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Biomedical subjects

A M Joseph

Publications and source records attributed to A M Joseph.

At least 19 recordsLinked to original sources

Biomarkers of tobacco exposure or harm: application to clinical and epidemiological studies. 25-26 October 2001, Minneapolis, Minnesota.

Adverse outcomes from tobacco use may take decades to develop. Biomarkers are measures that can be used in the early stages of tobacco use to assess exposure to tobacco toxins or to predict adverse health outcomes with which they are associated. Examples of biomarkers include specific chemical components of tobacco or their metabolites; early biochemical, histological, or physiological effects; and early health effects. Mechanistically relevant and quantitatively valid biomarkers are essential for assessing the ultimate impact of new products, treatments, preventive measures, and public health policies on tobacco-related disease. The tobacco industry's recent introduction of a variety of new tobacco products or devices with implied claims of reduced health risks highlights the need to develop methods for assessing their potential for benefit or harm. A wide variety of biomarkers for tobacco exposure or harm has been studied. Although many questions about their use remain unanswered, substantial data exist regarding their validity and utility. This conference reviewed both the general issues surrounding biomarker use and the current state of knowledge regarding the most widely studied and promising biomarkers.

Alkaloids↗

Targeting of Asian Americans and Pacific Islanders by the tobacco industry: results from the Minnesota Tobacco Document Depository.

OBJECTIVE: The study objective was to review internal tobacco industry documents written between 1985 and 1995 regarding the Asian American and Pacific Islander (AAPI) population in the USA. These documents detail opportunities and barriers to promotion of tobacco products, as viewed by the tobacco industry and its market research firms. DATA SOURCES: /methods: Researchers reviewed tobacco industry documents from the document depository in Minneapolis, Minnesota and the tobacco industry's website, The Tobacco Archive, in a systematic fashion. A combined technique was employed using title keywords, dates, and names to search the 4(b) index. FINDINGS: A review of internal tobacco company documents reveal that during the late 1980s, the industry and its market research firms recognised the importance of the AAPI community as a potential business market. Documents describe the population growth in this community, the high prevalence of smoking in countries of origin, high purchasing power of AAPI immigrants, cultural predisposition to smoking, opportunities afforded by the high proportion of retail businesses under AAPI ownership, barriers to developing the AAPI market, comprehensive campaigns, and political and lobbying efforts. Comprehensive campaigns were designed to integrate promotion efforts in AAPI consumer, retail, and business communities. CONCLUSIONS: The documents show that the tobacco industry developed specific promotion strategies to target the AAPI population. Tobacco control initiatives in the AAPI group have been slower to develop than in other targeted ethnic groups, and may benefit by increased awareness of industry methods to promote tobacco use.

Advertising↗

EBV persistence involves strict selection of latently infected B cells.

EBV is found preferentially in IgD- B cells in the peripheral blood. This has led to the proposal that the recirculating memory B cell pool is the site of long-lived persistent infection. In this paper we have used CD27, a newly identified specific marker for memory B cells, to test this hypothesis. We show that EBV is tightly restricted in its expression. Less than 1 in 1000 of the infected cells in the peripheral blood are naive (IgD+, CD27-) and <1 in 250 are IgD+ memory cells. Furthermore, EBV was undetectable in the self-renewing peripheral CD5+ or B1 cells, a subset that has not been through a germinal center. No such restriction was observed in tonsillar B cells. Therefore, the virus has access to a range of B cell subsets in the lymph nodes but is tightly restricted to a specific long-lived compartment of B cells, the IgD-, CD27+, and CD5- memory B cells, in the periphery. We suggest that access to this compartment is essential to allow the growth-promoting latent genes to be switched off to create a site of persistent infection that is neither pathogenic nor a target for immunosurveillance.

B-Lymphocyte Subsets↗

Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils.

In this paper we demonstrate, for the first time, that Epstein-Barr virus (EBV)-infected cells expressing the lymphoblastoid growth program are present in healthy carriers of the virus. Previously we observed that latently infected naive B cells are present in tonsils only when viral replication is detected, suggesting that these may represent newly infected B cells. We have tested this idea by performing a reverse transcription-PCR analysis for the expression of latent genes (EBNA2 and the EBNA3s) that are characteristically expressed only by newly infected cells expressing the growth latency program. EBNA2 expression is regularly detected in purified naive (IgD(+)) tonsillar B cells (13 of 16 tonsils tested) but was never found in the IgD(-) population (0 of 16). More detailed analysis revealed that the mRNAs for the latent genes EBNA1 (3 of 3 tonsils tested), EBNA3a (3 of 5), EBNA3b (3 of 5), EBNA3c (3 of 5), LMP1 (6 of 6), and LMP2 (5 of 6) were also present in the IgD(+) population, but the EBNA1Q-K transcript, characteristic of nonlymphoblastoid forms of latency, was never detected (0 of 6). Finally, we demonstrate that the latently infected naive (IgD(+)) cells express CD80 (B7.1), a marker characteristically expressed on activated naive lymphoblasts but absent from resting naive B cells. The infected naive (IgD(+)) population in the tonsil therefore has the viral and cellular phenotype of a B-cell directly infected with EBV-an activated lymphoblast expressing the growth program.

B-Lymphocytes↗

Withdrawal of chronic systemic corticosteroids in patients with COPD: a randomized trial.

The benefits of chronic systemic corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are not well established. To determine whether chronic corticosteroid treatment can be safely withdrawn in "steroid-dependent""COPD patients, we performed a double-blind, placebo-controlled study of 38 patients with steroid-dependent COPD. Patients were randomly assigned to receive their usual maintenance prednisone dose for 6 mo (continuous group) or to be withdrawn from prednisone at a rate of 5 mg per week (demand group). The number of COPD exacerbations per patient (primary outcome) was 2.5 +/- 2.7 (mean +/- SD) in the continuous group and 2.7 +/- 2.5 in the demand group (p = 0.60, 95% confidence interval for the difference: -1.1 to 1.7). Spirometric results, dyspnea, and health-related quality of life did not differ significantly in the two groups. The average daily corticosteroid dose was 10.7 +/- 5.2 mg in the continuous group and 6.3 +/- 6.4 mg in the demand group (p = 0.003). Weight decreased in the demand group by 4.8 +/- 2.0 kg, compared with an increase in the continuous group of 0.5 +/- 3.5 kg (p = 0.007). Discontinuation of chronic systemic corticosteroid treatment in steroid-dependent COPD patients did not cause a significant increase in COPD exacerbations, but did reduce total systemic corticosteroid use and body weight. Larger studies may be warranted to establish the relative risks and benefits of chronic corticosteroid treatment of patients with COPD.

Aged↗

The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease.

BACKGROUND: Transdermal nicotine therapy is widely used to aid smoking cessation, but there is uncertainty about its safety in patients with cardiac disease. METHODS: In a randomized, double-blind, placebo-controlled trial at 10 Veterans Affairs medical centers, we randomly assigned 584 outpatients (of whom 576 were men) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation. The subjects were monitored for a total of 14 weeks for the primary end points of the study (death, myocardial infarction, cardiac arrest, and admission to the hospital due to increased severity of angina, arrhythmia, or congestive heart failure); the secondary end points (admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease); any side effects of therapy; and abstinence from smoking. RESULTS: There were 48 primary and 78 secondary end points noted in a total of 95 subjects. At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group (difference, 2.5 percent; 95 percent confidence interval, -1.6 to 6.5 percent; P=0.23). In the nicotine group, 11.9 percent of the subjects had at least one of the secondary end points, as compared with 9.7 percent in the placebo group (difference, 2.2 percent; 95 percent confidence interval, -2.2 to 7.4 percent; P= 0.37). After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group, as compared with 9 percent in the placebo group (P=0.001), but after 24 weeks the abstinence rates were not significantly different (14 percent vs. 11 percent, P= 0.67). CONCLUSIONS: Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk outpatients with cardiac disease. However, the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time.

Administration, Cutaneous↗

Determinants of compliance with a national smoke-free hospital standard.

OBJECTIVE: To determine the extent of compliance with the new Joint Commission on Accreditation of Healthcare Organizations (JCAHO) standard requiring acute care hospitals to be smoke-free, and to identify predictors of adoption of smoke-free hospital policies. DESIGN: We conducted a survey of a national sample of acute care hospitals and developed a predictive model for implementation of smoke-free policies during multiple logistic regression. We examined numerous factors that might predict adoption of smoke-free policies, such as hospital characteristics, patient care services, and experience with smoke-free initiatives. SETTING AND PARTICIPANTS: A systematic 20% sample of JCAHO-accredited hospitals in the United States (n = 1278). Military, Department of Veterans Affairs, Indian Health Service, psychiatric, substance abuse treatment, and children's hospitals were excluded. MAIN OUTCOME MEASURE: Compliance with the JCAHO standard. RESULTS: The response rate was 85%. Six-five percent of hospitals were in compliance with the standard 16 months after it was introduced. Factors that were independently and positively associated with implementation of smoke-free policies were administrative support (odds ratio [OR], 7.82; 95% confidence interval [Cl], 2.05 to 29.65) and inpatient smoking cessation services (OR, 1.24; 95% Cl, 1.02 to 1.52). Factors negatively associated with implementation of smoke-free policy were the number of psychiatric treatment beds (OR, 0.57; 95% Cl, 0.14 to 0.81), number of substance abuse treatment beds (OR, 0.17; 95% Cl, 0.11 to 0.26), and presence of an active task force to address smoking policy (OR, 0.56; 95% Cl, 0.40 to 0.77). CONCLUSIONS: The majority of acute care hospitals are in compliance with the JCAHO national smoke-free policy initiative. The standard is well accepted by most patients and employees. It is critical to address the challenges presented by special populations, such as psychiatry patients, to accomplish the goal of completely smoke-free hospitals.

Accreditation↗

A strategy for improving the supervision and performance of moonlighting residents.

BACKGROUND: In 1990 the Ambulatory Care Service of the Ralph H. Johnson Department of Veterans Affairs Medical Center, affiliated with the Medical University of South Carolina College of Medicine, developed written clinical protocols for the management of patients with certain high-risk medical conditions. METHOD: Appropriateness of care was assessed by determining physician compliance to the protocols over a 24-month period (October 1990-September 1992). All physicians who did not comply received individualized feedback from the service chief. For the first 12 months, both staff physicians and moonlighting second- and third-year medical residents were assessed (a total of seven staff physicians and 20 residents participated in the study). For the second 12 months, only the residents were assessed. RESULTS: The moonlighting residents were notably less consistent than the staff physicians in protocol compliance (95-100% for the staff physicians; 78-100% for the moonlighters). Additional interventions were then implemented to improve the moonlighters' utilization of the protocols. Moonlighters' compliance over the subsequent 12 months was less variable (mean compliance of 92%, SD, 3%, the first year versus 95%, SD, 8%, the second year). CONCLUSION: The strategy seemed to improve the supervision and performance of the moonlighting residents and promoted consistent delivery of high-quality outpatient care.

Clinical Protocols↗

Stealth steroids.

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Adrenal Cortex Hormones↗

Beneficial effects of treatment of nicotine dependence during an inpatient substance abuse treatment program.

The Minneapolis Department of Veterans Affairs Medical Center began an intervention for tobacco use in its inpatient substance dependency treatment program on June 19, 1988, including an institutional smoke-free policy and a smoking cessation program. Sequential substance-dependent patients admitted before institution of the policy (n = 455) were compared with patients admitted after institution of the policy (n = 457). Patients completed self-administered questionnaires regarding smoking practices and attitudes. Seventy-six percent of patients were current cigarette smokers. Fifty-eight percent of patients after institution of the policy described themselves as "not smoking regularly," compared with 19% of patients admitted before the institution of the policy. Similar proportions of patients admitted before and after the institution of the policy believed that quitting smoking would threaten recovery. Forty-one percent of patients hospitalized after institution of the policy abstained from smoking for more than 1 week during their hospital stay. Rates of early termination of treatment did not change. We conclude that concurrent intervention for nicotine addiction during inpatient treatment of substance dependence is associated with a temporary reduction in smoking and increased motivation to quit smoking.

Adult↗

Smoking cessation in practice.

Smokers expect health care professionals to help them stop smoking. Brief physician advice effectively increases cessation rates and should be given in a supportive and positive atmosphere emphasizing short-term benefits of cessation. Accurate information on withdrawal, weight gain, and nicotine gum should be offered, and systematic follow-up should be provided.

Chewing Gum↗

Tapering of corticosteroid therapy following exacerbation of asthma. A randomized, double-blind, placebo-controlled trial.

Systemic corticosteroids are effective in the treatment of acute asthma, but the optimal schedule for steroid withdrawal following an asthma exacerbation has not been determined. This study was designed to test the hypothesis that tapering the corticosteroid dosage over a longer period of time reduces the number of reexacerbations. Non-steroid-dependent adult men hospitalized for asthma exacerbations during a one-year period (n = 43) were randomly assigned to corticosteroid tapering regimens of one or seven weeks, following an eight-day course of high-dose corticosteroid therapy. There were no significant differences between the long-taper and short-taper groups in rate of reexacerbation (41% vs 52%) or readmission (22% vs 21%) during the 12-week study period. Patients who did not have a reexacerbation during the 12 weeks were evaluated with spirometry, with no significant differences occurring between the two groups. More patients in the long-taper group reported corticosteroid side effects (41% vs 14%). Patients who required mechanical ventilation during the initial hospitalization (n = 7), or who reported more than two days of worse than usual dyspnea in the 12-week period (n = 20), had high rates of reexacerbation (86% and 80%, respectively). These results provide reasonable certainty (90%) that a long taper does not result in a large reduction (50% or more) in reexacerbations compared with a short taper. We conclude that the relapse rate is high in this population regardless of the corticosteroid tapering regimen used, and that a long taper does not appear to provide enough benefit to justify its routine use.

Adrenal Cortex Hormones↗