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Biomedical subjects

B Maharaj

Publications and source records attributed to B Maharaj.

At least 19 recordsLinked to original sources

HLA-A, -B, -DR and -DQ antigens in black patients with infective endocarditis.

In order to determine if genetically determined immune response factors could play a role in the pathogenesis of infective endocarditis in black patients, we performed HLA-A and HLA-B typing in 38 patients with this disease and HLA-DR and HLA-DQ typing in 33 and 27 of these individuals, respectively. HLA typing was also carried out in a control group of normal black adults. The HLA typing was done by means of a standard microlymphocytotoxicity test. No difference in HLA-A, HLA-B, HLA-DR and HLA-DQ antigen frequencies between patients and controls were noted. This study did not provide any evidence that genetic factors could contribute to a disposition to infective endocarditis.

Adolescent

Drug management of hypertensive disorders of pregnancy.

Drugs used in the acute and long-term management of hypertension in pregnancy and the preeclampsia-eclampsia syndrome have been reviewed and their therapeutic effects and maternal and fetal adverse effects have been considered. The review also focuses on recent developments in the areas of prevention and management of pre-eclampsia-eclampsia syndrome. Although a number of new drugs have emerged, as potentially useful in the management of hypertension in pregnancy and pre-eclampsia-eclampsia syndrome, some remain at the cornerstone of therapy; for example, methyldopa for long-term treatment of chronic hypertension, hydralazine or nifedipine for rapid reduction of severely elevated blood pressure, and magnesium sulphate for eclampsia. Some of these agents, especially the calcium antagonists, show promise in that their use is associated with fewer side effects. Safety for the fetus, however, has not been adequately evaluated yet. Neither aspirin nor calcium supplements appear to improve the outcome in pregnancy. Currently, the dilemma whether to treat hypertension in pregnancy and pre-eclampsia-eclampsia syndrome with old, established, cost-effective drugs or the promising newer drugs provides an interesting academic challenge.

Adrenergic Antagonists

HLA-A, B, DR, and DQ antigens in Indian patients with severe chronic rheumatic heart disease.

To determine whether genetic factors could be involved in the pathogenesis of rheumatic heart disease, we performed HLA-A and HLA-B typing in 59 Indian patients with severe chronic rheumatic heart disease requiring cardiac surgery, and HLA-DR and HLA-DQ typing in 58 of these patients. The HLA typing was done by a standard microlymphocytotoxicity method. Patients were 12 to 59 years old (mean 32.9 years). No significant differences in HLA-A, HLA-B, HLA-DR and HLA-DQ frequencies between patients and controls were noted. The role of genetically determined immune-response factors in the pathogenesis of chronic rheumatic heart disease was not evident in this study.

Adult

HLA-antigens in black patients with hepatocellular carcinoma.

To determine whether genetically determined immune response factors could be involved in the pathogenesis of hepatocellular carcinoma, we performed HLA-A and HLA-B typing in 55 black patients with histologically-proven hepatocellular carcinoma, and HLA-DR and HLA-DQ typing in 47 of these patients. The HLA typing was also carried out in a control group of normal black patients. The HLA typing was done by a standard microlymphocytotoxicity method. No difference in HLA-A, HLA-DR and HLA-DQ frequencies between patients and controls were noted. HLA-B21 was present in 10.9% of patients compared to 1.8% of control subjects (corrected p < 0.005; relative risk = 6.6) and HLA-B49 was present in 7.3% of patients compared with 1.1% of normal control subjects (corrected p < 0.007; relative risk = 7.1). These findings suggest that genetic factors may play a role in the pathogenesis of hepatocellular carcinoma.

Adult

Hexane cardiotoxicity--an experimental study.

Ventricular arrhythmia has been postulated as a possible cause of death in young black children who abuse volatile substances, primarily benzine and certain glues that contain n-hexane. A series of protocols were designed to determine the effect of n-hexane on myocardial function and morphology in male laboratory rats. In the first protocol, experiments were designed to study the effect of n-hexane in initiating ventricular fibrillation and in modifying myocardial magnesium and potassium levels. The results showed that the thresholds for ventricular fibrillation and myocardial magnesium and potassium levels were reduced compared to control values. In the second protocol, n-hexane-treated rats were supplemented with intragastric administration of magnesium and potassium salts. The outcome of the experiments indicated that although the myocardial magnesium and potassium levels were corrected, the threshold for ventricular fibrillation remained low compared to control values. In the third protocol, experiments were designed to examine myocardial morphology by electron microscopy. Cellular changes were observed in the myocardium as a result of administering n-hexane. These cellular changes were considered to be responsible for the decreased threshold for ventricular fibrillation. The present study indicates that n-hexane, a constituent of benzine and certain glues, is cardiotoxic.

Animals

The effect of a low dose versus a conventional dose of hydrochlorothiazide on ventricular fibrillation threshold and electrolyte levels in laboratory rats.

We studied the effect of hydrochlorothiazide on metabolic and electrolyte parameters. In the first protocol, six groups of rats were studied to determine whether changes in ventricular fibrillation threshold, and serum and myocardial potassium occur after treatment with different doses of hydrochlorothiazide; three groups (N = 15) served as controls and the other three groups (N = 15) were given different doses of hydrochlorothiazide for a 3 month period. Two rats from each group were sacrificed daily. One rat heart was perfused using the Langendorff perfusion apparatus and the other used for myocardial potassium analysis. Blood was also collected for serum potassium analysis. There was no change in the threshold for ventricular fibrillation in groups treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control values. There was a nonsignificant decrease in serum and myocardial potassium levels in rats treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control. Seven of the 15 rats treated with 0.18 mg hydrochlorothiazide showed significantly lower ventricular fibrillation threshold levels and decreased serum potassium (P < 0.02) compared to control animals. In addition, a significant decrease in myocardial potassium was noted (P < 0.05). In the second protocol, 8 of the 15 rats treated with 0.18 mg hydrochlorothiazide showed reduced ventricular fibrillation threshold and serum potassium levels (P < 0.05). A significant decrease in myocardial potassium was also observed (P < 0.05). These variables were corrected by the intragastric administration of potassium salts. The present study indicates that 0.04 mg and 0.09 mg hydrochlorothiazide have no effect on ventricular fibrillation threshold level or on serum or myocardial potassium levels. There was a significant decrease in ventricular fibrillation threshold and serum and myocardial potassium levels in 7 of the 15 animals studied in protocol one and 8 of the 15 animals studied in protocol two, treated with 0.18 mg hydrochlorothiazide and these variables were corrected by the intragastric administration of potassium salts.

Animals

Zinc, hydrochlorothiazide and sexual dysfunction.

This study was designed to test the hypothesis that hydrochlorothiazide a diuretic used to treat hypertension depletes body zinc and thereby cause sexual dysfunction. Serum zinc and sexual dysfunction were measured in 39 middle aged hypertensive men who had been taking hydrochlorothiazide in average daily doses of between 25 and 50 mg daily for at least six months, and a control group of 27 unmedicated middle aged normotensive men. The medicated group had a higher incidence of sexual dysfunction (56 pc) as compared to 11 pc in the control group. The use of hydrochlorothiazide did affect serum zinc levels significantly in 20 patients. Sexual dysfunction occurred more often in older and overweight patients (p < 0.004). Three of the normotensive men experienced sexual dysfunction probably related to old age. Twenty two of the 39 on hydrochlorothiazide and experiencing sexual dysfunction were divided into two groups of 11 patients. Bloods were taken from the 27 normotensive and 22 hypertensive men receiving hydrochlorothiazide for the analyses of zinc. Subsequently one group of the patients were supplemented with zinc 500 mg daily for 30 days while the other group was supplemented with magnesium chloride 1 g daily for 30 days. The normotensive men were not treated. After 30 days, bloods were again taken from the three groups of analyses for zinc and magnesium. Serum zinc was significantly decreased (p < 0.05) by hydrochlorothiazide and a non significant decrease in serum magnesium (p = ns) was observed. After supplementation with zinc, the serum zinc levels returned to normal only in eight patients. There was improvement in the symptoms of sexual dysfunction in five patients. Two patients gained weight. Hydrochlorothiazide decreased serum zinc levels (p < 0.05) and was unchanged with magnesium supplementation but the serum magnesium returned to normal values. Improvement of symptoms of sexual dysfunction was positive in one patient. This study shows that low serum zinc levels may be associated with sexual dysfunction but the definitive role of zinc in the pathogenesis of sexual dysfunction will remain controversial.

Aged

Intravenous isradipine in the management of severe hypertension in pregnant and nonpregnant patients. A pilot study.

To determine the appropriate dosage regimen of isradipine in black patients with severe hypertension of pregnancy, 10 patients (gestational age, 30 to 38 weeks; diastolic blood pressure [DBP], 110 to 148 mm Hg; no hypertensive crises; and normal central venous pressure) were given an isradipine infusion while the fetal heart rate was continuously recorded using a cardiotocograph. The infusion rate of isradipine was adjusted at regular intervals until control (DBP < 95 mm Hg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 micrograms/kg/min, with increments of 0.0025 micrograms/kg/min every 15 min until control is achieved. Thereafter, a maintenance infusion of 0.15 micrograms/kg/min can be commenced. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration. A second group of 10 patients (9 men and 1 woman) with DBP > 115 mm Hg (range, 117 to 135 mm Hg) and no features of hypertensive crises were also studied. The optimal dosage regimen in this patient group differed from the other in two respects: dosage increments could be made more rapidly (at 10-min intervals); and the dosage that produced blood pressure control needed to be continued for 30 min before the maintenance infusion was commenced. This regimen was not associated with hypotension.

Adolescent

Intravenous isradipine in the management of severe hypertension of pregnancy in black patients: a pilot study.

The ideal antihypertensive agent for lowering very high blood pressure levels rapidly in severe hypertension of pregnancy still eludes researchers. This pilot study was conducted to determine the appropriate dosage regimen for isradipine in black patients with severe hypertensive disorders of pregnancy. Ten black patients with gestational age > or = 30 (range 30-38) weeks and diastolic blood pressure (DBP) > or = 110 (range 110-148) mmHg following 2 h of bed rest were recruited following informed consent. None of the patients had symptoms or signs of hypertensive crisis. After correction of hypovolaemia (using central venous pressure monitoring) with Ringer's lactate, high blood pressure was lowered by an isradipine infusion. Fetal heart rate was continuously recorded using a cardiotocograph. All blood pressure measurements were made using the same mercury sphygmomanometer by a single observer. The infusion rate of isradipine was adjusted at regular intervals until blood pressure control (DBP < 95 mmHg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 microgram kg-1 min-1 with increments of 0.0025 micrograms kg-1 min-1 every 15 min until blood pressure control is achieved. Thereafter, a maintenance infusion of 0.15 microgram kg-1 min-1 can be initiated. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration.

Adolescent

A comparative study of isradipine SRO and enalapril in black patients with mild-to-moderate hypertension.

Fifty-two black men who had supine diastolic blood pressures (DBP) above 95 mm Hg at the end of a 2-week placebo wash-out period were randomized to receive either isradipine SRO at 2.5 mg/day or enalapril at 10 mg/day for 8 weeks. After 4 weeks, the dosages were doubled if DBP remained above 90 mm Hg. Reductions in blood pressure were comparable in both groups. Mean supine DBP was reduced from 100.6 to 93.9 mm Hg in the isradipine-treated group, and from 103.9 to 98.2 mm Hg in the enalapril-treated group. At the end of the study, 24/27 patients were taking 5 mg isradipine SRO once daily, and 20/25 patients were taking 20 mg enalapril once daily. There were no serious adverse events. The results of this study indicated that monotherapy with isradipine SRO at the recommended initial dosage of 5 mg once daily is appropriate in black patients with hypertension. This was, however, not the case with enalapril at 10 mg once daily. The concurrent administration of a diuretic with enalapril may be more appropriate.

Adult

The effect of therapeutic doses of paracetamol on liver function in the rat perfused liver.

The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0.02 g kg-1 paracetamol daily for ninety days. The livers of animals in the control group and in one of the experimental groups were perfused with a medium containing pyruvate. The animals in the second experimental and control group were perfused with a medium containing bromosulphthalein (10 mg/100 mL). The livers of the third experimental and control group were subjected to histological examination. The rate of glucose formation and glucose concentrations were decreased, while, lactate levels and lactate: pyruvate ratios were increased in paracetamol-treated rats. The mean concentration of bromosulphthalein in the perfusate and biliary excretion of the dye were decreased. Macro and micro vesicular fatty change was present in the livers of paracetamol-treated rats. This study demonstrates that chronic administration of therapeutic doses of paracetamol to rats adversely affects liver function, as evidenced by impaired gluconeogenesis and bromosulphthalein clearance from the perfusate, and excretion of the dye into the bile, and provides histological evidence of hepatic damage in rats.

Acetaminophen

Randomised double-blind comparative study of efficacy and safety of hydroflumethiazide and reserpine and chlortalidone and atenolol in the treatment of mild to moderate hypertension in black patients.

This randomised, double-blind study compared the efficacy and safety of a fixed combination of hydroflumethiazide 50 mg and reserpine 0.125 mg (H-R) and chlortalidone 12.5 mg and atenolol 50 mg (C-A) in adult black patients with mild to moderate hypertension (a resting supine diastolic blood pressure (DBP) between 95 and 115 mmHg after a two week placebo washout period). If the DBP did not reach 90 mmHg after four weeks, the dosage was doubled. There were 27 patients in the H-R group and 22 in the C-A group who completed the study. In the H-R group, supine systolic and diastolic BP were reduced from 156.5 (95% confidence intervals 150.1-162.9) and 102.0 (97.5-106.5) mmHg to 137.0 (130.6-143.4) and 87.4 (83.0-91.9) mmHg, respectively. The corresponding values in the C-A group were 154.1 (147.0-161.2) and 103.4 (98.5-108.4) mmHg to 136.4 (129.3-143.5) and 91.2 (86.2-96.1) mmHg, respectively. Normalisation, response and control of DBP was achieved in 88.9, 92.6 and 100% of patients, respectively, in the H-R group, and in 81.8, 95.5 and 95.5% of patients in the C-A group, respectively. The dose was doubled in 14.8% of patients on H-R and 40.1% on C-A. No clinically significant abnormalities in laboratory variables and no serious adverse effects were encountered. Both drugs have been shown to be efficacious and safe in the treatment of mild to moderate hypertension in black patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effects of hexane on rat myocardium: a morphometric and morphological study.

Specimens from the left ventricular myocardium of 10 rats that had been exposed to subcutaneously administered hexane for 30 days were morphometrically and morphologically examined. Other than the presence of occasional necrotic fibres in hexane-treated animals, there was little difference in the histological appearance of myofibres in control or experimental specimens. There was a slight reduction in the average diameter of cardiac myofibres after exposure to hexane. Pathological ultrastructural changes of the myofibres were noted in the experimental and not in the control groups. Mitochondrial oedema and necrosis and myofilament disorganization and dissolution were significant changes noted in the experimental group. These pathological changes suggest that hexane, a constituent of glue and benzine, is cardiotoxic.

Actin Cytoskeleton

A comparison of the acute hypotensive effects of two different doses of nifedipine.

To determine whether a dose of 5 mg of nifedipine would be useful in the treatment of hypertensive emergencies, we compared the acute hypotensive effects of two different doses of nifedipine, 5 mg and 10 mg, in patients with severe hypertension. In this prospective, randomized, double-blind study, 30 consecutive black patients with diastolic blood pressure that was equal to or greater than 115 mm Hg received either a 5 mg or 10 mg nifedipine capsule and a placebo capsule, which matched that of the alternative strength. Patients were asked to bite the capsules and swallow the contents. Blood pressure response over 4 hours and adverse effects were monitored. Mean systolic blood pressure was reduced from 191.7 mm Hg (95% confidence interval 170.8 to 212.7 mm Hg) to 157.9 mm Hg (137.0 to 178.9 mm Hg) and 206.1 mm Hg (185.1 to 227.0 mm Hg) to 153.7 mm Hg (132.8 to 174.7 mm Hg) in patients who were given 5 mg and 10 mg doses of nifedipine, respectively. Mean diastolic blood pressure in the group of patients that received 5 mg doses of nifedipine decreased from 128.2 mm Hg (115.6 to 140.7 mm Hg) to 105.2 mm Hg (92.7 to 117.7 mm Hg); the corresponding values in the group that received 10 mg doses of nifedipine were 129.9 mm Hg (117.4 to 142.5 mm Hg) and 97.5 mm Hg (85.0 to 110.1 mm Hg), respectively. The minimum mean systolic blood pressures occurred 20 and 25 minutes after administration of the 5 mg and 10 mg capsules, respectively; the minimum diastolic blood pressures were reached after 20 and 30 minutes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals.

Animals

Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken.

The diagnostic yield of blind percutaneous liver biopsy is improved when two or three specimens are taken during the procedure by redirecting the needle through a single entry-site, without exposing the patient to a greater risk of complications provided that standard precautions are taken. This study was designed to obtain further data on the safety of this procedure at King Edward VIII Hospital, Durban. During the period 1984-1990 (inclusive) a total of 2,646 biopsies were carried out: a single specimen was obtained in 834 patients, two specimens in 983 patients and three in 829 patients. Complications directly attributable to the procedure occurred in 24 patients who had one specimen, 20 who had two, and 19 who had three specimens taken during the biopsy. A single specimen had been obtained from three of the eight patients who had died, two specimens had been taken from another patient, and three specimens were obtained from the other four patients, i.e. patients in whom two or three specimens were taken did not have a higher incidence of pain, symptomatic hypotension, biliary peritonitis or death than those in whom one specimen was taken. Accordingly, when blind percutaneous needle biopsy of the liver is carried out, two specimens should be obtained by redirecting the needle through a single entry site as this improves the diagnostic yield without increasing complications. The morbidity and mortality associated with liver biopsy in this hospital is, however, high. Good technique, careful monitoring of patients after biopsy and prompt and aggressive resuscitation are essential if the mortality rate is to be reduced.

Biopsy, Needle