Biomedical subjects

S M Khedun

Publications and source records attributed to S M Khedun.

At least 19 recordsLinked to original sources

PubMed2002

Transforming growth factor beta(1) levels in platelet depleted plasma in African women with pre-eclampsia.

Recently it has been suggested that TGF-beta(1) may play an important role in trophoblast invasion of spiral arteries in pre-eclampsia. This study was designed to investigate TGF-beta(1) levels in pre-eclampsia. Platelet depleted plasma TGF-beta(1) levels were measured by ELISA in 43 normotensive healthy non-pregnant women, 30 normotensive healthy pregnant and 42 pre-eclamptic women: TGF-beta(1) levels were increased significantly in the pre-eclamptics (4.9+/-0.9 ng/ml) compared to the normotensive pregnant (1.9+/-0.54 ng/ml; P<0.001) and normotensive non-pregnant groups (2.1+/-0.41 ng/ml; P<0.0001). There was no significant difference in TGF-beta(1) levels between normotensive pregnant and non-pregnant groups (1.9+/-0.54 vs. 2.1+/-0.41 ng/ml; P=0.2). There was a highly significant correlation between neonatal weight (r=0.63; P<0.0001) and TGF-beta(1) levels. The finding of increased levels of plasma TGF-beta(1) suggests an aetiological role of this peptide in pre-eclampsia.

Adolescent↗

PubMed2000

Tissue kallikrein activity in pregnancy.

To determine tissue kallikrein (TK) activity in black African women with hypertensive disorders of pregnancy; 140 women were recruited and divided into the following groups: group A--35 preeclamptic women, group B--35 mild to moderate hypertensive pregnant women and group C--35 normotensive pregnant women, and group D--35 normotensive non-pregnant healthy women. The activity of tissue kallikrein was determined from a random untimed urine sample using a selective, synthetic chromogenic tripeptide substrate having the sequence H-D-Val-Leu-Arg-pNA (S-2266). Urinary sodium and potassium levels was determined by flame photometry. Tissue kallikrein activity was decreased in women with preeclampsia (1.54 +/- 0.95 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) and mild to moderate hypertensive group (2.03 +/- 0.76 vs 3.05 +/- 0.83 ngTK/microg protein; p < 0.0001) compared with normotensive pregnant women. There was also a significant difference in tissue kallikrein activity between the pregnancy groups (1.54 +/- 0.95 vs 2.03 +/- 0.76 ngTK/microg protein; p < 0.001). No difference in tissue kallikrein activity was observed between normotensive pregnant and normotensive non-pregnant healthy women (3.05 +/- 0.83 vs 3.14 +/- 0.88 ngTK/microg protein; p = 0.51). There was no difference in the excretion of urinary sodium and potassium in pregnancy groups compared to normotensive pregnant group. Tissue kallikrein activity is decreased in hypertensive disorders of pregnancy.

Adult↗

PubMed2000

How do South African obstetricians manage hypertensive disorders of pregnancy--a survey.

OBJECTIVE: To determine the current management of hypertensive disorders of pregnancy in South Africa. METHOD: A postal questionnaire was sent to 600 South African obstetricians. RESULTS: The response rate was 72% (432/600), with 425 questionnaires suitable for analysis. South African obstetricians disagree on the definitions of various hypertensive disorders of pregnancy. Methyldopa was the antihypertensive used most frequently for the treatment of mild to moderate hypertension (diastolic blood pressure between 90 and 109 mmHg), while intravenous dihydralazine was preferred in severe hypertension (diastolic blood pressure > or = 110 mmHg and proteinuria > or = +2). To stop convulsions in eclampsia, 256 respondents (60%) said they would use diazepam, 28 (11%) said they would continue with a diazepam infusion, and the remaining 228 (89%) preferred magnesium sulphate (MgSO4) to prevent further convulsions. The intramuscular route was the preferred method of administration for MgSO4. In cases of eclampsia, 273 respondents (64%) said they would use intravenous dihydralazine to lower high blood pressure (> or = 160/110 mmHg) and proteinuria; 98 respondents (23%) said they would use methyldopa, 38 (9%) nifedipine, and 8 (2%) apresoline. Eight (2%) said they would not use antihypertensives. In patients with severe pre-eclampsia and impending eclampsia, 330 respondents (78%) said they would use MgSO4 as prophylaxis, 46 (11%) diazepam, and 6 (1.4%) phenobarbitone. Forty-three of the respondents did not prescribe prophylactic anticonvulsant therapy. To prevent pre-eclampsia, 247 of the respondents (58%) said they would prescribe low-dose aspirin. CONCLUSION: This study demonstrates that South African obstetricians show great uniformity in terms of the treatment of hypertensive disorders of pregnancy.

Anticonvulsants↗

PubMed2000

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

BACKGROUND: To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. METHODS: Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. RESULTS: Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. CONCLUSION: Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

Adolescent↗

PubMed1999

Urinary tissue kallikrein excretion in black African women with severe pre-eclampsia.

BACKGROUND: A study of tissue kallikrein excretion in African women with severe pre-eclampsia. METHODS: Random untimed urine samples were collected from all women (n=198) recruited to this study; 66 women with severe pre-eclampsia, 66 normotensive pregnant women of similar length of gestation and 66 normotensive non-pregnant women. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (S2266) having the sequence H-D-Val-Leu-Arg-pNA. RESULTS: Urinary tissue kallikrein levels were decreased in women with severe pre-eclampsia compared with those of gestation matched normotensive pregnant women at 28 weeks of gestation (1.55+/-0.95 vs. 3.02+/-1.35 ng TK/microg protein; p<0.0001) and at near delivery date (1.21+/-0.53 vis. 3.11+/-1.2 ng TK/microg protein; p<0.0001). In the normotensive pregnant group, there was no significance difference in urinary tissue kallikrein excretion close at delivery date compared to 28 weeks of gestation (3.02+/-1.35 vs. 3.11+/-1.21 ngTK/microg protein; p=0.23). No statistical difference in urinary tissue kallikrein excretion was observed between normotensive pregnant and normotensive non pregnant women (3.02+/-1.35 vs. 2.97+/-1.12 ngTK/microg protein; p=0.16). Urinary tissue kallikrein excretion correlated positively with urinary creatinine levels at 28 weeks of gestation (r=0.69; p<0.0001) and close to delivery date (r=0.84; p<0.0001). There was no correlation between neonatal birthweight and urinary tissue kallikrein levels (r=-0.44; p=0.41). CONCLUSION: The decreased levels of urinary tissue kallikrein excretion in pre-eclamptic patients suggests an etiological role for this serine protease in hypertensive disorders of pregnancy.

Adult↗

PubMed1998

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↗

PubMed1997

Changes in urinary tissue kallikrein excretion in black African women with hypertensive disorders of pregnancy.

The aim of this study was firstly to establish whether tissue kallikrein (TK) was involved in the aetiology of hypertensive disorders of pregnancy. Secondly, to assess whether tissue kallikrein:creatinine ratios may differentiate normotensive pregnant women from those with hypertensive disorders of pregnancy and have a predictive value. Random untimed urine samples were collected from all women (n = 264) recruited to this study. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (H-D-Val-Leu-Arg-pNA). Urinary creatinine levels were measured using standard methods. There was a significant difference in the excretion of urinary tissue kallikrein between normotensive pregnant women (2.91 ng TK/microgram protein) and women with mild (2.52 ng TK/microgram protein; p < 0.0001) and severe (1.53 ng TK/microgram protein; p < 0.0001) hypertension in pregnancy. No statistical difference was observed with regard to urinary tissue kallikrein excretion between normotensive pregnant and normotensive non-pregnant women (2.87 ng TK/microgram protein; p = 0.16). A positive correlation was observed between the diastolic blood pressure and urinary tissue kallikrein excretion in women with hypertensive disorders of pregnancy. When compared to the normotensive pregnant group, the urinary kallikrein:creatinine ratios were significantly lower in the mild (0.6 versus 0.3; p < 0.0001) and severe (0.6 versus 0.12; p < 0.0001) hypertensive groups. The urinary creatinine excretion was significantly higher in the mild (9.55 +/- 2.6 mmol/l; p < 0.0001) and in severe (15.62 +/- 5.48 mmol/l; p < 0.0001) hypertensives when compared to normotensive pregnant values (5.65 +/- 2.6 mmol/l). The reduced urinary tissue kallikrein excretion in hypertensive disorders of pregnancy may be a significant factor in the development of the hypertension in pregnancy. Measurement of urinary tissue kallikrein: creatinine ratios may represent a simple and practical predictive test to differentiate women with hypertensive disorders of pregnancy from normotensive pregnant women.

Adult↗

PubMed1997

Localisation of tissue kallikrein in the kidney of black African women with early onset pre-eclampsia: a pilot study.

Increased renal production of vasodilator mediators like kinins would counteract the vasospasm of pre-eclampsia. This study examines the cellular localisation of tissue kallikrein (TK), the potent kinin forming enzyme within the nephron of patients with early onset pre-eclampsia. Using the peroxidase-antiperoxidase immunoenzyme complex, TK was immunolocalised in the principal cells of the distal connecting tubule and the cortical collecting duct cells of the distal nephron of control tissue. Moderate reactivity was observed in the epithelial cells lining the Bowmans capsule. In early onset pre-eclampsia, TK was additionally localised in the proximal tubule cells, however, the intensity of reactivity was reduced when compared to that of the distal tubule cells. In patients with hypertension of pregnancy, the occurrence of TK in the proximal tubule suggests either gene induction or emiocytosis of TK.

Adolescent↗

PubMed1997

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↗

PubMed1997

Correlation between histological changes and loss of anionic charge of the glomerular basement membrane in early-onset pre-eclampsia.

This study morphometrically evaluates the glomerular anionic charge and examines the renal pathology in African women with early-onset pre-eclampsia. Polyethyleneimine-labelled anionic sites were decreased within the glomerular basement membrane in the early-onset pre-eclampsia group as compared with the control group (p < or = 0.02). A strong correlation (r = -0.76) was obtained between the number of anionic sites and the severity of proteinuria. Renal biopsy specimens revealed the coexistence of decreased glomerular charge with pathology of glomerular basement membrane, endothelial cells, foot processes, and mesangial cell proliferation. The loss of glomerular charge induces structural alterations of the glomerular filtration barrier and may be the mechanism responsible for proteinuria in early-onset pre-eclampsia.

Anions↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1993

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↗