Association between various anthropometric measures of obesity and markers of subclinical atherosclerosis

Central obesity is a known cardiovascular risk factor and measures of visceral obesity are known to predict atherosclerosis. This study sought to explore the association between various anthropometric measures and markers of subclinical atherosclerosis (MoSCA) among low risk healthy individuals. Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of Caucasian (38%), Afro-American (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45–84 years, free from clinical cardiovascular disease. We performed a post hoc analysis of the limited access dataset of MESA subjects to evaluate the association between carotid intima media thickness and coronary artery calcium score (CACS), as MoSCA and various measures of obesity. Multivariable regression analyses adjusted for traditional cardiovascular risk factors, ethnicity and C-reactive protein were performed. Each unit increase in waist–hip ratio was strongly associated with increase in both common and internal carotid intima media thickness (beta: 0.12, 95% confidence interval (CI): 0.06 to 0.18, p < 0.001 and beta: 0.23, 95% CI: 0.03 to 0.43, p = 0.021, respectively). Measures of central obesity were superior to body mass index as demonstrated by their consistent association with each category of CACS when compared to the reference category (CACS = 0). Compared to body mass index, measures of visceral obesity were significantly associated with MoSCA in this multiethnic healthy population. Waist–hip ratio seems to be more consistent in its association with various MoSCA compared to other anthropometric measures.     

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bons marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.     

Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial

INTRODUCTION: Long-term glycemic control trials in type 2 diabetes show as the main clinical benefit a difference in retinal photocoagulation (3/1000 in the UK Prospective Diabetes Study [UKPDS]), but no effect on visual acuity or renal failure. No intensive glycemic control trial has yet affected cardiovascular (CV) events, the main cause of morbidity and mortality. By contrast, modest blood pressure reduction has protective effects on visual acuity, renal function, CV events, and mortality. Optimal glycemic control goals are not established in elderly, obese persons with advanced complications, the most common patients in the Veterans Affairs (VA) system. The earlier feasibility trial in such patients (VA-CSDM) suggested potentially worse CV outcomes with lower attained hemoglobin A1c (HbA1c) levels. OBJECTIVES: The primary objective of the Veterans Affairs Diabetes Trial (VADT) is the assessment of the effect of intensive glycemic treatment on CV events. Other objectives are effects on microangiopathy, quality of life, and cost effectiveness. RESEARCH DESIGN AND METHODS: The VADT, started in December 2000, is enrolling 1700 men and women previously uncontrolled on insulin or maximum doses of oral agents at 20 VA medical centers. Accrual is 2 years and follow-up is 5-7 years, with visits every 1.5 months. The study has a power of 86% to detect a 21% relative reduction in major CV events (CV death, myocardial infarction [MI], cerebrovascular accident [CVA], congestive heart failure [CHF], revascularization and amputation for ischemia). Subjects are randomized to an intensive arm aiming at normal HbA1c levels or to a standard arm with usual, improved glycemic control. An HbA1c separation of >1.5% is to be maintained (expected 2%). Both arms receive step therapy: glimepiride or metformin plus rosiglitazone and addition of insulin or other oral agents to achieve goals. Strict control of blood pressure and dyslipidemia, daily aspirin, diet, and education are identical in both arms. Plasma fibrinogen, plasminogen-activating inhibitor I (PAI-I), lipids, renal function parameters, and ECG are measured throughout. Stereo retinal photographs are obtained at entry and 5 years, eye examinations yearly, and intervention as needed to prevent visual deterioration. Recruitment is proceeding on schedule: the current mean HbA1c at entry is 9.4+/-1.6% and mean duration of diagnosed diabetes 11+/-8 years.     

Effects of the progesterone receptor modulator VA2914 in a continuous low dose on the hypothalamic-pituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial

CONTEXT: Progestin-only pills, the main hormonal alternative to ethinyl estradiol-containing pills in women bearing vascular risk factors, are poorly tolerated due to irregular bleeding. In contrast, progesterone receptor modulators can inhibit ovulation, alter endometrial receptivity, and improve cycle control. OBJECTIVE: We evaluated the effects of a new progesterone receptor modulator, VA2914, administered continuously for 3 months, on ovulation and endometrial maturation. DESIGN, SETTINGS, AND PATIENTS: Forty-six normal women were included in a prospective, placebo-controlled, randomized trial, conducted in four referral centers. INTERVENTION: VA2914 (2.5, 5, or 10 mg/d) was administered continuously for 84 d. Pelvic ultrasound (treatment d 67 and 77), hormonal monitoring (FSH, LH, estradiol, and progesterone on treatment d 59, 63, 67, 70, 74, 77, 80, and 84), and endometrial biopsy (treatment d 77) were performed. MAIN OUTCOME MEASURE: Ovulation inhibition was assessed by the absence of progesterone values above 3 ng/ml at any time during treatment month 3. RESULTS: Anovulation was observed in 81.8% women in the 5-mg group and 80% in the 10-mg group, and amenorrhea occurred in 81.2 and 90% of cases in the 5- and 10-mg groups. We did not detect any cases of endometrial hyperplasia despite estradiol levels that remained in the physiological follicular phase range throughout treatment cycle 3. CONCLUSIONS: Continuous low-dose VA2914 can induce amenorrhea and inhibit ovulation without down-regulating estradiol levels or inducing endometrial hyperplasia in normal women. Long-term studies with a larger population are required to confirm the contraceptive efficacy of this regimen.     

Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention

Regulated on activation, normal T cell expressed and secreted (RANTES) gene promoter is a regulatory region and a site of notable genetic diversity. In order to explore a possible interaction between RANTES promoter genetic diversity and susceptibility to coronary artery disease (CAD) and in stent restenosis (ISR), we initially sequenced a locus extending from - 516 to 40 covering the entire region of the RANTES promoter in 100 subjects randomly selected from our cohort. Four single nucleotide polymorphisms (SNPs) were identified: - 403G/A, - 256G/A, - 109C/T and - 28C/G. The frequency of the - 109C/T and - 256G/A variations was < 0.01, and was considered to be of limited significance. The frequency of the - 403G/A and - 28C/G polymorphisms was evaluated in the entire sample, which consisted of 118 patients subjected to percutaneous coronary intervention (PCI) without ISR on angiographic re-evaluation (no IRS group), 74 CAD patients with ISR on angiographic re-evaluation (IRS group) and 146 controls without angiographic evidence of CAD (no CAD group). No association was established between the RANTES promoter genotype and ISR. A genotype-phenotype interaction was observed between the - 403G/A polymorphism and CAD. The - 403A homozygotes were significantly more common in the CAD group than in the controls. The severity of CAD among case subjects, expressed as the mean number of diseased vessels, was significantly higher among - 403A homozygotes as compared to wild-type homozygotes and heterozygotes. In conclusion, the RANTES - 403A allele was associated with the presence and severity of CAD independently of conventional cardiovascular risk factors. The RANTES promoter genotype did not influence susceptibility to ISR in patients subjected to PCI.     

Contrast‐induced early repolarization pattern and ventricular fibrillation

Malignant arrhythmias during coronary angiography consist a complication of the procedure. Clinicians should be aware that intracoronary infusion of contrast medium can lead to physiological changes that lower the ventricular fibrillation threshold.     

Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy

Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s-B12) and plasma pyridoxal-5'-phosphate (p-PLP) were measured in epileptic children before and after a 20-week period of sodium valproate (group A, n=32) and carbamazepine (group B, n=20) monotherapy. P-tHcy significantly increased in both groups, s-F and s-B12 significantly increased in group A, while s-F and p-PLP significantly decreased in group B. Our study showed an early effect of antiepileptic drug treatment on homocysteine metabolism.     

Predictors of Health Utility among 60-Day Survivors of Acute Kidney Injury in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study

Background and objectives: Health-related quality of life (HRQOL) after acute kidney injury (AKI) is an area of great importance to patients. It was hypothesized that HRQOL after AKI would relate to intensity of dialysis during AKI and dialysis dependence at follow-up.Design, setting, participants, & measurements: The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive versus less intensive renal replacement therapy in critically ill patients with AKI. Of 1124 participants, 415 survived at least 60 days and completed the Health Utilities Index (HUI), which measures 8 health attributes and calculates an overall HRQOL score, also called a utility score. How strongly pre–intensive care unit (ICU) health, severity of illness, hospital course, intensity of dialysis, and outcome were associated with 60-day HUI scores was assessed, after adjustment for demographics.Results: The overall HUI score was 0.40 ± 0.37, indicating severely compromised health utility and was associated with only admission from home and hospital and ICU length of stay (LOS). Ambulation was better among those with a shorter hospital and ICU LOS. Better cognition was associated with dialysis independence and with fewer comorbid chronic illnesses. Emotion was associated with only hospital LOS. Pain was associated with ICU LOS.Conclusions: Health utility was low in this cohort of patients after AKI, and intensity of dialysis did not affect subsequent health utility. The effects of a lengthy hospitalization generally outweighed the effects of delayed recovery of kidney function on HRQOL after AKI.A cute kidney injury (AKI) is common among hospitalized patients and is particularly prevalent among patients cared for in the intensive care unit (ICU) setting (1–3). AKI has been associated with increased morbidity, mortality, and costs (1–4). It remains unclear to what extent treatment of or recovery from AKI influences health-related quality of life in survivors of AKI. There have been several reports of health-related quality of life (HRQOL) among survivors of AKI in the ICU (5–10). However, many of these studies are limited by small sample size and low response rate. In addition, follow-up times are variable among and sometimes within studies, ranging from 3 months to several years. Several measures of HRQOL have been used, including the Medical Outcomes Study Short Form 36-item health survey (SF-36) (9), EuroQol (EQ-5D) (5), and Nottingham Health Profile (6,8,10), and also health utilities by time trade-off (7) or visual analog scale (5) and Activities of Daily Living (7,8). Perhaps because of this variability, results are mixed. On balance, limitations in mobility were fairly common, ranging from 29 to 60% (6,8). However, patients generally reported a favorable health status, with 62 to 77% of patients reporting “good” or “excellent” health status (7,10). Health utility on the EQ-5D index was 0.68 compared with an age- and sex-matched norm of 0.86 (5), but in the same study utility by visual analog scale was not different from the general population. Health utility by the time trade-off method was reported by Hamel et al. to be 0.84, but no normative data were presented (7).The availability of HRQOL data in a large cohort of survivors of AKI requiring renal replacement therapy (RRT) provides a unique opportunity to study HRQOL and its potential determinants in this population. The Veterans Affairs/National Institutes of Health (VA/NIH) Acute Renal Failure Trial Network (ATN) study (ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00076219","term_id":"NCT00076219"}}NCT00076219) was a multicenter randomized trial of intensive versus less intensive renal replacement therapy in critically ill patients with acute kidney injury conducted between November 2003 and July 2007 at 27 VA and university-affiliated medical centers (11,12). Although the major goals of the ATN study were to assess the effects of treatment assignment on 60-day mortality, in-hospital mortality, and recovery of renal function, HRQOL was also assessed at 60 days among survivors with the intention of establishing the effect of dialysis intensity on HRQOL and of assigning health utilities to facilitate performance of cost-effectiveness analysis.We hypothesized that study treatment assignment and ongoing dialysis dependence at 60 days would be potential determinants of HRQOL. Although intensive dialysis did not lead to shorter hospital stays or more rapid recovery of renal function (12), both of which might have contributed to improved HRQOL at 60 days, we postulated that better control of uremia could have direct effects on HRQOL. In addition, given that patients receiving maintenance dialysis routinely report impaired HRQOL (13–15), we also hypothesized that ongoing need for dialysis would be an important determinant of HRQOL at 60 days.