The relationship between health status and blood pressure in urban African Americans.

African Americans have higher rates of hypertension and poorer health status than their white counterparts. This study assessed the relationship between health status, cardiovascular risk factors, and measured blood pressure. Free blood pressure screenings were performed at businesses and organizations located in west Baltimore. All individuals with cardiovascular risk factors were offered health education. Also, participants with a measured blood pressure of > or = 140/90 mm Hg were referred for free medical treatment. Participants completed a questionnaire that included demographics, cardiovascular risk factors, the Medical Outcomes Study SF 36, and two tests on cholesterol and heart disease knowledge. A total of 1389 African-American men and women were screened; 20% were found to have high normal blood pressure and 31% had stage 1 hypertension or higher. Those with hypertension reported lower physical functioning and poorer general health than those without high blood pressure. When compared with US normative data, participants reported higher levels in vitality and physical and emotional role functioning, more bodily pain, and poorer general health, but they were similar in physical functioning, social functioning, and mental health. Preliminary data suggest that hypertension does have an effect on health function.     

A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: −0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by −0.48 mg/dL (95% CI: −0.98, 0.01) compared to DDG by −0.05 mg/dL (95% CI: −0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: −34.0, −8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.     

Effect of methylmercury on midbrain cell proliferation during organogenesis: potential cross-species differences and implications for risk assessment.

5'-bromodeoxyuridine (BrdU) labeling was employed to explore the effects of methylmercury (MeHg) on cell cycle kinetics in the developing rat midbrain during gestational days (GDs) 11 to 14. Contrary to what has been previously reported in mice, no effects of MeHg on cell cycle kinetics were observed up to embryonic brain concentrations of 3-4 microg/g. The absence of an effect was confirmed using stereology and counts of midbrain cell number. Treatment with colchicine, the positive control, resulted in significant effects on cell cycle kinetics in the developing rat midbrain. The parallelogram method, borrowed from genetic toxicology, was subsequently used to place the data obtained in the present study in the context of previously collected in vitroand in vivo data on MeHg developmental neurotoxicity. This required developing a common dose metric (microg Hg/g cellular material) to allow in vitro and in vivo study comparisons. Evaluation suggested that MeHg's effects on neuronal cell proliferation show a reasonable degree of concordance across mice, rats, and humans, spanning approximately an order of magnitude. Comparisons among the in vivo data suggest that humans are at least or more sensitive than the rodent and that mice may be a slightly better model for MeHg human developmental neurotoxicity than the rat. Such comparisons can provide both a quantitative and a qualitative framework for utilizing both in vivo and in vitro data in human health risk assessment.     

Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence.     

Morphological characteristics of clinically significant coronary artery stenosis in stable angina

All segments of clinically significant stenosis in the coronary arteries of 54 men with stable angina were categorised according to the position of the plaques (eccentric or concentric) and the presence or absence of a pool of extracellular lipid. In the group as a whole, stenosis of greater than 50% by diameter was caused by concentric fibrous plaques in 48% of lesions, by concentric lipid plaques in 28%, by eccentric fibrous plaques in 12%, and by eccentric lipid plaques in 12%. In addition, 43 of the 54 patients had one or more stenoses with multiple channels (recanalisation). Eccentric plaques with an arc of normal vessel wall occupying more than 16% of the circumference of the residual lumen were considered to have a vasospastic potential and made up 15% of all lesions with stenosis of greater than 50% by diameter. Forty four per cent of plaques causing stenosis between 30% and 50% by diameter were eccentric and retained a considerable arc of normal media. These lesions were often in series with segments of higher grade stenosis that did not have an arc of normal media. The overall frequency of plaque types gave no indication of the proportions of different plaque types within an individual. In 15% of patients all the plaques causing greater than 50% diameter stenosis were fibrous and in 13% of patients all the plaques were of the lipid type. Most patients had mixtures of all plaque types in varying proportions. Plaques with a large pool of lipid were not found in 33% of patients whereas they formed greater than 90% of the plaques in 9% of patients. No segments of stenosis > 50% by diameter with a vasospastic potential were found in 44% of the patients but one or more such plaques was present in the the remaining 56%. Three patients (6%) each had five separate segments of stenosis with a vasospastic potential. The results indicate that even in a population of men with stable angina in whom diabetes is excluded the distribution of types of atheromatous lesions is very heterogenous.     

Medication compliance in ischaemic stroke patients

Aim: This study aimed to assess the degree of patient compliance with medications prescribed at hospital discharge following ischaemic stroke, and concordance between self‐reported medication use and general practitioner (GP) records. Methods: The Auckland City Hospital Stroke database was used to identify consecutive patients with ischaemic stroke over a three‐month period. Participants were contacted and invited to participate in a telephone questionnaire that asked about current medications. GPs were also asked to list the medications their patients were taking. Results: Fifty‐one patients were approached to participate of whom 48 consented to be interviewed at 6 weeks and 47 at 6 months. At 6 weeks, 36 of 38 (95%) were compliant with aspirin, 12 of 13 (92%) dipyridamole, 8 of 9 (88%) warfarin, 36 of 41 (88%) statins, 33 of 38 (87%) antihypertensive medications, and 7 of 7 (100%) diabetes medications. At 6 months, 97% were compliant with aspirin, 100% dipyridamole, 100% warfarin, 94% statins, 91% antihypertensive medications, and 100% diabetes medications. Natural or herbal remedy use was reported by 10 of 48 (21%) at 6 weeks and 11 of 47 (23%) at 6 months. Blister packs were used by 8 of 48 (17%) at 6 weeks and 5 of 47 (11%) at 6 months. Conclusion: Adherence to secondary stroke prevention medication was between 87% and 100% at 6 weeks with similar findings at 6 months after discharge. We speculate that these high compliance rates may be due to one‐on‐one stroke nurse counselling and the use of stroke information packs, which include information about the importance of adherence to secondary prevention medication.     

Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.