Shaun M. Khedun

Quantitative analysis of trophoblast invasion in preeclampsia

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.

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.

Transforming growth factor β 1 levels in platelet depleted plasma in African women with pre-eclampsia

Recently it has been suggested that TGF- g 1 may play an important role in trophoblast invasion of spiral arteries in pre-eclampsia. This study was designed to investigate TGF- g 1 levels in pre-eclampsia. Platelet depleted plasma TGF- g 1 levels were measured by ELISA in 43 normotensive healthy non-pregnant women, 30 normotensive healthy pregnant and 42 pre-eclamptic women: TGF- g 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- g 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- g 1 levels. The finding of increased levels of plasma TGF- g 1 suggests an aetiological role of this peptide in pre-eclampsia.

Endothelin-1 activity in pregnancy.

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; P < 0·0001), normotensive pregnant (1·2 - 0·4 pg/ml; P < 0·0001) group and the aproteinuric hypertensive group (1·4 - 0·7 pg/ml; P < 0·0001). 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 non-pregnant (1·0 - 0·8 pg/ml; P < 0·01) and the normotensive pregnant group (1·2 - 0·4 pg/ml; P < 0·06). The birth weight in the pre-eclamptic group (2·48 - 0·61kg) was significantly lower than that of the normotensive pregnant group (2·85 - 0·33 kg ; P < 0·001) and the aproteinuric hypertensive group (2·99 - 0·46 kg; P < 0·001). 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 Pearsons correlation of plasma endothelin-l versus birth weight in the pre-eclamptic group was obtained ( r = 0·64; P < 0·0001). 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.

A COMPARATIVE STUDY OF INTRAVENOUS ISRADIPINE AND DIHYDRALAZINE IN THE TREATMENT OF SEVERE HYPERTENSION OF PREGNANCY IN BLACK PATIENTS

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...

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.

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.

Sexual activity during pregnancy: a questionnaire-based study

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.

Urinary heparan sulfate proteoglycan excretion in black African women with pre‐eclampsia

Background.  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.

PLASMA AND RED CELL MAGNESIUM LEVELS IN BLACK AFRICAN WOMEN WITH HYPERTENSIVE DISORDERS OF PREGNANCY

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 ±...