bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast Cell–Mediated Stimulation of Angiogenesis
Authors: Feoktistov Igor , Ryzhov Sergey , Goldstein Anna E. , Biaggioni Italo
Published: March 2003

Adenosine is released during tissue injury, ischemia and tumor growth, and promotes angiogenesis. Because mast cells accumulate in the proximity of new blood vessel development, we examined if they may contribute to adenosine-induced angiogenesis. We found that HMC-1 human mast cells express A
2A
, A
2B
, and A
3
adenosine receptors. The adenosine agonist NECA (100 μmol/L) increased interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and angiopoietin-2 mRNA expression. NECA-induced secretion of IL-8 and VEGF was verified by ELISA. A
2B
receptors mediate VEGF and IL-8 secretion because neither CGS21680 (selective A
2A
agonist) nor IB-MECA (selective A
3
agonist) produced this effect, and it was inhibited by the selective A
2B
antagonist IPDX but not by the selective A
2A
antagonist SCH58261 or the selective A
3
antagonist MRS1191. In contrast, the selective A
3
agonist IB-MECA (EC
50
1 nmol/L) stimulated angiopoietin-2 expression. Conditioned media from NECA-activated HMC-1 stimulated human umbilical vein endothelial cell proliferation and migration, and induced capillary tube formation. Capillary formation induced by mast cell–conditioned media was maximal if both HMC-1 A
2B
and A
3
receptors were activated, whereas activation of A
2B
receptor alone was less effective. Thus, adenosine A
2B
and A
3
receptors act in a functional cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from human mast cells.
Wavebreak Formation During Ventricular Fibrillation in the Isolated, Regionally Ischemic Pig Heart
Authors: Zaitsev Alexey V. , Guha Prabal K. , Sarmast Farzad , Kolli Arun , Berenfeld Omer , Pertsov Arkady M. , de Groot Joris R. , Coronel Ruben , Jalife José
Published: March 2003

Both fixed and dynamic heterogeneities were implicated in the mechanism of wavebreak (WB) generation during ventricular fibrillation (VF). However, their relative roles remain unclear. We hypothesized that during ischemic VF, the WBs are produced primarily because of a fixed heterogeneity; namely, the gradient of refractoriness across the ischemic border zone (BZ). Ischemia was induced in 15 isolated blood-perfused hearts by occluding the left anterior descending coronary artery. Simultaneous video imaging (≈32×32 mm
2
) of Di-4-ANEPPS fluorescence in the ischemic zone (IZ), the BZ, and the nonischemic zone (NIZ) was performed. Dominant-frequency maps were constructed to assess gradients of refractoriness during VF. We used singularity points analysis to quantify the incidence of WBs per square centimeter per second. During preischemic VF, the distribution of WBs was relatively uniform. Ischemia caused an increase of WBs in the BZ (from 6.2±2.8 to 10.8±4.0) and a decrease of WBs in the IZ (from 5.8±2.8 to 2.8±1.4), without a significant change in NIZ (from 6.4±2.3 to 4.1±1.7). This finding is fully consistent with the dominant-frequency distribution during ischemic VF: the average dominant frequency was significantly slower in IZ than in NIZ (7.8±0.7 versus 10.1±1.0 Hz), suggesting a large gradient in refractory periods across the BZ. We concluded that acute regional ischemia plays a dual role in the maintenance of VF, decreasing the incidence of WB in the IZ while increasing it in the BZ. This suggests a predominant role of fixed heterogeneities in the formation of WB during VF in acute regional ischemia.
Locus on Chromosome 6p Linked to Elevated HDL Cholesterol Serum Levels and to Protection Against Premature Atherosclerosis in a Kindred With Familial Hypercholesterolemia
Authors: Canizales-Quinteros Samuel , Aguilar-Salinas Carlos A. , Reyes-Rodríguez Eduardo , Riba Laura , Rodríguez-Torres Maribel , Ramírez-Jiménez Salvador , Huertas-Vázquez Adriana , Fragoso-Ontiveros Verónica , Zentella-Dehesa Alejandro , Ventura-Gallegos José L. , Vega-Hernández Gerardo , López-Estrada Angelina , Aurón-Gómez Moisés , Gómez-Pérez Francisco , Rull Juan , Cox Nancy J. , Bell Graeme I. , Tusié-Luna Maria Teresa
Published: March 2003

Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (
P
=0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.
Ca
2+
Sparks in Rabbit Ventricular Myocytes Evoked by Action Potentials
Authors: Inoue Masashi , Bridge John H.B.
Published: March 2003

It is not clear how many L-type Ca
2+
channels (LCCs) are required to ensure that a Ca
2+
spark is triggered during a normal mammalian action potential (AP). We investigated this in rabbit ventricular myocytes by examining both the properties of sparks evoked by APs and the activity of LCCs. We measured Ca
2+
sparks evoked by repeated APs with pipettes containing 2 mmol/L EGTA and single LCC activity in cell-attached patches depolarized to +50 mV using pipettes containing 110 mmol/L Ba
2+
. With 2 mmol/L Ca
2+
in the external solution, we observed sparks at the beginning of every evoked AP at numerous locations. Each spark was observed repeatedly at a fixed location and began during a limited interval after the AP peak. These sparks occurred with a probability of approximately unity. However, the chance that an LCC does not open during the interval when a spark is triggered is quite high (≈0.13). Therefore, because single channels open with a probability significantly lower than 1, more than one LCC must be available to ensure that sparks are triggered with a probability of approximately unity. We conclude that it is likely that a cluster of LCCs is involved in gating a cluster of ryanodine receptors at the beginning of an AP.
Cardiac Neuronal Nitric Oxide Synthase Isoform Regulates Myocardial Contraction and Calcium Handling
Authors: Sears Claire E. , Bryant Simon M. , Ashley Euan A. , Lygate Craig A. , Rakovic Stevan , Wallis Helen L. , Neubauer Stefan , Terrar Derek A. , Casadei B.
Published: March 2003

A neuronal isoform of nitric oxide synthase (nNOS) has recently been located to the cardiac sarcoplasmic reticulum (SR). Subcellular localization of a constitutive NOS in the proximity of an activating source of Ca
2+
suggests that cardiac nNOS-derived NO may regulate contraction by exerting a highly specific and localized action on ion channels/transporters involved in Ca
2+
cycling. To test this hypothesis, we have investigated myocardial Ca
2+
handling and contractility in nNOS knockout mice (nNOS
−/−
) and in control mice (C) after acute nNOS inhibition with 100 μmol/L L-VNIO. nNOS gene disruption or L-VNIO increased basal contraction both in left ventricular (LV) myocytes (steady-state cell shortening 10.3±0.6% in nNOS
−/−
versus 8.1±0.5% in C;
P
<0.05) and in vivo (LV ejection fraction 53.5±2.7 in nNOS
−/−
versus 44.9±1.5% in C;
P
<0.05). nNOS disruption increased
I
Ca
density (in pA/pF, at 0 mV, −11.4±0.5 in nNOS
−/−
versus −9.1±0.5 in C;
P
<0.05) and prolonged the slow time constant of inactivation of
I
Ca
by 38% (
P
<0.05), leading to an increased Ca
2+
influx and a greater SR load in nNOS
−/−
myocytes (in pC/pF, 0.78±0.04 in nNOS
−/−
versus 0.64±0.03 in C;
P
<0.05). Consistent with these data, [Ca
2+
]
i
transient (indo-1) peak amplitude was greater in nNOS
−/−
myocytes (410/495 ratio 0.34±0.01 in nNOS
−/−
versus 0.31±0.01 in C;
P
<0.05). These findings have uncovered a novel mechanism by which intracellular Ca
2+
is regulated in LV myocytes and indicate that nNOS is an important determinant of basal contractility in the mammalian myocardium. The full text of this article is available at http://www.circresaha.org.
Functional impairment in fibrosing alveolitis: relationship to reversible disease on thin section computed tomography
Authors: Wells AU , Rubens MB , du Bois RM , Hansell DM
Published: March 2003

Thin-section computed tomography (CT) provides a reproducible method of quantifying global disease extent and can also discriminate between fibrotic disease, with predominance of reticular abnormalities, and reversible inflammatory cell infiltration, shown as ground-glass attenuation. The aim of this study was to determine whether functional impairment varied according to the presence of ground-glass attenuation on CT, independently of extent of disease on CT, demographic factors, smoking history, therapeutic status, and the type of fibrosing alveolitis (lone cryptogenic fibrosing alveolitis (CFA) versus fibrosing alveolitis associated with systemic sclerosis (FASSc)). Patients with concurrent emphysema on CT (n = 16) and FASSc patients with end-stage pulmonary hypertension (n = 5) were excluded. One hundred and eleven patients were studied (CFA, n = 54; FASSc, n = 57). The severity of functional impairment did not vary independently with the presence of predominant ground-glass attenuation, mixed appearance and predominant reticulation on CT. In 34 treated patients undergoing serial CT scanning, the severity of functional impairment did not differ independently between patients with and without regression of ground-glass attenuation at follow-up. We conclude that the severity of functional impairment does not discriminate between inflammatory and fibrotic disease in fibrosing alveolitis, as judged by initial and serial computed tomographic scanning, after adjustment for the morphological extent of disease on computed tomography.
Long-term follow-up of pulmonary function in chronic eosinophilic pneumonia. Groupe d'Etude en Pathologie Interstitielle de la Societe de Pathologie Thoracique du Nord
Authors: Durieu J , Wallaert B , Tonnel AB
Published: March 2003

The prognosis of chronic eosinophilic pneumonia (CEP) is usually good under corticosteroid therapy (CST). The main complications are relapses when treatment is tapered or discontinued. The aim of this retrospective, multicentre study was to evaluate the long-term consequences of CEP on pulmonary function tests. Nineteen patients (mean +/- SEM age 51 +/- 16 yrs) with CEP were studied. Lung function tests were performed at the time of diagnosis and at follow-up, and included flow-volume curve. The results of the first pulmonary function test were normal in six patients, restrictive in nine, and obstructive in four. Relapses (recurrence of initial signs) occurred in nine patients. The last evaluation (mean +/- SEM follow-up of 49 +/- 44 months, range 12-142 months) showed a complete recovery in 8 of the 19 patients. One patient developed bilateral apical fibrosis. The remaining 10 patients, exhibited obstructive pulmonary function without relapse of CEP at this time. Bronchoalveolar lavage (BAL) eosinophilia at the time of the initial evaluation tended to be higher (p = 0.05) in these 10 patients than in those with normal pulmonary function findings at follow-up. This study demonstrates: firstly, that the development of an obstructive ventilatory defect is a common finding during the course of chronic eosinophilic pneumonia (CEP); secondly, that bronchial obstruction might appear despite the absence of clinical and radiological signs of relapse; and, thirdly, that a markedly increased bronchoalveolar lavage eosinophilia at the initial evaluation is associated with a higher risk of development of bronchial obstruction. These results suggest that pulmonary function tests should be included in the management of chronic eosinophilic pneumonia.
The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics
Authors: Carroll N , Cooke C , James A
Published: March 2003

Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma. In cases of fatal asthma (n = 10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n = 10), and control cases (sudden death with no history of respiratory illness, n = 10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin. Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p < 0.001). Eosinophils were increased (p < 0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r = 0.60; p < 0.0001), and to a lesser extent in the nonfatal (r = 0.34; p = 0.001) and control groups (r = 0.32; p = 0.001). These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.
Lung immunopathology in cases of sudden asthma death
Authors: Faul JL , Tormey VJ , Leonard C , Burke CM , Farmer J , Horne SJ , Poulter LW
Published: March 2003

The histopathology of airway inflammation in rare cases of sudden asphyxic asthma death (SAAD) is unclear. This study examines, for the first time, the relative disposition of lymphocyte and macrophage subsets and eosinophils in proximal and distal tissues of such cases. Multiple resection specimens from five cases of SAAD were studied. Tissue blocks were obtained at necroscopy and immediately frozen in liquid nitrogen within 18 hours of death (death occurring within 1 h of the onset of an unprovoked asphyxic asthma attack). After immunohistological staining, frozen sections underwent semi-quantitative analysis (cell counts per unit area) for T-cells, macrophages and eosinophils using computerized imaging systems. Subsets of T-cells and macrophages were estimated using double immunofluorescence techniques. Variability within samples, between samples and between cases was compared. These cases of fatal asthma showed infiltrates of T-cells, macrophages and eosinophils within peribronchial tissues. Distinct from stable asthma, a CD8+ T-cell dominance was found. A high proportion of eosinophils were activated (EG2+), whereas the relative proportion of antigen-presenting cells (RFD1+) did not seem to be abnormal, although numbers of these cells were high. These features were seen both in proximal and distal tissues. The variability of these parameters within an individual was 9.4-15.2%, however, the variability between individual cases was greater. Sudden asphyxic asthma is associated with inflammatory infiltrates both of proximal and distal lung tissues. In contrast to stable asthma, this infiltrate contains large numbers of CD8+ T-cells, suggesting distinct qualitative as well as quantitative characteristics in the immunopathology of sudden asthma death.
L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro
Authors: Aizawa H , Tanaka H , Sakai J , Takata S , Hara N , Ito Y
Published: March 2003

The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N omega-nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat. To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10(-5) M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin. These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation.
Effects of long-acting and short-acting beta-agonists on methacholine dose-response curves in asthmatics
Authors: Wong AG , O'Shaughnessy AD , Walker CM , Sears MR
Published: March 2003

Regular use of short-acting beta-agonists may decrease control of asthma and increase airway responsiveness to bronchoconstrictor stimuli. The aim of this study was to determine the effects of regular treatment with the long-acting beta-agonist, salmeterol, on the methacholine dose-response curve (DRC) in mild-to-moderate asthmatics. Changes in methacholine airway responsiveness were measured in 14 stable adult asthmatics, randomized in a double-blind, three-way cross-over design to receive salmeterol 50 micrograms, salbutamol 200 micrograms or placebo, each twice daily for 4 days. Two baseline methacholine DRC, were performed, one without premedication and one following a single dose of 200 micrograms salbutamol. Following 4 days of regular treatment, methacholine DRC to plateau were carried out commencing 15 min after the final dose of trial medication. There were no significant differences in mean baseline forced expiratory volume in one second (FEV1) between treatments. Four days treatment with salmeterol and salbutamol shifted the DRC to the right, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling doses, respectively, compared to placebo (p < or = 0.001), and the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20) increased 1.6 and 3.1 doubling doses, respectively (p < or = 0.001). The slope of the DRC was increased slightly by both beta-agonists compared to placebo (log slope 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respectively). This effect of regular salmeterol on slope was more marked in subjects with lower baseline FEV1. Maximal response plateaus did not differ between the three treatments. These results suggest that regular use either of short- or long-acting beta-agonists could increase the risk of a more precipitous asthma episode associated with "breakthrough" bronchoconstrictor responses, particularly in those with more severe initial airflow obstruction, if subjects are exposed to a sufficiently potent stimulus.
A hospital-based case-control study of quality of life in older asthmatics
Authors: Dyer CA , Sinclair AJ
Published: March 2003

Asthma is a common but neglected problem in older people, the impact of which is relatively unstudied. The aim of this study was to objectively assess quality of life and depression in older asthmatics. The subjects studied were 50 hospitalized known asthmatics, over 55 yrs of age (mean age 72 yrs). Of these, 40 had objective evidence of asthma, and were compared to 40 age- and sex-matched controls. Using a structured questionnaire, the Geriatric Depression Score, subjective health status (short form (SF)-36), and other comparative disability data were recorded. Spirometric results were also recorded. Depressive symptoms were common in both groups but were not significantly different. Mean SF-36 scores were significantly worse in the asthmatics, especially for components of physical function (p = 0.04), physical role limitation (p = 0.01), energy (p = 0.01), health change (p = 0.01), and general health perception (p = 0.01). However mental, mental role and social scores were similar in both groups. We conclude that quality of life is impaired in hospitalized asthmatics compared to controls. Physical components appear to be most adversely affected. Depressive symptoms are common but no overall difference was found for psychological disability. Older asthmatics appear to adapt well to adverse situations.
Chronic cough and wheeze in children: do they all have asthma?
Authors: Seear M , Wensley D
Published: March 2003

In the experience of both authors, children referred for investigation of a chronic productive cough often do not fit conventional diagnostic categories. The aim of this study was to answer two questions: 1) do such diagnostic orphans exist? and, 2) if so, can they be classified in a clinically useful manner? Eighty one previously undiagnosed children referred with a history of more than 3 months productive or rattly cough were studied prospectively. Investigations consisted of a detailed history, physical examination, and an extensive set of clinical investigations. Sixty randomly selected asthmatic children served as demographic controls. Children fell into three groups: 23 had newly diagnosed conditions, such as cystic fibrosis, or were indistinguishable from asthma; 24 had a history of major medical interventions (cardiac surgery, chemotherapy, tracheo-oesophageal fistula repair); 34 had a history of significant early respiratory tract infections, usually combined with poor social conditions. The latter group differed significantly from asthmatic controls in a wide range of demographic and clinical comparisons. Native American children were overrepresented. The results of this study suggest that early respiratory insults (whether viral or medical) can induce self-perpetuating inflammation, manifesting as a chronic productive cough and intermittent wheeze. The associations between poverty and infant chest infections or early invasive medical treatment with subsequent chronic respiratory disease are clearly definable and probably justify diagnostic terms distinct from asthma, particularly for use in epidemiological studies.
Prevalence of asthma and allergy in Hong Kong schoolchildren: an ISAAC study
Authors: Leung R , Wong G , Lau J , Ho A , Chan JK , Choy D , Douglass C , Lai CK
Published: March 2003

Asthma and allergic disease in children is increasing in many Western countries but such trend has not been well-defined in Chinese populations. This paper aims to determine the prevalence of asthma and allergic disease in Hong Kong schoolchildren and compare it with previous data to identify a changing trend. We studied 4,665 schoolchildren aged 13-14 yrs using the International Study of Asthma and Allergy in Childhood (ISAAC) protocol to determine prevalence rates for asthma, wheeze, respiratory symptoms, rhinitis and eczema in 1994-1995. Additional questions on education levels of the parents and smoking status were also asked. Concordance between responses to the written and video questionnaires was good (76% for wheeze ever, 80% for current wheeze). Prevalence rates for asthma ever, wheeze ever, and current wheeze were 11, 20 and 12%, respectively, and were greater in boys (p < 0.05). Rhinitis affected slightly over half of the subjects (52%), and eczema was reported by a sixth (15%), whilst current rhinitis and current eczema were present in 44% and 3.6% of children, respectively. In multiple logistic regression: odds ratio male sex (OR) 1.47; (95% confidence interval (95% CI) 1.15-1.86); current rhinitis (OR 3.00; 95% CI 2.36-3.81); current eczema (OR 2.34; 95% CI 1.40-3.93); and active smoking (OR 2.00; 95% CI 1.38-2.89) were associated with current wheeze; whilst severe wheezing attack was associated with: current rhinitis (OR 2.72; 95% CI 1.47-5.02); current eczema (OR 6.13; 95% CI 2.82-13.33); and active smoking (OR 4.62; 95% CI 2.43-8.76). Age, parental education and passive smoking were not important factors. When compared to previous epidemiological data obtained in 1992, the prevalence rates for asthma ever and wheeze ever had increased by 71 and 255%, respectively, in Hong Kong schoolchildren. The severity of asthma and respiratory symptoms showed a similar increasing trend. Further studies should aim to identify the role of the environment in the pathogenesis of asthma.
Increased number of activated lymphocytes in human lung following swine dust inhalation
Authors: Muller-Suur C , Larsson K , Malmberg P , Larsson PH
Published: March 2003

Inhalation of swine dust causes intense alveolar inflammation, with recruitment of inflammatory cells, predominantly neutrophils, but also alveolar macrophages and lymphocytes. The present study focuses on the lymphocyte response to inhaled swine dust. Twenty four healthy, nonsmoking, nonallergic subjects were exposed to swine dust for 3 h in a swine confinement building. Bronchoalveolar lavage (BAL) was performed before and 24 h after the start of exposure, and blood samples were drawn before, and at 7 and 24 h after exposure. Total and differential cell counts were carried out. Monoclonal antibodies recognizing T-cells, T-cell subsets, T-cell activation markers, and B-cells were analysed by flow cytometry. The number of granulocytes increased more than 50 times and alveolar macrophages and lymphocytes increased two- to three-fold in BAL fluid. The exposure did not alter the proportion of T-cells but increased the number of activated T-cells in BAL fluid. The interleukin-2 (IL-2) receptor (CD25), human leucocyte antigen-DR (HLA-DR) major histocompatibility complex (MHC) class II and the early activation marker CD69 were expressed by 8.4% (25-75th percentiles 6.4-9.6%), 9.9% (8.2-21.6%) and 22.0% (18.1-24.3%) of the lymphocytes prior to exposure, and 11.6% (9.0-16.4%) (p < 0.01), 18.8% (12.9-30.4%) (p < 0.01) and 42.1% (38.4-47.3%) (p < 0.05), respectively, after the exposure. In peripheral blood, the concentration of T-cells decreased after exposure and B-cells increased slightly but significantly. The ratio naive/memory T-cells (CD45RA/RO) did not change in blood. In conclusion, 3 h of swine dust inhalation led to an influx of lymphocytes into the lower airways and increased expression of lymphocyte activation markers on the cell surface in previously unexposed subjects. The finding suggests a role for T-cells, in conjunction with other cells, in the inflammatory response to inhaled swine dust.
Inhalation of swine dust induces cytokine release in the upper and lower airways
Authors: Wang Z , Larsson K , Palmberg L , Malmberg P , Larsson P , Larsson L
Published: March 2003

In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Each subject carried personal samplers for exposure measurements. Inhalable dust and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (> 38 degrees C) in three subjects, and approximately 25% of the subjects experienced symptoms. Bronchial responsiveness to methacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75th percentile)). Following exposure, granulocytes increased more than 50 fold in BAL fluid and more than 40 fold in nasal lavage fluid. IL-1 alpha and IL-1 beta increased significantly in BAL fluid (p < 0.05) and nasal lavage fluid (p < 0.01). IL-6 increased 25 fold in BAL and 15 fold in nasal lavage fluid (p < 0.001). TNF-alpha was below detection limit (0.25 ng.L-1) in most subjects before exposure and increased following exposure to 3.8 (2.4-5.7) and 1.3 (0.6-2.3) ng.L-1 in BAL and nasal lavage fluid, respectively, (p < 0.001). Total inhalable dust was 20.5 (14.6-30.0) mg.m-3 and the concentrations of airborne endotoxin, 3-OH fatty acid and muramic acid were 1.2 (0.8-1.4), 3.5 (2.2-4.5) and 0.9 (0.3-1.9) microgram.m-3, respectively. There was a significant correlation between the IL-6 response in BAL fluid and exposure to dust endotoxin activity and 3-OH fatty acids (p < 0.05). Otherwise, no significant correlations were found between exposure and the cytokine response. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.
Pulmonary endocrine cells in anthracosilicotic lungs
Authors: Gosney  , Peers J , Beesley C , Gradwell E
Published: March 2003

It has been suggested by some studies of human and animal lungs that the products of pulmonary endocrine cells, particularly gastrin-releasing peptide, might play a role in fibrogenesis, but more recent detailed studies of fibrotic human lungs have failed to confirm this. We have made a detailed quantitative examination of a series of fibrotic human lungs to see if we could determine whether there was any relationship between endocrine cells and fibrosis. Using immunocytochemistry, we investigated the morphology, content, distribution and number of pulmonary endocrine cells in 15 pairs of fibrotic lungs from coal miners, and compared their features with those of equivalent cells in age-matched controls. Proliferation of endocrine cells was seen in the lungs of just two miners, in which it was focal and associated with acute bronchitis and bronchopneumonia. There was no difference between the miners and controls in the appearance (mostly solitary cells), content (predominantly gastrin-releasing peptide and calcitonin), distribution (mainly in small bronchi and bronchioles), or number (4.5 vs 4.1 cells per 10,000 epithelial cells, respectively) of endocrine cells. It seems unlikely that the substances secreted by these cells play any role in stimulating fibrosis in human lungs, but rather that they have a function in the inflammatory response to pulmonary injury.
Immunohistochemical differences between hyaluronan- and non-hyaluronan-producing malignant mesothelioma
Authors: Thylen A , Levin-Jacobsen AM , Hjerpe A , Martensson G
Published: March 2003

In many but not all cases, malignant mesothelioma is associated with an elevated content of hyaluronan in pleural fluid. The hyaluronan-producing mesothelioma has not yet been immunohistochemically characterized; therefore, the purpose of this study was to compare the immunohistochemical reactivity patterns in relation to the ability of this tumour to produce hyaluronan. Pleural fluid samples from 33 patients with malignant mesothelioma were analysed for content hyaluronan using a quantitative high performance liquid chromatographic method. Biopsy specimens from the patients were studied immunohistochemically, using monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), a low molecular weight cytokeratin antigen (CAM 5.2) and vimentin. An elevated hyaluronan content, i.e. > 100 mg.L-1, was noted in 23 patients (70%). There was no reactivity to the monoclonal antibody raised against CEA in any case. There was a significantly higher reactivity to EMA (p = 0.026), a higher reactivity to CAM 5.2 (p = 0.053) and a lower reactivity to vimentin (p = 0.057) in the hyaluronan-producing mesotheliomas as compared to those with normal levels of hyaluronan. Mesotheliomas that produced hyaluronan differed immunohistochemically from those that did not. The connection between the ability to produce different antigens and hyaluronan may relate to the degree of differentiation of the tumour. Both of these characteristics (immunophenotype and ability to produce hyaluronan) may, therefore, be of importance in studies concerning the prognosis and treatment of the malignant mesothelioma.
Comparison of video-assisted thoracoscopic talcage for recurrent primary versus persistent secondary spontaneous pneumothorax
Authors: Noppen M , Meysman M , d'Haese J , Monsieur I , Verhaeghe W , Schlesser M , Vincken W
Published: March 2003

Thoracoscopic talcage (TT) is a safe and effective prophylactic treatment for patients suffering from recurrent primary spontaneous pneumothorax (PSP). Empirically, TT is considered equally effective in the treatment of persistent secondary spontaneous pneumothorax (SSP), although this has not yet been proved. In this study, the efficacy and safety of TT was prospectively evaluated in 28 patients (17 males and 11 females, mean age 27 +/- 8 yrs), with 31 episodes of recurrent PSP, and in 20 patients (13 males and 7 females, mean age 43 +/- 21 yrs) with persistent SSP. TT proved to be equally effective in achieving pleurodesis in both groups; there were 6.5% recurrences in the PSP group and 8.7% in the SSP group during a mean follow-up period of 18 months (p > 0.05). In the SSP group, there were significantly more prolonged postoperative air leaks (26 vs 0%; p = 0.004) and a longer postoperative chest tube drainage time (35.5 +/- 18 vs 24.9 +/- 3.2 hrs; p = 0.002) was necessary. All air leaks, however, ceased spontaneously during drainage. Duration of hospitalization was significantly longer in the SSP group (4.7 +/- 2 vs 3.2 +/- 0.5 days; p < 0.0001). Postoperative pain (90 vs 43%; p < 0.0001) and fever (65 vs 17%; p = 0.001) were more frequent in the PSP group than in the SSP group. There were no major peri- or postoperative complications in either group. We conclude that thoracoscopic talcage is as efficient and safe in achieving pleurodesis in persistent spontaneous pnuemothorax as in recurrent primary spontaneous pneumothorax.
The effect of lung transplantation on the neural drive to the diaphragm in patients with severe COPD
Authors: Brath H , Lahrmann H , Wanke T , Wisser W , Wild M , Schlechta B , Zwick H , Klepetko W , Burghuber OC
Published: March 2003

Little is known about the effects of lung transplantation (LT) on the neural drive to the diaphragm and on the endurance of respiratory muscles in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate these effects of single-lung (SLT) and double-lung transplantation (DLT). The neural drive to the diaphragm was assessed during fatiguing inspiratory threshold loading manoeuvres in six SLT recipients, six DLT recipients and seven patients with severe COPD, by using diaphragmatic surface electromyograms. During threshold loading, the patients had to generate 80% of their maximal transdiaphragmatic pressure with each breath. The endurance of inspiratory muscles was defined as the time from the beginning of a resistive breathing trial until exhaustion (t lim). In DLT recipients and even in SLT recipients (on both sides), neural activation of the diaphragm was significantly lower than in COPD patients (p < 0.05). However, no statistically significant difference in t lim was seen between LT recipients and COPD patients. The data suggest that single-lung and double-lung transplantations cause a significant decrease of the neural drive to the diaphragm, while the endurance of inspiratory muscles is well-preserved in patients with advanced chronic obstructive pulmonary disease. This may contribute to reduced sensation of inspiratory effort during ventilatory stress, thus improving the quality of life.
Comparison of invasive and noninvasive saturation monitoring in prescribing oxygen during exercise in COPD patients
Authors: Carone M , Patessio A , Appendini L , Purro A , Czernicka E , Zanaboni S , Donner CF
Published: March 2003

The aim of this study was to determine whether it is possible using ear-oximetry to prescribe the correct oxygen flow rates during exercise in chronic obstructive pulmonary disease (COPD) patients on long-term oxygen therapy (LTOT). Twenty COPD patients on LTOT, with exercise desaturation breathing oxygen at resting flow rates, performed a series of 6-min treadmill walking tests, with a progressive increase in oxygen flows until oxygen saturation measured by ear- or pulse-oximetry (Sp,O2) was above 90%. The exercise studies were repeated the next day, saturation being measured both noninvasively by ear-oximetry (Sp,O2) and invasively by CO-oximeter (Sa,O2). The exercise studies continued until both Sa,O2 and Sp,O2 were above 90%. Reproducibility and agreement of the results were analysed according to Bland and Altman. Sp,O2 was significantly lower than Sa,O2 by, on average, 0.7% (p < 0.004). Sp,O2 reproducibility between the two days was good. The invasive and noninvasive oxygen flow prescriptions agreed in only 10 subjects; in six subjects ear-oximetry over-estimated the oxygen supply (p < 0.0005), whilst in four subjects it underestimated (p < 0.01). Contingency table analysis with coded raw data for the values of the sixth minute (that of the deepest desaturation) showed poor agreement between CO- and pulse-oximetry (Chi-squared p < 0.003). However, theoretically, if the Sp,O2 target had been raised to 93%, there would have been hardly any underestimations of Sa,O2 p = NS). We concluded that noninvasive measurement of oxygen saturation is not adequate for estimating arterial saturation in chronic obstructive pulmonary disease. We suggest, as a working solution, that a new cut-off limit of 93% oxygen saturation measured by pulse oximetry should be used as the value below which exercise-induced desaturation should be corrected in order to allow oxygen to be properly prescribed during activities of daily life.
Aerosol bolus dispersion in healthy subjects
Authors: Brand P , Rieger C , Schulz H , Beinert T , Heyder J
Published: March 2003

Aerosol bolus dispersion is a physiological test of lungs, which uses monodisperse submicron particles to measure intrapulmonary convective gas mixing. In this study, aerosol bolus dispersion was measured in healthy subjects in order to assess reference values for possible clinical applications, to assess the reproducibility of these values, and to identify physical and physiological factors influencing aerosol bolus dispersion. Aerosol bolus dispersion was measured in 79 healthy subjects using 20 cm3 aerosol boluses consisting of monodisperse di-2-ethylhexyl sebacate (DEHS) particles. The reproducibility of parameters characterizing the width of the exhaled bolus was of the same order as that of parameters of the flow-volume curve (10%). Aerosol bolus dispersion was independent of the level of lung inflation, and the slope of the relationship between flow rate and dispersion was on average not significantly different from zero (range 100-700 cm3.s-1). Multiple linear regression showed that aerosol bolus dispersion increased with increasing total lung capacity of the subject. We conclude that differences in total lung capacity between individuals should be taken into account when using measures of aerosol bolus dispersion for possible clinical applications.
On the causes of lung hyperinflation during bronchoconstriction
Authors: Pellegrino R , Brusasco V
Published: March 2003

Airway obstruction in asthma and chronic obstructive pulmonary disease (COPD) is often associated with lung hyperinflation. In this review, we examine the mechanisms that may cause functional residual capacity (FRC), residual volume (RV) and total lung capacity (TLC) to increase during acute and chronic airway obstruction. Normally, FRC at rest is determined by the static characteristics of the lung and chest wall. When airways narrow, FRC may be also be determined by dynamic factors. There are data suggesting that expiratory flow limitation during tidal breathing represents the starting trigger for FRC to increase, in order to allow breathing at higher flows. Indeed, the increase in FRC during induced bronchoconstriction in asthma is closely associated with the occurrence of flow limitation, i.e. the achievement of maximum flow during tidal breathing. Conversely, the decrease in FRC following bronchodilatation in COPD is closely associated with flow limitation disappearing or occurring at lower lung volumes. In normal young people, RV is determined by the static characteristics of the chest wall. During bronchoconstriction RV may also be determined by dynamic factors; therefore, changes in flow or airway calibre at low lung volumes may modulate RV during bronchoconstriction. During acutely induced bronchoconstriction, RV achieved with an expiration from TLC is less than with an expiration from tidal breathing, and this effect appears to be linked to the bronchodilator effect of the deep inhalation. The reasons for the increase in TLC during airway narrowing are not clear, but the duration of the bronchoconstriction by itself may play a role.
The role of pulmonary surfactant in obstructive airways disease
Authors: Hohlfeld J , Fabel H , Hamm H
Published: March 2003

Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged. Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma. Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies. Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.
Treatment of massive haemoptysis with microcoil embolization after en bloc double-lung transplantation with bronchial artery revascularization
Authors: Carlsen J , Svendsen UG , Efsen F , Pettersson G
Published: March 2003

Successful treatment of a severe haemoptysis with microcoil embolization in an en block double-lung transplanted patient is described. A 53 year old woman with advanced bronchiolitis obliterans syndrome experienced severe haemoptysis 26 months after an en bloc double-lung transplantation with direct bronchial artery revascularization using the left internal mammary artery. Bronchoscopy showed that the haemoptysis originated from the lingula. Only two months after the transplant, left internal mammary arteriograms revealed proliferation and enlargement of the bronchial arteries in the lingula. The early occurrence of the vascular malformation indicated a pre-existing bronchiectasis in the donor lung, possibly due to tobacco smoking. After uncomplicated microcoil embolization of the left internal mammary artery, the patient experienced no further episodes of haemoptysis. Microcoil embolization can be used successfully to treat massive haemoptysis related to proliferated and enlarged bronchial arteries in transplanted lungs with bronchial artery revascularization.
Goitre: a cause of obstructive sleep apnoea in euthyroid patients
Authors: Deegan PC , McNamara VM , Morgan WE
Published: March 2003

While hypothyroidism is considered to predispose to obstructive sleep apnoea (OSA), the presence of a goitre itself is not a recognized cause of OSA. We present the cases of two euthyroid patients with large goitres and clinical evidence of OSA, whose OSA symptoms significantly improved following partial thyroidectomy. This finding suggests that the goitre contributed to their symptoms.
Surgical skills training in middle-ear surgery
Authors: Mills Robert , Lee Patrick
Published: March 2003

Until recently the practice of otological procedures on cadaver temporal bones was a common occurrence in otolaryngology departments. The difficulty in acquiring specimens has led to alternative techniques which involve artificial and computer-aided models. This article looks at the present situation in these rapidly developing areas and describes an artificial model developed by the senior author for training in middle-ear procedures.
Simple snoring: current practice
Authors: Trotter M. I. , D’Souza A. R. , Morgan D. W.
Published: March 2003

Snoring is a significant problem with both social and medical manifestations. This article addresses the current management of the simple snorer from initial out-patient assessment to definitive treatment.