Publications

OBJECTIVES

Adherence to antiretroviral therapy (ART) remains a challenge in efforts to maximize HIV treatment benefits. Previous studies of antiretroviral adherence are limited by low statistical power, homogeneous samples, and biased assessment methods. Based on Social Action Theory and using a large, diverse sample of men and women living with HIV, the objectives of the current study are to clarify correlates of nonadherence to ART and to provide theory-guided, empirically supported direction for intervening on ART nonadherence.

DESIGN

Cross-sectional interview study utilizing a computerized interview.

SETTING

Recruited from clinics, agencies, and via media ads in four U.S. cities from June 2000 to January 2002.

PARTICIPANTS

Two thousand seven hundred and sixty-five HIV-positive adults taking ART.

MAIN OUTCOME MEASURE

Computer-assessed self-reported antiretroviral adherence.

RESULTS

Thirty-two percent reported less than 90% adherence to ART in the prior 3 days. A number of factors were related to nonadherence in univariate analysis. Multivariate analyses identified that being African American, being in a primary relationship, and a history of injection drug use or homelessness in the past year were associated with greater likelihood of nonadherence. Furthermore, adherence self-efficacy, and being able to manage side effects and fit medications into daily routines were protective against nonadherence. Being tired of taking medications was associated with poorer adherence whereas a belief that nonadherence can make the virus stronger was associated with better adherence.

CONCLUSIONS

Results support the need for multifocused interventions to improve medication adherence that address logistical barriers, substance use, attitudes and expectancies, as well as skills building and self-efficacy enhancement. Further exploration of issues related to adherence for African Americans and men in primary relationships is warranted.

The direct binding of Streptococcus mitis to human platelets is mediated in part by two proteins (PblA and PblB) encoded by a lysogenic bacteriophage (SM1). Since SM1 is the first prophage of S. mitis that has been identified and because of the possible role of these phage-encoded proteins in virulence, we sought to characterize SM1 in greater detail. Sequencing of the SM1 genome revealed that it consisted of 34,692 bp, with an overall G+C content of 39 mol%. Fifty-six genes encoding proteins of 40 or more amino acids were identified. The genes of SM1 appear to be arranged in a modular, life cycle-specific organization. BLAST analysis also revealed that the proteins of SM1 have homologies to proteins from a wide variety of lambdoid phages. Bioinformatic analyses, in addition to N-terminal sequencing of the proteins, led to the assignment of possible functions to a number of proteins, including the integrase, the terminase, and two major structural proteins. Examination of the phage structural components indicates that the phage head may assemble using stable multimers of the major capsid protein, in a process similar to that of phage r1t. These findings indicate that SM1 may be part of a discrete subfamily of the Siphoviridae that includes at least phages r1t of Lactococcus lactis and SF370.3 of Streptococcus pyogenes.

Heterozygous mutations in the coding sequence of the serpentine melanocortin 4 receptor (MC4R) are the most frequent genetic cause of severe human obesity. Since haploinsufficiency has been proposed as a causal mechanism of obesity associated with these mutations, reduction in gene transcription caused by mutations in the transcriptionally essential regions of the MC4R promoter may also be a cause of severe obesity in humans. To test this hypothesis we defined the minimal promoter region of the human MC4R and evaluated the extent of genetic variation in this region compared with the coding region in two cohorts of severely obese subjects. 5'RACE followed by functional promoter analysis in multiple cell lines indicates that an 80-bp region is essential for the transcriptional activity of the MC4R promoter. Systematic screening of 431 obese children and adults for mutations in the coding sequence and the minimal core promoter of MC4R reveals that genetic variation in the transcriptionally essential region of the MC4R promoter is not a significant cause of severe obesity in humans.

Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4-10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10-65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2-4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism.

The enumeration of antigen-specific T cell responses has been greatly facilitated in recent years by the development of methods based on the detection of cytokines. In particular, the enzyme-linked immunospot (ELISPOT) and cytokine flow cytometry (CFC) assays have become popular. Since both assays are likely to continue to be in widespread use, it is important to evaluate whether their results are comparable. In the current study, we compared the results obtained in the ELISPOT and CFC assays using peptide pools corresponding to CMV and HIV-1 proteins in chronically HIV-1-infected individuals. Analysis of T cell responses to peptide pools indicated that the CMV pp65 and HIV-1 Gag CFC and ELISPOT-derived results were statistically correlated. However, the results obtained with each assay differed in important ways: the magnitude of the response was consistently higher in the CFC assay while the CFC assay was less likely than the ELISPOT assay to detect low-level responses. Furthermore, there was a lack of numeric agreement between ELISPOT and CFC results. For studies that require the detection of low-level responses, or definition of responses as positive or negative, the ELISPOT assay may be preferable. In contrast, the CFC has a greater dynamic range and allows for phenotypic discrimination of responding cells, making it the assay of choice for most other applications.

OBJECTIVES

We examined the effect of race, socioeconomic status, and health insurance status on the prevalence of overweight among children and adolescents.

METHODS

We studied an observational cohort from the 1996 Medical Expenditure Panel Survey Household Component.

RESULTS

In the younger group, both Black and Latino children had a greater likelihood of being overweight compared with White children. Among the adolescent group, Latinos and Asian/Pacific Islanders were more likely to be overweight. Among adolescents, lacking health insurance and having public insurance were both positively associated with the prevalence of overweight. A relationship between insurance status and overweight was not observed for younger children.

CONCLUSIONS

There are substantial racial differences in the prevalence of overweight for children and adolescents. Health insurance status is associated with the prevalence of overweight among adolescents.

BACKGROUND

Asthma guidelines urge teaching patients the knowledge and skills required for self-management, based on the assumption that education will lead to improved skills and better asthma control.

METHODS

In a prospective, randomized controlled trial of 65 adults with mild-to-moderate asthma, we examined whether an educational self-management intervention would improve adherence to inhaled corticosteroid therapy, decrease markers of airway inflammation, and improve clinical control. Peak flow, symptoms, and adherence were monitored for 7 weeks. After a 1-week run-in, subjects were assigned randomly to either the educational intervention or control group. The 30-minute intervention was delivered and reinforced at biweekly intervals.

RESULTS

Compared with the control group, the intervention group had improvements in adherence to inhaled corticosteroid therapy (by 30% vs. -5%, P = 0.01), self-reported control of asthma (by 14% vs. 5%, P = 0.04), and perhaps quality of life (by 37% vs. 21%, P = 0.06). The direction of change for all other clinical outcomes was more favorable in the intervention group, but not significantly so. Markers of inflammation in sputum decreased more in the intervention group, with sputum eosinophils declining significantly (P = 0.02).

CONCLUSION

In asthmatic patients treated with inhaled corticosteroids, education and training in self-management improves adherence with inhaled therapy, perceived control of asthma, and sputum eosinophilia.

Correlated neuronal activity is believed to play an important role in refining and maintaining cortical circuitry during early development. Here we provide evidence that globally and locally correlated activity mediate different forms of adult plasticity. Pulses of broad-spectrum noise were used to activate time-locked responses across large areas of the rat auditory cortex, globally synchronizing cortical activity. Brief tone pips were used to activate relatively small groups of neurons, generating locally correlated activity. Pairing pulsed noises with nucleus basalis (NB) stimulation in awake rats for 4 weeks broadened spectral tuning, disrupted tonotopic maps, and reduced spontaneous discharge correlation in the primary auditory cortex (AI), as examined under anesthesia. Those effects caused AI neurons to appear qualitatively similar to neurons in nonprimary auditory fields of naive animals. Subsequent pairing of tone pips with NB stimulation for a period of 4 weeks completely reversed these effects induced by previous noise-NB pairing. These findings further demonstrate that the adult auditory cortex retains a substantial capacity for receptive field plasticity and tonotopic map reorganization and that locally correlated activity plays an important role in plasticity in the adult, as in the developing cortex.