bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathogenicity of Mycobacterium tuberculosis during chemotherapy
Authors: Clancy LJ , Kelly P , O'Reilly L , Byrne C , Costello E
Published: November 2022

We used the guinea pig as an experimental model to investigate the pathogenicity of Mycobacterium tuberculosis. Sputum samples were injected subcutaneously into guinea pigs and the animals were killed and an autopsy performed after eight weeks. The likelihood of the sputum samples producing tuberculosis in the guinea pig was related to culture positivity rather than to duration of chemotherapy. This study does not support the belief that a change in pathogenicity occurs during treatment of pulmonary tuberculosis.
Effects of corticosteroid treatment on pulmonary haemodynamics in patients with sarcoidosis
Authors: Gluskowski J , Hawrylkiewicz I , Zych D , Zielinski J
Published: November 2022

Effects of 12 months steroid treatment on pulmonary haemodynamics in 24 patients with pulmonary sarcoidosis, stage II and III, were investigated. All patients had a chest radiograph, lung function tests, and pulmonary haemodynamics (measured at rest and during submaximal exercise) prior to the treatment. Resting pulmonary hypertension was found in 3 patients. In 18 an abnormal increase in pulmonary arterial mean pressure (PAP) on exercise was observed. All investigations were repeated after a year of treatment. In almost all patients (22) a regression of radiological changes in the lungs and improvement of pulmonary function were observed. The changes in pulmonary circulation were less uniform. In only half of the patients studied was regression of the disease seen on chest X-ray and improvement in lung function accompanied by improvement in pulmonary haemodynamics.
Mechanisms of hyperinflation in asthma
Authors: Cormier Y , Lecours R , Legris C
Published: November 2022

We studied 11 mild asthmatics to verify whether the mechanisms of hyperinflation in asthma could be inhibited or overcome by passively changing lung volumes. On day 1, we induced a fall in forced expiratory volume in one second (FEV1) of 30-60% by methacholine inhalation and measured the resulting increase in FRC (delta FRC). The delta FRC was 729 +/- 378 ml (mean +/- SD). On day 2, with the subject supine in an iron lung, we measured oesophageal (Poes), gastric (Pgas) and transdiaphragmatic (Pdi) pressures, and changes in functional residual capacity (FRC) (delta V) induced by extrathoracic pressures from -20 to +20 cmH2O before and after bronchoprovocation. With positive pressures, the FRC decreased and reached a plateau at 10 cmH2O pressure or higher. This plateau was at a mean FRC of 839 ml higher after the bronchoprovocation than before. Pdi at FRC varied in the same direction as the extrathoracic pressure and was not modified by the bronchospasm. Peak inspiratory Pdi, without pressure applied in the iron lung, increased from 13.6 +/- 5.4 to 28.1 +/- 13.5 cmH2O after methacholine; extrathoracic pressure of -20 cmH2O decreased this latter value to 15.4 +/- 7.3 cmH2O (p less than 0.01). The increased lung volume and the displaced chest wall recoil curve after provocation were not inhibited by positive or negative extrathoracic pressures. Our data show that the mechanisms of hyperinflation are not eliminated or overcome by passively changing lung volumes and support the hypothesis that persisting activity of inspiratory muscles other than the diaphragm during expiration and perhaps a prolonged expiratory time constant are responsible for hyperinflation in asthma.
Alpha 1-protease inhibitor moderates human neutrophil elastase-induced emphysema and secretory cell metaplasia in hamsters
Authors: Stone PJ , Lucey EC , Virca GD , Christensen TG , Breuer R , Snider GL
Published: November 2022

A study was undertaken to determine whether emphysema and airway secretory cell metaplasia, induced in hamsters by intratracheal treatment with human neutrophil elastase (HNE), could be moderated by pretreatment with human alpha 1-protease inhibitor (API). API (4.9 mg) was given intratracheally to hamsters 1 h before 0.3 mg HNE. Eight weeks later, lung volumes and pressure-volume relationships were measured in the anaesthetized animals. Mean linear intercepts and secretory cell indices were measured in lung sections. API given 1 h before HNE moderated the development of bronchial secretory cell metaplasia. The severity of emphysema was reduced by 75%. Clearance studies indicated that 80% of the functional activity of instilled API could be lavaged from the lungs after 1 h, indicating a 4 h half-life in the lavageable compartment of the lungs. We calculate that for 50% protection from emphysema the molar ratio of lavageable API to HNE at the time of HNE instillation was 4.8 as compared with 0.78 for 50% inhibition of elastolytic activity in vitro, indicating that API is only 16% as efficient in vivo as compared with its in vitro HNE inhibitory effectiveness. Nevertheless, we conclude that human API given intratracheally is efficacious against HNE-induced emphysema and secretory cell metaplasia.
Distribution of inhaled 99mtechnetium labelled ultrafine carbon particle aerosol (Technegas) in human lungs
Authors: Amis TC , Crawford AB , Davison A , Engel LA
Published: November 2022

Using a gamma camera, we quantified the topographical intrapulmonary distribution of inhaled 100 ml boluses of Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTc, and 133Xenon (Xe) in six seated, normal subjects, inhaling from residual volume (RV) and from within a 1 l volume range above functional residual capacity (FRC) at a flow less than 0.5 l.s-1. Following inspiration of air to total lung capacity (TLC) counts were recorded during a 20 s breathhold. Twenty min after administration of the final TG bolus (TGF) counts were again recorded (TG20). Upper (U), middle (M) and lower (L) zones, as well as central (C) and peripheral (P) regions were identified in each lung. The relative fractional concentration (Fr) of TG and Xe was calculated for all zones after RV and FRC boluses, using counts obtained during Xe equilibration. The U/M or U/L ratios for XeFr did not differ significantly from those for TGFr (paired t-test; p greater than 0.1). The P/C count ratio constitutes a penetration index, which for TG was 1.07 +/- 0.13 (mean +/- SD) that of Xe. After correction for radioactive decay, TG20 counts were no different from TGF counts. The results suggest that the intrapulmonary distribution and penetration of TG in normal lungs is no different from Xe and that stable deposition in the lung periphery makes TG suitable for multiple-view imaging of ventilation distribution.
The airways effects of inhaled chlorbutol in asthmatic subjects
Authors: Windom H , Burgess C , Crane J , Beasley R
Published: November 2022

Chlorbutol is an antibacterial and antifungal agent incorporated in terbutaline (Bricanyl) nebulizer solution. Ten stable atopic asthmatic subjects undertook bronchial challenge testing, according to a double-blind protocol. Patients inhaled doubling concentrations of either methacholine (0.13-4.0 mg.ml-1) or chlorbutol (0.16-5.0 mg.ml-1) for 2 min until the forced expiratory volume in one second (FEV1) had fallen by 20% from baseline. If this had not occurred following the administration of the final concentration, then this highest concentration was repeated for 4 min. The nine subjects completing the study had a geometric mean provocation concentration producing a 20% fall from baseline FEV1 (PC20) methacholine of 0.16 mg.ml-1 (range less than 0.125-0.475 mg.ml-1). After inhalation of 2.5 mg.ml-1 chlorbutol one subject experienced a fall in FEV1 greater than 20%. In the remaining eight subjects, inhalation of chlorbutol did not affect airway calibre. We conclude that chlorbutol, in the concentration present in Bricanyl nebulizer solution, has no clinically significant effect on airway calibre.
The effects of osmotic challenge on bronchial responsiveness to methacholine in non-asthmatic subjects
Authors: Antoniou D , Pavlakou G , Rees PJ
Published: November 2022

We have measured the airway responses to methacholine on three days in sixteen non-asthmatic subjects. On the first day the methacholine challenge alone was performed. The other two days were randomized between pretreatment with distilled water or hypertonic saline administered by ultrasonic nebulizer. Distilled water and hypertonic saline did not affect baseline specific conductance (sGaw). Provocative dose producing a 35% fall in sGaw (PD35sGaw) was slightly reduced by both distilled water and hypertonic saline (15.83 to 8.55 mumol with distilled water and to 11.80 mumol with hypertonic saline). Six out of 16 subjects reached a plateau of maximal response with methacholine. The level of this plateau was not affected by pretreatment with distilled water or hypertonic saline. These results show that distilled water and 3.6% saline produced small increases in non-specific reactivity in normal subjects and confirm that substantial osmotic challenge does not change airway calibre in non-asthmatic subjects.
Manufacturer's information insert and subjective theophylline side-effects
Authors: Vesco D , Toumi M , Faraj F , Razzouk H , Orehek J
Published: November 2022

In Western Europe medicine packages contain an insert prepared by the manufacturer which enumerates the drug side-effects. We investigated the influence of this insert on alleged theophylline side-effects. Forty literate adult asthmatics were randomly allocated into two groups (n = 20 each): theophylline packages contained the manufacturer's insert in group A but not in group B. Theophylline was prescribed (10 mg.kg-1 body weight qd) for one week. During this period the patients filled a diary grading 13 different symptoms from 0 to 3; 5 of these symptoms were listed on the insert as theophylline side-effects. On the eighth day the patients were interviewed and theophylline blood levels measured. Theophylline side-effects were significantly more marked in group A than in group B, whereas the other symptoms were of similar magnitude. Eight patients prematurely stopped their treatment in group A vs 3 in group B, because of alleged intolerance. Theophylline blood levels did not differ significantly in the two groups; neither did they in the subgroup which stopped treatment and in the one which complied to prescription. We conclude that side-effects were suggested to the patients by the insert and/or that the insert increased their awareness of side-effects, with a subsequent detrimental influence upon compliance to therapy.
The reversible effect of lignocaine on the stimulated metabolic activity of bronchoalveolar lavage cells
Authors: Duddridge M , Kelly CA , Ward C , Hendrick DJ , Walters EH
Published: November 2022

Lignocaine concentrations were measured in the aspirate from a low volume (100 ml) bronchoalveolar lavage (BAL) in twenty patients who had received topical 4% lignocaine as required, and compared to those found in the aspirate from a 180 ml BAL in ten patients who had received 1.5% isotonic lignocaine. The median BAL supernatant lignocaine concentration was significantly lower at 0.14 mM (range 0.07-0.44 mM) in the group who received 1.5% lignocaine, compared to 1.08 mM (range 0.03-7.05 mM) in those given 4% lignocaine (p less than 0.01). The effect of increasing concentrations of lignocaine on BAL neutrophil and pulmonary macrophage metabolic activity, as assessed by latex-stimulated luminol- and lucigenin-amplified chemiluminescence (CL), respectively, in mixed BAL cell populations, were measured following preincubation of "washed" harvested BAL cells with 0.4-8.0 mM lignocaine. There was no demonstrable decline in either cell activity with lignocaine concentrations of up to 2 mM, with dose-dependent inhibition of both above this threshold. Cell viability was unaffected. In a further experiment, the inhibition induced by 8 mM lignocaine on both pulmonary macrophage (lucigenin-amplified CL of harvested BAL cells) and isolated peripheral blood neutrophil metabolic activity was completely reversed by a single "wash", following both 30 and 60 min incubations at 4 degrees C, which was equivalent to resuspending harvested BAL cells in fresh medium after separation from BAL supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)
Ketotifen inhibits PAF-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1
Authors: Morita M , Tsuruta S , Mori KJ , Mayumi M , Mikawa H
Published: November 2022

The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.
Subclinical alveolitis in immunological systemic disorders. Transition between health and disease?
Authors: Wallaert B , Dugas M , Dansin E , Perez T , Marquette CH , Ramon P , Tonnel AB , Voisin C
Published: November 2022

A subclinical inflammatory alveolitis as assessed by BAL cell analysis may be present in a high proportion of symptomless patients with immunological systemic disorders and with normal chest roentgenogram. Subclinical alveolitis can be characterized by the relative proportions of the different cell populations comprising the alveolitis and by the activated state of the cells. Thus, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. Lymphocyte alveolitis is frequently found in patients with extrathoracic granulomatosis (Crohn's disease, primary biliary cirrhosis, extrathoracic sarcoidosis) or with some collagen vascular diseases (Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus). Neutrophil alveolitis is a main finding in collagen vascular diseases, especially progressive systemic sclerosis, dermatopolymyositis and mixed connective tissue disease. In addition, alveolar macrophages may be spontaneously activated and release various mediators that could be relevant to the pathogenesis of interstitial lung disease. On the other hand, some other alveolar macrophage functions (antibacterial activity may be severely impaired in some diseases, for example systemic lupus erythematosus). Alveolar inflammation is associated with an increase in the permeability of the alveolar membrane responsible for an increased influx of blood proteins in the alveolar spaces. Although subclinical inflammation may also be detected by high resolution computed tomography (HRCT) scan and/or lung permeability scintigraphic studies, the significance and prognostic value remains unclear and clearly differs according to both the disease and the pattern of alveolitis.
Antigen-presenting capacity of alveolar macrophages and monocytes in pulmonary tuberculosis
Authors: Ina Y , Takada K , Yamamoto M , Morishita M , Yoshikawa K
Published: November 2022

Using purified protein derivative of tuberculin (PPD) as an antigen, antigen-presenting capacity by monocytes (Mo) and alveolar macrophages (AM) was determined in 17 patients with pulmonary tuberculosis and nine healthy controls. All of the patients and healthy controls were positive for PPD skin test. Although Mo obtained from both the control and tubercular subjects revealed antigen-presenting capacity to autologous blood T-lymphocytes, no significant difference was observed between the two groups. In contrast, AM obtained from the tubercular patients, but not from the controls, showed antigen-presenting capacity to autologous blood T-lymphocytes and to lung T-lymphocytes. No significant difference was shown in HLA-DR antigen expression on AM between the control and tubercular patients. Besides, the exogenous addition of interleukin-1 (IL-1) did not induce antigen-presenting capacity by AM obtained from the controls. These results suggest that neither increased HLA-DR antigen expression on AM nor an increased release of IL-1 from AM is responsible for the enhanced antigen-presenting capacity in tuberculosis.
Unilateral lung infiltrate. Lipoid pneumonia
Authors: Guntupalli KK , Francis PB
Published: November 2022

A case of unilateral lipoid pneumonia, proven by alveolar lavage and transbronchial lung biopsy, is presented. Following a stroke, which resulted in difficulty in swallowing, the patient slept only on his right side accounting for the unilateral lung infiltrate. He had been taking mineral oil for several years accounting for the lipoid pneumonia.
Evidence for local platelet activation in pulmonary vessels in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease
Authors: Rostagno C , Prisco D , Boddi M , Poggesi L
Published: November 2022

To investigate the relationships between local platelet activation in pulmonary vessels and pulmonary artery pressure circulating platelet aggregates and plasma beta-thromboglobulin (beta-TG) levels were evaluated in peripheral venous blood and blood from different sites of pulmonary circulation (right ventricle, pulmonary artery and arteriolo-capillary bed) in 29 patients with COPD. Fifteen had pulmonary hypertension and 14 normal pulmonary artery pressure. In normotensive COPD no significant differences could be found in platelet aggregation and beta-TG levels among different sampling sites. On the contrary in patients with pulmonary hypertension a significant increase of platelet aggregates and beta-TG levels was found in blood withdrawn from the arteriolo-capillary bed. A significant correlation was demonstrated between platelet aggregation and both mean pulmonary artery pressure and pulmonary vascular resistance. These results indicate that in patients with pulmonary hypertension secondary to COPD a local platelet activation in pulmonary vessels does occur and may contribute to the maintainance of elevated pulmonary vascular resistance.
The use of a new breath-actuated inhaler by patients with severe airflow obstruction
Authors: Fergusson RJ , Lenney J , McHardy GJ , Crompton GK
Published: November 2022

The ability of patients with severe airflow limitation (forced expiratory volume in one second less than 1.0 l or peak expiratory flow rate less than 200 l.min.1) to use a new breath-actuated inhaler (BAI) was assessed. One hundred and fifty six patients attending two respiratory units entered and completed the study. Subjects were instructed how to use the device and after attempting to trigger the BAI had flow-volume loops measured. One hundred and fifty one (97%) were able to actuate the inhaler on their first (146) or second (5) attempt. The five unsuccessful patients did not have the most severe airways obstruction. It is concluded that this new device, which is actuated at low inspiratory flow rates, can be used by patients with severe airflow limitation and represents an important advance in inhaler technology.
Thoracic gas volume at functional residual capacity measured with an integrated-flow plethysmograph in infants and young children
Authors: Marchal F , Duvivier C , Peslin R , Haouzi P , Crance JP
Published: November 2022

Thoracic gas volume (TGV) was measured with an integrated flow plethysmograph in 15 infants aged 2-34 months. End-expiratory (TGVe) and end-inspiratory (TGVi) airway occlusions were compared, after correction of TGV for the occluded volume above functional residual capacity (FRC). The relationship between pressure at the airway opening (Pao) and volume displaced from the box during airway occlusion (Vg) was studied numerically by: 1) an algorithm including a correction for the drift of Vg and linear regression analysis (LR); and 2) Fourier analysis of the signals (FFT). TGVe was significantly higher than TGVi (256 vs 237 ml, 20.4 (square root of residual variance; p less than 0.002). The correlation coefficient of the Pao-Vg relationship was slightly but significantly higher for TGVi than for TGVe: 0.9968 (0.9937-0.9995) vs 0.9947 (0.9840-0.9990) (means and range). No difference was observed between LR and FFT, although the intra-individual coefficient of variation was lower for LR than FFT: 5.2% (1.6-11.3) vs 7.9% (1.9-21.0) (means and range). Model simulations suggested that the difference between TGVe and TGVi could be mainly attributed to gas compression in the instrumental deadspace and upper airway wall motion and/or to uneven distribution of alveolar and pleural pressure associated with chest wall distortion.
Long-acting beta 2-adrenoceptor agonists: a new perspective in the treatment of asthma
Authors: Lofdahl CG , Chung KF
Published: November 2022

New long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, may soon appear in several European countries for treatment of asthma. This review examines currently available information and compares the basic pharmacology and describes the clinical effects of these new drugs. The long duration of bronchodilation seen in clinical studies seems to be similar, whereas in isolated tissues there might be a difference in the binding characteristics to the beta 2-adrenoceptor. Long-acting beta 2-agonists could have an inhibitory effect on inflammatory events related to asthma, but the clinical relevance of these effects is not clear at present. Long-term studies up to one year with both new drugs have not shown any unexpected side-effects, and no tachyphylaxis to beta-adrenoceptor stimulation has been reported. Patients appear to strongly prefer the new drugs compared to the short-acting beta 2-agonists. The potential place for these drugs in the treatment of asthma is discussed and some pitfalls pointed out. It is likely that the long-acting beta 2-agonists will be beneficial to many asthmatic patients.
Late onset asthma?
Authors: Aleva RM , Wouters B , Kraan J , Postmus PE
Published: November 2022

A 77 yr old male was referred for dyspnoea and recurrent infections of the lower airways for the previous five months. On the lateral chest roentgenogram a process in the tracheal area was found, and during bronchoscopy a polypoid tumour was seen about four centimetres above the main carina. It appeared to be a benign endotracheal tumour which was removed after coagulation by a Neodymium yttrium aluminium garnet (YAG) laser.
Bronchodilator response in adult patients with cystic fibrosis: effects on large and small airways
Authors: van Haren EH , Lammers JW , Festen J , van Herwaarden CL
Published: November 2022

Spirometry, body plethysmography, maximal expiratory flow-volume curves (MEFV-curves) with air and with heliox (80% He + 20% O2) before and after inhalation of bronchodilators were studied in a group of 20 adult cystic fibrosis (CF) patients. Most of them showed prominent bronchial obstruction and seven also had evidence of restrictive pulmonary disease. Large differences were observed between total lung capacity as measured with body plethysmography and with a helium dilution technique. A calculated air trapping index correlated well with parameters of peripheral airway obstruction. Both inhalation of terbutaline and ipratropium bromide caused dose-related bronchodilatation. Density dependence of expiratory flow increased significantly after terbutaline but not after ipratropium bromide. We conclude that adult CF patients with varying degrees of obstructive and restrictive pulmonary function limitation show a dose-related improvement of lung function after terbutaline and ipratropium bromide with terbutaline being probably more effective on peripheral airways than ipratropium bromide.
Role of simulated repetitive coughing in mucus clearance
Authors: Zahm JM , King M , Duvivier C , Pierrot D , Girod S , Puchelle E
Published: November 2022

The role of repetitive simulated coughing on the clearance of gel mucus simulant was investigated in vitro, by using a simulated cough machine. The repetition of cough induced a significant increase (p less than 0.01) in mucus simulant clearance (139.3 +/- 78.7 mm) in comparison to a single cough (24.9 +/- 27.5 mm). Moreover, the increase in frequency of the repetitive coughing induced a marked and significant increase in mucus simulant clearance (75.4 +/- 51.1 mm and 139.3 +/- 78.7 mm at 0.1 Hz and 1.6 Hz frequency, respectively). A significant (p less than 0.05) correlation was observed between the percentage increase of clearance and both shear-thinning index (r = 0.62) and the thixotropic index (r = 0.63). These results suggest that the shear-dependent properties of mucus, associated with a repetitive coughing, may increase the efficiency of mucus clearance by air flow mechanisms.
Effect of cytostatic agents on the number of alveolar phagocytes and the efficacy of ceftriaxone in an experimental murine lung infection
Authors: Calame W , Mattie H
Published: November 2022

Mice made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide were infected by exposure to an aerosol containing Klebsiella pneumoniae. Eighteen hours later ceftriaxone was administered and three hours after that the experiment was ended. At the time of infection and at 18 and 21 h the numbers of alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid were significantly lower in the cyclophosphamide-pretreated animals than in the controls. Furthermore, outgrowth of K. pneumoniae in the lungs was significantly stronger in cyclophosphamide-pretreated mice and a fourfold higher dose of ceftriaxone was needed to obtain the same antibacterial effect as in the controls. In the etoposide-pretreated mice the number of alveolar macrophages in BAL was not significantly lower than that in the controls, but the number of granulocytes was. Compared with the controls, there was no significant difference in the number of K. pneumoniae in the lungs, and the efficacy of ceftriaxone did not differ either.
Alveolar accumulation of hyaluronan and alveolar cellular response in bleomycin-induced alveolitis
Authors: Nettelbladt O , Scheynius A , Bergh J , Tengblad A , Hallgren R
Published: November 2022

Hyaluronan (HA) accumulating in the alveolar interstitial tissue of rats injured by a single intratracheal instillation of bleomycin has been visualized histologically and assayed. HA was present already by Day 1 after bleomycin treatment, increased to a maximum value on Days 3 and 7 and then declined. A time-dependent relationship between this early connective tissue response and the invasion of inflammatory cells in the alveolar tissue was apparent. The dominating invading cells by Day 1 were granulocytes showing positive staining for the monoclonal antibody OX-42 reflecting the C3b receptor. The numbers of macrophages expressing class II antigens started to increase on Day 1, reaching a maximum on Days 3-7 and then declined. Macrophages were the dominating OX-42+ cells by Day 7. The appearance of W3/13+ cells ("pan-T-lymphocytes") showed a similar pattern to that for the class II expressing macrophages. The number of cells expressing CD4 antigen increased until Day 3 and levelled off on Day 30 whilst the largest number of cells expressing CD8 antigen was seen on Day 30. Few cells expressing B-cell phenotype outside lymph nodules were identified. Alveolar lining epithelial cells, probably epithelial type II cells, expressed class II antigens by Days 3-14. The time-related accumulation of HA and the appearance of T-cells, macrophages and granulocytes expressing signs of activation suggests that these cells may be involved in the early connective tissue response of the lung injured by bleomycin.
Hyperreactivity and 45Ca movements in sensitized guinea-pig tracheal muscle
Authors: Perpina M , Cortijo J , Fornas E , Palau M , Ortiz JL , Morcillo E
Published: November 2022

Responses to KCl and histamine and 45Ca movements were studied in trachea from normal and actively sensitized guinea-pigs. Sensitized tracheas were hyperresponsive and hypersensitive to KCl and histamine. 45Ca uptake experiments show that sensitized tracheal muscle behaves as normal except that the uptake of 45Ca in low concentration (0.03 mM) Ca2+ solution was higher and the number of binding sites for the high affinity component of 45Ca uptake (as estimated by Scatchard-coordinate plot) was augmented. Additionally, in sensitized tracheal muscle, incubation in low (0.03 mM) Ca2+ solution followed by La3+ wash-out resulted in a greater amount of residual 45Ca than in normal tissues. KCl, but not histamine, increased the La3+ resistant 45Ca content. This increase was greater in sensitized than in normal trachea. This demonstrates the existence of hyperreactivity and altered 45Ca movements in sensitized trachealis muscle.
Neurilemmoma of the intrathoracic vagus nerve
Authors: Davis CJ , Butchart EG , Gibbs AR
Published: November 2022

A neurilemmoma (Schwannoma) of the left intrathoracic vagus nerve was discovered on a chest radiograph of a 28 yr old woman and was removed via a left thoracotomy. Although neurogenic tumours are the most common tumours of the mediastinum, they rarely involve the intrathoracic vagus nerve.
The distribution of myeloperoxidase, eosinophil cationic protein, albumin and urea in sequential bronchoalveolar lavage
Authors: Schmekel B , Venge P
Published: November 2022

The distribution of myeloperoxidase (MPO) and eosinophil cationic protein (ECP), secreted from activated neutrophils and eosinophils, was estimated in bronchoalveolar lavage fluid in a sequential lavage study performed on 12 healthy subjects. Four 50 ml aliquots were sequentially injected into the right middle lobe and immediately aspirated. Recent studies, using radiological methods, have revealed proximal airway distribution of the first infused lavage aliquot, and more peripheral distribution of the following ones. We found significantly higher concentrations of MPO (p less than 0.001) and ECP (p less than 0.001) in the first aspirated aliquots as compared to the following three. These findings are compatible with the concept that these substances are, to a substantial part, distributed to the surface of the proximal airways. In contrast, the sequential recovery of albumin and urea showed a homogeneous recovery pattern. The findings were compatible with those of a small series of sixteen 10 ml lavage aliquots, sequentially infused and aspirated, also indicating a continuous diffusion of these small molecules through the lung membranes into the lavage fluid during the lavage process. We conclude that the difference in recovery pattern and distribution on the bronchial surface makes albumin and urea unsuitable as denominators in ratios to MPO and ECP, for the estimation of quantitative local concentration in epithelial lining fluid.
Platelet-activating factor impairs mucociliary transport and increases plasma leukotriene B4 in man
Authors: Nieminen MM , Moilanen EK , Nyholm J-E , Koskinen MO , Karvonen JI , Metsa-Ketela TJ , Vapaatalo H
Published: November 2022

We assessed the effect of inhaled platelet-activating factor (PAF) on tracheobronchial clearance, pulmonary function and blood pressure in seven healthy volunteers. After inhalation of 500 micrograms of PAF, retention of radioaerosol in ciliated airways measured at 4 h was 80% higher than in the control recording, and the clearance was reduced by 33% (p less than 0.005). Acetylsalicylic acid (ASA) did not abolish the phenomenon. PAF also decreased forced expiratory volume in one second (FEV1) by 16% (p less than 0.01), which was markedly attenuated by acetylsalicylic acid. The decrease in blood pressure after PAF (p less than 0.01) was not influenced by acetylsalicylic acid. Plasma leukotriene B4 (LTB4) was increased at 20 min after PAF inhalation (without and with ASA: mean 240 and 299 pg.ml.1, respectively) as compared to the baseline (144 and 166 pg.ml.1) and the values at 60 min after the challenge (133 and 178 pg.ml.1; p less than 0.05 and p less than 0.01, respectively). Only three out of seven subjects showed a bronchial hyperresponsiveness to methacholine measured 24 h after PAF. The PAF-induced reduction of mucociliary transport seems to be independent of cyclo-oxygenase products of arachidonic acid metabolism. These autacoids are, however, believed to contribute to the acute bronchial obstruction after PAF inhalation. In addition, inhaled PAF causes a transient increase in plasma LTB4.
Isoniazid resistant tuberculosis in a school outbreak: the protective effect of BCG
Authors: Shannon A , Kelly P , Lucey M , Cooney M , Corcoran P , Clancy L
Published: November 2022

An outbreak of isoniazid resistant tuberculosis occurred in a large second level school. A total of 1,160 teenage pupils were at risk. Nineteen cases of tuberculosis were diagnosed, 15 were students, 9 of whom were among 251 non-vaccinated students and 6 among 909 vaccinated students. Two cases of miliary tuberculosis, one of whom also had tuberculous (TB) meningitis, occurred in the non-vaccinated group. The number of children with Heaf grade +3 or +4 was significantly greater among children who had been given Bacille Calmette-Guerin (BCG) vaccination (8 vs 4.4%). This suggests a boosting effect on the response in vaccinated children. The protective effect of neonatal BCG vaccination in this school outbreak suggests that it provides significant protection against tuberculosis lasting into adolescence.
S-erythropoietin levels decrease in patients with chronic hypoxia starting domiciliary oxygen therapy
Authors: Strom K , Odeberg H , Andersson AC , Boe J , Singer J , Svensson G
Published: November 2022

Consecutive determinations of erythropoietin in serum (s-Epo) were made in ten patients with chronic hypoxia starting domiciliary long-term oxygen therapy (LTO). After 24 h of supplementary oxygen treatment there was a fall in the median s-Epo level from 11.3 to 4.4 IU.l-1 (p less than 0.01). The initial decrease in s-Epo in conjunction with oxygen treatment was not sustained after one and three months of LTO. S-Epo levels above the reference range (3.3-13.5 IU.l-1) were found in three patients before and during LTO and in another two patients during LTO. Markedly elevated s-Epo levels were found in two patients with hypoxia and hypercapnia at the time of blood sampling. A significant negative relationship was found between the arterial oxygen tension and the log value for the s-Epo level (r = 0.40, p less than 0.005). The s-Epo levels were found to be normal in half of the measurements in patients using oxygen less than 15 h daily, a fact that indicates that s-Epo measurements are probably not suitable as indicators of compliance with LTO.
Effects of indomethacin and PEEP on oleic acid induced pulmonary oedema in rabbits
Authors: Panaretto KS , Phillips C , Berend N
Published: November 2022

This study was designed to determine whether indomethacin, a suggested treatment for adult respiratory distress syndrome (ARDS), would inhibit the efficacy of positive end-expiratory pressure (PEEP) in an animal model of ARDS. Functional residual capacity (FRC), alveolar-to-arterial oxygen difference (A-aPo2) and total lung water were measured in rabbits: 30 controls and 30 with oleic acid induced pulmonary oedema. Within each group, four treatments were administered: diluent (n = 12), PEEP (n = 6), indomethacin (n = 6), or PEEP + indomethacin (n = 6). Lung injury was induced at 30 mins and treatment commenced at 45 min. Oleic acid caused a significant increase at 3 h in % increase in A-aPo2 from baseline (105 +/- 12%) attenuated by PEEP (59 +/- 17%) and indomethacin (57 +/- 7%), with the combination of PEEP + indomethacin preventing a significant increase (26 +/- 9%). PEEP increase FRC in both saline and oleic acid animals; this was not reversed by indomethacin. Oleic acid caused an increase in total lung water (5.16 to 6.58 +/- 0.16 g), not influenced by any treatment. These findings suggest that indomethacin did not inhibit the efficacy of PEEP in this model of ARDS.
Bronchiolitis obliterans organizing pneumonia and rheumatoid arthritis
Authors: van Thiel RJ , van der Burg S , Groote AD , Nossent GD , Wills SH
Published: November 2022

Bronchiolitis obliterans, with or without organizing pneumonia, can be a serious and life-threatening complication of rheumatoid arthritis. We describe a case of bronchiolitis obliterans organizing pneumonia in a patient who recently developed rheumatoid arthritis, presenting as a severe respiratory insufficiency. Diagnosis was made by means of open lung biopsy. Treatment with corticosteroids induced a quick response and substantial improvement of the respiratory symptoms. A simultaneous strong rise in titres of serological tests suggests a relationship between the bronchiolitis obliterans organizing pneumonia and the rheumatoid arthritis.
Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome
Authors: Eiser N , Denman WT , West C , Luce P
Published: November 2022

The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension (PCO2) levels ("pink puffer" syndrome). In this double-blind, cross-over, randomized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 "pink puffer" patients. Their mean resting forced expiratory volume in one second (FEV1) was 36% predicted normal, mean arterial oxygen tension (PaO2) was 9.2 kPa and mean PaCO2 was 5.2 kPa. Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks, recording on a diary card dyspnoea, sleepiness and well-being on a visual analogue scale (VAS). The final treatment was given 30 min before measuring spirometry, arterial blood gases, plasma morphine levels, 6 min walking distances, time walked on treadmill and self-assessment of dyspnoea on a VAS scale after exercise. On two further days, eight patients took two doses, 4 h apart, of either diamorphine 7.5 mg or placebo elixir. Spirometry, 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose. Morphine levels and blood gases were also measured. Whether given in single or repeated doses, oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo. Diamorphine 2.5-7.5 mg produced neither sleepiness nor a deterioration in blood gases. However, plasma levels associated with analgesic efficacy were not achieved with these doses. Thus, as given in this study, oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the "pink puffer" syndrome.
Total respiratory resistance and reactance in ankylosing spondylitis and kyphoscoliosis
Authors: van Noord JA , Cauberghs M , Van de Woestijne KP , Demedts M
Published: November 2022

Ankylosing spondylitis and kyphoscoliosis both alter the function of the lung by modifying the mechanical properties of the thoracic cage. The purpose of the present study was to assess the changes in total respiratory resistance (Rrs) and reactance (Xrs) in these patients and to compare these data with conventional pulmonary function tests. In 16 patients with ankylosing spondylitis and seven with kyphoscoliosis we measured lung volumes, maximal flows, diffusing capacity, airway resistance, lung compliance and Rrs and Xrs between 2-26 Hz by means of the forced oscillation technique (FOT). In the patients with ankylosing spondylitis mean total lung capacity was 83% predicted (range 60-105%). Mean values of Rrs were normal; there was a small decrease in Xrs at the lowest frequency. In the patients with kyphoscoliosis mean total lung capacity (TLC) was 41% predicted for arm span (range 26-75%). Mean Rrs was elevated with a negative frequency dependence, and mean Xrs was decreased. The observed differences in Rrs and Xrs between the two groups of patients are related to differences in severity of the restriction. There is evidence that the changes in Rrs and Xrs in both groups are mainly attributable to an increase in chest wall resistance and a decrease in chest wall compliance, while in the patients with kyphoscoliosis an increase in airway resistance and a decrease in lung compliance also intervenes.
Ventilatory parameters in healthy nonsmoking adults of Adriatic islands (Yugoslavia)
Authors: Smolej-Narancic N , Pavlovic M , Rudan P
Published: November 2022

Forced expiratory volumes and flows (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) peak expiratory flow (PEF), maximal expiratory flow at 25% (MEF25%), 50% (MEF50%) and 75% (MEF75%) of the FVC) have been measured in 909 healthy nonsmoking men and women, ranging in age from 18-86 yrs, who live on Eastern Adriatic islands (Yugoslavia). This area is essentially free from air pollution. The results have been analysed in terms of age and height and regression equations for each sex were derived. The equations for FVC and FEV1 were reliable and those for forced expiratory flows were not. Comparisons were made with prediction equations derived for other populations, especially with those which are commonly used in daily medical practice.
The interaction of acetylcholine and histamine on human bronchial smooth muscle contraction
Authors: Knight DA , Phillips MJ , Stewart GA , Thompson PJ
Published: November 2022

The interaction of histamine (Hist) and acetylcholine (ACh) on human isolated bronchial smooth muscle (HIBSM) contraction, and the influence of the epithelium, was assessed using HIBSM obtained from 15 patients undergoing thoracotomy. Cumulative concentration effect curves for ACh and Hist, together with combinations of equipotent concentrations of both agonists, were generated using both epithelium-intact and epithelium-denuded HIBSM. In epithelium-denuded HIBSM both ACh (p less than 0.05) and Hist (p less than 0.005) produced a significantly enhanced maximal response and a 2.1 fold increase in the potency of ACh (p less than 0.02, n = 13). When ACh and Hist were added simultaneously, in equipotent concentrations, to epithelium-intact HIBSM, a significantly less (p less than 0.0005, n = 13) than additive response occurred with only 60% of the predicted maximum response being observed. However, following epithelium removal, an additive interaction between the two agonists (n = 8) occurred. Using HIBSM from five of the original 15 patients, similar experiments were performed to determine the influence of the muscarinic receptor antagonist atropine (0.1 microM) and the H1 receptor antagonist mepyramine (10 microM). Both resulted in a significantly less than additive interaction (40-50% of predicted tensions). Similar experiments were also performed in the presence of the cyclo-oxygenase inhibitor indomethacin (5 microM) and these failed to reverse the inhibition observed in HIBSM contraction (n = 5). The inhibitory interaction between ACh and Hist appears to be epithelium dependent and is not mediated via the release of prostanoids. Thus, there appears to be a complex interaction between contractile agonists and the epithelium, which is not just a simple summation of the activation of individual receptors on HIBSM.
Does PEEP facilitate the resolution of extravascular lung water after experimental hydrostatic pulmonary oedema?
Authors: Blomqvist H , Wickerts CJ , Berg B , Frostell C , Jolin A , Hedenstierna G
Published: November 2022

The effect of mechanical ventilation with positive end-expiratory pressure on the resolution of hydrostatic pulmonary oedema created by temporary left atrial balloon inflation was studied in mechanically ventilated dogs. Immediately after the hydrostatic process was terminated, by deflating the left atrial balloon, the animals were ventilated for 4 h with zero end-expiratory pressure (ZEEP, n = 6) or with a positive end-expiratory pressure (PEEP, n = 6) of 1.0 kPa (10 cmH2O). Gas exchange and extravascular lung water content (EVLW) with the double indicator dilution technique (dye/cold) were studied and gravimetric determination of lung water was made postmortem. EVLW decreased from 31.6 +/- 7.3 mean +/- SD ml.kg.1 during maximal oedema to 14.5 +/- 2.1 ml.kg.1 (p less than 0.001) 4 h after deflation of the left atrial balloon in dogs ventilated with ZEEP. The corresponding values in dogs ventilated with PEEP were a reduction in EVLW from 28.0 +/- 4.1 to 20.7 +/- 4.0 ml.kg.1 (p less than 0.01) (mean decrease 7.3 +/- 4.0 ml.kg.1). EVLW was significantly higher after 4 h on PEEP than after ZEEP (p less than 0.01). Gravimetric values at the end of the experiment were 12.4 +/- 2.8 ml.kg.1 (ZEEP) and 14.7 +/- 4.5 ml.kg.1 (PEEP) (NS). Oxygenation improved in both groups during the resolution of oedema with a more evident and early effect in the PEEP group. It is concluded that mechanical ventilation with PEEP of 1.0 kPa (10 cmH2O) in the resolution phase after experimental hydrostatic oedema improves oxygenation but retards the resolution of oedema.
The effect of altering airway tone on the sensitivity of the cough reflex in normal volunteers
Authors: Smith CA , Adamson DL , Choudry NB , Fuller RW
Published: November 2022

Cough is frequently the presenting symptom of bronchial asthma, although cough can result from a wide variety of other respiratory disease. Treatment of chronic cough has proved extremely difficult. It has been suggested that treatment with bronchodilators may reduce the symptom of cough. In this study the effect of altering airway tone on the sensitivity of the cough reflex was determined. Twelve normal, healthy volunteers took part. The number of coughs following inhalations of single breaths of doubling concentrations of capsaicin (1.95-500 microM) was recorded before and after doses of salbutamol, methacholine and saline which altered forced expiratory volume in one second (FEV1) by 6.2 +/- 2.6%, -8.8 +/- 3.2% and -0.18 +/- 1.38%, respectively. In a further study the cough response was recorded before and after doses of salbutamol and ipratropium bromide, both of which reduced baseline respiratory resistance and resistance measured after capsaicin. Ipratropium bromide, salbutamol and methacholine, despite having significant effects on airway tone, did not change the sensitivity of capsaicin-induced cough. Thus, if bronchodilator drugs are antitussive in non-asthmatic patients, then this is unlikely to be due to an effect on the sensitivity of the cough reflex.
Oxygen delivery to tissues
Authors: Samsel RW , Schumacker PT
Published: November 2022

For health, well perfused tissues, oxygen uptake is determined primarily by metabolic need rather than by oxygen supply. Tissue hypoxia supervenes when tissue oxygen tension (PO2) falls below a critical point, and the point where this occurs can be predicted from the systemic oxygen delivery or extraction ratio. A growing body of evidence suggest that tissue oxygen extraction may be impaired in adult respiratory distress syndrome (ARDS) and sepsis. In these syndromes the minimum oxygen delivery needed to maintain a normal oxygen uptake appears to be increased, as tissues become hypoxic despite high levels of delivery. However, controversy surrounds every phase of this observation, from its experimental basis, to potential causes, to its implications for patient care. In this review, we discuss the physiology of oxygen transport, the determinants of tissue oxygenation in normal and pathological states, and the therapeutic implications of oxygen transport.