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Biomedical subjects

M S Simmons

Publications and source records attributed to M S Simmons.

At least 19 recordsLinked to original sources

Smoking reduction and the rate of decline in FEV(1): results from the Lung Health Study.

Previous findings from the Lung Health Study have shown that smoking cessation and sustained abstinence substantially reduce the rate of decline in forced expiratory volume (FEV(1)) among smokers with early chronic obstructive pulmonary disease (COPD) when compared with continuing smoking. Intermittent quitters demonstrated rates of FEV(1) decline intermediate between those of sustained quitters and continuing smokers. In this study, data from 1,980 participants were analysed from 10 centres of the Lung Health Study in the USA and Canada. All participants were smokers with mild-to-moderate COPD who were unable to quit smoking at any time during the 1st yr of the study. No linear relationship was found between reduction in cigarettes per day and changes in FEV(1) during the 1st yr of the study. However, examination of the data revealed that this relationship was nonlinear. Further analysis found that smokers who reduced their cigarettes per day to very low amounts had smaller declines in FEV(1) than those who did not. Reduction in cigarettes per day was associated with only minimal changes in the presence of chronic respiratory symptoms. In conclusion, compensatory changes in smoking behaviour may account for the limited and unpredictable impact of smoking reduction on lung function decline and symptom prevalence when compared with smoking cessation.

Administration, Inhalation↗

Unpredictability of deception in compliance with physician-prescribed bronchodilator inhaler use in a clinical trial.

OBJECTIVE: To identify subject characteristics that may be predictive of intentional dumping of metered-dose inhalers (MDIs) during a clinical trial. DESIGN: Nebulizer Chronologs (NCs; Medtrac Technologies; Lakewood, CO), which record the date and time of each MDI actuation, were attached to the MDIs of participants who were given a prescribed medication schedule to follow in a clinical trial. Participants were not informed of the function of the NC or that their medication use was being monitored. SETTING: The Lung Health Study, a 5-year clinical trial to evaluate the effect of intensive smoking cessation counseling and regular use of an inhaled bronchodilator on the progression of COPD. PARTICIPANTS: One hundred one smokers, 35 to 60 years of age, with mild to moderate airways obstruction enrolled in The Lung Health Study. MEASUREMENTS AND RESULTS: Thirty of these 101 participants (30%) actuated their inhalers > 100 times within a 3-h interval on at least one occasion during the first year of this 5-year trial. Only 1 of an additional 135 participants who had full foreknowledge of the MDI monitoring capability of the NC did so. Most of these dumping episodes occurred shortly before a clinic follow-up visit, suggesting an active attempt to hide noncompliance from the clinic staff. Whereas self-reported inhaler usage and canister weights were similar for the "dumpers" and "nondumpers," NC data indicated significantly lower compliance rates for dumpers (chi(2); p < 0.05). When demographic variables, treatment and clinic assignments, smoking status, pulmonary function test results, respiratory symptoms, and disease history of dumpers and nondumpers were analyzed, no predictors of dumping could be found. CONCLUSIONS: Deception among noncompliers occurs frequently in clinical trials, is often not revealed by the usual methods of monitoring, and cannot be predicted by data readily available in clinical trials.

Administration, Inhalation↗

Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue.

BACKGROUND: The gastrointestinal carcinoma antigen GA733 is a potential target for passive and active immunotherapy for patients with colorectal carcinoma. This antigen has been characterized previously as a homophilic adhesion (i.e., adhesion to self) protein, but the functional consequences of homophilic adhesion for tumor growth and invasion are unknown. The availability of a murine homologue of GA733, i.e., murine epithelial glycoprotein (mEGP), allows for functional analysis of cell adhesion as it relates to tumor growth and invasion, both in vitro and in vivo. METHODS: CT-26 murine colorectal carcinoma cells were transfected with complementary DNAs encoding either the human or the murine antigen. GA733- or mEGP-producing cells were evaluated for homophilic adhesion, growth on plastic surfaces, colony formation in soft agar, and invasion through a reconstructed basement membrane (Matrigel). mEGP-producing cells were also examined for their capacity to metastasize in mice. Reported P values are two-sided. RESULTS: Compared with control cells, mEGP-producing cells showed significantly lower growth rates, colony formation, and invasion through Matrigel in vitro (all P values <.05). Compared with vector-only transfected cells and parental cells, mEGP-producing cells showed a reduction in metastatic potential in syngeneic immunodeficient and immunocompetent mice (all P values <.05). In contrast to mEGP-transfected cells, GA733-transfected cells did not exhibit significantly reduced growth or colony formation in vitro (all P values >.05). However, GA733-transfected cells did show reduced invasion through Matrigel compared with vector-only transfected cells or parental cells (all P values <.05). CONCLUSION: The adhesion proteins GA733 and mEGP inhibit invasion of tumor cells.

Animals↗

Validation of the Doser, a new device for monitoring metered-dose inhaler use.

BACKGROUND: Electronic monitoring of medication use has proved valuable in both clinical and research settings. The Doser, a new and inexpensive commercially available device for monitoring metered-dose inhaler (MDI) use, displays 3 measures of daily use of an attached MDI: (1) the daily total of actuations, (2) the number of doses remaining in the MDI, and (3) the number of actuations on each of the preceding 30 days for later recall. OBJECTIVE: We sought to validate the accuracy of the Doser with several commonly prescribed MDIs. METHODS: In the laboratory, clinic personnel actuated an MDI with an attached Doser several times in succession on 3 consecutive days and recorded each of the 3 measures of MDI use (study 1). In study 2 clinic personnel carried an MDI and attached Doser with them for 4 weeks, actuating the MDI according to a prescribed protocol each morning and evening and again recording each of the 3 measures of daily use. In addition, during 2 weeks of study 2, a thermistor-based Nebulizer Chronolog was attached to the MDI to electronically record the date and time of each actuation. In study 3 clinic patients had both a Doser and Nebulizer Chronolog attached to their routinely used inhalers for 2 weeks and a Doser alone during a separate 2-week period. RESULTS: In study 1 agreement was 99% to 100% among the 3 Doser measures, and each measure agreed with actual use by self-report 97% of the time. In study 2 agreement among the 3 Doser measures of use ranged from 98% to 99%. Agreement between each of the 3 Doser measures and the Nebulizer Chronolog ranged from 90% to 93%. Agreement between each of the 3 Doser measures and actual use ranged from 96% to 97%, and the Nebulizer Chronolog agreed with actual use 93% of the time. In study 3 Doser and Nebulizer Chronolog agreement with patient self-report were 85% and 80%, respectively. Agreement between the Doser and Nebulizer Chronolog was 76%. Several failures of the thermistor-based Nebulizer Chronolog occurred, and occasional mechanical problems occurred with the Doser, primarily on particular types of MDI canisters. CONCLUSION: The Doser provides an accurate measure of MDI use with most commonly prescribed medications and may be useful for monitoring MDI use by investigators, clinicians, and patients.

Administration, Inhalation↗

Effects of varying marijuana potency on deposition of tar and delta9-THC in the lung during smoking.

To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired level of intoxication ("high") reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (deltaHR) and "high" during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger MJ preparation.

Adult↗

Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1 with age.

To assess the possible role of daily smoking of marijuana in the development of chronic obstructive pulmonary disease (COPD), we evaluated the effect of habitual use of marijuana with or without tobacco on the age-related change in lung function (measured as FEV1) in comparison with the effect of nonsmoking and regular tobacco smoking. A convenience sample of 394 healthy young Caucasian adults (68% men; age: 33 +/- 6 yr; mean +/- SD) including, at study entry, 131 heavy, habitual smokers of marijuana alone, 112 smokers of marijuana plus tobacco, 65 regular smokers of tobacco alone, and 86 nonsmokers of either substance were recruited from the greater Los Angeles community. FEV1 was measured in all 394 participants at study entry and in 255 subjects (65 %) on up to six additional occasions at intervals of > or = 1 yr (1.7 +/- 1.1 yr) over a period of 8 yr. Random-effects models were used to estimate mean rates of decline in FEV1 and to compare these rates between smoking groups. Although men showed a significant effect of tobacco on FEV1 decline (p < 0.05), in neither men nor women was marijuana smoking associated with greater declines in FEV1 than was nonsmoking, nor was an additive effect of marijuana and tobacco noted, or a significant relationship found between the number of marijuana cigarettes smoked per day and the rate of decline in FEV1. We conclude that regular tobacco, but not marijuana, smoking is associated with greater annual rates of decline in lung function than is nonsmoking. These findings do not support an association between regular marijuana smoking and chronic COPD but do not exclude the possibility of other adverse respiratory effects.

Adult↗

Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco.

BACKGROUND: Marijuana and alkaloidal cocaine ("crack") are the two most commonly smoked substances in the United States after tobacco. While regular tobacco smoking has been found to be associated with extensive microscopic alterations in bronchial mucosa, little information is available concerning the effect of crack cocaine and marijuana on tracheobronchial histopathology. STUDY OBJECTIVE: To determine the relative impact of smoked substances (cocaine, marijuana, and tobacco) alone and in combination on the histopathology of the tracheobronchial mucosa and to assess whether the effects of habitual smoking of two or more substances (cocaine, marijuana, and/or tobacco) are additive. DESIGN: Observational cohort study. SUBJECTS: Fifty-three nonsmoking control subjects (NS), 14 current, habitual smokers of crack cocaine only (CS), 40 current, regular smokers of marijuana only (MS), 31 regular smokers of tobacco only (TS), 16 current smokers of both cocaine and marijuana (CMS), 12 current smokers of both cocaine and tobacco (CTS), 44 current smokers of both marijuana and tobacco (MTS), and 31 current smokers of cocaine, marijuana, and tobacco (CMTS). METHODS: After preliminary screening evaluation, including a detailed respiratory and general health questionnaire and routine pulmonary function studies, subjects underwent fiberoptic bronchoscopy with endobronchial biopsies of the mucosa of the primary carina and randomly selected secondary or tertiary carinae. Biopsy specimens were processed for light microscopy, stained with hematoxylin-eosin or periodic acid-Schiff, and examined to assess epithelial, basement membrane, and submucosal alterations by one or two pathologists who were masked to the smoking status of the subject. RESULTS: Smokers of cocaine, marijuana, or tobacco alone all exhibited more frequent abnormalities than NS in 10 (CS) or all 11 (MS and TS) of the histopathologic features assessed. For most features, MS and TS showed significantly more frequent alterations than NS (p < or = 0.02), while CS showed significantly more frequent abnormalities than NS in only three features (p<0.05) and nearly significant differences from NS in two additional features (p < or = 0.09). Alterations were noted most frequently in CTS (six features) and MTS (three features), while abnormalities were relatively infrequent in CMS. For 10 features, MTS had more frequent alterations than MS and TS. With a single exception, CMTS did not show more frequent alterations than CTS or MTS. CONCLUSION: Marijuana and tobacco smoking each produces significant bronchial mucosal histopathology and the effects of marijuana and tobacco appear additive. Cocaine appears to lead to fewer significant bronchial mucosal alterations than marijuana or tobacco when smoked alone and does not add to the changes associated with marijuana. When smoked together with tobacco, however, cocaine appears to augment the bronchial injury caused by tobacco smoking.

Adult↗

Characteristics of smoked drug use among cocaine smokers.

The authors collected data by structured interview from a convenience sample of 228 physically healthy, largely (82%) treatment-seeking, cocaine smokers with minimal histories of other smoked (other than tobacco and marijuana) or injection drug use. The vast majority of subjects also smoked either marijuana only (17.5%), tobacco only (17%), or both (61%), with onset of such smoking almost always (97%) preceding the initiation of regular cocaine smoking. There were few significant differences in sociodemographic or cocaine use characteristics among the subgroups of subjects smoking either cocaine only or cocaine and marijuana and/or tobacco. More than one-third of marijuana smokers quit (45%) or decreased (38%) their use after starting regular cocaine smoking, whereas only 5% of tobacco smokers did so. These findings suggest that marijuana smoking is more influenced by regular cocaine smoking than is tobacco smoking.

Adult↗

Trends in compliance with bronchodilator inhaler use between follow-up visits in a clinical trial.

STUDY OBJECTIVE: To assess objectively measured, long-term trends in compliance with physician-prescribed metered-dose inhaler (MDI) use during a clinical trial. DESIGN: A prospective study. SETTING: The Lung Health Study, a 5-year clinical trial to determine the effect of special intervention with an intensive smoking cessation program and bronchodilator therapy in cigarette smokers 35 to 60 years of age with minimal to moderate airflow limitation due to COPD. PARTICIPANTS: Two hundred thirty-one participants who were issued an MDI with an attached Nebulizer Chronolog (NC) (Forefront Technologies Inc; Lakewood, Colo) which electronically records the date and time of each MDI actuation. One hundred two participants were not informed of the recording capabilities of the attached NC, while 129 participants were aware of the NC's monitoring function. INTERVENTION: Following an initial 12-week period of counseling, participants returned to the clinic every 4 months. MEASUREMENTS AND RESULTS: Analysis of the data from the NC collected over a period of 2 years indicates that compliance with the prescribed medication regimen was best immediately following each follow-up visit and gradually declined during the interval between follow-up visits. The level of compliance after each visit was lower for each successive follow-up. These trends could not be observed from self-report or weighting the medication canisters at follow-up visits. The participants who were informed of the NC's function and who were provided with detailed feedback about their inhaler use generally showed better compliance.

Adult↗

The relationship of tobacco and marijuana smoking characteristics.

In an ongoing study of the pulmonary effects of heavy, habitual marijuana smoking, detailed marijuana and tobacco smoking histories were obtained from 467 adult regular smokers of marijuana and/or tobacco. Frequency and cumulative amounts of tobacco and marijuana smoking were similar for smokers and nonsmokers of tobacco, except that pack-years and cigarettes/day at the time of the interview were both significantly less for tobacco smokers who also smoked marijuana compared those who did not. For all subjects who smoked both substances at any time, changes in tobacco and marijuana smoking amounts after commencement of regular smoking of the other substance were similar for tobacco and marijuana; the existing smoking habit decreased in approximately one third of the subjects and remained the same in slightly more than one half of the subjects. Of the dual smokers, 49% began smoking tobacco before marijuana, while 33% began smoking marijuana first; 85% of marijuana smokers who quit tobacco smoking did so after beginning regular marijuana smoking. Self-reported depth of inhalation and breath-holding time of marijuana smoke were similar for tobacco and non-tobacco smokers; smoking topography for tobacco was also comparable for smokers and non-smokers of marijuana.

Adult↗

Effects of smoking marijuana, tobacco or cocaine alone or in combination on DNA damage in human alveolar macrophages.

This study examined the role of marijuana smoking in the pathogenesis of human lung cancer by measuring DNA damage in alveolar macrophages (AM). The alkaline unwinding method was used to determine DNA single-strand breaks in AM lavaged from non-smokers [NS] and smokers of marijuana [MS], tobacco [TS] or cocaine [CS], either alone or in combination. DNA damage was related to superoxide anion (O2-) production by AM stimulated with phorbol myristate acetate (PMA) and to nitric oxide content of smoke using cellular nitrite (NO2-) concentrations. The percentage of double-stranded DNA present after alkaline unwinding was higher in AM of NS (41 +/- 5% [11]) and CS (41 +/- 4% [9]) versus that of MS (31 +/- 4% [8]), TS (35 +/- 3% [11]), MTS (26 +/- 4% [3]), and CTS (27 +/- 5%* [10]), mean +/- SEM [n], * = p < 0.1 vs. NS). PMA stimulated O2- production by AM from NS and CS was lower than that of other smokers, but the differences were not significant. O2- release, however, had an inverse correlation with DNA single-strand breaks (r = -0.38, p = 0.009). Nitrite content of AM from NS and CS was less than that of other smokers' cells (p < 0.1 for TS & CTS vs. NS), but DNA damage had no relationship to NO2- concentration. We conclude that AM recovered from MS, either alone or in combination with tobacco smoking, show a trend towards DNA damage. Studies utilizing a larger population should verify our findings and further define its relationship to enhanced oxidant production by macrophages.

Cocaine↗

Interrelationships between pulmonary and extrapulmonary involvement in systemic sclerosis. A longitudinal analysis.

PURPOSE: (1) To evaluate the relationship between the degree of pulmonary involvement by systemic sclerosis (SSc) and the degree of involvement of other organ systems by SSc at baseline. (2) To assess the degree of impairment in lung function at presentation and the annual rate of change in lung function to predict the rate of progression of involvement of extrapulmonary organ systems by SSc over time. (3) To determine whether survival in patients with SSc can be predicted from the degree of lung function impairment at baseline or from the annual rate of change in lung function. METHODS: Semiquantitative indices of pulmonary and extrapulmonary involvement and pulmonary function tests (PFTs) were analyzed and compared in 62 nonsmoking scleroderma patients enrolled in a 3-year prospective drug trial, vs 47 in a "study group" who underwent serial evaluation. The other 16 "early withdrawals" withdrew prior to the second evaluation. The indices of organ system involvement were based on clinical, physiologic, and biochemical findings as previously published. The PFTs included total lung capacity (TLC), forced vital capacity (FVC), FEV1, and single-breath diffusing capacity for carbon monoxide (Dsb). Annualized rates of change in PFTs and indices of extrapulmonary involvement were calculated for each subject from data collected on at least 2 separate occasions at least 6 months apart. Spearman rank correlations were performed between individual baseline PFTs (expressed as percent predicted) and (a) indices of extrapulmonary involvement at baseline, (b) annualized rates of change in PFTs, and (c) annualized rates of change in indices of extrapulmonary involvement. Correlations also were performed between the rate of change in each lung function measure and rates of change in indices of extrapulmonary involvement. The ability of PFTs at baseline and their rates of change to predict cumulative survival was assessed by Cox stepwise regression. RESULTS: The degree of impairment in baseline PFTs was related to involvement of the right side of the heart but not to other extrapulmonary system involvement. Baseline PFTs were not related to the rate of subsequent decline of lung function or worsening of extrapulmonary organ system involvement. Subsequent annual rates of decline in lung function were related to worsening skin and upper gastrointestinal involvement. Cumulative survival may be related to the rate of decline in DCO, TLC, and FVC, but was not predicted by impairment in any measure of lung function. CONCLUSION: With the exception of involvement of the right side of the heart consistent with cor pulmonale, the degree of pulmonary involvement by SSc was not correlated with the extent of extrapulmonary involvement. The degree of pulmonary involvement by SSc did not predict subsequent worsening of either pulmonary or extrapulmonary involvement. Worsening pulmonary involvement by SSc, in general, does not correlate with worsening involvement of extrapulmonary organ systems, except for the skin and upper gastrointestinal tract. A rapid decline in DCO or lung volumes may predict poor survival.

Bone Diseases↗

Lymphocytic subpopulation profiles in bronchoalveolar lavage fluid and peripheral blood from tobacco and marijuana smokers.

The effect of heavy, habitual marijuana use compared with tobacco smoking on the composition of bronchoalveolar and peripheral blood lymphocytic phenotypes was examined. Bronchoalveolar lavage (BAL) and peripheral blood (PB) samples were taken from 14 nonsmokers (NS), 14 tobacco smokers (TS), 19 heavy, habitual marijuana smokers (MS), and 9 marijuana and tobacco smokers (MTS). In BAL fluid, marijuana use was associated with significantly higher alveolar macrophage concentrations, whereas tobacco smoking was associated with significantly higher alveolar macrophage, as well as higher bronchoalveolar lymphocyte and neutrophil concentrations. The bronchoalveolar T-lymphocytic phenotypic profiles of marijuana users differed from those of tobacco smokers. Tobacco, not marijuana, was found to have a significant effect toward lower percentages of bronchoalveolar CD4 cells, toward higher concentrations of bronchoalveolar CD8 cells, and toward lower bronchoalveolar CD4:CD8 ratios. Marijuana use had a significant effect toward lower percentages of bronchoalveolar CD8 cells. In peripheral blood, marijuana, but not tobacco, use was associated with significantly higher percentages of CD4 cells, lower percentages of CD8 cells, and higher CD4:CD8 ratios. These findings suggest that tobacco and marijuana have effects on bronchoalveolar and peripheral blood immunoregulatory T-lymphocytic subpopulations that differ in type or magnitude.

Adult↗

Subcapital fractures of the femoral neck: prevalence and cause of radiographic appearance simulating pathologic fracture.

OBJECTIVE: Subcapital fractures of the femoral neck are common in elderly persons who have osteoporosis. Occasionally, radiographs of the hip in these patients show a radiolucency in the superolateral, subcapital region of the femoral neck that mimics the features of a pathologic fracture. Our purpose was to determine the prevalence of this finding and the anatomic variations of fracture alignment that cause this appearance. MATERIALS AND METHODS: All subcapital nonpathologic hip fractures (n = 111) that occurred at our institution during a 5-year period were reviewed. Radiographs were available in 100 of these cases. Review of intraoperative biopsy specimens, available in 69 patients, revealed no evidence of neoplasm in any case. In the other patients, follow-up radiographs, clinical evaluation, and pathology reports were used to exclude neoplastic involvement. Preoperative radiographs were analyzed for the presence of findings suggesting a pathologic fracture. Fracture configuration was classified by using the Garden staging system. Cadaveric femurs (n = 6) were fractured and studied radiographically. RESULTS: Seventeen (17%) of the 100 subcapital fractures had a radiographic appearance similar to that of a pathologic fracture. This finding occurred only with Garden stage III fractures (n = 7, 32% of Garden stage III fractures) or Garden stage IV fractures (n = 10, 24% of Garden stage IV fractures). Study of the cadaveric femoral specimens showed that the radiographic appearance simulating a pathologic fracture was primarily caused by external rotation of the distal fracture fragment and was accentuated by displacement between fracture fragments. CONCLUSION: The radiographic appearance of subcapital fractures of the femoral neck unrelated to neoplasm is often similar to that of pathologic fractures. This appearance is caused primarily by rotation of the fracture fragments, and the finding is accentuated by displacement. Recognition of the appearance of subcapital hip fractures mimicking pathologic fractures and knowledge of the cause of this finding are important for prescribing appropriate treatment.

Adolescent↗

Effects of smoked substance abuse on nonspecific airway hyperresponsiveness.

Previous data suggest that regular tobacco smoking may lead to nonspecific airway hyperresponsiveness (AHR) independent of airway obstruction, possibly because of effects on bronchial inflammation or mucosal permeability. Little is known concerning the effects on AHR of other widely smoked substances besides tobacco such as marijuana or cocaine. The smoke of both marijuana and cocaine contains respiratory irritants that elicit cough and produce abnormalities in airway dynamics and bronchial mucosal histopathology in habitual smokers. Therefore, regular smoking of one or both of these illicit substances could cause AHR or augment the AHR associated with tobacco smoking. The present study examined the influence of habitual smoking of marijuana, cocaine, and/or tobacco on nonspecific AHR in 542 (456 male) healthy participants (mean age, 34.8 +/- 6.8 SD yr) in an ongoing cohort study of the pulmonary effects of habitual smoking of illicit substances. Subjects with a history of intravenous drug abuse, significant occupational exposures, asthma, or recent upper respiratory tract infection were excluded. Inhalation challenge studies were performed using solutions of diluent and methacholine chloride (1.25 to 25 mg/ml) aerosolized by a DeVilbiss no. 646 nebulizer attached to a breath-activated dosimeter inhaled by three to five inspiratory capacity breaths. Positive responses to methacholine were defined by > or = 20% or > or = 10% declines in FEV1 from the postdiluent control value after inhalation of each concentration of methacholine. Participants were categorized by smoking status (nonsmoking and smoking of marijuana, cocaine, and/or tobacco alone and in combination); most analyses were performed in men and women separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improving inhaler adherence in a clinical trial through the use of the nebulizer chronolog.

This study examined whether utilizing an electronic medication monitor (Nebulizer Chronolog) to provide participants with detailed feedback on their metered-dose inhaler (ipratropium bromide or placebo) usage patterns would result in closer adherence to the prescribed regimen of two inhalations three times daily compared to a control group not receiving feedback. Adherence was also measured by canister weighing and self-report. Two-hundred fifty-one consecutive special intervention participants from the University of California, Los Angeles, and Johns Hopkins University centers of a National Heart, Lung, and Blood Institute-sponsored clinical trial were enrolled in this ancillary study. Compared to controls, feedback participants at the 4-month follow-up adhered more closely to the prescribed three sets per day (mean 1.95 vs 1.65) and used the prescribed two actuations in a greater percentage of sets (80 percent vs 60.3 percent). These results indicate that electronic monitoring of metered-dose inhaler use with a Nebulizer Chronolog in a clinical trial not only provides a more accurate assessment of adherence to prescribed inhaler use, but also enhances adherence when participants are given feedback of the monitoring results.

Adult↗

Auricular electrical stimulation and dental pain threshold.

A modified double-blind evaluation of naloxone reversibility of dental analgesia produced by auricular electrical stimulation (AES) was examined in 40 subjects assigned randomly to one of four groups: AES followed by saline (AS), AES followed by naloxone (AN), placebo AES followed by saline (PS), and placebo AES followed by naloxone (PN). Dental pain threshold was tested using a hand-held dental pulp tester. A second investigator administered the true or placebo AES using an electrical stimulator. A third investigator injected intravenously saline or naloxone. The subjects and investigators 1 and 3 were blind to all treatment conditions. A repeated measures analysis of variance revealed a significant difference among the four groups. The AES groups exhibited a statistically significant 18% elevation of pain threshold, whereas the two placebo stimulation groups (PS and PN) remained essentially unchanged. The mean pain threshold increased to more than 23% for group AS, but fell to less than 12% for the subjects in group AN, who were given naloxone. These findings indicate a small but significant elevation of pain threshold by AES, an effect partially blocked by naloxone, suggesting an endogenous opioid system as one mechanism for AES analgesia.

Acupuncture Analgesia↗

Pulmonary status of habitual cocaine smokers.

We determined the prevalence of respiratory symptoms and lung dysfunction in a large sample of habitual smokers of freebase cocaine ("crack") alone and in combination with tobacco and/or marijuana. In addition, we compared these findings with those in an age- and race-matched sample of nonusers of crack who did or did not smoke tobacco and/or marijuana. A detailed respiratory and drug use questionnaire and a battery of lung function tests were administered to (1) a convenience sample of 202 habitual smokers of cocaine (cases) who denied intravenous drug abuse and (2) a reference sample of 99 nonusers of cocaine (control subjects). The cocaine smokers (85% black) included the following: 68 never-smokers of marijuana, of whom 43 currently smoked tobacco and 25 did not, and 134 ever-smokers of marijuana (42 current and 92 former), of whom 92 currently smoked tobacco and 42 did not. The control subjects (96% black) included the following: 69 never-smokers of marijuana, of whom 26 currently smoked tobacco and 43 did not, and 30 ever-smokers of marijuana (18 current and 12 former), of whom 21 currently smoked tobacco and 9 did not. Cases smoked an average of 6.5 g cocaine per week for a mean of 53 months. The median time of the most recent use of crack prior to study was 19 days (range less than 1 to 180 days). After controlling for the use of other smoked substances, frequent crack use was associated with: (1) a high prevalence of at least occasional occurrences of acute cardiorespiratory symptoms within 1 to 12 h after smoking cocaine (cough productive of black sputum [43.7%], hemoptysis [5.7%], chest pain [38.5%], usually worse with deep breathing, and cardiac palpitations [52.6%]) and (2) a mild but significant impairment in the diffusing capacity of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗