Biomedical subjects
Publications and source records attributed to M J Tobin.
The purpose of this communication is to review obstructive and central breathing abnormalities that may occur during sleep, such as obstructive sleep apnea, and Cheyne-Stokes respiration. Emphasis is placed on noninvasive monitoring of the breathing pattern and intrapleural pressure swings by respiratory and surface inductive plethysmography, respectively, which establish the diagnosis of these abnormal breathing patterns.
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Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia. We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic stenosis, and three patients had a prosthetic valve. We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features. Diagnosis was established by finding and elevated complement-fixing antibody to Phase I C. burnetii antigen. Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as as the sole antibiotic agent. Optimal duration of therapy is unknown. In one patient, relapse followed when treatment was stopped after 18 months. Valve replacement was necessary in five patients, because of hemodynamic problems. Five patients died, and the means survival is 36 months with a range of five to 66 months. We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.
In a multicentred survey of alpha 1-antitrypsin deficiency, radiological details have been obtained in 165 subjects homozygous for Pi type Z and in 23 subjects heterozygous for type SZ. Eight-five per cent of all type Z subjects had radiological evidence of pulmonary emphysema which was commoner in smokers than in those who had never smoked and which predominantly affected the lower zones of the lungs; 66% of the type Z subjects identified through family studies also had emphysema. Emphysema in subjects of Pi type SZ was limited to those who had smoked; this phenotype may not carry a specific risk of emphysema.
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In patients with radiological evidence of pulmonary emphysema the bronchodilator drugs fenoterol and ipratropium bromide produced a considerable increase in vital capacity and reduction in residual volume. The response to fenoterol was virtually complete 15 minutes after administration, but after ipratropium bromide vital capacity was still increasing at 60 minutes. The change in vital capacity was slightly greater with a combination of the two drugs than with either used alone. Changes in FEV1 and peak flow rate were small.
We developed a nonobtrusive technique to measure the volume puffed during smoking. An inductive plethysmographic coli placed around the cheeks was calibrated by coaching the subject to take graded puffs from an unlit cigarette connected in series to a 2-L Krogh spirometer. The device had a linear volume response that was unaltered by smoking filtered or unfiltered cigarettes or by the length of the cigarette. It remained calibrated after smoking 4 cigarettes over 150 min. Ten subjects smoked a high tar content (HTC) and a low tar content (LTC) cigarette, each with and without a cigarette holder. The mean puff volume from LTC of 52 +/- 15 ml was significantly higher than HTC of 39 +/- 10 ml (p less than 0.001). The number of puffs per cigarette (8.4 +/- 2.1 for LTC, 8.3 +/- 2.0 for HTC), the volume of inhaled (841 +/- 517 ml for LTC and 748 +/- 323 ml for HTC), and the duration of inhalation and associated breathhold (5.5 +/- 2.6 s for LTC and 5.6 +/- 2.4 s for HTC) as measured by respiratory inductive plethysmography were comparable. The perception of intensity of inhalation by the subjects bore little relationship to the objective measurement. A cigarette holder increased the number of puffs per cigarette to 12.6 +/- 4.8 for LTC (p less than 0.02) and to 11.9 +/- 3.6 for HTC (p less than 0.01 and increased the puff volume for HTC to 50 +/- 12 ml (p less than 0.01) and the duration of inhalation to 6.6 +/- 2.5 s for LTC (p less than 0.005). These results show that (1) smokers switched acutely from HTC to LTC draw larger puffs from LTC thereby possibly circumventing the perceived benefits of smoking LTC, (2) cigarette holders modify smoking pattern and hence if used with an incorporated flowmeter to monitor the natural pattern of smoking might give spurious information.
Response to bronchodilator aerosols delivered by metered dose inhalers (MDI) depends in part upon the amount of drug depositing on the airways. Ideally, the MDI should be actuated during a slow deep inhalation followed by a breathholding pause, an impossible maneuver for many patients. We developed a new reservoir aerosol delivery system (RADS) consisting of a 700-ml collapsible bag in which aerosol could be injected. The mouthpiece-canister was filtered with a reed that vibrated at inspiratory flows greater than 0.3 L/s to produce a noise. Patients were instructed to keep inhalation silent while breathing from RADS. One puff of metaproterenol (650 microgram) administered via RADS (with one breath rebreathed) was compared with one puff of metaproterenol (650 micrograms) from usual MDI using serial measurements of body plethysmography and spirometry. Respiratory inductive plethysmography measured the point of MDI actuation, volume of inhalation, inspiratory flow, and breathholding pause. Ten patients with chronic airflow limitation caused by asthma or chronic bronchitis were given typed instructions on MDI usage and trained shortly before the study. Metaproterenol via RADS produced significantly greater maximal increase in SGaw (195 +/- 52% SE) compared with metaproterenol via conventional MDI (101 +/- 24%, p less than 0.003). Bronchodilator response in 4 patients unable to coordinate actuation of the MDI with inspiration was significantly less than in 6 patients with good MDI technique (p less than 0.005). The mean flow rates were 0.54 +/- 0.16 L/s during inhalation of metaproterenol compared with 0.19 +/- 0.02 L/s and 0.24 +/- 0.03 L/s during the first and second inhalations, respectively, using RADS. This reservoir aerosol delivery system, which was well accepted by the patients, promotes more effective bronchodilation than the conventional metered dose inhaler.
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The pattern of cigarette smoke inhalation was studied in 19 smokers with respiratory inductive plethysmography, a reliable unobtrusive ventilatory monitoring device. The mean volumes inhaled varied widely from 0.27 to 1.97 L, with a group mean (+/- SD) of 0.79 +/- 0.45 L. Mean duration of smoke inhalation varied from 2.0 to 6.8 seconds, with a group mean of 4.5 +/- 1.3 seconds. An inhalation fraction was derived by dividing the inhaled volume by the vital capacity; this fraction varied from 0.09 to 0.47, with a group mean of 0.20 +/- 0.10. Subjects rated the depth that they inhaled smoke into their lungs on a visual analog scale and on a grading system. Correlation between visual analog scale and inhalation fraction was poor (r = -0.15). Also, inhalation fraction bore no relationship to smoking pack-years or current pulmonary function. The smokers' inaccurate assessment of their inhalation pattern may help to explain the poor correlation reported between cigarette smoke inhalation and severity of obstructive lung disease.
Extensive research, stimulated by the recognition of an association between alpha 1-antitrypsin (alpha 1-AT) deficiency and emphysema, has greatly advanced our understanding of emphysema in general. In this article, we review the literature concerning the basic defect, inheritance, pathogenesis of lung disease, clinical, physiologic, and roentgenographic findings in patients with severe (Pi SZ) deficiency of alpha 1-AT. Data obtained in relatives with alpha 1-AT deficiency, who have not been seen by a physician, should more truly reflect the risk of having lung disease. These studies confirm the increased risk of developing lung disease in cigarette smokers. The implications of the finding that subjects with Pi SZ are probably not at an increased risk of lung disease is discussed with regards to replacement therapy. The natural history of unselected subjects with alpha 1-AT deficiency remains unknown.
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We studied 25 adolescent and adult patients with cystic fibrosis (CF) and 25 control subjects to determine if the prevalence of atopy and bronchial hyperreactivity was increased in this disease. Results showed that atopic symptoms, as defined by history, were more frequently present in the CF patients. Prick testing of the skin produced positive reactions in 88% of the CF group and 36% of the control subjects (p less than 0.001), and the mean number of reactions per subject was significantly higher in the former group (p less than 0.001); reactions to fungal antigens were strikingly positive in the CF group. The CF patients had a significantly higher mean serum IgG4 (p less than 0.001), IgE (p less than 0.01), and higher mean eosinophil count (p less than 0.05). Clear-cut bronchial hyperreactivity was demonstrated in the CF group compared with control subjects. Bronchial provocation with 400 micrograms of histamine led to a greater than 15% fall in the preinhalation FEV1 in 35% of the CF subjects compared with 4% of the control group, with a mean percentage fall of 15% and 3% respectively (p less than 0.001). In the CF group a greater than 15% rise in PEFR occurred in 32% after inhalation of the parasympatholytic, ipratropium bromide (54 micrograms), and in 27% after inhalation of the sympathomimetic, fenoterol (400 micrograms). No correlation was found between bronchial reactivity and atopic status, HLA phenotype pattern, or disease severity. The cause of the increased prevalence of atopy and bronchial reactivity in CF patients remains unknown. However, it is clear that a trial of bronchodilator therapy is warranted in adolescents and young adults with CF.
The benefits of pyridoxine in the suppression of lactation were assessed in a double blind controlled trial on 175 puerperal women. No significant differences were demonstrated between pyridoxine and the placebo whether assessed by subjective discomfort or by the persistence of lactation.
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