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Biomedical subjects

D Abrams

Publications and source records attributed to D Abrams.

At least 37 records · Page 2Linked to original sources

Surfactant versus saline as a vehicle for corticosteroid delivery to the lungs of ventilated rabbits.

Local administration of steroids to the lungs in ventilated newborn infants can minimize the harmful side effects that occur with systemic administration. An efficient system of drug delivery that provides uniform distribution within the lungs is essential for the treatment of bronchopulmonary dysplasia. In this study we compare surfactant with 0.9% saline solution as vehicles for the direct instillation of a steroid (budesonide) into the lungs. Twenty-two anesthetized, ventilated rabbits received [3H]budesonide in either 0.9% saline or surfactant, administered through an endotracheal tube. Before drug administration, bronchial lavage was performed on half of the animals to serve as a model for surfactant deficiency. Lung samples were analyzed by both autoradiography (alveolar versus airway distribution) and liquid scintillation counting (central versus peripheral deposition). As expected, the delivered concentration of [3H]budesonide decreased as airway size decreased and branching increased. Significantly less [3H]budesonide was deposited in the alveolar spaces of all study groups compared with that deposited in the small and large airways (p < 0.05). However, both vehicles were equally efficient in delivering [3H]budesonide to the lungs. Although the alveolar and peripheral areas received less (4-11%) of the drug than the central tissue (14-28%), this was consistent among all the groups and was not affected by altered lung compliance. Therefore, either surfactant or saline could be used to efficiently and reliably deliver budesonide to the lungs at a level greater than that reported using nebulizers. Because normal saline is currently used for tracheal toilette, it is likely to be preferred considering the increased costs associated with surfactant.

Adrenal Cortex Hormones↗

Durability, dissemination, and institutionalization of worksite tobacco control programs: results from the Working Well trial.

Durability, dissemination and institutionalization o f tobacco control activities are reported, based on the Working Well worksite cancer control intervention study (n = 83 worksites). Tobacco control activities increased significantly in intervention worksites as a result of research-supported activities but were not sustained 2 years after the conclusion of the intervention. Intervention sites were more likely than control sites to initiate and maintain structures for institutionalizing programs, such as assigning a committee responsibility for health-promotion programs or providing a budget for health-promoting activities. Dissemination of the program to control worksites had little impact on the level of smoking control activities in control worksites. Although program durability was not a primary aim of this intervention study, these analyses provide an important assessment of program maintenance beyond a funded intervention and underscore the need for additional research to identify effective organizational strategies for institutionalization of worksite health-promotion programs.

Journal Article↗

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. METHODS: A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. RESULTS: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. CONCLUSIONS: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.

Acquired Immunodeficiency Syndrome↗

Religiosity, gender, and the double standard.

Scottish teenagers (N = 690) participated in a survey concerning the relationship between religiosity, gender, and social judgments of sexual activity. Respondents estimated the number of sexual partners of 20-year old men and women and made evaluative judgments of sexually active men and women on positive and negative dimensions. On both tasks, evidence was obtained for the operation of a double standard. Women were expected to have fewer sexual partners than men, and their sexual activity was judged more negatively on evaluatively negative dimensions. Contrary to findings of previous studies in this area, gender differences in endorsement of the double standard were not found. Only moderate support was found for the view that religiosity contributes to different standards of sexual behavior for men and women, although religiosity had significantly greater influence on judgments made by women than on judgments made by men.

Adolescent↗

The Working Well Trial: baseline dietary and smoking behaviors of employees and related worksite characteristics. The Working Well Research Group.

BACKGROUND: The Working Well Trial, the largest randomized worksite health promotion trial to date, tests the effects of cancer prevention and control interventions on dietary and smoking behaviors of employees and the worksite environment. The trial is a 5-year cooperative agreement conducted in 57 matched pairs of worksites in 16 states by four study centers, a coordinating center, and the National Cancer Institute. The dual aims of this paper are to: (a) present a baseline description of the dietary and smoking habits of 20,801 employees, who are predominantly blue-collar workers; and (b) describe the social and physical environments of their worksites that may facilitate or hinder health behavior changes. METHODS: The self-administered baseline survey of individuals consisted of a core set of questions common across all study centers on diet and smoking. The organizational survey consisted of eight instruments administered via interviews with key informants in each worksite. Continuous variable were analyzed by a mixed linear model and binary data were analyzed by the Generalized Estimating Equation. RESULTS: The population represented is largely male (67.5%) and blue collar (53.5%). Mean levels of fat and fiber intakes were close to the national averages (36.6% of calories as fat and 13.1 g of fiber). Smoking prevalence (25.2%) was slightly lower than the national average. The worksites had a high level of health promotion activities (42% had nutrition programs, 53% had smoking control programs), but lacked environmental support for dietary behavior change and perceived support for smoking cessation. CONCLUSIONS: These findings replicate and extend previous research results to a large sample of diverse, largely blue-collar worksites. In addition the baseline results lay a foundation for the development of new insights into the relationship between individual and organizational level variables that may interact to influence behavioral and cultural norms.

Adult↗

Insights from monitoring the CPCRA didanosine/zalcitabine trial. Terry Beirn Community Programs for Clinical Research on AIDS.

The design, conduct, and analysis of clinical trials that evaluate the safety and efficacy of treatment interventions in patients with HIV infection provide many scientific challenges. A recently completed randomized trial of didanosine (ddI) and zalcitabine (ddC), sponsored by the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA), is an especially valuable resource for illustrating these challenging issues and for providing insights into how they might be properly addressed. Establishing equivalence of treatment effects on clinical efficacy end points is illustrated through the use of the confidence interval approach. The striking changes in treatment efficacy results that occurred during the course of the CPCRA trial provide important insights into how a data and safety monitoring board can reduce the risk of inappropriate early study termination. The trial also provides valuable insights into how treatment effects should be assessed, revealing inconsistencies between effects on the CD4 surrogate end point and effects on primary clinical efficacy end points and showing the incompleteness of the standardly employed definition of AIDS progression. Finally, the results of this ddI/ddC trial are used to examine the role of covariate adjustment.

Antiviral Agents↗

ETS exposure in the workplace. Perceptions and reactions by employees in 114 work sites. Working Well Research Group [corrected].

Employees are often exposed to and bothered by environmental tobacco smoke (ETS) in the workplace; however, little is known about correlates of workers' perceptions of their exposure. In this study, 20,801 employees in 114 work sites in the United States were surveyed; variables related to perceptions of exposure and being bothered by ETS were entered into regression models. Many of the workplaces had total or partial restrictions on smoking in the workplace; however, over half of the respondents (52.4%) reported they were exposed to ETS at work. Smoking policy, smoking status, age, gender, living with a smoker, and occupation contributed to models for perceived exposure and being bothered by tobacco smoke. Work site smoking restrictions seem to have an impact on employee attitudes concerning exposure to ETS. About 35% of employees were bothered regularly by smokiness at their workplaces, which made their working conditions both uncomfortable and exposed them to an unsafe working environment.

Adult↗

Co-activation of D1- and D2-like receptors is unnecessary for stimulated motor behavior in rats depleted of dopamine during development.

The motoric effects of the D1-like agonist SKF 38393 (5.0 or 20.0 mg/kg) and the D2-like agonist quinpirole (0.2, 1.0, or 3.0 mg/kg) were determined in adult rats treated with 6-OHDA (100 micrograms) or its vehicle on postnatal Day 3. Quinpirole, but not SKF 38393, produced stereotypy and modest motor activity in vehicle-treated rats. These effects of quinpirole were blocked by either the D1-like antagonist SCH 23390 (0.2 or 0.4 mg/kg) or the D2-like antagonist clebopride (10.0 mg/kg). In contrast, administration of either D1- or D2-like agonists enhanced stereotypy and motor behavior in animals depleted of dopamine with 6-OHDA. However, in these animals, only the D1-like antagonist was able to block D1-induced behaviors and only the D2-like antagonist was able to block D2-induced behaviors. A separate group of adult rats, treated with 6-OHDA (200 micrograms) on postnatal Day 20, was studied to determine whether these effects depended upon age at the time of DA depletion. Animals depleted on Day 20 resembled animals depleted on Day 3 in that D2-, but not D1-like antagonists, blocked D2 agonist-induced responses. These results demonstrate that in animals depleted of DA during development, qualitative changes in D1/D2 receptor interactions result in the ability of each receptor subtype to independently activate stereotypy and motor behavior.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Primary prophylaxis with pyrimethamine for toxoplasmic encephalitis in patients with advanced human immunodeficiency virus disease: results of a randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS.

Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of < 200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.

AIDS-Related Opportunistic Infections↗

Health beliefs and promotion of HIV-preventive intentions among teenagers: a Scottish perspective.

Beliefs concerning the spread of the human immunodeficiency virus (HIV) and preventive behaviors were examined in a sample of 351 sexually active Scottish teenagers. A postal questionnaire, including measures of variables specified by the health belief model (HBM) and preventive intentions, was employed. The relation between HBM measures and reported endorsement of HIV-preventive intentions was investigated. Results indicated that, in general, respondents intended to use condoms with new sexual partners. The majority also intended to carry condoms if they thought they might have sex with a new partner and to ask potential partners about their previous sexual history. Multiple-regression analyses showed that measures of health beliefs, gender, age, sexual experience, and previous condom use accounted for 17.8% to 24.3% of the variance in reported preventive intentions. Perceived barriers to preventive behaviors were found to be important predictors. However, the overall pattern of results raised questions concerning the adequacy of the HBM as a model of the determinants of HIV-preventive intentions, and the need for an extended model is discussed. Separate analyses were conducted for men and women and for 16- and 18-year-olds, and the implications for modeling intention formation in these subgroups are considered. The relevance of these findings to HIV-preventive campaigns is also discussed.

Adolescent↗

High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker.

We report a method for introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in NSO myeloma cells. A cell line was isolated after a single round of selection for vector amplification which contains approximately 4 copies of the vector, secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system. Productivity is stable in the absence of MSX selection.

Animals↗

Context and content: the impact of school-leaving and school-based health education on AIDS-relevant cognitions.

A survey examined health beliefs and intentions among 690 16-18 year-olds in Dundee. Respondents in the younger cohort (n = 363) were classified according to their educational situation (at school vs left) and self-reports of having received AIDS/HIV-relevant health education. Both remaining in school and receiving AIDS/HIV-relevant health education had independent beneficial effects, but the effects of leaving school also interacted with sex of respondent and with amount of relevant education received prior to leaving. Males' and females' reliance on mass media and other information sources diverged once they left school, indicating that males who leave school early are most likely to disregard useful or important information regarding AIDS. Consistent with this finding, leaving school reduced the difference between males' and females' intention to use condoms with a new partner. The beneficial impact of having previously received AIDS/HIV-relevant education on beliefs concerning the controllability of the epidemic and on feeling worried about everyday contact with a person with HIV/AIDS, was most marked among those who had left school. The results are discussed in terms of their implications for health education strategies.

Adolescent↗

Physicians' attitudes toward assisted suicide in AIDS.

We investigated factors influencing attitudes and practices among San Francisco physicians toward physician-assisted suicide in the context of AIDS. To explore this topic a questionnaire was developed for use in comparing two physician groups. This self-administered instrument was completed by 69 physician members of the San Francisco County Community Consortium (CCC), a community-based clinical research organization whose members care for persons with human immunodeficiency virus (HIV) disease. A comparison group consisted of 86 randomly sampled San Francisco physicians recruited from the California Medical Association mailing list. Anonymity of respondents was maintained. Chi-squares and t-tests were conducted to compare physician groups with regard to demographics and experiences with AIDS. Factor analytic techniques and correlational analyses were used to identify attitudinal and behavioral predictors of willingness to assist in a patient suicide. Twenty-three percent of the total sample would be likely to grant the patient's initial request for assistance in committing suicide. When faced with an adamant request, CCC members would be more likely to assist than comparison group physicians. Ethical beliefs were the strongest predictor of physicians' intention to assist. Identification with the AIDS patient also had significant predictive value.

Acquired Immunodeficiency Syndrome↗

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study.

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4+ cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN: Retrospective study of changes in laboratory markers and survival. SETTING: Multicentre trial at university hospital clinics. SUBJECTS: 90 Patients with AIDS or AIDS related complex. INTERVENTION: Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES: Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS: The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION: These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

AIDS-Related Complex↗

Young people learning about AIDS: a study of beliefs and information sources.

A study of the views of Scottish teenagers and undergraduates on health education issues relevant to human immunodeficiency virus (HIV) spread is reported. A sample of 1008 young people (690 teenagers and 318 students) returned a postal questionnaire designed to measure a range of relevant cognitions. These included levels of concern, perceived knowledge, perceived vulnerability, perceived seriousness, recall of health education campaigns, preferred information sources and views on the discussion of HIV/AIDS with significant others. Low levels of perceived vulnerability, high levels of recall for national campaigns, and discrepancies between used and credible sources of information are reported. Cohort and gender differences and correspondences with American and Australian studies are discussed. The implications of these findings for future AIDS education campaigns are also considered.

Acquired Immunodeficiency Syndrome↗

Effectiveness of three types of spouse-involved behavioral alcoholism treatment.

Treatment was provided to 45 alcoholics and their spouses in one of three out-patient behavioral treatment conditions: (1) minimal spouse involvement (MSI) (n = 14), (2) alcohol-focused spouse involvement (AFSI) (n = 12), or (3) alcohol-focused spouse involvement plus behavioral marital therapy (ABMT) (n = 19). Subjects were followed for 18 months after treatment. Subjects in all conditions reported significant decreases in frequency of drinking and frequency of heavy drinking, and reported increased life satisfaction. This information was corroborated by independent reports of the spouses. Patterns of outcome varied across the three treatment conditions, with ABMT subjects showing gradual improvement in proportions of abstinent days and abstinent plus light drinking days over the last 9 months of follow-up. Subjects in the other two treatment conditions showed gradual deterioration in proportion of abstinent days and abstinent plus light drinking days. Subjects assigned to the ABMT condition were less likely to experience marital separations, and reported greater improvement in marital satisfaction and subjective well-being than the other experimental groups. Clinical and theoretical significance of these findings are discussed.

Adult↗