CAPRISA 018: a phase I/II clinical trial study protocol to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide subdermal implant for HIV prevention in women.

INTRODUCTION: Young African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution. METHODS AND ANALYSIS: CAPRISA 018 is a phase I/II trial to evaluate the safety, acceptability, tolerability and pharmacokinetics (PKs) of a TAF free base subdermal silicone implant containing 110 mg of TAF with an anticipated 0.25 mg/day release rate.The phase I trial (n=60) will assess the safety of one implant inserted in six participants (Group 1), followed by dose escalation components (Groups 2 and 3) assessing the safety, tolerability and PK of one to four TAF 110 mg implants releasing between 0.25 mg and 1 mg daily in 54 healthy women at low risk for HIV infection. Data from this phase I trial will be used to determine the dosing, implant location and implant replacement interval for the phase II trial.The phase II component (Group 4) will assess extended safety, PK, tolerability and acceptability of the implant in 490 at risk women, randomised in a 1:1 ratio to the TAF implant and placebo tablet or to the placebo implant and an oral pre-exposure prophylaxis tablet. Safety will be assessed by calculating the percentage change in creatinine clearance from baseline at weeks 4, 12, 24, 36, 72, 96 and 120, compared with the percentage change in the control group. ETHICS AND DISSEMINATION: The South African Health Products Regulatory Authority and the University of KwaZulu-Natal's Biomedical Research Ethics Committee have approved the trial. Results will be disseminated through open access peer reviewed publications, conference presentations, public stakeholder engagement and upload of data into the clinical trials registry. TRIAL REGISTRATION NUMBER: PACTR201809520959443.

Information-Theoretic Model and Analysis of Molecular Signaling in Targeted Drug Delivery.

Targeted drug delivery (TDD) modality promises a smart localization of appropriate dose of therapeutic drugs to the targeted part of the body at reduced system toxicity. To achieve the desired goals of TDD, accurate analysis of the system is important. Recent advances in molecular communication (MC) present prospects to analyzing the TDD process using engineering concepts and tools. Specifically, the MC platform supports the abstraction of TDD process as a communication engineering problem in which the injection and transportation of drug particles in the human body and the delivery to a specific tissue or organ can be analyzed using communication engineering tools. In this paper we stand on the MC platform to present the information-theoretic model and analysis of the TDD systems. We present a modular structure of the TDD system and the probabilistic models of the MC-abstracted modules in an intuitive manner. Simulated results of information-theoretic measures such as the mutual information are employed to analyze the performance of the TDD system. Results indicate that uncertainties in drug injection/release systems, nanoparticles propagation channel and nanoreceiver systems influence the mutual information of the system, which is relative to the system's bioequivalence measure.

Pilot evaluation of a second-generation electronic pill box for adherence to Bedaquiline and antiretroviral therapy in drug-resistant TB/HIV co-infected patients in KwaZulu-Natal, South Africa.

BACKGROUND: The introduction of Bedaquiline, the first new antimycobacterial drug in over 40 years, has highlighted the critical importance of medication adherence in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug-resistance and derive sustained benefit. Real-time electronic dose monitoring (EDM) accurately measures adherence and allows for titration of adherence support for anti-retroviral therapy (ART). The goal of this study was to evaluate the accuracy and acceptability of a next-generation electronic pillbox (Wisepill RT2000) for Bedaquiline-containing TB regimens. METHODS: Eligible patients were DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline-containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover design was used to evaluate levels of adherence and patient acceptance of EDM. Each patient was given a Wisepill device which was filled with ART, Levofloxacin or Bedaquiline over three consecutive weeks. Medication adherence was measured using Wisepill counts, patient-reported seven-day recall, and weekly pill count. An open-ended qualitative questionnaire at the end of the study evaluated participant acceptability of the Wisepill device. RESULTS: We enrolled 21 DR-TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from August through September 2016. In aggregate patients were similarly adherent to Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count. Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting non-adherence events (p = 0.02). Patients reported positive experiences with Wisepill and expressed willingness to use the device during a full course of DR-TB treatment. There were no concerns about stigma, confidentiality, or remote monitoring. CONCLUSION: In this pilot study patients were highly adherent to Bedaquiline by all adherence measures. However, there was lower adherence to ART by pill count and Wisepill suggesting a possible challenge for adherence with ART. The use of EDM identified significantly more missed doses than seven-day recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and is a promising modality to support and monitor medication adherence in complex treatment regimens.

Implementing isoniazid preventive therapy in a tuberculosis treatment-experienced cohort on ART.

SETTING: Urban clinical research site in Durban, South Africa. OBJECTIVE: To describe outcomes associated with the implementation of isoniazid preventive therapy (IPT) in a cohort of tuberculosis (TB) treatment-experienced human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART). DESIGN: We conducted a secondary analysis of data collected between October 2009 and October 2013 from patients enrolled in a prospective cohort study conducted in Durban, South Africa. RESULTS: Of the 402 patients enrolled in the parent study, 344 (85.6%) were eligible for IPT, 212 of whom (61.6%) initiated IPT. Of those who initiated IPT, 184 (86.8%) completed the 6-month course, while 24 (11.3%) permanently discontinued IPT, 3.8% of whom due to side effects. More women than men initiated IPT (n = 130, 61.3% vs. n = 82, 38.7%, P = 0.001). Overall median adherence to IPT was 97.6% (interquartile range 94.2-99.4). There were 22 cases of incident TB in this cohort: 13 occurred before IPT and 9 after (incidence rate ratio 0.67, 95%CI 0.29-1.58, P = 0.362). CONCLUSIONS: IPT implementation among ART and TB treatment-experienced patients was well tolerated, with good completion rates and fewer TB cases diagnosed after IPT.

Molecular Communication Model for Targeted Drug Delivery in Multiple Disease Sites With Diversely Expressed Enzymes.

Targeted drug delivery (TDD) for disease therapy using liposomes as nanocarriers has received extensive attention in the literature. The liposome's ability to incorporate capabilities such as long circulation, stimuli responsiveness, and targeting characteristics, makes it a versatile nanocarrier. Timely drug release at the targeted site requires that trigger stimuli such as pH, light, and enzymes be uniquely overexpressed at the targeted site. However, in some cases, the targeted sites may not express trigger stimuli significantly, hence, achieving effective TDD at those sites is challenging. In this paper, we present a molecular communication-based TDD model for the delivery of therapeutic drugs to multiple sites that may or may not express trigger stimuli. The nanotransmitter and nanoreceiver models for the molecular communication system are presented. Here, the nanotransmitter and nanoreceiver are injected into the targeted body system's blood network. The compartmental pharmacokinetics model is employed to model the transportation of these therapeutic nanocarriers to the targeted sites where they are meant to anchor before the delivery process commences. We also provide analytical expressions for the delivered drug concentration. The effectiveness of the proposed model is investigated for drug delivery on tissue surfaces. Results show that the effectiveness of the proposed molecular communication-based TDD depends on parameters such as the total transmitter volume capacity, the receiver radius, the diffusion characteristic of the microenvironment of the targeted sites, and the concentration of the enzymes associated with the nanotransmitter and the nanoreceiver designs.

Investigation of dengue related knowledge, attitudes and practices among form three secondary school students in the seven counties of Trinidad

OBJECTIVE: To investigate dengue related knowledge, attitudes and practices among secondary school students in Trinidad. DESIGN AND METHODS: A cross-sectional study was undertaken. All counties were included; one school from each county was randomly selected. Form Three students of the 7 schools were invited to participate. Data collection was conducted using a questionnaire. RESULTS: Almost three-quarters of respondents (73.1%) demonstrated sufficient knowledge about dengue. There appeared to be a link with preventative practices among households and adequate knowledge. Moreover, students associated with persons who had been previously diagnosed with dengue demonstrated a greater level of knowledge than those without. In fact, the school with highest knowledge levels also had the greatest proportion who reported a relative with a past diagnosis of dengue. Furthermore, 53.3% agreed that dengue was a community concern, while 59.6% believed that control and eradication of the dengue vector was primarily the responsibility of Health Authorities. CONCLUSION: It appears that students with greater knowledge engaged in preventative measures and vice versa. Knowledge, attitudes and practices may be influenced by several rather than a single factor. With a greater proportion stating that vector control was the responsibility of the health authorities, the findings, though encouraging in parts, highlighted a need for further targeted health education measures.

Awareness and knowledge of prophylaxis for infective endocarditis in patients with severe rheumatic heart disease.

Prevention of infective endocardit s (IE) is mportant because it has a high mortalty rate.This study sets out to to gather information from patients who were at risk of developing IE of their knowledge of the need for prophylaxis for the disease. Forty-one black patients suffering from severe rheumatic heart disease (RHD) were interviewed. Only one patient (2.4%) was regularly visiting a dentist to maintain good oral health and only five (12.2%) had received advice about the need for antibiotic cover prior to dental extraction. The vast majority of patients (97.5%) visited a dentist only when driven by dental pain, 36.6 % had to travel for more than an hour to reach their nearest dentist, and 87.8% indicated that they brushed their teeth. It may be concluded that in this group of black patients with severe RHD there was a lack of knowledge of the need for and of measures recommended for prophylaxs against IE. In addition, attempts by the health care team to ensure good oral health and access to dental care for these patients were inadequate, if not non-existent.

Effect of desloratadine on patients with allergic rhinitis and exercise-induced bronchoconstriction: a placebo controlled study.

BACKGROUND: Exercise induced broncho-constriction (EIB) is a significant problem in asthmatic patients. The link between allergic rhinitis and asthma is now well established. Patients with allergic rhinitis may have EIB. OBJECTIVE: This study compared the effects of desloratadine and placebo on EIB in a group of patients with allergic rhinitis and EIB. METHODS: This was a double blind placebo controlled, randomized, crossover study. Exercise challenge tests were performed before and after 7 days of treatment with either 5 mg desloratadine or placebo. Patients then underwent a washout period for 7 days and were crossed over to receive either 5mg desloratadine or placebo. The exercise challenge tests were repeated. RESULTS: Desloratadine had no effect on the reduction in percentage fall in FEV(1), the AUC (0-60 min) and the time to recovery. CONCLUSIONS: Desloratadine has no effect in attenuating the broncho-constriction caused by exercise in patients with allergic rhinitis and exercise induced broncho-constriction. CLINICAL IMPLICATIONS: Patients with allergic rhinitis and exercise induced broncho-constriction must be treated with either a beta(2)-agonist or LRTA for relief or prophylaxis of their EIB. CAPSULE SUMMARY: Desloratadine does not have an effect on exercise induced bronchoconstriction. Patients with allergic rhinitis with exercise induced bronchoconstriction who are on desloratadine will still require treatment with beta(2) agonist or leukotriene receptor antagonist for their symptoms.

Effects of antihypertensive drugs on the unborn child: what is known, and how should this influence prescribing?

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.

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.

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.

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.

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.

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.

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.

Safe food for our people: fact or myth

Over a six-year period, January 1990 to October 1995, 7,578 samples of cooked food were apparently randomly obtained from the countries and boroughs of Trinidad, and also in Tobago, by Public Health Inspectors. These were then submitted to the Trinidad Public Health Laboratory for analysis. These samples were analyzed using standard microbiological assays. Two thousand six hundred and fifty-two (35 percent) of these samples were deemed microbiologically unsafe as they failed to meet laboratory criteria for cooked foods. The spectrum of pathogens isolated included, predominantly, Klebsiella Escherichia coli, Pseudomonas and Staphylococcus aureus. There were also isolates of Salmonellae, Proteus spp. and Shigella. Data analysis using Geographic Information System Technology showed where all data collected was linked to cartographic maps after being automated. This was then overlaid to show the relation between the areas of high, moderate and low incidence of food contamination leading to food-borne illnesses. Several regions showed a high incidence of food contamination. This technology was seen as a valuable epidemiological and planning tool which aided in determining areas where preventive measures and manpower resources could be deployed to ensure that safe food is served to the nation (AU)

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.

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.

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.