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Biomedical subjects

R D Fairshter

Publications and source records attributed to R D Fairshter.

At least 55 records · Page 3Linked to original sources

Site and duration of bronchodilation in asthmatic patients after oral administration of terbutaline.

We compared pulmonary function in 15 asthmatic subjects before and after ingestion of 5 mg terbutaline and placebo. Measurements of maximal expiratory flow (VEmax), density-dependence of VEmax (delta VEmax50), volume of isoflow (Viso V), residual volume (RV), and closing capacity (CC) were performed before and 15, 135, 255, and 375 minutes after both treatments. After placebo VEmax improved mildly (P < 0.05) but no significant changes occurred in delta VEmax50, VisoV, RV, or CC. After terbutaline, VEmax increased significantly and VisoV, RV, and CC decreased significantly at all time periods studied. In addition delta VEmax50 increased compared to baseline at 15 and 135 minutes (P < 0.05) and compared to placebo at 135 and 255 minutes (P < 0.05). In our study, orally administered terbutaline apparently caused predominant peripheral airways bronchodilatation in the first few hours after ingestion. Afterwards, the predominant small airways effect appeared to wane, and large and small airways were dilated proportionately equally 375 minutes after oral administration of terbutaline.

Adult↗

Effects of breathing retraining in patients with chronic obstructive pulmonary disease.

Subjects with severe chronic obstructive pulmonary disease (COPD) were studied to evaluate the effects of breathing retraining (BRT) on exercise tolerance. Twenty-two subjects exercised on a treadmill three times weekly for six weeks. Twelve of the subjects (controls) then exercised for three more weeks; the other ten subjects received three more weeks of exercise reconditioning plus BRT. Results of routine pulmonary function and exercise tests were similar in both groups at the beginning of the study and after six weeks of exercise. However, in the last three weeks of the study, increments in exercise performance were significantly greater in the BRT subjects than in controls (P less than .002). Following BRT, respiratory rate during exercise decreased (P less than .005) and tidal volume and PaO2 during exercise increased (P less than .05). Thus, these data suggest that BRT increases exercise performance in subjects with severe COPD.

Breathing Exercises↗

In vivo and in vitro cell-mediated immunity to tetanus toxoid in adults.

The purpose of this study was to evaluate tetanus toxoid (TT) as an indicator of cutaneous delayed hypersensitivity (CDH) in adults. Fifty-two normal subjects, aged 25 to 64 yr, were skin tested with TT and streptokinase-streptodornase (SK/SD). Lymphocyte transformation was studied in seven normal TT reactors, four normal TT nonreactors, and seven hospitalized anergic patients. CDH was common with both TT and SK/SD; 90% of the adults, aged 25 to 39 yr, had CDH reactions to TT and 79% had CDH reactions to SK/SD. In adults aged 40 to 64 yr, 75% had DCH reactions to TT and 59% had CDH reactions to SK/SD. Lymphocyte transformation to TT correlated well with TT skin-test results. Punch biopsy specimens of TT reactions 48 hr after skin testing demonstrated DCH. We conclude that TT is an excellent antigen for assessing the presence or absence of CDH in adults aged 25 to 64 yr.

Adult↗

Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies.

Of the twenty-three employees at a pharmaceutical plant manufacturing a new product containing papain, twelve had respiratory symptoms of cough, wheezing, dyspnoea, or chest paint. Most were studied with in-depth interviews by a doctor, extensive pulmonary function tests, and immunoserological tests for IgE and precipitating antibodies specific for papain, as well as total IgE antibodies to common natural allergens. There were significant correlates (all P values < 0.05) between the presence of specific IgE antibodies to papain and decreases of FEV1, FEF75--85, TLC, RV, and response to bronchodilators as percentage change from baseline for all spirographic flow rates. Atopic workers developed pulmonary symptoms and antipapain antibodies significantly sooner after papain exposure than did the others. Duration of exposure had no effect on symptomatology, pulmonary function, or immunological response. However, those judged to have the greatest amount of dust exposure per work-day had significantly more pulmonary symptoms (P < 0.005). Papain produced lung diseases by acting as an inhalant allergen rather than a proteolytic enzyme. Papain is a potent sensitizer in humans for the production of respiratory disease. The pulmonary reactions, based on physiological data, seem to involve small airways, alveolar, and interstitial lung tissue in an inflammatory rather than destructive manner, and thus resemble bronchitis and interstitial lung disease rather than pulmonary emphysema or typical bronchial asthma.

Adult↗

Relationship between the site of airflow limitation and localization of the bronchodilator response in asthma.

In an effort to determine the relationship between the major sites of airflow limitation and bronchodilator action, physiologic studies were performed in 65 asthmatics before and after the administration of isoproterenol, metaproterenol, or terbutaline. Before the administration of a bronchodilator, the results of routine pulmonary function tests were abnormal; the mean increment in maximal expiratory flow at 50% of forced vital capacity (delta VEmax50) after breathing 80% helium-20% oxygen (He-O2) was reduced (p < 0.001). Prebronchodilator values of delta VEmax50 correlated linearly with VEmax50 breathing air (r = + 0.68, p < 0.001). These data suggested that airflow limitation becomes more peripheral as asthma becomes more severe. After the bronchodilator administration, the results of routine pulmonary function studies improved; delta VEmax50 either increased or decreased, depending upon the prebronchodilator values. Density-dependence tended to (1) increase in subjects with low prebronchodilator values of delta VEmax50, and (2) decrease in subjects with high prebronchodilator values of delta VEmax50. Hence, these results suggested that predominant sites of bronchodilatation in asthmatics are related to the prebronchodilator sites of airflow limitation.

Adult↗

Response to inhaled metaproterenol and isoproterenol in asthmatic and normal subjects.

Pulmonary function tests were performed before and after inhalation of 1.3 mg of metaproterenol sulfate or 150 microgram of isoproterenol hydrochloride by 40 asthmatic and 40 normal subjects. PHysiologic measurements included spirometric testing, plethysmographic studies, and maximal expiratory flow-volume curves obtained after inhalation of air and a mixture of 80 percent helium and 20 percent oxygen. In the normal subjects, pulmonary function improved significantly after inhalation of both metaproterenol and isoproterenol. There was no significant difference in responsiveness to either bronchodilator drug. In the asthmatic subjects, pulmonary function also improved significantly after both bronchodilator agents. The sites of predominant bronchodilatation were similar in the asthmatic subjects after both metaproterenol and isoproterenol; however, bronchodilatation was better overall (P less than 0.005) and for most individual tests with metaproterenol. The greater efficacy of metaproterenol in asthmatic subjects but not in normal subjects can be explained by (1) different doses of the bronchodilator drug and (2) differing bronchodilator dose-response relationships in asthmatic and normal subjects.

Adult↗

P pulmonale in status asthmaticus.

We studied 129 patients during acute, severe asthmatic attacks. Electrocardiograms showed P pulmonale in 49% of patients who had an arterial carbon dioxide tension (PaCo2) greater than or equal to 45 mm Hg and an arterial pH less than or equal to 7.37, whereas P pulmonale was present in only 2.5% of asthmatics who had a PaCO2 less than or equal to 44 mm Hg and a pH greater than or equal to 7.38 (p less than 0.001). P wave and QRS axes were 79 +/- 8 degrees and 80 +/- 20 degrees, respectively, in the presence of P pulmonale. When P pulmonale disappeared, the P wave and QRS axes shifted significantly to the left (p less than 0.001). Electrocardiographic P pulmonale persisted 12 to 60 hr after correction of hypoxemia, hypercapnia, and acidosis. In 7 patients with P pulmonale and respiratory acidosis, cardiac catheterization demonstrated normal artery pressures (PAPs) measured relative to atmospheric pressure. In 12 of these peak inspiratory pulmonary artery transmural pressures (PATPs) were increased. Since increased right heart transumural pressures could result in chamber distention, these data are consistent with the hypothesis that reversible P pulmonale in status asthmaticus is explainable on the basis of markedly negative tidal pleural pressures and increased right heart transmural pressures.

Adolescent↗

Large airway constriction in allergic rhinitis: response to inhalation of helium-oxygen.

Pulmonary function results were compared in 15 allergic rhinitis and 30 normal subjects. Airways resistance (RAW) was higher (p less than 0.01) and specific conductance (SGAW) and lower (p less than 0.01) in the rhinitis group. Maximal expiratory flow (VeMax), lung volumes, and results of tests measuring airways closure, distribution of ventilation, diffusing capacity, volume of isoflow, and density-dependence of VeMax at 50% of vital capacity (deltaVeMax50) did not differ significantly between the two groups. Following inhalation of isoproterenol, RAW decreased and SGAW and VeMax increased significantly in both groups. On the other hand, delta-VeMax50 decreased significantly in the rhinitis group (p less than 0.01) and increased significantly in the control group (p less than 0.05). In addition to comparing pulmonary function in rhinitis patients and control subjects, physiologic measurements were also made on two separate occasions in the rhinitis subjects (minimal or no symptoms; very symptomatic). Although rhinitis symptomatology varied considerably (p less than 0.001), pulmonary function results were not significantly different. Hence we conclude that: (1) Rhinitis subjects have large airway constriction which does not vary with season or symptoms. (2) As in normal control subjects, airflow limitation occurs in the large airways of rhinitis subjects. (3) The predominant site of isoproterenol-associated bronchodilatation differs between allergic rhinitis and normal subjects.

Adult↗

Relative sensitivities and specificities of tests for small airways obstruction.

This study compared several physiologic maneuvers for detecting small airways obstruction (SAO). Volume of isoflow best separated young smokers (average age--27.6; average cigarette consumption--9.3 pack years) from nonsmokers; this was true for comparisons of both population means and incidence of individual abnormality. However, assessment of individual abnormality by any test was greatly influenced by the criteria used to define abnormality. The best combination of test sensitivity and specificity was achieved by using the 95% confidence limits derived from a control population from the same laboratory. Even so, test results did not correlate significantly with pack years of cigarette smoking. Then, although tests for SAO are very sensitive, their prognostic value in young smokers is uncertain since abnormality presumably should correlate with extent of smoking.

Adult↗

Nephrotoxicity of paraquat in man.

Renal function studies were performed in three cases of paraquat poisoning. Acute renal failure was observed in all three cases. Glomerular filtration rate improved for two patients who survived three weeks, illustrating the reversible nature of paraquat-induced acute renal failure. A mild to moderate transient proteinuria was observed during the first and second weeks following paraquat ingestion. Renal glucosuria, marked amino aciduria, and increased fractional excretion of phosphorus, sodium, and uric acid were observed. These findings, which have not been previously described in man, are indicative of proximal tubular dysfunction and parallel observations previously made in experimental animals.

Acute Kidney Injury↗

Large bronchial casts.

Unusually large bronchial casts developed in four patients. In two, the casts were associated with pneumonia. In one, a large RBC cast resulted from a complication of fiberoptic bronchoscopy. Bronchial casts developed in an additional patient as a manifestation of plastic bronchitis. Although unusual, bronchial cast formation may complicate a number of hypersecretory pulmonary diseases. Therapy ordinarily includes specific measures to treat the underlying disease state and maneuvers designed to remove or facilitate the expectoration of bronchial casts.

Adult↗

Pulmonary ultrastructure of the late aspects of human paraquat poisoning.

The pulmonary ultrastructure of the late aspects of a case of human paraquat poisoning is investigated and compared with normal human pulmonary ultrastructure. Alveoli in the paraquat patient are numerically reduced in comparison to the control. They are filled with edematous proteinaceous plasma-like fluid containing erythrocytes, macrophages, leukocytes, fibroblast-like cells, platelets, and fibrin. These alveoli are lined by granular pneumocytes. Interstitial areas in the paraquat patient are greatly expanded and there are no alveolar septums. Interstitial areas contain proteinaceous plasma-like material, collagen, fibrin, platelets, mature fibroblasts, plasma cells, many leukocytes, numerous erythrocytes, and capillaries. Capillary permeability seems to be enhanced in the paraquat patient either by vesicles forming transendothelial channels or pores or by disruption of endothelial cells.

Adolescent↗

Large airway constriction in allergic rhinitis.

Extensive pulmonary function tests, including most of the sensitive new techniques capable of detecting small airways obstruction, were performed in 16 asymptomatic patients with allergic rhinitis and 31 normal control subjects. Mean flow rates, lung volumes, and results of tests measuring airways closure, distribution of ventilation, and diffusing capacity for carbon monoxide/alveolar volume did not differ significantly between the groups. Airways resistance (RAW) was significantly higher and specific conductance (SGAW) was significantly lower in subjects with rhinitis. Following administration of nebulized isoproterenol, RAW decreased (p less than 0.001) and SGAW increased (p less than 0.001) to mean values statistically indistinguishable from results obtained in control subjects. Individual results were normal for all tests except RAW and SGAW which were both abnormal in 3 subjects with rhinitis. The results of this investigation indicate that asymptomatic subjects with allergic have large airway (trachea and/or major bronchi) narrowing due to bronchoconstriction and no evidence of diffuse, or small airways, obstruction.

Airway Obstruction↗

Volume of isoflow: effect of distribution of ventilation.

Volume of isoflow was determined in smokers and nonsmokers following one (VisoV1) and three (VisoV3) inhalations 80% helium 20% oxygen. In addition, distribution of ventilation was measured by single breath nitrogen washout and end-tidal helium concentration was determined following 1-3 breaths of a helium-oxygen mixture. In all subjects (smokers and non smokers), VisoV1 was significantly higher than VisoV3. Furthermore, VisoV1 was abnormal in 55.6% of smokers, whereas VisoV3 was abnormal in only 38.9%. Differences between VisoV1 and VisoV3 (VisoV1 - VisoV3 = deltaVisoV) were significantly larger in smokers. Non-uniform distribution of ventilation was associated with larger values of delta VisoV and lower end-tidal helium concentrations. VisoV1 is a more effective method than VisoV3 in distinguishing smokers with small airways obstruction from nonsmokers. This enhanced sensitivity can be explained by the observation that the effects of maldistribution of ventilation upon helium concentration in the late expirate are minimized after three breaths of a helium-oxygen mixture.

Adult↗

Paraquat poisoning: new aspects of therapy.

Clinical, laboratory, and pulmonary physiologic features of three fatal cases of paraquat poisoning are presented. Experimental investigations and clinical experience would suggest several possible means of modifying paraquat toxicity. The following specific therapeutic interventions, several of which had previously been applied only in experimental circumstances, were used: (1) inhibition of absorption of paraquat with Fuller's Earth and catharsis by magnesium sulfate, (2) elimination of absorbed paraquat by hemodialysis with ultrafiltration and forced diuresis, (3) competition by d-propranolol for tissue binding sites, (4) modification of direct pulmonary tissue effects of paraquat by hypoxic breathing mixtures, superoxide dismutase, and corticosteroids. Treatment was unsuccessful. However, our clinical experience and data concerning paraquat concentration in body and dialysis fluids suggest a therapeutic approach aimed at preventing early and progressive tissue damage. A combination of Fuller's Earth and magnesium sulphate should be used immediately and in frequently repeated doses to prevent absorption. Diuresis and haemodialysis should be instituted as soon as possible to increase excretion. Hypoxic atomspheres should be created urgently to produce a PaO2 of 40-45 mmHg, and the use of superoxide dismutase be further investigated. It is hoped that the high mortality of paraquat poisoning will be modified by this combined approach of early and intensive treatment.

Adolescent↗