bluuebunny/crossref_metadata_2025 huggingface dataset:
Idiopathic bronchiolitis obliterans organizing pneumonia with multiple cavitary lung nodules
Authors: Haro M , Vizcaya M , Texido A , Aguilar X , Arevalo M
Published: June 2003

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pulmonary disorder with a wide spectrum of radiological features. We report the case of a 58 year old woman, in whom the radiological appearance was multiple cavitary nodules in both lungs, that responded with a complete resolution after corticosteroid therapy. This finding justifies the inclusion of BOOP in the differential diagnosis of multiple cavitary nodules.
Psychogenic vocal cord dysfunction simulating bronchial asthma
Authors: Mobeireek A , Alhamad A , Al-Subaei A , Alzeer A
Published: June 2003

Upper airway obstruction can mimic bronchial asthma. A particular type results from psychogenic dysfunction of the vocal cord, and presents as bronchial asthma or organic upper airways obstruction. If not recognized, ineffective and potentially harmful therapy is given instead of focusing on the underlying psychopathology. We report three Saudi females with this condition, in whom polygamy and a large family system created associated social stress. Spirometry with a flow volume loop showed characteristic features, and in all three this test was the most important clinical tool that led to the correct diagnosis. Clinicians should perform spirometry and flow-volume loop tests routinely in patients presenting with asthmatic symptoms, and look for clues suggestive of this condition, including a psychosocial assessment.
Pulmonary veno-occlusive disease in a HIV-infected intravenous drug abuser
Authors: Escamilla R , Hermant C , Berjaud J , Mazerolles C , Daussy X
Published: June 2003

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Its origin remains unknown but in some cases a viral aetiology has been suggested. Recently primary pulmonary hypertension has been increasingly observed in patients with human immunodeficiency virus (HIV) infection, but only one case of pulmonary veno-occlusive disease has so far been described. We report the case of a 27 year old male intravenous drug abuser with HIV infection and pulmonary hypertension. Open lung biopsy led to the diagnosis of pulmonary veno-occlusive disease. This second case of pulmonary veno-occlusive disease raises the question of a relationship between HIV infection and lesions involving the pulmonary veins. However, the pathogenesis of vascular changes remains to be elucidated.
Outcome of wheeze in childhood: the influence of atopy
Authors: Ross S , Godden DJ , Abdalla M , McMurray D , Douglas A , Oldman D , Friend JA , Legge JS , Douglas JG
Published: June 2003

We have previously demonstrated that the adult outcome of childhood asthma differs from that of wheeze occurring only in the presence of infection. This paper examines the role of atopy in relation to outcome. We investigated the atopic status, current symptoms and bronchial reactivity to methacholine of 235 subjects aged 34-40 yrs, originally classified at age 10-15 yrs as having asthma (asthma group), wheeze only in the presence of infection (wheezy group), or no respiratory symptoms (comparison group). Subjects from the original asthma group were more likely to be atopic as defined by skin test reactivity, total serum immunoglobulin E (IgE) measurement or specific IgE radio allergosorbent test (RAST) measurement than those from the wheezy group. The wheezy group differed significantly from the reference group only in RAST results, when other variables were taken into account. In a logistic regression model, the important independent predictors for adult wheezing symptoms were original group, atopy and current smoking. Methacholine responsiveness was independently associated with original group (the asthma group were more likely to respond positively), atopy and female gender. The results suggest that atopy is an important predictor for wheeze and bronchial hyperreactivity in middle age. However, the difference in outcome for children who had asthma compared to those who had wheeze only in the presence of infection cannot be explained by atopy alone.
Spontaneous cervical subcutaneous and mediastinal emphysema secondary to occult sigmoid diverticulitis
Authors: Hur T , Chen Y , Shu GH , Chang JM , Cheng KC
Published: June 2003

We present a case of spontaneous mediastinal and subcutaneous cervical emphysema due to perforation of an occult sigmoid diverticulitis. Mediastinal emphysema should alert the physician to the possibility of retroperitoneal gastrointestinal perforation, even in patients without signs of distinct peritoneal irritation.
Treatment of community-acquired pneumonia: a randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and erythromycin
Authors: Lode H , Garau J , Grassi C , Hosie J , Huchon G , Legakis N , Segev S , Wijnands G
Published: June 2003

The treatment of community-acquired pneumonia is empirical in most cases and must cover a wide range of potential pathogens, such as Streptococcus pneumoniae, including penicillin-resistant strains, Haemophilus influenzae and intracellular microorganisms. The objective of this double-blind, randomized, parallel group study was to compare the efficacy and safety of sparfloxacin (400 mg loading dose, followed by 200 mg o.d.) with that of oral amoxycillin-clavulanic acid (500/125 mg t.i.d.) or oral erythromycin (1 g b.i.d.), during 7-14 days in 808 patients with confirmed community-acquired pneumonia. The overall success rates for sparfloxacin (87%), amoxycillin-clavulanic acid (80%) and erythromycin (85%) were similar in evaluable patients, and the equivalence hypothesis used for the statistical analysis showed at least an equivalent efficacy for the three antibiotics tested. The analysis of microbiologically documented infections (40% of the patients) showed that overall success rates were similar for S. pneumoniae and H. influenzae infections. Treatment withdrawal was necessary in 3.5, 2.5 and 7.7% of the patients treated with sparfloxacin, amoxycillin-clavulanic acid and erythromycin, respectively. This study indicates that sparfloxacin was at least as effective as amoxycillin-clavulanic acid or erythromycin in the treatment of mild-to-moderate community-acquired pneumonia and that the adverse effects were similar in the three groups.
Evaluation of a novel tuberculosis complex-specific 34 kDa protein in the serological diagnosis of tuberculosis
Authors: Amicosante M , Barnini S , Corsini V , Paone G , Read CA  , Tartoni PL , Singh M , Albera C , Bisetti A , Senesi S , et al.
Published: June 2003

Tuberculosis (TB) serological testing with antigen complexes, although very sensitive, is not always as specific due to reactive serum antibodies in patients with inactive TB or nontuberculous infections. Since the use of recombinant M. tuberculosis proteins may enhance specificity, this study was designed to evaluate a novel 34 kDa tuberculosis complex-specific protein as a component of an antigen panel of recombinant proteins. Seventy patients with active TB (41 positive and 29 negative for acid-fast bacilli (AFB) in sputum) were evaluated, in comparison with 30 tuberculin purified protein derivative skin test positive (PPD+) and 30 PPD- normals, 20 subjects with inactive TB and 20 PPD+ subjects with nontuberculous pneumonia as controls. Serum antibody levels were quantified using enzyme linked immunosorbent assay (ELISA) tests with MS2-34, a fusion protein comprising the NH2-terminal 16 kDa of the 34 kDa protein, a recombinant 38 kDa protein (p38), and PPD. Using MS2-34 and p38 as an antigen panel in active TB patients yielded higher sensitivity and negative predictive value (sensitivity 86%; negative predictive value 91%) than using PPD (sensitivity 66%; negative predictive value 81%). Importantly, the MS2-34+p38 panel yielded a higher sensitivity (83%) than PPD (66%) in the subset of AFB- active TB patients. Thus, this novel protein increases sensitivity and specificity of serological testing for TB when used in panels of recombinant proteins.
Pulmonary vascular dilatation and diffusion-dependent impairment of gas exchange in liver cirrhosis
Authors: Crawford AB , Regnis J , Laks L , Donnelly P , Engel LA , Young IH
Published: June 2003

To test the hypothesis that diffusion-limitation for oxygen is due to abnormal vascular dilatation and significantly contributes to the arterial hypoxaemia of liver cirrhosis requires an experimental approach that detects both diffusion-limitation for oxygen and the presence of abnormal dilatation of pulmonary vessels exposed to alveolar gas. We therefore studied the gas exchange of a 64 year old man with alcoholic liver cirrhosis and severe resting arterial hypoxaemia (arterial oxygen tension (Pa,O2) 7.5 kPa) whilst breathing air and 100% O2 using conventional blood gas (CBG) analysis, the multiple inert gas elimination technique (MIGET) and whole body scintigraphy (WBS) following the i.v. administration of radiolabelled boli of macroaggregates with a minimum diameter of 15 microM. During air breathing, there was a consistently positive difference between the arterial oxygen tension predicted by MIGET and that actually measured (P-M Pa,O2, average 0.9 kPa). During O2 breathing, P-M Pa,O2 became negative, (average -12.2 kPa), and shunt estimated by the O2 method (% of Q') was consistently less than that measured by MIGET. Whereas both O2 method and MIGET estimates of shunt never exceeded 25%, the WBS shunt was 40%, indicating that a substantial fraction of cardiac output flowed through abnormally dilated pulmonary vessels, some of which were exposed to alveolar gas and, hence, participated in gas exchange. Although our observations pertain to one subject, we believe they provide the most convincing in vivo evidence to date that abnormal dilatation of interalveolar vessels may, per se, result in a significant diffusion impairment for O2. Furthermore, in view of the consistently negative P-M Pa,O2 observed during oxygen breathing, we speculate that such abnormal vascular dilatation may also have produced a significant diffusive impairment of one or more of the less soluble inert gases used in the MIGET analysis.
Ventilatory and gas exchange abnormalities on exercise in chronic heart failure
Authors: Al-Rawas OA , Carter R , Richens D , Stevenson RD , Naik SK , Tweddel A , Wheatley DJ
Published: June 2003

The mechanism of breathlessness on exertion in patients with chronic heart failure are still not fully understood. We therefore investigated the effects of ventilatory and gas exchange abnormalities on exercise capacity in chronic heart failure. Exercise testing was performed in 30 patients with exertional breathlessness due to chronic heart failure and in 30 controls, using continuous transcutaneous blood gas monitoring. Maximal symptom-limited oxygen consumption as (V'O2) as a percentage predicted was reduced in patients (45 +/- 10%; mean +/- SD) compared to controls (87 +/- 7). The ventilatory response (minute ventilation/carbon dioxide production (V'E/V'CO2)) was significantly increased in patients compared to controls (39.9 +/- 7.7 and 25.9 +/- 3.6, respectively). The dead space to tidal volume ratio (VD/VT) was raised in patients compared to controls at rest (0.45 +/- 0.04 vs 0.35 +/- 0.02, respectively) and this persisted on exertion (0.40 +/- 0.05 in patients and 0.20 +/- 0.05 in controls). At maximal symptom-limited exercise, V'E/V'CO2 was inversely related to the % predicted V'O2 in patients, but not in controls (r = -0.62 and r = -0.24, respectively). In patients, V'E/V'CO2 was significantly correlated with VD/VT at maximum exercise (r = 0.82). Patients with chronic heart failure have a significant degree of "wasted ventilation" on exertion, which is associated with increased ventilatory response. The increased ventilatory response on exertion appears to contribute to exercise limitation in these patients.
Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites
Authors: Mannan MM , Springall DR , Enard C , Moradoghli-Haftvani A , Eddahibi S , Adnot S , Polak JM
Published: June 2003

Levels of calcitonin gene-related peptide (CGRP), a vasodilator peptide present in nerves and airway endocrine cells of the rat respiratory tract, are increased in hypoxic lung and decreased in plasma, suggesting impaired CGRP release. We wanted to determine whether there was an adaptive functional response to reduced CGRP levels in hypoxia. Density of binding sites for CGRP were compared with its vascular actions following hypoxia, and with binding following administration of the sensory neurotoxin capsaicin to deplete neural CGRP. Autoradiography of lung sections incubated with 125I-labelled CGRP and other vasoactive peptides was used to quantify their binding sites, in male Wistar rats exposed to periods of hypoxia (inspiratory oxygen fraction (FI,O2) = 0.1) ranging 0-10 days (n = 5 each), in controls, and in rats treated neonatally with capsaicin. Relaxation to CGRP was compared in pulmonary artery of control and hypoxic rats. CGRP binding was seen in the vascular endothelium and was significantly elevated after 5 days of hypoxia (mean +/- SEM: control 4.6 +/- 0.4 versus hypoxic 16.6 +/- 2.4 amol.mm-2). CGRP-induced (5 x 10(-7)M) relaxation of pulmonary artery was reduced, compared with controls, following 8 and 21 days of hypoxia (mean +/- SEM) percentage of relaxation to phenylephrine: 78 +/- 3, 36 +/- 5 and 32 +/- 3, respectively) and was abolished by removal of endothelium. Capsaicin treatment also significantly elevated vascular CGRP binding. Atrial natriuretic peptide (ANP) binding levels were decreased in smooth muscle of all blood vessels after 7 days of hypoxia, but endothelin-1 (ET-1) and vasoactive intestinal peptide (VIP) binding was unchanged. We conclude that the vasodilator effects of CGRP are endothelium-dependent and, whilst they are reduced in hypoxic lung, this is not due to reduction in receptors, thereby implicating alterations in the nitric oxide guanylyl cyclase system. Furthermore, adaptive responses in some peptide binding sites occur in hypoxia, which may be due to changes in endogenous peptide levels.
Inhibition of factor Xa-mediated procoagulant activity of human lung fibroblasts and pleural mesothelial cells
Authors: Kumar A , Koenig KB , Johnson AR , Fair DS , Idell S
Published: June 2003

Extravascular fibrin deposition characterizes diverse forms of lung and pleural injury. Fibrin formation in these compartments is locally potentiated by the assembly and expression of the prothrombinase procoagulant complex (factors Xa, Va and II) at the surface of human lung fibroblasts and pleural mesothelial cells. We sought to identify structural domains on factor Xa that mediate expression of prothrombinase activity by these cells. In order to accomplish this objective, we used panels of monoclonal antibodies (MoAbs) to factor X to block prothrombinase assembly and function on the surface of cultured human lung fibroblasts and pleural mesothelial cells. Of 30 factor X MoAbs that recognized native factors X and Xa, 10 completely inhibited factor Xa function (prothrombin activation), and five others neutralized Xa function without affecting cell-binding, presumably by blocking the prothrombin binding site. Western blots showed that these inhibitory MoAbs reacted with the Xa heavy-chain. One MoAb that recognized the factor Xa light-chain blocked prothrombin activation at the factor Va binding site. Our results indicate that prothrombinase activity at the surface of lung parachymal or pleural cells can be blocked by MoAbs that interact with either the heavy- or light-chain of factors X. Antibodies that neutralize cell surface-expressed prothrombin activation offer a potential means to arrest pericellular fibrin formation in the lung and pleural space.
Cross-sectional assessment of workers with repeated exposure to chlorine over a three year period
Authors: Gautrin D , Leroyer C , L'Archeveque J , Dufour JG , Girard D , Malo JL
Published: June 2003

Airflow obstruction has been described in workers who experienced symptoms after acute exposure to chlorine. Persistent bronchial hyperresponsiveness has also been assessed, but mainly in case studies. In this cross-sectional study, we have assessed the relationship between inhalational accidents ("puffs") involving chlorine and persistent symptoms as well as hyperresponsiveness in 239 out of 255 at-risk workers (94%). No relationship was found between persistent symptoms and the exposure variables studied. Forced vital capacity (FVC) was higher in subjects who had had no symptoms after a "puff", compared with those who had experienced mild symptoms. Forced expiratory volume in one second (FEV1) and FVC were significantly lower in subjects who experienced more than 10 puffs with mild symptoms than in subjects who reported no symptomatic puff. The presence of bronchial hyperresponsiveness was not related to exposure, but the methacholine dose-response slope showed a tendency to increased bronchial responsiveness with increased exposure. A significant difference was shown in subjects who experienced more than 10 puffs with mild symptoms. In this group of workers, repeated exposure to chlorine with acute respiratory symptoms was associated with a slight but significant reduction in expiratory flow rates, together with an increase in bronchial responsiveness, without long-term symptoms.
Respiratory symptoms in elderly Chinese living in Hong Kong
Authors: Lai CK , Ho SC , Lau J , Yuen YK , Ho SS , Chan CH , Woo J
Published: June 2003

Respiratory diseases can cause considerable disability in the elderly because of their limited respiratory reserve as a result of ageing. We have investigated the prevalence of respiratory symptoms and diseases in elderly Chinese in Hong Kong and compared these data with those in elderly Caucasian populations. Two thousand and thirty two (999 male and 1,033 female) subjects, selected by age-stratified random sampling from a register of Hong Kong residents aged 70 yrs and over were interviewed to complete a respiratory questionnaire. Total serum immunoglobulin E (IgE) was measured in 195 subjects. At least one respiratory symptom was reported by 56% of subjects. The most frequently reported symptoms were morning phlegm (26%), chronic cough with phlegm (10%) and wheeze in the past 12 months (8%). Of the self-reported diseases, the commonest was chronic bronchitis (7%), followed by asthma (5%), pulmonary tuberculosis (3%) and emphysema (2%). Of the 218 subjects with obstructive airway diseases, 128 (59%) had sought medical advice in the past 12 months. The most important determinants for respiratory symptoms and diseases were smoking and social class. Total serum IgE was significantly higher in current smokers than nonsmokers and also in those with chronic cough and phlegm than those without these complaints. Our study shows that respiratory ailments in Hong Kong elderly are as common as those reported in Sweden and the USA but less than those in England.
Home treatment for chronic respiratory failure in children: a prospective study
Authors: Fauroux B , Sardet A , Foret D
Published: June 2003

Home treatment for children with chronic respiratory failure (CRF) is increasing. However, the causes of CRF in children and the details of their home treatment are not well-known. The aim of this study was to describe the causes of CRF in the paediatric population and the treatments that the patients received at home. We surveyed all children (aged < or = 18 yrs) entering the Association Nationale pour le Traitement a Domicile de l'Insuffisance Respiratoire chronique (ANTADIR) for home treatment of CRF between March 1992 and March 1993. Two hundred and eighty seven children (178 boys, 62%) started home treatment for CRF during the year. One hundred and eleven patients had obstructive respiratory disease: cystic fibrosis (CF) (n = 24); bronchopulmonary dysplasia (BPD) (n = 79); other obstructive respiratory disease (n = 8). One hundred and seventy six patients had restrictive lung disease: neuromuscular disease (n = 87); kyphoscoliosis (n = 21); pulmonary fibrosis (n = 6); cardiac disease (n = 14); stomatological disease (n = 10); other restrictive respiratory disease (n = 9); and 29 miscellaneous causes. One hundred and thirteen patients received oxygen therapy, with a mean daily use of 17.7 h (20 h.day-1 for BPD patients and 12.3 h.day-1 for CF patients). Oxygen was delivered by a concentrator in 88% of cases. One hundred and fifty eight children received mechanical ventilation (MV). Five children received nasal continuous positive airway pressure ventilation for sleep apnoea, four had pneumatic belt ventilation, and 12 had a tracheostomy without MV. Treatment was stopped in 21 children, because of death in nine and improvement in the other 12. Home treatment for children with CRF is well developed in France via the ANTADIR network. Causes of CRF in children are heterogeneous, with a relatively good prognosis.
Lung function measurement in awake young children
Authors: Bisgaard H , Klug B
Published: June 2003

The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint) and transcutaneous measurements of oxygen tension (Ptc,O2) were compared with concomitant measurements of specific airway resistance (sRaw) and forced expiratory volume in one second (FEV1) by whole body plethysmography and spirometry, respectively, during methacholine challenge in 21 young children aged 4-6 yrs, with suspected asthma. Measurements with each technique were repeated after each challenge step. A special face-mask was developed with an integrated mouthpiece which ensured mouth breathing during the measurements. The order of sensitivity of the techniques to assess methacholine-induced changes in lung function was ZIOS > sRaw > Ptc,O2 > FEV1 > Rint. ZIOS was significantly more sensitive than all subsequent methods, and Ptc,O2 was significantly more sensitive than FEV1. ZIOS, sRaw and Rint, but not Ptc,O2 and FEV1, detected the subclinical increase in bronchial muscle tone in the children during baseline, which was revealed by the significantly reduced airway obstruction after inhalation of a beta 2-agonist as compared to baseline. It is concluded that ZIOS, Rint and Ptc,O2 change in parallel with sRaw and FEV1 and with a comparable sensitivity during simultanoeous measurements of the response to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children.
Frequency of nocturnal symptoms in asthmatic children attending a hospital out-patient clinic
Authors: Meijer GG , Postma DS , Wempe JB , Gerritsen J , Knol K , van Aalderen WM
Published: June 2003

Since nocturnal symptoms indicate more severe asthma, we investigated their frequency in a hospital-based population of asthmatic children. Recognition of these symptoms offers the possibility to introduce appropriate treatment. We studied 796 consecutive children with asthma (mean (SD) age 9 (4) yrs) attending a hospital clinic, to determine whether these nocturnal symptoms predicted that daytime activities would be affected, and also the patients' perception of disease severity. At the end of a regular out-patient clinic visit, the answers to seven different questions concerning nocturnal symptoms in the previous 3 weeks were recorded. The forced expiratory volume in one second (FEV1) was > or = 90% predicted in 98% of the population that was able to perform lung function measurements (72% of the total population). In 38% of the patients with nocturnal symptoms, these symptoms were reported spontaneously. When asked for, nocturnal symptoms were reported by 47% of the children; 6% every night and 34% at least once a week. Cough was the most frequently reported symptom (31%). Children with nocturnal symptoms had a lower FEV1, scored their perception of asthma as more severe, and had their daytime activities affected more than those without nocturnal symptoms. Doctors should specifically ask about nocturnal symptoms, as not all patients with nocturnal symptoms report them spontaneously and they predict more severe disease.
Facial cooling, but not nasal breathing of cold air, induces bronchoconstriction: a study in asthmatic and healthy subjects
Authors: Koskela H , Tukiainen H
Published: June 2003

Reflex-mediated bronchoconstriction in cold climates may be more important than it has previously been thought. This issue has seldom been studied using physiological methods. We wanted to investigate, using physiological methods, what triggers the bronchoconstriction occurring at cold ambient temperature during resting nasal ventilation: cooling of the skin of the face or cooling of the nasal cavity. Three experiments were carried out in 15 stable asthmatics and 10 healthy volunteers: 1) a whole-body exposure to subfreezing temperature in an environmental chamber, during which the subjects breathed cold air through the nose; 2) a similar exposure to subfreezing temperature except that the subjects now breathed warm air through the mouth from outside the chamber; and 3) nasal breathing of subfreezing air from a heat exchanger whilst the subjects sat at room temperature. Spirometric values and facial skin temperature were measured both during and after the exposures. Maximal decrements (means +/- standard errors) of forced expiratory volume in one second (FEV1) in experiments 1, 2 and 3 were: 5.8 +/- 0.8, 5.1 +/- 0.7 and 2.1 +/- 0.5%, respectively (p < 0.001). Only the two experiments in the environmental chamber induced significant bronchoconstriction. All responses were of similar magnitude in the asthmatic and the healthy subjects. The cooling of the skin of the face seems to be the trigger for the bronchoconstriction during resting nasal ventilation at cold ambient temperature both in asthmatic and nonasthmatic subjects.
Histamine-induced end-tidal inspiratory activity and lung receptors in cats
Authors: Meeseen NE , van der Grinten CP , Folgering HT , Luijendijk SC
Published: June 2003

Hyperinflation in acute asthma has been associated with inspiratory muscle activity, which persist during expiration. The main objective of the present study was to evaluate the role of rapidly adapting receptors (RARs), slowly adapting receptors (SARs) and C-fibre endings in generating end-tidal inspiratory activity (ETIA). ETIA was induced by intravenous administration of histamine and continuous negative airway pressure (CNAP) in anaesthetized, spontaneously breathing cats. To differentiate between reflex activities from the three types of lung receptors, both vagus nerves were cooled to eight different temperatures (Tvg) between 4 and 37 degrees C. It is known that CNAP stimulates RARs and inhibits SARs. Histamine was used to stimulate RARs, and this was combined with continuous positive airway pressure (CPAP) to further stimulate SARs. ETIA was evoked in the diaphragm and in parasternal intercostal muscles by both stimuli (histamine and CNAP) in 8 out of 18 cats. After vagotomy, neither histamine nor CNAP evoked ETIA any more. At Tvg = 37 degrees C, CPAP suppressed histamine-induced ETIA; whereas, this suppression was diminished at Tvg between 14 and 8 degrees C. ETIA sharply declined for Tvg between 8 degrees and 4 degrees C, and at Tvg = 4 degrees C ETIA had virtually disappeared. At Tvg = 37 degrees and 22 degrees C values of ETIA during CNAP were larger than those in response to histamine; whereas, at Tvg = 10 degrees C comparable ETIA values were obtained. It was shown that ETIA is a vagal reflex activity in which C-fibre endings are not involved. Histamine-induced ETIA originates from stimulation of RARs, and is inhibited by stimulation of SARs. Mechanical stimulation of RARs is a forceful stimulus to induce ETIA. This suggests that hyperinflation in acute asthma might be due, at least in part, to ETIA resulting from an imbalance between SAR and RAR activity.
Xanthine derivatives inhibit the increase in intracellular Ca2+ concentration induced by acetylcholine in nasal gland acinar cells of the guinea-pig
Authors: Ishitani K , Ikeda K , Sunose H , Wu D , Honda H , Takasaka T
Published: June 2003

Intracellular calcium is considered to play a major role in secretory responses of various exocrine cell types. We examined whether xanthine derivatives can inhibit Ca2+ mobilization and entry in secretory cells in the airways. Therefore, the inhibitory effect of xanthines in the intracellular Ca2+ concentration ([Ca2+]i) in the isolated submucosal acinar cells of the guinea-pig nasal septum was investigated by means of fluorescence ratio microscopy. The inhibitory effects on Ca2+ release from stores was examined in Ca(2+)-free conditions. Effects on Ca2+ entry were estimated by two different protocols; 1) the sustained phase in a long-term application of acetylcholine (ACh) and 2) the [Ca2+]i overshoot following removal of ACh in Ca(2+)-free conditions. Xanthine derivatives, 3-isobutyl-1-methyl-xanthine (IBMX), caffeine, and theophylline, significantly inhibited the increase in [Ca2+]i evoked by ACh; both mobilization from internal Ca2+ stores and Ca2+ entry from the external space. The rank order of potency of these xanthine derivatives was IBMX > theophylline > caffeine. The addition of dibutyryl-cyclic adenosine monophosphate (cAMP) and forskolin to nasal gland acinar cells failed to inhibit the ACh-evoked increase in [Ca2+]i. Furthermore, a protein kinase A inhibitor, H-89, did not affect the inhibitory effect of the xanthine derivatives. The action of xanthines on the present acinar cells did not involve Ca(2+)-induced Ca2+ release (CICR) or an interaction with purinergic receptors. Thus, xanthines have a direct inhibitory effect both on Ca2+ release and entry in nasal gland acinar cells, and might thereby have antisecretory activity within the airways.
The acoustic properties of snores
Authors: Beck R , Odeh M , Oliven A , Gavriely N
Published: June 2003

This study was undertaken in an attempt to characterize the acoustic properties of snoring sounds in the time and frequency domains, and to correlate between these properties and the mechanical events underlying their production. Three experimental set-ups were used: 1) Dog model--six mongrel dogs, in which partial upper airway obstruction was created by an implanted supraglottic balloon. Flow, supraglottic pressure, and snoring sounds were recorded during different degrees of obstruction. Fifteen to 20 snores from each dog (total 100 snores) were analysed. 2) Simulated human snores--Six simulated snores from each of four subjects were recorded in two locations (trachea and ambient) with simultaneous airflow, and their correlations examined. 3) Snoring patients--snores were recorded with an ambient microphone from nine subjects with "heavy" snoring and no obstructive sleep apnoea (OSA). Forty to 50 snores from each subject were analysed (total of 400 snores). The snoring sound was analysed in the time (time-expanded waveform) and frequency (power spectrum) domains. After analysing these snores, we were able to identify two dominant patterns which are distinctly different from each other: the "simple-waveform" and the "complex-waveform". The complex-waveform snore is characterized by repetitive, equally-spaced, train of sound structures, starting with a large deflection followed by a decaying amplitude wave. In the frequency domain, it is characterized by multiple, equally-spaced peaks of power (comb-like spectrum). Simple-waveform snores have a quasi-sinusoidal waveform, with a range of variants, and almost no secondary internal oscillations. Their power spectrum contains only 1-3 peaks, of which the first is the most prominent. We developed a mathematical representation of these waveforms, which is presented along with its implications. The complex-waveform snores result from colliding of the airway walls and represent actual brief airway closure. Simple-waveform snores are of higher frequency and probably result from oscillation around a neutral position without actual closure of the lumen.
Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension
Authors: Voelkel NF , Tuder RM
Published: June 2003

Chronic pulmonary hypertension leads to structural alterations of the lung vessels. The pathophysiology of this remodelling process is still poorly understood. Furthermore, the structural damage of the lung vessels limits the clinical success of vasodilator treatment. Given a genetic susceptibility, shear stress and inflammation are the principal pathogenetic factors involved in lung vessel remodelling. In this overview, we compared the lung vascular histology of patients with unexplained pulmonary hypertension, scleroderma, or acquired immune deficiency syndrome (AIDS)-associated pulmonary hypertension. We demonstrate the presence of inflammatory cells (T- and B-lymphocytes and macrophages) in plexiform lesions and discuss the potential role of growth factors (platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) in pulmonary hypertensive remodelling. Ultimately, we need to develop an in-depth understanding of the key mechanisms of gene expression and signalling pathways, which transduce signals generated from increased chronic shear stress (or from chronic hypoxia) and lead to vascular injury and repair.
Crackles: recording, analysis and clinical significance
Authors: Piirila P , Sovijarvi AR
Published: June 2003

Crackles are short interrupted breath sounds usually associated with pulmonary disorders. According to present opinion, a crackle is generated when an abnormally closed airway opens during inspiration or closes at the end of expiration. The timing of crackles in breathing cycles can be assessed with phonopneumography, their duration with time-expanded waveform analysis, and their pitch with analysis of frequency spectra. The timing, pitch and waveform of crackles are different in pulmonary disorders reflecting different pulmonary pathophysiology. This review deals with the genesis, auscultation, recording and analysis of crackles, with an emphasis on modern signal-processing methods.
Respiratory health effects of man-made vitreous (mineral) fibres
Authors: De Vuyst P , Dumortier P , Swaen GM , Pairon JC , Brochard P
Published: June 2003

The group of man-made mineral or vitreous fibres (MMMFs or MMVFs) includes glass wool, rock wool, slag wool, glass filaments and microfibres, and refractory ceramic fibres (RCFs). Experimental observations have provided evidence that some types of MMVF are bioactive under certain conditions. The critical role of size parameters has been demonstrated in cellular and animal experiments, when intact fibres are in direct contact with the target cells. It is, however, difficult to extrapolate the results from these studies to humans since they bypass inhalation, deposition, clearance and translocation mechanisms. Inhalation studies are more realistic, but show differences between animal species regarding their sensibility to tumour induction by fibres. Fibre biopersistence is an important factor, as suggested by recent inhalation studies, which demonstrate positive results with RCF for fibrosis, lung tumours and mesothelioma. There is no firm evidence that exposure to glass-, rock- and slag wool is associated with lung fibrosis, pleural lesions, or nonspecific respiratory disease in humans. Exposure to RCF could enhance the effects of smoking in causing airways obstruction. An elevated standard mortality ratio for lung cancer has been demonstrated in cohorts of workers exposed to MMVF, especially in the early technological phase of mineral (rock slag) wool production. During that period, several carcinogenic agents (arsenic, asbestos, polycyclic aromatic hydrocarbons (PAH)) were also present at the workplace and quantitative data about smoking and fibre levels are lacking. It is not possible from these data to determine whether the risk of lung cancer is due to the MMVFs themselves. No increased risk of mesothelioma has been demonstrated in the cohorts of workers exposed to glass-, slag- or rock wool. There are in fact insufficient epidemiological data available concerning neoplastic diseases in RCF production workers because of the small size of the workforce and the relatively recent industrial production.
Corynebacterium parvum versus tetracycline as pleural sclerosing agents in rabbits
Authors: Vargas FS , Wang NS , Teixeira LR , Carmo AO , Silva LM , Light RW
Published: June 2003

Tetracycline has been one of the most commonly used agents for producing a pleurodesis. However, it is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether Corynebacterium parvum is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anaesthetized male rabbits: tetracycline 35 mg.kg-1 or C. parvum 4 or 8 mg, all diluted with bacteriostatic saline solution. Twenty eight days after the instillation, the animals were sacrificed and the pleural spaces assessed macroscopically for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of C. parvum was ineffective in creating pleural fibrosis. The mean degree of pleurodesis in the 10 rabbits who received tetracycline was 3.5 +/- 0.7 (scale 0-4) whilst in the 10 rabbits that received 4 mg C. parvum it was 0.0 +/- 0.0, and in the 10 rabbits that received 8 mg C. parvum it was 0.5 +/- 0.8. Based on this study, we recommend that C. parvum should not be used as a pleural sclerosant in patients with normal pleura.
Actual pentamidine dose delivered by Respigard II nebulizer
Authors: Kim CS , Garcia L , Wanner A
Published: June 2003

The Respigard II nebulizer system is the approved method to deliver pentamidine aerosols in the USA. Although continuous operation of the nebulizer until dryness is a designated regimen, the actual pentamidine dose delivered under the operating condition has not been thoroughly studied. Pentamidine solutions (300 mg in 6 mL water) were nebulized continuously with the Respigard II nebulizer system until dryness (40 min operation). Aerosols were delivered to the lower airways via an oropharyngeal model and sampled on a filter with a standard breathing mode of 20 breaths.min-1 frequency and 750 mL tidal volume. Intermediate samples were also obtained for the initial 20 min delivery. The pentamidine dose delivered to the mouth was 1.6% of the dose placed in the nebulizer. Of the dose delivered to the mouth, 92% was delivered during the initial 20 min period. Aerosol loss in the oropharyngeal model was 15% of the dose delivered to the mouth or 0.24% of the dose initially placed in the nebulizer. Pentamidine dose delivered to the lower airways was a very small fraction of the initial dose in the nebulizer. A partial delivery for the initial 20 min was nearly comparable to complete delivery.
Fatal haemorrhage from mesenchymal cystic hamartoma of the lung
Authors: Chadwick SL , Corrin B , Hansell DM , Geddes DM
Published: June 2003

A 34 year old women was admitted to the hospital with a 9 year history of intermittent haemoptysis associated with increasing breathlessness. A working diagnosis of lymphangioleiomyomatosis was made, based on clinical, radiological and histological findings. Three years later, the patient was admitted to hospital with worsening haemoptysis, which rapidly progressed and resulted in death from massive pulmonary haemorrhage. Postmortem examination and histology revealed findings consistent with multiple mesenchymal cystic hamartomas of the lungs. This is a rare condition which has previously been described as having a good prognosis. This case is the first fatality resulting directly from the disease to be reported.
Bronchogenic cyst presenting as mediastinal mass with pleural effusion
Authors: Khalil A , Carette MF , Milleron B , Grivaux M , Bigot JM
Published: June 2003

Mediastinal bronchogenic cysts are usually identified on computed tomography (CT) as well-defined masses of variable density that may contain rim calcifications. Pleural effusion has never been described in association with these cysts. We report two cases of bronchogenic cysts with unusual presentation because of an association with a pleural effusion not explained by pulmonary infection. The patients were studied with CT scan (n = 2) and magnetic resonance imaging (MRI) of the chest (n = 1). In the first case, the pleural effusion directed diagnosis towards lung tumour; and the diagnosis of bronchogenic cyst was made on thoracotomy. In the second case, bronchogenic cyst was suspected on MRI findings. Inflammatory reaction was also suspected on the CT scan, which showed enhancement of the cyst edge. In both cases, surgical excision of the cyst was difficult because of pericystic adhesions to adjacent organs. Therefore, solely on the finding of a pleural effusion, pericystic inflammation had to be suspected.
Constrictive bronchiolitis obliterans following gold therapy for psoriatic arthritis
Authors: Schwartzman KJ , Bowie DM , Yeadon C , Fraser R , Sutton ED , Levy RD
Published: June 2003

A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.
Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness
Authors: Underwood S , Foster M , Raeburn D , Bottoms S , Karlsson JA
Published: June 2003

The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness. Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness. Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (< 48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days. The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.
Targeting the cell cycle machinery for the treatment of cardiovascular disease
Authors: Bicknell Katrina A , Surry Elizabeth L , Brooks Gavin
Published: June 2003

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.
Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin
Authors: Fang Jia-You , Hung Chi-Feng , Chiu Hsien-Chih , Wang Jhi-Joung , Chan Te-Fu
Published: June 2003

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers.