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Biomedical subjects

Phyllis August

Publications and source records attributed to Phyllis August.

11 recordsLinked to original sources

Modifications of coronary risk factors.

In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

Algorithms↗

Genetic thrombophilias and preeclampsia: a meta-analysis.

OBJECTIVE: To assess the relationship between the factor V Leiden (1691 G-A) single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data on these polymorphisms and the risk of preeclampsia. DATA SOURCES: MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002). Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "protein C," "MTHFR," "methylenetetrahydrofolate reductase," "homocysteine," and "prothrombin gene 20210." METHODS OF STUDY SELECTION: Case-control studies of genetic thrombophilias and preeclampsia were included. TABULATION, INTEGRATION, AND RESULTS: We identified 349 titles and reviewed 47 articles for inclusion and exclusion criteria. Thirty-one studies with 7,522 patients were included in the meta-analysis. Data from patients characterized as having severe preeclampsia were extracted and analyzed separately. The pooled odds ratio (OR) for the association of factor V Leiden and all cases of preeclampsia was 1.81 (95% confidence interval [CI] 1.14-2.87) and 2.24 (95% CI 1.28-3.94) for cases of severe preeclampsia. The pooled OR for the MTHFR 677 TT genotype and all preeclampsia was 1.01 (95% CI 0.79-1.29) and 1.38 (95% CI 0.93-2.06) for severe preeclampsia. The OR for the prothrombin 20210 polymorphism and all preeclampsia was 1.37 (95% CI 0.72-2.57) and 1.98 (.94-4.17) for severe preeclampsia. CONCLUSION: This meta-analysis suggests that the factor V Leiden SNP is associated with an increased risk of preeclampsia. Further studies are warranted to determine whether subgroups of high-risk women should be screened for this mutation.

Case-Control Studies↗

Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.

Female↗

A prediction model for superimposed preeclampsia in women with chronic hypertension during pregnancy.

OBJECTIVE: Women with chronic hypertension are at increased risk for superimposed preeclampsia. We developed a prediction algorithm for superimposed preeclampsia using clinical and laboratory information that were measured early in pregnancy. STUDY DESIGN: A secondary analysis of data that were collected from 110 women with chronic hypertension who were enrolled in a trial of calcium supplementation was performed. Blood pressure, the renin-angiotensin system, and calcium metabolism were assessed at 12, 20, 28, and 36 weeks of gestation and 6 weeks after delivery. Multivariable logistic regression was used to develop the predictive model. RESULTS: Thirty-seven women had superimposed preeclampsia. The final model included systolic blood pressure, serum uric acid, and plasma renin activity, which were all measured at 20 weeks of gestation. Women with high systolic blood pressure (>140 mm Hg), elevated uric acid (>3.6 mg/dL), and low plasma renin activity (<4 ng/mL/hr) had an 86% probability of having superimposed preeclampsia. Women with 2 risk factors had a 62% probability of superimposed preeclampsia, and women with only 1 risk factor had a 30% to 40% probability of superimposed preeclampsia. CONCLUSION: We developed a prediction algorithm that can be validated in future studies for superimposed preeclampsia for women with chronic hypertension.

Adult↗

Antihypertensive therapy in pregnancy.

The benefits of antihypertensive therapy in pregnancy remain uncertain. Blood pressure control to prevent or correct severe hypertension can avert maternal target organ damage and may allow obstetricians to prolong pregnancy or avoid hospitalization. Several factors limit the conclusions derived from systematic review of the available studies, including failure to distinguish among women with preeclampsia, gestational hypertension, or whose hypertension antedated pregnancy. As well, the application of consensus guidelines is limited by the unfortunate tendency to measure blood pressure by use of oscillometric devices rather than auscultation. We review the basis for using specific antihypertensive drugs in pregnancy and highlight important shortcomings in therapeutic knowledge that should be addressed in future studies.

Antihypertensive Agents↗

Transforming growth factor beta and progression of renal disease.

End-stage renal disease (ESRD) is more frequent in African Americans compared to whites. Many factors may be responsible, including genetic differences, increased prevalence of risk factors, and socioeconomic factors; however, to date, these proposed genetic or environmental factors have not provided a satisfactory explanation for the increased risk of ESRD in African Americans. Because renal fibrosis is a correlate of progressive renal failure and a dominant feature of ESRD, and because transforming growth factor beta 1 (TGF-beta1) can induce fibrosis and renal insufficiency, we explored the hypothesis that TGF-beta1 hyperexpression is more frequent in African Americans compared to whites. We tested our hypotheses by measuring TGF-beta1 levels in African Americans and white patients with ESRD, hypertension, and in normal patients. In hypertensive and normal patients, we also evaluated TGF-beta1 mRNA levels, and TGF-beta1 DNA polymorphisms. We demonstrated that circulating levels of TGF-beta1 are higher in African American ESRD patients, hypertensive patients, and normal control patients compared to their white counterparts. We also reported that TGF-beta1 mRNA levels are higher in hypertensives compared to normotensives. Our preliminary genetic analyses suggest that TGF-beta1 DNA polymorphisms may distinguish hypertensives from normotensives, and our laboratory is currently investigating racial differences in TGF-beta1 DNA polymorphisms. Our observations of hyperexpression of TGF-beta1 in African Americans suggest a mechanism for the increased prevalence of renal failure and hypertensive target organ damage in this population.

Black or African American↗

Preeclampsia: New Thoughts on an Ancient Problem.

Preeclampsia is a hypertensive disorder unique to pregnancy and is of unknown cause. It is both a maternal as well as fetal syndrome. It affects 2%-10% of nulliparas, and is more prevalent when preexisting hypertension, renal disease, or diabetes is present. The main clinical features of the disorder are maternal hypertension, proteinuria, and abnormal renal, hepatic, and central nervous system function. The fetal syndrome includes growth restriction, intrauterine death, and premature delivery. Abnormalities in the development of the placental circulation are believed to be important causal features of the pathogensis of preeclampsia and are present early in pregnancy. The link between the placental disease and the maternal syndrome remains mysterious. Clinical trials of low dose aspirin and calcium in the prevention of preeclampsia have not demonstrated significant benefits of treatment. The current approach to treatment is close monitoring of maternal and fetal health, bed rest, judicious use of antihypertensive therapy to prevent maternal complications, and seizure prophylaxis with magnesium sulfate. (c)2000 by Le Jacq Communications, Inc.

Journal Article↗