Introduction: the ethics of publishing research sponsored by the tobacco industry in ATS/ALA journals.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M L Osborne.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Little information is available on the utility of spending resources to recruit hard-to-reach subjects. In particular, the compliance of such subjects with study protocols and visit schedules has not been documented. We present recruitment data from a two-phase survey of asthma prevalence in which a subset of respondents to a brief screening survey was recruited to attend a 90-min clinic visit. Although 39% of phase I subjects responding to initial contact attempts participated in the second phase of the study, this dropped to 12% among those responding to the sixth contact attempt (a phone follow-up). In studies in which the representatives of the sample is not of paramount importance, we see little benefit in aggressively seeking to recruit hard-to-reach subjects.
Mortality and health care utilization (HCU) statistics for asthma reflect both the acute and chronic aspects of this condition. We present a conceptual model that incorporates this dichotomy and also distinguishes between measures of disease occurrence (e.g., incidence and prevalence) and measures of disease management. We also discuss the use of mortality and HCU statistics in the literature, review their limitations and advantages, and make a number of general recommendations for their use.
Explore the source record for details and available documents.
An analogue task of instrumental and hostile aggression during a competitive game, modified to minimize overlap between aggressive responses, was evaluated in 8- to 14-year-old clinically referred boys (n = 33). Postgame interviews indicated that the hostile response, an aversive noise, was perceived by over 80% of subjects as hostile and not instrumental. In contrast, the instrumental response, blocking the opponent's game, was perceived about equally as having instrumental and hostile functions. The hostile aggressive response was uniquely correlated with continuous performance task impulsive commission errors (r = .51), which supported the theoretical relation of hostile aggression to poor impulse control. These results suggest that instrumental and hostile aggression can be distinguished and when precisely defined are distinct in theoretically important ways.
The effectiveness of curricula designed to enhance a child's understanding of AIDS may hinge partially upon incorporating information adjusted to the child's developmental status. Accordingly, we examined the developmental progression of children's understanding of illness transmission in general and AIDS in particular, as well as explored the relation between a child's knowledge of AIDS and his/her attitudes toward persons with AIDS. Knowledge of AIDS was manipulated through use of a brief educational intervention. Results support a developmental progression in knowledge about AIDS that is consistent with progressions related to illnesses in general. Knowledge enhancement was associated with positive changes in attitude.
Studies reporting increased asthma hospitalizations and mortality in the United States and abroad have heightened concern about the changing epidemiology of asthma. We studied 20-yr patterns of acute asthma care occurring at two large community hospitals among members of a large health maintenance organization. The presentation focuses on the conceptualization and operationalization of an "episode" of asthma care, defined as a collection of encounters (emergency room visits, urgency care visits, and hospital admissions) that cluster in time, as well as on changes in episode rates over time. We found a statistically significant increase in asthma episodes among boys younger than 5 yr of age that continued unabated from 1967 to 1987 despite a drop in asthma hospitalization rates starting in 1985. We hypothesize that this difference may reflect a change in emergency room management practices and not a true change in the underlying epidemiology of asthma. The concept of an episode of acute asthma care has not been studied in the literature and represents a potentially useful methodologic innovation. Particularly in the context of managed health care systems, studies of such episodes may be less sensitive than studies of hospital admissions to changes in the organization and delivery of acute asthma care, and thus may be better suited for studying changes in the epidemiology of asthma.
Reported asthma morbidity and mortality are increasing in the U.S. We addressed one explanation, that the accuracy of the diagnosis of asthma is changing. The diagnosis of asthma was evaluated in 320 inpatient and outpatient records bearing the diagnosis of asthma for the periods 1970-73 and 1980-83 in a health maintenance organization (HMO). We determined whether or not our agreement with the chart diagnosis was a function of: sex, period of treatment, inpatient vs outpatient setting, whether or not asthma was the primary or secondary diagnosis, and patient age. The standard of comparison was an expert panel review in which asthma was divided into six categories. In both inpatient (97%) and outpatient settings (94%), the majority of charts examined exhibited a clinical picture consistent with asthma. The rate of the narrowly defined "definite asthma" category varied with respect to age, with the highest proportion in the under 20-year age group (74%) and the lowest (46%) in the over 60 age groups, probably because older individuals often have coexisting smoking related diseases. The increase in "definite asthma" among outpatients from the 1970s to the 1980s likely reflects increasing chart documentation among physicians, illustrating the need for clear, consistent chart documentation of signs and symptoms of asthma.
We examined trends in hospitalizations for asthma from 1967 to 1987 among members of a large health maintenance organization. During this time asthma discharges increased significantly among children, and especially among boys under the age of 5 years. Ninety-five percent of the increase in discharges among boys was explained by a corresponding increase in the number of boys who were hospitalized. Increased readmissions did not account for the rise. Changes in the International Classification of Diseases coding of asthma and diagnostic shift by physicians accounted for only part of the increase. A decline in hospitalizations since 1984 may reflect changes in the management of asthma in the emergency room and not a decline in severe asthma episodes.
Explore the source record for details and available documents.
The acute effects of cigarette smoking on the pulmonary vasculature are poorly understood--both vasodilatory and vasoconstrictive effects have been described. To investigate the mechanisms involved, strips of pig intrapulmonary arteries with and without intact endothelium were exposed to an extract of cigarette smoke made by bubbling smoke through phosphate-buffered saline. After contraction with norepinephrine (2.5 X 10(-7) M), smoke extract (concentration range 0.001 to 0.5%) caused a biphasic response in strips with intact endothelium--relaxation at lower concentrations and contraction at higher concentrations. Both relaxation and contraction responses were absent in strips without endothelium. Blockade of muscarinic, beta adrenergic, serotonergic, and histamine type 1 and 2 receptors did not alter the effects. Indomethacin (5 X 10(-6) M) or acetylsalicylic acid (10(-4) M) blocked the relaxation but not contraction effects of smoke extract, suggesting that relaxation was due to cyclooxygenase products of arachidonic acid. Nicotine caused endothelium-dependent contraction of intrapulmonary arteries and the contractile effects of both nicotine and smoke extract were blocked by hexamethonium (10(-6) M). However, the contractile effects of cigarette smoke components are more potent than those of nicotine. These findings help explain previously described acute effects of smoking on the pulmonary vasculature and provide insight into the mechanisms involved.
Studies of rodent mast cells have demonstrated that subpopulations differ in regard to their response to inhibitors of histamine release. To determine whether such compounds have different effects on mast cells from Basenji-Greyhound (BG) dogs with airway hyperreactivity and from mongrel dogs, we investigated the effect of cromolyn sodium, nedocromil sodium, theophylline, and quercetin on calcium ionophore A23187-induced histamine release from mast cells recovered by bronchoalveolar lavage. Mast cells recovered from BG and mongrel dogs were similar in respect to morphology and spontaneous and calcium ionophore-induce histamine release. Histamine release from mast cells from both BG and mongrel dogs was inhibited by quercetin (10(-4) M) and nedocromil sodium (5 x 10(-5) M). In contrast, only the histamine release from mast cells recovered from mongrel dogs was inhibited by cromolyn sodium (10(-4) M) and theophylline (5 x 10(-3) M). Thus, mast cells that are similar in regard to morphology and response to histamine liberators may differ in their response to inhibitors of histamine release.
Mast cells are believed to play an important role in the pathogenesis of asthma, and several investigators have suggested that increased numbers of mast cells in the airway lumen or increased releasability of histamine from these mast cells are responsible for chronic airway hyperreactivity. To determine whether mast cells in the lumen of the airways of hyperreactive Basenji greyhound (BG) dogs differ from those of mongrel dogs with normal airway reactivity, we investigated the morphologic and functional characteristics of mast cells recovered by bronchoalveolar lavage (BAL). BAL was performed in five BG and five mongrel dogs with 900 cc of a buffered salt solution. The recovered lavage fluid contained 115 +/- 19 X 10(6) and 116 +/- 14 X 10(6) (mean +/- SEM) cells in BG and mongrel dogs, respectively. The proportion of all mast cells within the recovered cell population as enumerated after fixation with basic lead acetate and staining with alcian blue was not different in BG and mongrel dogs and averaged 0.80 +/- 0.07% and 1.1 +/- 0.3%, respectively. Typical mast cells as identified after fixation with paraformaldehyde were rare; however, significantly more mast cells were found in mongrel (0.03 +/- 0.009%) than in BG dogs (0.004 +/- 0.002%; p less than 0.02). Mast cells recovered from BG and mongrel dogs were not different in their low spontaneous histamine release (2.0 +/- 0.5% and 2.9 +/- 0.8%), their histamine release on stimulation with the calcium ionophore A23187 (maximum release 44.8 +/- 5.7% and 41.5 +/- 3.9%), and their lack of response to compound 48/80 (maximum release 5.8 +/- 1.8% and 6.1 +/- 6.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
An abnormally large number of mast cells in the airway lumen may be an important factor in the pathogenesis of bronchial hyperreactivity. However, it is unclear just how many mast cells are present in the lumen of normal or hyperreactive airways, in part because of differences in the histochemical techniques that have been used to identify mast cells and questions about the heterogeneity of mast cells. The present study was done (1) to compare the effectiveness of six techniques in the identification of mast cells obtained from dogs by bronchoalveolar lavage (BAL), (2) to compare the mast cells in the airways of normal mongrel dogs with those from a breed of dog (Basenji-Greyhound) known to have bronchial hyperreactivity, and (3) to determine whether the two-type histochemical classification used for rodent mast cells (formaldehyde-resistant or typical and formaldehyde-sensitive or atypical) applies meaningfully to the mast cells in BAL fluid from dogs. Cells obtained by BAL were fixed with Mota's basic lead acetate or formaldehyde. Mast cells were identified by metachromatic staining with toluidine blue or methylene blue, staining of highly sulfated proteoglycans with Alcian blue or berberine sulfate, and a histochemical reaction for chloroacetate esterase (mast cell chymase). After Mota's fixation, the methods were relatively similar in their effectiveness in determining the number of mast cells in lavage fluid from the mongrel dogs, in that all of the values fell within a narrow range: 0.53 to 0.96% of the total number of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.
To determine whether thromboxane A2 released from aggregating platelets increases the contractile response of airway smooth muscle to cholinergic nerve stimulation and, if so, what the mechanism of action is, we studied in vitro bronchial segments from dogs under isometric conditions. The contractile responses to electrical field stimulation at 30 s and 1 min after the addition of autologous platelets were increased by 11.1 +/- 3.2 (SD) and 20.7 +/- 5.4%, respectively, and were accompanied by the release of thromboxane A2. These effects were inhibited either by pretreatment of platelets with indomethacin or by addition of the thromboxane A2 receptor antagonist SQ 29548. Likewise, the thromboxane A2 mimetic U 46619, in subthreshold doses (i.e., insufficient to increase base-line tension), increased electrical field stimulation-induced contraction by 18.7 +/- 4.8%. The increase was greater in the presence of a concentration of physostigmine that did not cause spontaneous contraction and was blocked by SQ 29548 but not by hexamethonium or by phentolamine. Methacholine-induced contractions were unaffected by U 46619. These results indicate that aggregating platelets, by releasing thromboxane A2, increase the airway contractile response to neural stimulation probably by the accelerated release of acetylcholine.
Because basenji-greyhound dogs have greater bronchial reactivity to a range of inhaled stimuli than mongrel dogs do, and because bronchial hyperreactivity to nonspecific stimuli is characteristic of asthma, we asked whether basenji-greyhound dogs have greater bronchial reactivity to hypotonic and isotonic aerosols than mongrel dogs do. We assessed bronchial reactivity by measuring both the total pulmonary resistance and the bronchial response to an acetylcholine aerosol, before and after delivery of hypotonic and isotonic aerosols. Bronchial reactivity as measured by a change in total pulmonary resistance increased 9-fold after delivery of hypotonic and 5-fold after delivery of isotonic aerosols in 5 anesthetized basenji-greyhound dogs, but not in 3 similarly challenged mongrel dogs (p less than 0.01). Bronchial reactivity as measured by an increased bronchial response to acetylcholine aerosol increased 3-fold in basenji-greyhound dogs but not in mongrel dogs. Thus, hypotonic and isotonic aerosols increase bronchial reactivity in basenji-greyhound dogs. We also asked whether vagal or nonvagal pathways are involved in the increase in total pulmonary resistance induced by a hypotonic aerosol. Both vagal and nonvagal pathways appear to be involved, since blockade of the vagal pathway by intravenously administered atropine only partially inhibited the bronchoconstriction induced by a hypotonic aerosol (54%). Disodium cromoglycate, which inhibits vagal and nonvagal pathways, partially inhibited the bronchoconstriction (57%), but even in combination with atropine, did not completely inhibit it (68%). Our observations in basenji-greyhound dogs are similar to results in asthmatic subjects, suggesting that basenji-greyhound dogs are useful experimental animals in which to study the mechanisms by which hypotonic and isotonic aerosols increase bronchial reactivity.