nitroglycerin experienced no pain compared with 10 (33%) in the placebo group. Eleven in the placebo group experienced moderate or severe pain during injection compared with only one in the active group. The time of onset of pain in more than half the subjects occurred 10 s or longer after commencement of injection, and, in more than half the patients, the site at which pain was felt was above the injection site (with three subjects experiencing it in the shoulder). No patient had a headache or experienced postural hypotension. We conclude that nitroglycerin ointment applied to the back of the hand before injection reduces the incidence of painful injection with propofol.
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A gas chromatographic-mass spectrometric (GC-MS) method is described which quantitates 5-fluorouracil (5-FU) plasma levels ranging from 0.5 to 50 ng/ml. The analysis uses two internal standards, 1,3-[15N2]-5-fluorouracil and 5-chlorouracil. Extraction and derivatization of the pyrimidine bases were accomplished in a single step using acetonitrile. Compounds were analyzed as their 1,3-dipentafluorobenzyl derivatives by electron-impact MS, and the GC-MS analysis was automated with respect to sample injection and data reduction. Stability of the analysis was demonstrated by continuous unattended analysis of 5-FU in human plasma for periods of up to three days with no deterioration of the quantitative results. The method is applicable to quantitating 5-FU plasma levels in patients receiving protracted infusions of the drug for colorectal cancer or other malignancies.
We describe the molecular cloning of a receptor tyrosine kinase from a cell line (LK63) derived from a case of human pre-B-cell leukemia. We have previously shown that a monoclonal antibody (IIIA4) raised against LK63 recognized a glycosylated, cell-surface 135-kDa molecule (HEK), which displayed tyrosine kinase activity in vitro. The HEK protein was purified by using a IIIA4 antibody column and both N-terminal and internal amino acid sequences were obtained. A 51-mer degenerate oligonucleotide based on the internal amino acid sequence was used to screen an LK63-derived lambda gt10 cDNA library under low-stringency hybridization conditions. One clone of 2.5 kilobases (kb) was isolated and characterized and used to rescreen the library under more-stringent hybridization conditions. A 4.5-kb clone containing the entire HEK coding region was isolated and its complete DNA sequence was determined. The 4.5-kb insert was subcloned into the expression vector CDM8 and transfected into COS cells. COS cells transfected with the sense HEK/CDM8 construct stained specifically with the IIIA4 antibody, thereby confirming that the antigen recognized by the IIIA4 antibody and the expressed protein product of the HEK cDNA clone were identical. DNA sequence analysis revealed that HEK is a newly discovered member of the EPH/ELK family of receptor tyrosine kinases. Northern blot analysis of a number of cell lines demonstrated the expression of 5.5- to 6.0-kb HEK transcripts in LK63 and the T-cell lines JM and HSB-2. Southern blot analysis of DNA from LK63 suggested that the HEK gene was neither amplified nor rearranged in the LK63 tumor.