Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr.

In a longitudinal study of the effects of moderate (70%) dietary restriction (DR) on aging, plasma glucose and insulin concentrations were measured from semiannual, frequently sampled intravenous glucose tolerance tests (FSIGTT) in 30 adult male rhesus monkeys. FSIGTT data were analyzed with Bergman's minimal model, and analysis of covariance revealed that restricted (R) monkeys exhibited increased insulin sensitivity (S(I), P < 0.001) and plasma glucose disappearance rate (K(G), P = 0.015), and reduced fasting plasma insulin (I(b), P < 0.001) and insulin response to glucose (AIR(G), P = 0.023) compared with control (C; ad libitum-fed) monkeys. DR reduced the baseline fasting hyperinsulinemia of two R monkeys, whereas four C monkeys have maintained from baseline, or subsequently developed, fasting hyperinsulinemia; one has progressed to diabetes. Compared with only the normoinsulinemic C monkeys, R monkeys exhibited similarly improved FSIGTT and minimal-model parameters. Thus chronic DR not only has protected against the development of insulin resistance in aging rhesus monkeys, but has also improved glucoregulatory parameters compared with those of otherwise normoinsulinemic monkeys.

Correlation of serum L-carnitine and dehydro-epiandrosterone sulphate levels with age and sex in healthy adults.

OBJECTIVES: L-carnitine and dehydro-epiandrosterone (DHEA) independently promote mitochondrial energy metabolism. We therefore wondered if an age-related deficiency of L-carnitine or DHEA may account for the declining energy metabolism associated with age. METHODS: we evaluated serum levels of L-carnitine and the sulphated derivative of DHEA (DHEAS) in cross-sectional study of 216 healthy adults, aged 20-95. RESULTS: serum DHEAS levels declined, while total carnitine levels increased with age (P < 0.0001). Total and free carnitine and DHEAS levels were lower in women than men (P < 0.0001). Esterified/free (E/F) carnitine (inversely related to carnitine availability) increased with age in both sexes (P=0.012). CONCLUSION: reduced carnitine availability correlates with the age-related decline of DHEAS levels. These results are consistent with the hypothesis that decreased energy metabolism with age relates to DHEAS levels and carnitine availability.

Symptoms associated with oophorectomy and tamoxifen treatment for breast cancer in premenopausal Vietnamese women.

There are very few data about the efficacy and toxicity of adjuvant systemic therapies for breast cancer in non-western populations. In 1993 in Vietnam we began a randomized controlled clinical trial on premenopausal women with operable breast cancer comparing adjuvant surgical oophorectomy plus tamoxifen with observation and this same combined hormonal treatment on recurrence. We evaluated the symptoms reported at regular follow-up visits by the first 482 premenopausal women entered in this clinical trial and treated with surgical oophorectomy plus tamoxifen or observation. Hot flash frequency and intensity, vaginal discharge, and genital pruritus were the only symptoms to occur more frequently in oophorectomy and tamoxifen-treated subjects. Seventy-seven percent of oophorectomy/tamoxifen subjects reported grade 1 or more and 44% grade 2 or more hot flash frequency symptoms in the first 12 months, versus 9% and 1% of observation subjects, respectively. Twenty percent of oophorectomy/tamoxifen subjects had grade 2 or greater intensity of hot flashes some time in the first 12 months versus 0% in observation subjects. Through three years, vasomotor symptoms were reported more frequently in oophorectomy/tamoxifen-treated women (in 23% vs. 3% at three years, mostly grade 1 toxicities). While noted and persistent vasomotor symptoms were found with oophorectomy plus tamoxifen in this population of Vietnamese women, these were of lower grades and tolerable. This adjuvant treatment may be widely accepted if it is demonstrated to be effective in this population.

Asthma in non-inner city Head Start children.

OBJECTIVE: Asthma is a significant cause of morbidity and mortality in children. The objective of this study was to determine whether the federal program Head Start in Dane County, Wisconsin, could be used as a mechanism to identify preschool-aged children with asthma. DESIGN: Five-year, cross-sectional survey of parents with children enrolled in Head Start. METHODS: Investigator-administered asthma screening questionnaire to parents of enrolling Head Start children in Dane County, Wisconsin. MEASUREMENTS: Asthma prevalence and asthma-related health care use, including emergency department visits, hospitalizations, and medication usage, were measured using an asthma screening questionnaire developed by investigators. RESULTS: Information was gathered on 2215 children. The prevalence of physician-diagnosed asthma in the screened children was 15.8%. Parental reports of physician-diagnosed asthma were validated in a subset of 133 children, with a 98.5% confirmation rate. Independent risk factors for asthma included male gender (relative risk, 1.4) and African-American ethnicity (relative risk, 1.4). Asthma-related morbidity was substantial with 26.7% of identified children hospitalized for asthma and 54.5% with an emergency department visit during their lifetime. The majority of children (46.4%) were treated with intermittent, quick relief medications (beta-agonists) alone, whereas only 6.1% were on daily, long-term controller medications. CONCLUSIONS: Asthma screening through a Head Start program provides an effective means of targeting preschool-aged children from socioeconomic groups at high risk for asthma. Identification of children early in the disease course and those at high risk for asthma provides an ideal opportunity for the implementation of preventive and therapeutic interventions.

Autoantibody testing for connective tissue diseases. Comparison of immunodiffusion, immunoblot, and enzyme immunoassay.

We evaluated 500 consecutive patient serum samples for the presence of six autoantibodies by three antibody detection methods: immunodiffusion, immunoblot, and enzyme immunoassay. Clinical data were reviewed for each patient with positive antibody test results. Serum samples from 60 patients revealed antibodies to Sm, ribonucleoprotein (RNP), SSA/Ro, SSB/La, Scl-70, or Jo-1. There were 7 false-positive test results (1%). All three methods detected autoantibodies in 36 (68%) of 53 patients with connective tissue disease. Immunoblot was the most sensitive method to detect autoantibodies (92%). Enzyme immunoassay and immunodiffusion were less sensitive (81% and 74%, respectively). Antiribonucleoprotein and anti-SSB/La antibodies were more often detected by immunoblotting, whereas anti-SSA/Ro antibodies were more often detected by enzyme immunoassay. Newer antibody detection methods (immunoblot and enzyme immunoassay) are less time consuming than immunodiffusion and show good interassay sensitivity without loss of specificity. A combination of immunoblot and enzyme immunoassay yielded excellent assay sensitivity (100%) and specificity (99%) for detection of autoantibodies.

Adverse effects of low dose amiodarone: a meta-analysis.

OBJECTIVES: We sought to assess the odds of experiencing adverse effects with low dose amiodarone therapy compared with placebo. BACKGROUND: An estimate of the likelihood of experiencing amiodarone-related adverse effects with exposure to low daily doses of the drug is lacking in the published reports, and little information is available on adverse effect event rates in control groups not receiving the drug. METHODS: Data from four published trials involving 1,465 patients were included in a meta-analysis design. The criteria for inclusion were 1) double-blind, placebo-controlled design; 2) absence of a crossover design between patient groups; 3) mean follow-up of at least 12 months; 4) maintenance amiodarone dose < or = 400 mg/day; and 5) presence of an explicit description of adverse effects. Data were pooled after testing for homogeneity of treatment effects across trials, and summary odds ratios were calculated by the Peto-modified Mantel-Haenszel method for each adverse effect. RESULTS: The mean amiodarone dose per day ranged from 152 to 330 mg; 738 patients were randomized to receive amiodarone and 727 placebo. Exposure to amiodarone in this dose range, for a minimal duration of 12 months, resulted in odds similar to those of placebo for hepatic and gastrointestinal adverse effects, but in significantly higher odds than those of placebo (p < 0.05) for experiencing thyroid (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to 3.7), skin (OR 2.5, 95% CI 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and bradycardic (OR 2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased odds of pulmonary toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did not reach statistical significance (p = 0.07). The unadjusted total incidence of drug discontinuation was 22.9% in the amiodarone group and 15.4% in the placebo group. The odds of discontinuing the drug in the amiodarone group was approximately 1.5 times that of the placebo group (OR 1.52, 95% CI 1.2 to 1.9) (p = 0.003). CONCLUSIONS: Compared with placebo, there is a higher likelihood of experiencing several amiodarone-related adverse effects with exposure to low daily doses of the drug. Thus, although low dose amiodarone may be well tolerated, it is not free of adverse effects.

Meta-analysis of randomized control trials addressing brief interventions in heavy alcohol drinkers.

OBJECTIVE: To assess the effectiveness of brief interventions in heavy drinkers by analyzing the outcome data and methodologic quality. DESIGN: (1) Qualitative analysis of randomized control trials (RCTs) using criteria from Chalmers' scoring system; (2) calculating and combining odds ratios (ORs) of RCTs using the One-Step (Peto) and the Mantel-Haenszel methods. STUDY SELECTION AND ANALYSIS: A MEDLINE and PsycLIT search identified RCTs testing brief interventions in heavy alcohol drinkers. Brief interventions were less than 1 hour and incorporated simple motivational counseling techniques much like outpatient smoking cessation programs. By a single-reviewer, nonblinded format, eligible studies were selected for adult subjects, sample sizes greater than 30, a randomized control design, and incorporation of brief alcohol interventions. Methodologic quality was assessed using an established scoring system developed by Chalmers and colleagues. Outcome data were combined by the One-Step (Peto) method; confidence limits and chi 2 test for heterogeneity were calculated. RESULTS: Twelve RCTs met all inclusion criteria, with an average quality score of 0.49 + or - 0.17. This was comparable to published average scores in other areas of research (0.42 + or - 0.16). Outcome data from RCTs were pooled, and a combined OR was close to 2 (1.91; 95% confidence interval 1.61-2.27) in favor of brief alcohol interventions over no intervention. This was consistent across gender, intensity of intervention, type of clinical setting, and higher-quality clinical trials. CONCLUSIONS: Heavy drinkers who received a brief intervention were twice as likely to moderate their drinking 6 to 12 months after an intervention when compared with heavy drinkers who received no intervention. Brief intervention is a low-cost, effective preventive measure for heavy drinkers in outpatient settings.