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Biomedical subjects

P D Pare

Publications and source records attributed to P D Pare.

At least 19 recordsLinked to original sources

Acute effect of cigarette smoking on the carbon monoxide diffusing capacity of the lung.

To determine the acute effect of smoking on DLCO, we studied 12 smokers (mean age, 36 yr; range, 19 to 52 yr, six men and six women) before and after they had smoked as many cigarettes as they could (mean, 6.0; SD, 1.9) over a period of 1 h. Blood COHb was estimated using a rebreathing-breathholding technique after a vital capacity inhalation of O2. Capillary blood volume (VC) was determined from DLCO performed at inspired O2 concentrations of 25 and 90%. DLCO (in ml/min/mm Hg) corrected for COHb back pressure decreased from 22.5 (SD, 6.6) before smoking to 21.0 (SD, 6.6) after smoking (p = 0.003). After correction for the "anemia effect" of COHb, DLCO still significantly decreased, from 22.8 (SD, 6.3) before smoking to 21.8 (SD, 6.4) after smoking p = 0.01). VC (corrected for the reduction in hemoglobin by COHb) was 52.0 (SD, 20.1) ml before smoking and 46.4 (SD, 22.7) ml after smoking; this difference did not achieve statistical significance (p = 0.056). There was no significant change in DLCO or VC in six control subjects tested before and after 1 h of sham smoking of an unlit cigarette. In 12 control subjects studied before and after inhalation of 0.1% CO to result in mean COHb levels of 10.6% (SD, 1.4%), there was a slight but significant decrease in VC (mean change, 21%) and in DLCO (mean change, 4%) after correction for COHb back pressure and reduction in available hemoglobin, suggesting that CO inhalation may have a direct effect on DLCO by reducing VC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Smooth muscle mechanics: implications for airway hyperresponsiveness.

Human bronchial smooth muscle preparations from 10 freshly dissected pneumonectomy samples were evaluated for their mechanical characteristics and compared with results obtained for similar samples obtained from porcine trachea. Length-tension relationships of in vitro smooth muscle were evaluated for passive stretching as well as active isometric force generation and isotonic shortening using electrical field stimulation. At the length (Lmax) producing maximal force (Pmax) resting tension was very high (60.0 +/- 8.8% Pmax) compared with porcine trachealis (5.2 +/- 2.3% Pmax). Maximum shortening was 25.0 +/- 9.0% at a length of 75% Lmax with suboptimal shortening occurring at Lmax (12.0 +/- 3.4%) for the human bronchus, whereas optimal shortening of porcine trachealis (71.4 +/- 3.6%) occurred at Lmax. Morphometric evaluation revealed threefold less muscle per cross-sectional area of tissue for human (8.7 +/- 1.5%) versus porcine (24.8 +/- 1.9%) preparations. We conclude that the high passive tension and the decreased maximum shortening are produced by a relatively large load which must be overcome for the muscle to shorten, presumably provided by the greater connective tissue elastic component present in the airway. We suggest that a decrease in airway wall elastance would increase smooth muscle shortening, thereby leading to excessive responses to contractile agonists as seen in vivo in asthma.

Animals

Respiratory muscle weakness and dyspnea in thyrotoxic patients.

Dyspnea on exertion is a frequently reported symptom of thyrotoxicosis. In the majority of cases, there is no obvious cause of dyspnea, but as skeletal myopathy is also common in thyrotoxic patients, it has been postulated that increased dyspnea could be secondary to respiratory muscle weakness. We sought to determine whether thyrotoxic patients were in fact more dyspneic on exertion than age- and sex-matched controls, and if so, whether the increased dyspnea was secondary to respiratory muscle weakness. The study group consisted of 12 thyrotoxic patients and 12 control subjects matched for age and gender. We measured lung volumes, compliance, elastic recoil, respiratory muscle strength, maximal exercise performance, and the intensity of breathlessness (modified Borg scale) at various levels of exercise in all subjects. The respiratory muscles were weaker in patients than controls. This weakness improved in treated patients (p less than 0.05) with concomitant increases in VC, IC, and TLC (all p less than 0.05). Despite this, we found no differences in breathlessness intensity scores between patients and controls or in patients before and after successful antithyroid therapy.

Adult

The effects of freezing and antibiotics on the viability of Acanthamoeba cysts.

The effects of cryotherapy and antibiotics (paromomycin, neomycin, or propamidine isethionate) on the viability of Acanthamoeba polyphaga and Acanthamoeba castellani cysts were studied in vitro. Either cryotherapy or exposure to antibiotic led to a decrease in the number of viable A castellani detected; A polyphaga showed variable response to the antibiotics tested. The combination of cryotherapy and antibiotic therapy was more cysticidal than either modality alone and eliminated detectable viable organisms in five of six experiments. Of the antibiotic solutions tested, paromomycin (15 mg/mL) was the most effective.

Acanthamoeba

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve.

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.

Adult

An effective combination of anaesthetics for 6-h experimentation in the golden Syrian hamster.

The anaesthetics described for use in hamsters to date are suitable for the performance of short-term experimentation. However, an anaesthetic regimen was required which would provide a stable preparation for 6 h and hence, a suitable combination was developed. In the first set of experiments, the effect of anaesthetics (chloralose, urethane, and pentobarbital) were examined alone and in combination on arterial blood measurements. In the second set of experiments the effect of the combination of anaesthetics on arterial blood measurements and minute ventilation was examined for up to 6 h. Chloralose, urethane and pentobarbital when used alone in the hamster were considered inadequate for our needs. Chloralose did not produce adequate surgical anaesthesia whereas urethane and pentobarbital resulted in marked respiratory depression. Urethane also produced a trend towards metabolic acidosis. In contrast, the combination of agents resulted in surgical anaesthesia and the arterial blood measurements were adequate. Further, the use of the combination of anaesthetics in hamsters resulted in a stable preparation where arterial blood measurements and minute ventilation were maintained in a good range for up to 6 h. The combination of chloralose, urethane and sodium pentobarbital in hamsters should prove useful in long-term non-recovery experimentation which requires early surgical intervention, minimal respiratory depression and an even depth of anaesthesia.

Anesthesia

The changes in airways structure associated with reduced forced expiratory volume in one second.

We compared the structure of the membranous and respiratory bronchioles of resected lungs from 111 patients with a normal predicted forced expiratory volume in one second (FEV1) to the structure of these airways from 45 patients with an FEV1 reduced below the 95% confidence limits for height and age. Membranous and respiratory bronchioles of less than 2 mm in internal diameter were counted and their diameter and wall thickness were measured. The data show that there were more membranous bronchioles of internal diameter less than 0.4 mm in patients with reduced FEV1. The wall thickness of respiratory bronchioles was increased in the obstructed group and there was also an increase in the ratio of wall thickness to lumen diameter in these airways. The walls of membranous bronchioles were not increased in thickness but there was an increase in the ratio of wall thickness to lumen diameter. Although the data is consistent with the hypothesis that airways obstruction in patients with chronic obstructive pulmonary disease is due to thickening of the airway wall and narrowing of the airway lumen, we cannot rule out distortion of the membranous bronchioles by loss of elastic recoil.

Aging

Airway inflammation and peribronchiolar attachments in the lungs of nonsmokers, current and ex-smokers.

To determine the effect of smoking cessation on the number and type of inflammatory cells in the walls of the small airways, we examined the lungs of 13 lifetime nonsmokers, 25 patients who had stopped smoking for at least 6 months, and 49 current smokers. We found that, compared to nonsmokers, both ex-smokers and current smokers had significantly increased numbers of total inflammatory cells and polymorphonuclear leukocytes in the walls of the membranous, but not the respiratory bronchioles. These differences were found even when there was no emphysema present in the gross lung specimen, and current and ex-smokers were matched with the nonsmokers for age. The current and ex-smokers had similar numbers and types of inflammatory cells in the airway wall, and in both current and ex-smokers there was no difference in inflammatory cell number or type when the groups were subdivided based on emphysema score less than or greater than 5. Analysis of peribronchiolar alveolar attachments showed an increase in percentage of alveoli destroyed associated with an increased interalveolar distance in both the current and ex-smokers, which did not change with the presence of emphysema. Pulmonary function was similar in the current and ex-smokers, and the group with emphysema showed greater functional abnormalities compared to the group with little or no emphysema. We conclude that the cigarette smoking habit induces a stereotypical inflammatory response in the small airways. This inflammatory response does not abate after smoking cessation, and in this cross-sectional study, appears to be independent of the presence or absence of emphysema, but related to destruction of the peribronchiolar alveolar attachments.

Aged

The effect on airway function of inspired air conditions after isocapnic hyperventilation with dry air.

The magnitude of postexercise or posthyperventilation bronchoconstriction in patients with asthma is related to the temperature and the water content of the inspired air during the exercise or hyperventilation period. Recent studies have suggested that the inspired air conditions during recovery from exercise may also be important in determining the magnitude of postexercise airway narrowing. In the present study, normal subjects (n = 8) and patients with asthma (n = 12) were studied on separate days. On day 1 the subjects performed isocapnic hyperventilation with warm dry air and recovered breathing warm dry air. On the second day, an identical warm dry air challenge was administered, but recovery occurred while they were breathing warm humid air. There was no significant bronchoconstriction in the normal subjects, irrespective of the inspired air conditions during recovery. The patients with asthma showed greater bronchoconstriction during recovery in warm, humid air (maximal decrease in FEV1 31% +/- 17%) than in dry air (maximal decrease in FEV1 19% +/- 20%; p less than 0.05). These results suggest that the inspired air condition during recovery from isocapnic hyperventilation of dry air is also a determinant of the magnitude of the bronchoconstrictor response.

Adult

Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room.

The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy.

Administration, Intranasal

A rabbit model of hypersensitivity to plicatic acid, the agent responsible for red cedar asthma.

We describe a rabbit model for the study of the immunogenicity and allergenicity of plicatic acid (PA), the small molecular weight compound in western red cedar responsible for occupational asthma in exposed workers. Specific anti-PA IgE as well as IgG antibodies could be raised, depending on the method of immunization. The sensitized rabbits reacted to antigenic challenge with PA-protein conjugates intravenously, with increases in respiratory frequency and pulmonary resistance. This animal model may be used for the further elucidation of the mechanism of occupational asthma induced by small molecular weight chemical compounds.

Animals

A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial pneumonia, and small airways disease.

This report is based on 43 cases where a diagnosis of either bronchiolitis obliterans with organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), or small airways disease (SAD) was established by lung biopsy. The severity of histologic abnormalities in the peripheral airways and interstitial spaces were measured on these biopsies using semiquantitative techniques and compared with the clinical data available in 42 of 43 cases, preoperative chest radiographs in 31 of 43, and preoperative pulmonary function tests in 29 of 43. The data show that when a diagnosis of BOOP was made, there was a higher total pathologic score for membraneous bronchiolitis (MB) and respiratory bronchiolitis (RB) than for UIP and SAD (p less than 0.005). This was due to peribronchiolar inflammation and the presence of loose connective tissue in the RB lumen. The pathologic changes in the interstitial space were less severe in SAD than in BOOP or UIP (p less than 0.005). Clubbing was more frequent in UIP (p less than 0.01), and symptoms were of shorter duration in BOOP (p less than 0.05). The radiographic assessment showed that the characteristic finding in BOOP was patchy air-space consolidation, a finding that was not present in UIP or SAD.

Bronchial Diseases

Reassessment of inflammation of airways in chronic bronchitis.

The term chronic bronchitis has been criticised because it is associated with hypersecretion of mucus rather than bronchial inflammation. This study was designed to establish the presence or absence of clinical chronic bronchitis and measure pulmonary function in 45 patients about to undergo resection of the lung. The condition in the cartilaginous and small airways and the severity of the emphysema were then measured in the resected specimen. The results from 20 patients who had clinical chronic bronchitis were compared with those in 25 patients who did not. The data show that patients with chronic bronchitis had greater inflammation (a) on mucosal surfaces (p less than 0.05) of all bronchi larger than 2 mm luminal diameter and (b) around glands (p less than 0.005) and gland ducts (p less than 0.05) in bronchi larger than 4 mm diameter. A variable degree of inflammation was present in the submucosa of smaller bronchi. The groups had equivalent proportions of mucous glands and Reid's indices in central airways, and no differences were noted in measurements of pulmonary function, condition of small airways, or emphysema. These data show that the term chronic bronchitis is justified by inflammation of cartilaginous airways and suggest that this abnormality may be the cause of the chronic productive cough.

Bronchi

Airways disease: evolution, pathology, and recognition.

Obstruction to airflow in the lung was studied in 150 patients who presented with coin lesions necessitating surgical resection of the lung. Pulmonary function tests were performed before surgery, and the structure of the lung or lobe was analysed by means of morphometric techniques. The evolution of obstructive airways disease appeared to be based on a progressive chronic inflammatory reaction in the respiratory and membranous bronchioles. This led to progressive airway obstruction and was associated with destruction of the lung surface. The early pulmonary vascular problems appeared to be related to progressive airways obstruction that may have increased pulmonary artery pressure by causing alveolar pressure to increase more than pleural pressure during the hyperventilation of exercise.

Adult

Bronchopulmonary anastomotic and noncoronary collateral blood flow in humans during cardiopulmonary bypass.

The sole source of blood returning to the left atrium during cardiopulmonary bypass, while the aorta is cross-clamped, is the bronchopulmonary anastomotic blood flow. In addition, there is noncoronary collateral blood flow which returns to the right atrium. Routinely, the bronchopulmonary anastomotic flow is drained from the left ventricle by a cannula and returned to the main circuitry via a cardiotomy reservoir. The noncoronary collateral flow may be vented similarly by introducing a cannula into the right atrium. Both the anastomotic and the noncoronary collateral flow can be measured with no further surgical intervention. We measured bronchopulmonary anastomotic flow in 40 patients undergoing coronary artery bypass surgery and the noncoronary collateral blood flow in 27 of these patients. Results from this study show that the bronchopulmonary anastomotic flow for the 40 patients was 140 +/- 182 ml/min (range 8 to 1,043 ml/min), representing 3.23 +/- 4.15 percent of the pump flow (equivalent to the cardiac output), and the noncoronary collateral flow in the 27 patients was 48 +/- 74 ml/min (range 0 to 261 ml/min), representing 1.11 +/- 1.67 percent of the pump flow.

Adult