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Background: Second-stage Caesarean sections (CSs) are known to be associated with increased complications but most reports originate from tertiary hospitals, which attend to high-risk patients. Complication rates may differ in district hospitals, which attend to low-risk patients. Methods: This was a retrospective study carried out at a district maternity unit in Durban. The hospital records of all CSs over an eight-month period were reviewed and obstetric and neonatal complications of second-stage CSs were compared with a group of first-stage CSs performed during the study period. Results: There were 4 654 deliveries, including 1 257 CSs, in the study period. The CS rate was 27.2%. Of 617 (8.5%) emergency CSs, 53 were performed in the second stage of labour. The maternal and neonatal complication rates were low and no statistical differences were found between the patients who had second-stage or those who had first-stage CSs, except for increased blood loss, blood-stained urine, prolonged operative times and postoperative fever for secondstage CSs. Conclusions: Second-stage CSs performed in a district hospital are associated with increased maternal complication rates but not with neonatal complications. This article has been peer reviewed. SA Fam Pract 2009;51(4):328-331

Background. The process of physiological conversion of spiral arteries is dependent on the invasion of the interstitium and spiral arteries of the uterine wall by invasive extravillous trophoblast thereby creating a high flow-low resistance vessel. Quantitative data on restriction of trophoblast invasion and failure of spiral artery transformation are limited in preeclampsia. Aim. This study morphometrically analyzes interstitial trophoblast cells and trophoblast cells embedded in the wall of the converted spiral arteries within the decidua and myometrium of normotensive and preeclamptic Black African pregnant women. Methods. Placental bed biopsies were obtained from 25 normotensive pregnant women and 30 pregnant women complicated with hypertensive disorders. Biopsies were processed and immunostained for trophoblast cell identification, using anti-MNF 116 antibody. Image analysis of the trophoblast population within the decidua, myometrium and the spiral arteries was performed in the normotensive and in t...

The heparan sulfate proteoglycan of the glomerular basement membrane is considered to be mainly responsible for the charge selectivity of the glomerular basement membrane. Decreased heparan sulfate proteoglycan results in a decreased anionic charge of the glomerular basement membrane with increased heparan sulfate proteoglycan in the urine and is believed to be responsible for the proteinuria in pre-eclampsia. Aim. To determine the urinary heparan and chondroitin sulfate proteoglycan levels in women with pre-eclampsia. Materials and methods. Eighty-four patients were studied: 28 were normotensive pregnant 28 were nonproteinuric hypertensive and 28 were pre-eclamptic. Urine samples were obtained and urinary glycosaminoglycan concentrations were determined using the dimethyl-methylene blue assay. Plotting absorbance against the concentrations of heparan and chondroitin sulfate proteoglycans drew a standard curve. The concentration of heparan and chondroitin sulfate proteoglycans was read-off from the linear portion of the standard curve. The standard solutions contained 25 50 100 and 200 mg/l heparan or chondroitin sulfate. The Mann-Whitney U-test was used to detect differences between the three groups and the Pearsons correlation coefficient was calculated for clinical data correlation of the pre-eclamptic group. Results. Urinary excretion of heparan sulfate proteoglycan (123.1 +/- 22.1mg/l) was significantly increased in the pre-eclamptic group with the normotensive pregnant group (60.5 +/- 5.1 mg/l; p

Plasma endothelin-1 activity was measured by radioimmunoassay in 24 normotensive non-pregnant women and in 24 normotensive pregnant, 24-aproteinuric hypertensive and 24 pre-eclamptic women. Endothelin-1 activity was increased in the pre-eclamptic group (2.7 +/- 06 pg/ml) compared to the normotensive non-pregnant (1.0 +/- 0.8 pg/ml; P0.0001), normotensive pregnant (1.2 +/- 0.4 pg/ml; P0.0001) group and the aproteinuric hypertensive group (1.4 +/- 0.7 pg/ml; P0.0001). There was no difference in endothelin-1 activity between the normotensive non-pregnant and normotensive pregnant group (1.0 +/- 0.8 vs. 1.2 +/- 0.4 pg/ml; P = 0.3). However, there was a difference between the aproteinuric hypertensive group (1.4 +/- 0.7 pg/ml) and both the normotensive nonpregnant (1.0 +/- 0.8 pg/ml; P0.01) and the normotensive pregnant group (1.2 +/- 0.4 pg/ml; P0.06). The birth weight in the pre-eclamptic group (2.48 +/- 0.61 kg) was significantly lower than that of the normotensive pregnant group (2.85 +/- 0.33 kg; P0.001) and the aproteinuric hypertensive group (2.99 +/- 0.46 kg; P0.001). In addition, there was no difference in birth weight between the normotensive pregnant group and aproteinuric hypertensive group (2.85 +/- 0.33 vs. 2.99 +/- 0.46 kg; P = 0.3). A significant Pearson's correlation of plasma endothelin-l versus birth weight in the pre-eclamptic group was obtained (r = 0.64; P0.0001). Endothelin-1 activity is increased with pre-eclampsia in black African women with pre-eclampsia. The results of our study also suggests an ethnic difference in plasma endothelin-1 activity when compared to result of studies carried out in Caucasian women with hypertensive disorders of pregnancy.

The objective of the study was to determine changes in frequency of sexual activity during pregnancy. A prospective study was conducted using a structured questionnaire to interview 611 healthy pregnant women at a regional hospital in KwaZulu-Natal. Data were analysed using descriptive statistics. Five hundred and fifty-six (91.0 %) of the 611 women were sexually active during pregnancy. Sexual desire was increased in 102 (18%), decreased in 299 (40%) and was unchanged in 210 (34%). Four hundred and twenty-two (69%) engaged in sexual activity until the third trimester of pregnancy. Three hundred and seventy-nine (62%) used condoms. The majority (63%) found it easier to discuss the topic of sexual activity with midwives rather than with doctors. One hundred and thirty-eight (23%) experienced adverse events attributed to sexual intercourse during pregnancy. Religious and traditional practices played a minor role in guiding the practice of sexual activity during pregnancy. Twenty-eight (5%) of the 611 women were guided by religious rules while 27 (4%) were guided by traditional rules. Our findings confirm that sexual activity is commonly practised in pregnancy. Given the high HIV rates and sexually transmitted infections in the local population, this has important implications for information provided during antenatal care.

Background. Early initiation of antiretroviral therapy reduces transmission of HIV and prolongs life. Expansion of HIV testing is therefore pivotal in overcoming the HIV pandemic. Provider-initiated counselling and testing (PICT) at first clinical contact is one way of increasing the number of individuals tested. Our impression is that not all patients admitted to a general gynaecological ward are offered PICT. Objective. To assess whether patients admitted to a gynaecological ward in a district-level hospital in KwaZulu-Natal, South Africa, are being offered PICT. Methods. We conducted a retrospective chart review over an 8-month period. Patients who had a hospital stay of ≤3 days were enrolled. The case records were reviewed and relevant data, including demographic information and whether the patients were offered HIV testing, were recorded. Results. Of 1 014 patients, 451 reported that they had been tested previously; 98 (21.7%) of these were HIV-infected. There were therefore 916 patients (563 not tested previously and 353 who reported that they had tested negatively previously) who should have been offered PICT. Of these, 157 (17.1%) were offered it; 116 (73.9%) accepted and 41 declined. Forty-five (38.8%) tested positive. Conclusion. A large number of patients who stayed for ≤3 days in a gynaecology ward of a district-level hospital were not offered PICT. However, the high rate of HIV infection in those who accepted the offer of testing strengthens the case for PICT.

This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism. Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus. Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (6 weeks) beta-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression. In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy.

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 pu...

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

Objective: To measure plasma and red cell magnesium levels in black African women with hypertensive disorders of pregnancy.Methods: Plasma and red cell magnesium levels were analyzed using atomic absorption spectrophotometer in 27 patients presenting with severe hypertension in pregnancy, 27 patients with mild hypertension in pregnancy, and 27 healthy normotensive pregnant women.Results: There were no significant differences in plasma magnesium concentrations between the hypertensive groups compared to the normotensive group [mild vs. normotensive (0.82 ± 0.03 vs. 0.84 ± 0.03 mmol/L; P = 0.12); severe hypertension vs. normotensive (0.80 ± 0.03 vs. 0.84 ± 0.03 mmol/L; P = 0.15)]. There were not statistical differences in plasma magnesium levels between the hypertensive groups.There was a significant difference in the red cell magnesium concentrations between normotensive women and those with mild hypertension (2.3 ± 0.3 vs. 2.6 ± 0.5 mmol/L; P < 0.05) and those with severe hypertension in pregnancy (1.35 ±...

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.

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; p0.0001) and severe (1.53 ng TK/microgram protein; p0.0001) 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; p0.0001) and severe (0.6 versus 0.12; p0.0001) hypertensive groups. The urinary creatinine excretion was significantly higher in the mild (9.55 +/- 2.6 mmol/l; p0.0001) and in severe (15.62 +/- 5.48 mmol/l; p0.0001) 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.

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.

Objective: To compare the efficacy and safety of intravenous isradipine with dihydralazine in severe hypertension of pregnancy in Black patients.Methods: In this randomized study 40 Black patients with severe hypertension of pregnancy (DBP ≥ 110 mm Hg) at a tertiary referral hospital received intravenous isradipine [an initial dose of 0.15μ,g kg-1 min-1 for 15 min with increments of 0.0025 ixg kg-1 min-1 every 15 min until diastolic blood pressure (DBP) control (DBP < 95 mm Hg) was achieved, followed by a maintenance infusion of 0.15 μg kg-1 min-1 which was given for 15 min] or dihydralazine (6.25 mg given intravenously over 10 min; the dosage was repeated after 20 min if control was not achieved).Mean Outcome Measures: DBP < 95 mm Hg; fetal heart rate deceleration; fetal outcome.Results: Mean systolic blood pressure was reduced from 190.9 (95% CI 182.7-199.0) mm Hg to 137.6 (131.9-143.3) mm Hg in the isradipine group and from 187.9 (180.0-195.7) to 142.4 (133.0-151.7) mm Hg in the dihydralazine group. Th...

Background: It was alleged that the termination of pregnancy (TOP) services in a certain district health facility were forgoing the opportunity to offer screening tests for human immunodeficiency virus (HIV) and syphilis for women seeking legal medical abortions. In addition, there were concerns regarding the lack of provision of contraceptive services, particularly in view of media reports of young women having repeated TOP procedures as a family planning method. It was therefore decided to perform an audit of the TOP services at this district health facility.Method: A semi-structured questionnaire was used to obtain information from all women undergoing a TOP during a sixmonth period at a district hospital in KwaZulu-Natal. Demographic information, clinical details and attitudes towards TOP were obtained. All women were interviewed in private prior to discharge from the clinic.Results: A total of 645 women were enrolled. Their mean age was 23 (range 15-44) years and 437 (67.8%) were primiparous. Of the 645 women, contraceptive failure (condom) occurred in 38 cases (6%). Two hundred and twenty-two (34.4%) had previously used a family planning method, the most common being depot preparations (35.1%), followed by condoms (28.9%) and oral contraception (15.8%). One hundred and nine (16.9%) women accepted the condoms offered while the remainder indicated that they would obtain contraceptives from the family planning clinic in their area of residence. Twentynine (5%) had at least one previous TOP while 25 (86%) and four (14%) had second and third requests for TOP respectively. None of the women had any serological screening tests performed or were given information about testing for sexually transmitted diseases, including HIV screening, prior to discharge from the clinic.Conclusion: Women having TOP at this district hospital are not offered counselling and information on screening for sexually transmitted diseases. In addition, few women take up the offer of contraceptives. There is a need for health care providers to strengthen reproductive health services at TOP clinics.Keywords: surgical termination of pregnancy, contraception, unwanted pregnancy, Durban, South Africa

Objective. The aim of this study was to determine wound complication rates following the use of suture materials and staples for skin closure at caesarean section (CS). Study design: A randomised, controlled, prospective study was undertaken. Results. A total of 1 100 women was assigned randomly into 3 groups: polyglycolic acid (PGA) suture group (N=361), skin staple (SS) group (N=373) and nylon suture group (N=366). The overall wound infection rate was 7%. There was no difference in respect of number of patients, age, parity and gestation between the study groups. Those who had nylon sutures as opposed to PGA sutures were 9.5 times more likely to experience wound infection (p=0.055). Women who had SS were at 6.93 times higher risk of wound infection than those who had PGA sutures (p=0.014). Other factors influencing wound infection rates included: rupture of membranes >12 hours were 13.7 times (95% confidence interval (CI) 3.9 - 47.9, p

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.

SA Fam Pract 2010;52(1):64-68 Introduction: The Term Breech Trial has led to obstetricians opting for Caesarean section as the mode of delivery for this presentation, even in poor countries. Concerns related to this approach are the resultant increase in Caesarean section rates and their associated complications, particularly in under-resourced countries, which are faced with financial and human-resource expertise constraints. Method: This was a retrospective chart review of women who presented at term with a singleton breech presentation at the antenatal clinic and in labour, from January 2005 to December 2007, at a district level hospital in South Africa. Results: There was a total of 19 197 deliveries, of which 466 were singleton term breech deliveries, giving a rate of 2.4%. Of the 297 women who had antenatal care and had been allocated to planned Caesarean section, 271 had the planned operation. There were no neonatal deaths in the planned Caesarean section group. The emergency Caesarean section group and the group in which no decision was made on the mode of delivery were associated with higher maternal complication rates than in the group that had planned Caesarean sections. The highest neonatal complication rate was in the group that had unplanned vaginal deliveries. Conclusion: In a district hospital in South Africa, the mode of delivery for breech presentations is usually a planned Caesarean section. Unplanned vaginal deliveries are associated with significant perinatal mortality. Peer reviewed. (Submitted: 2009-03-05, Accepted: 2009-08-10). © SAAFP

Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats.

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

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

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.

To determine the current management of hypertensive disorders of pregnancy in South Africa.A postal questionnaire was sent to 600 South African obstetricians.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 pressureor = 110 mmHg and proteinuriaor = +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.This study demonstrates that South African obstetricians show great uniformity in terms of the treatment of hypertensive disorders of pregnancy.

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.

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 p0.005; relative risk = 6.6) and HLA-B49 was present in 7.3% of patients compared with 1.1% of normal control subjects (corrected p0.007; relative risk = 7.1). These findings suggest that genetic factors may play a role in the pathogenesis of hepatocellular carcinoma.

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.

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.

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 (P0.02) compared to control animals. In addition, a significant decrease in myocardial potassium was noted (P0.05). In the second protocol, 8 of the 15 rats treated with 0.18 mg hydrochlorothiazide showed reduced ventricular fibrillation threshold and serum potassium levels (P0.05). A significant decrease in myocardial potassium was also observed (P0.05). 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.

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.

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 (p0.004). 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 (p0.05) 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 (p0.05) 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.

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 (DBP95 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 DBP115 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.

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 ageor = 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 (DBP95 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.

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.

The isolated liver perfusion model was used to study the effects of supra-therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein (BSP) clearance from the perfusate and biliary excretion of the dye in the rat. Three groups of rats randomly assigned to a control and two experimental groups were studied; those in the experimental groups were given 4 mg rifampicin per os daily for 90 days. The control group was untreated. The livers of the control and one experimental group were perfused with a medium containing pyruvate and subsequently these livers were perfused with a medium containing bromosulphthalein. The livers of the second experimental group were subjected to histological examination. The rate and the concentration of glucose was decreased, lactate levels and lactate: pyruvate ratios were increased in the experimental animals. The mean perfusate BSP and biliary excretion of the dye was decreased in the experimental group. Fatty change was present in the livers of rifampicin treated rats. This study demonstrates that the isolated liver model has proved to be both suitable and useful for the study of the effects of drugs and that chronic administration of supra-therapeutic doses of rifampicin to rats adversely affected liver function. It also produces histological evidence of hepatic damage in rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.