Prediction of adherence to antiretroviral therapy: a one-year longitudinal study.

The aim of this longitudinal study was to identify the determinants of adherence to antiretroviral therapy (ART) in HIV patients over a period of 12 months. A total of 376 individuals living with HIV treated with ART participated in the study. Data were collected at baseline and at three, six, nine and 12 months. Variables assessed were adherence, attitude, outcome expectancies, self-efficacy, patient satisfaction with the relationship with their physician, provision of social support, optimism, CD4 cell count, viral load and side effects. Predictors of adherence in the Generalized Estimated Equation (GEE) were: high perception of self-efficacy (OR=1.68; 95%CI 1.27-2.22), positive attitude towards taking medication (OR=1.56; 95%CI 1.18-2.06), not living alone (OR=1.47; 95%CI 1.04-2.08) and being a male (OR=2.81; 95%CI 1.47-5.34). Subsequent analysis showed that a positive attitude towards taking medication was associated with a high level of patient satisfaction with their physician, high perceived social support, being optimistic, living with HIV for five years or less and experiencing no side effects. Also, a strong sense of self-efficacy was associated with positive perception of social support, high level of patient satisfaction with their physician and not living alone. These results suggest that interventions aimed at improving adherence to ART should focus on reinforcing self-efficacy and developing a positive attitude towards taking medication.

Evaluation of a theoretically based AIDS/STD peer education program on postponing sexual intercourse and on condom use among adolescents attending high school.

The effectiveness of an intervention based upon the theories of Ajzen and Triandis was evaluated among 698 junior and 306 senior high school students. The intervention to juniors was offered by senior students who were trained during a course integrated into the school curriculum. Respondents in the control and experimental groups completed a questionnaire at baseline and 9 months after the program. Compared to junior respondents in the control group, those in the experimental group positively modified their attitude, perceived behavioral control, personal normative beliefs, perceived role beliefs, anticipated regret and intention with respect to postponing sexual intercourse and with respect to condom use, as well as perceived self-efficacy to negotiate both behaviors. Compared to senior respondents in the control group, those in the experimental group showed a significant positive modification of all the above variables except perceived behavioral control (indirect measure), anticipated regret and intention with respect to postponing sexual intercourse. At post-test, seniors in the experimental group were more likely to use condoms on a regular basis than those in the control group. Program effects occurred among both sexes, but a few differences in response were observed among males and females. Results suggest this type of theory-based program is effective in modifying psychosocial variables related to postponing sexual intercourse and related to condom use among adolescents. Personal involvement in designing intervention appears to be effective in modifying the behavior of peer educators.

Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone.

Despite the discovery of many ions and molecules that activate the Ca2+ receptor, there are no known ligands that block this receptor. Reported here are the pharmacodynamic properties of a small molecule, NPS 2143, which acts as an antagonist at the Ca2+ receptor. This compound blocked (IC50 of 43 nM) increases in cytoplasmic Ca2+ concentrations [Ca2+]i elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS 2143, even when tested at much higher concentrations (3 microM), did not affect the activity of a number of other G protein-coupled receptors, including those most structurally homologous to the Ca2+ receptor. NPS 2143 stimulated parathyroid hormone (PTH) secretion from bovine parathyroid cells (EC50 of 41 nM) over a range of extracellular Ca2+ concentrations and reversed the effects of the calcimimetic compound NPS R-467 on [Ca2+]i and on secretion of PTH. When infused intravenously in normal rats, NPS 2143 caused a rapid and large increase in plasma levels of PTH. Ca2+ receptor antagonists are termed calcilytics and NPS 2143 is the first substance (either atomic or molecular) shown to possess such activity. The pharmacodynamic properties of NPS 2143 together with the recently demonstrated effects of this compound on bone formation support the view that orally active calcilytic compounds might provide a novel anabolic therapy for osteoporosis.

Stimulation of calcitonin secretion by calcium receptor activators: evaluation using a new, highly sensitive, homologous immunoradiometric assay for rat calcitonin.

Current rat calcitonin immunoassays use human calcitonin antisera, and suffer from poor sensitivity, long incubation periods, nonspecific interferences, and unreliability. The homologous immunoradiometric assay (IRMA) for rat calcitonin described here overcomes these problems. Overnight incubation yields a detection limit of 0.4 pg/mL, a standard curve that is linear to >1800 pg/mL, and intra- and interassay coefficients of variation of <7%. Gel filtration chromatography of rat plasma and rat medullary thyroid carcinoma 44-2 cell media showed that the vast majority of immunoreactivity coeluted with calcitonin standard. In 44-2 cells, increasing extracellular Ca2+ concentration or incubation with the calcimimetic compound NPS R-467 markedly increased calcitonin secretion. Plasma calcitonin levels were elevated in rats anesthetized with ketamine/xylazine and in conscious rats with chronic renal insufficiency. Calcitonin levels decreased following EGTA-induced hypocalcemia and were undetectable after thyroparathyroidectomy. In normal conscious rats, plasma calcitonin levels averaged 3-5 pg/mL and increased up to 100-fold following calcium (Ca) infusion or NPS R-467 administration. The assay also quantified calcitonin in plasma of normal and Ca-injected mice. This assay has revealed that plasma calcitonin levels in normal rats are much lower than the detection limits of most existing assays, but can increase by 100-fold on activation of the C-cell Ca2+ receptor.

Circadian activity of topical 0.05% betamethasone dipropionate in human skin in vivo.

The influence of treatment duration, vehicle, and time of day of application on topical 0.05% betamethasone dipropionate uptake into human stratum corneum and the resulting skin-blanching response was investigated in human subjects. Drug uptake into stratum corneum and the resulting skin color changes measured with a chromameter demonstrate an equilibrium delay. Maximal drug uptake occurred at 2 h, whereas maximal skin color changes occurred 6 h after a single application. Extent of decreased skin color was dependent on vehicle, treatment duration, and time of day of application. Time of maximal decreased skin color occurred at midnight independent of vehicle, treatment duration, or time of day of application. This time of maximal drug activity coincides with the well-known time period of lowest circulating cortisol concentrations (2000-0400 h). Application of a single 2- or 6-h dose of the 0.05% cream at 1600 h produced more extensive and prolonged changes in skin color over 24 h than a 0900-h application in the same subject. These data demonstrate that the extent and duration of topical corticosteroid activity in human skin is influenced by vehicle, treatment duration, and time of day of application. The prolonged changes in skin color measured with a single dose applied at 1600 h suggest that a once-a-day dosing regimen in the late afternoon may be sufficient for dermatologic therapy. Elucidation of these circadian responses with topical corticosteroids may provide a rational basis for the future re-evaluation of the appropriate therapeutic regimen with this class of drugs in dermatologic medicine.

Age, cognitive style, and traffic signs.

This study assessed the efficiency with which young and older adults of varying field dependence extract information from traffic signs. It also identified some visual attributes of signs which affect recognition time. Two experiments were conducted. In Exp. 1, digitized signs, embedded in rural and urban backgrounds, were presented on a computer monitor. Subjects indicated on which side a target sign had appeared. Analysis showed that recognition times were dependent on age and field-dependence scores. Also, visual backgrounds and spatial frequency of pictographs affected RTs. In Exp. 2, recognition RT to 2 signs with redesigned pictographs was measured as well as time taken to detect signs. The signs showing reduced spatial frequency were the fastest to recognize, although no effect was noticed during detection. The subjects who showed the worst performance when facing the original signs benefitted the most from the modifications.

Disparity of in vitro and in vivo oleic acid-enhanced beta-estradiol percutaneous absorption across human skin.

The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. beta-Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic acid (5%) did not alter beta-estradiol permeability in vivo but increased permeability six-fold in vitro in symmetrical diffusion cells. beta-Estradiol permeability in oleic acid was not different from that in ETOH, however, using asymmetrical diffusion cells. Stratum corneum-to-vehicle partition coefficients of beta-estradiol in the vehicles were similar, yet fourfold more steroid was detected in skin biopsies from the in vitro symmetrical diffusion cells. Thus, oleic acid increased beta-estradiol permeability in vitro only when skin was equilibrated with fatty acid. Attention to in vitro diffusion cell design and its relevance in vivo is critical to defining the mechanisms of enhanced solute permeation.

Mechanism of ethanol-enhanced estradiol permeation across human skin in vivo.

The influence of ethanol on the permeation of 17 beta-estradiol (estradiol) across viable human skin in vivo was investigated with the human skin sandwich flap model. Maintaining continuous delivery of a constant concentration of the solute in phosphate-buffered saline, pH 7.4 (PBS), or mixtures of ethanol in PBS to the skin surface revealed that steady-state flux of estradiol was achieved within 30-60 min and maintained throughout 4 hr. The 10-fold decrease in in vivo flux and permeability coefficient (Kp) of tracer estradiol solutions in ethanol or ethanol solutions compared with PBS vehicle reflected the 10-fold difference in the apparent partition coefficients (Km) of estradiol from the respective vehicles into isolated human stratum corneum. Neither the stratum corneum thickness nor the diffusion coefficient of estradiol was significantly different among the vehicles tested. In vivo flux of estradiol in ethanol or ethanol solutions across viable human skin was increased with saturated solutions of estradiol. Further, in vivo flux of estradiol from vehicles such as PBS, ethanol, and ethanol mixtures, which minimally alter the rate-limiting barrier, can be successfully predicted with knowledge of only two physicochemical parameters, the estradiol concentration in the vehicle and the Km of estradiol from the vehicle into isolated human stratum corneum.