bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholinergic control of rabbit tracheal transepithelial potential difference in vivo
Authors: Tamaoki J , Chiyotani A , Tagaya E , Takemura H , Konno K
Published: May 2003

The aim of the present study was to investigate the role of the autonomic nervous system in the regulation of airway epithelial ion transport in vivo. Rabbits were anaesthetized and mechanically-ventilated through a cannula inserted above the carina. The upper tracheal mucosa was exposed, and the electrical potential difference (PD) between the mucosal surface and the submucosal space was continuously measured by a high-impedance voltmeter under open-circuit conditions. Perfusion of the mucosa with atropine caused a rapid decline in PD from -20.1+/-2.0 to -15.2+/-0.9 mV (p<0.01), whereas phentolamine, propranolol, or the tachykinin antagonist, FK224, had no effect. Cutting both cervical vagus nerves decreased PD to the same degree as did atropine. Exogenously applied acetylcholine increased PD in a dose-dependent manner. Topical application of ipratropium bromide reduced the baseline value PD in a dose-dependent manner. The maximal decrease in PD was 43 +/- 0.3 mV (p<0.01), and the dose required to produce a half-maximal effect was 34 microg. Perfusion with either amiloride, a Na channel blocker, and diphenylamine-2-carboxylate, a Cl channel blocker, decreased the baseline PD, and the subsequent application of ipratropium bromide further decreased the PD in each case. We conclude that a cholinergic neural component may play a role in the generation of tracheal potential difference in vivo, probably involving stimulation by endogenously released acetylcholine of both Cl secretion and Na absorption across the airway epithelium.
Adaptation of pulmonary receptors in the spontaneously breathing anaesthetized rat
Authors: Davies A , Pirie L , Eyre-Todd RA
Published: May 2003

It has been suggested that species with high breathing frequencies have pulmonary stretch receptors which adapt more rapidly than species with low breathing frequencies. This has proved not to be so. Our hypothesis is that this theory is in fact correct if modified so that overall rate of adaptation of afferent vagal activity, i.e. the sum of stretch and rapidly adapting receptors, is considered. A rapidly breathing species, such as the rat, would thus have a greater proportion of rapidly adapting receptors, than a more slowly breathing species. To test this hypothesis, we measured the proportion of rapidly adapting pulmonary mechanoreceptors in spontaneously breathing rats for comparison with existing results from more slowly breathing species. We found there to be one rapidly adapting receptor for every three slowly adapting receptors present. This measurement has not previously been made in spontaneously breathing rats. The ratio of rapidly to slowly adapting pulmonary receptors in the species sequence cat-rabbit-rat is the same as the ratio of their breathing frequencies (3:4:10). We propose that the difference in proportion of slowly to rapidly adapting pulmonary receptors in different species may be related to their eupnoeic breathing frequency.
Tumour necrosis factor receptor gene expression and shedding in human whole lung tissue and pulmonary epithelium
Authors: Nakamura H , Hino T , Kato S , Shibata Y , Takahashi H , Tomoike H
Published: May 2003

This study aimed to investigate the expression of tumour necrosis factor receptor (TNF-R) at the gene and surface level, and its shedding in human lung tissue and a pulmonary epithelial cell line, A549. Levels of gene expression of TNF-R were evaluated by Northern blot analysis. Human lung tissue expressed both type I and type II TNF-R gene, while A549 cells expressed only type I TNF-R gene. Phorbol ester upregulated and TNF-alpha down-regulated the TNF-R gene expression in A549 cells. Consistent with these modulations of TNF-R gene expression, 125I-TNF binding capacities were increased with phorbol ester stimulation and decreased with TNF stimulation after 24 h in A549 cells. The shedding of TNF-R from A549 cells was investigated using enzyme-linked immunosorbent assay (ELISA) for soluble type I TNF-R. Not only lung tissues but also A549 cells spontaneously released soluble type I TNF-R into the culture medium. Both phorbol ester and TNF stimulation accelerated the shedding of soluble TNF-R from A549 cells. These results suggest that type I TNF-R gene expression and shedding of soluble TNF-R are differentially regulated in A549 cells. We conclude that tumour necrosis factor receptor surface expression is regulated, at least in part, at the gene expression level and shedding of soluble tumour necrosis factor receptor is modulated by inflammatory mediators, such as tumour necrosis factor in A549 cells.
Serum type I and type III procollagen peptide levels in sarcoidosis
Authors: Bacchella L , Tinelli C , Gile LS , Peona V , Aprile C , Gorrini M , Pasturenzi L , Cetta G , Luisetti M
Published: May 2003

Type I and type III are the most abundant collagens in the lung. The aim of our study was to compare type I and III procollagen peptides in sera of sarcoid patients. Sixty eight patients with sarcoidosis were studied (19 with newly recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in stable remission). Thirty healthy volunteers served as controls. The levels of procollagen I and III peptides were determined by radioimmunoassay. Angiotensin-converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In patients with newly recognized sarcoidosis, both serum procollagen I and III peptide levels were increased with respect to controls (p=0.0014 and p<0.00001, respectively). There was a poor correlation between levels of procollagen I and III (r=0.26), whereas there was a closer correlation between procollagen III and ACE (r=0.69). Procollagen I peptide level did not identify patients in roentgenological stage III. In conclusion, in patients with newly recognized sarcoidosis there is a significant increase in the serum level of procollagen I peptide. However, procollagen I peptide is not a marker of sarcoid patients with fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than that of procollagen III peptide.
Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumatoid pleurisy
Authors: Soderblom T , Nyberg P , Teppo AM , Klockars M , Riska H , Pettersson T
Published: May 2003

Tuberculous and rheumatoid pleural effusions show features suggesting a strong local cellular immune response. Pleural fluid (Pf) from patients with tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102 patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest median Pf-IFN-gamma was observed in those patients who showed a positive pleural fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1) and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous and rheumatoid pleural effusions share several biochemical features, they are strikingly different with respect to interferon-gamma.
Intrapleural urokinase in the treatment of complicated parapneumonic pleural effusions and empyema
Authors: Bouros D , Schiza S , Tzanakis N , Drositis J , Siafakas N
Published: May 2003

Intrapleural urokinase has not been evaluated systemically in terms of efficacy, safety, and cost of treatment in a large series of patients with complicated (parapneumonic) pleural effusions (CPE) and pleural empyemas (PE). Furthermore, the optimal dose and duration of treatment is not known. Twenty consecutive patients with multiloculated parapneumonic effusions (13 with CPE and 7 with PE), in whom a single chest tube failed to drain the fluid, were studied prospectively. The age of the patients ranged 15-92 yrs (median 51 yrs). Urokinase was administered intrapleurally, in a low single daily dose of 50,000 U in 100 mL normal saline via the chest tube. Previous intrapleural instillation of 100 mL normal saline failed to promote drainage in all patients. Urokinase enhanced drainage in all patients. Clinical and radiological improvement was noted in all but one patient. The mean (SD) volume of fluid significantly increased in the first 24 h post-urokinase (p<0.001). The number of urokinase instillations ranged 3-7 (median 5). Radiological evaluation showed excellent improvement in 13 of the 20 (65%) patients. Urokinase was well-tolerated in all patients. The clinical course of patients was uneventful at a mean follow-up of 15 months (range 6-30 months) later. Mean total cost of treatment was $530 +/- 34.6. Our results show that intrapleural instillation of small doses of urokinase is a cost-effective and safe mode of treatment of complicated pleural effusions and pleural empyema and could be the fibrinolytic of choice.
Thoracoscopic sympathicolysis for essential hyperhidrosis: effects on pulmonary function
Authors: Noppen M , Vincken W
Published: May 2003

Bilateral interruption of the upper dorsal sympathetic chain at the D2 and D3 level represents the only permanent cure for essential hyperhidrosis. Following surgical sympathectomy, significant and symptomatic changes in pulmonary function have been observed. Since functional effects of the surgical intervention cannot be excluded, we wondered whether such alterations also occurred after thoracoscopic sympathicolysis; these should then be attributable to the surgical denervation itself. Pulmonary function tests (PFTs), including spirometry and body plethysmographic measurement of lung volumes and airway resistance and conductance, were compared before and 6 weeks after thoracoscopic sympathicolysis in 47 patients. In order to virtually exclude any effects of thoracoscopy on the test results PFTs were repeated 6 months after thoracoscopic sympathicolysis in 35 patients. Essential hyperhidrosis was completely relieved in all patients, thereby confirming the interruption of the D2-D3 sympathetic chain. None of the patients developed respiratory symptoms after thoracoscopic sympathicolysis. Forced expiratory volume in one second (FEV1) (-3%), forced expiratory flow after exhaling 75% of vital capacity (FEF75) (-8%) and total lung capacity (TLC) (-3%) were slightly but significantly reduced at six weeks after thoracoscopic sympathicolysis; whereas airway resistance (Raw) had increased (+12%). After correction for the small decrease in lung volume (FEV1/forced vital capacity (FVC), specific airway resistance (sRaw), specific airway conductance (sGaw))significant changes in "volume-dependent" PFT parameters were no longer observed. Smoking status had no influence on the reduction in FEF75. At 6 months after thoracoscopic sympathicolysis, TLC had returned to preoperative values, whereas FEF75 remained decreased (-8.6%). The decrease in airway calibre was confirmed by small but significant changes in FEV1/FVC (-2%) and Raw (+29%). We conclude that thoracoscopic sympathicolysis in patients with essential hyperhidrosis causes only minimal and subclinical changes in pulmonary function secondary to a temporary small decrease in lung volume, which in turn is probably inherent to the thoracoscopic procedure. D2-D3 sympathicolysis, in itself, is responsible only for a small and permanent decrease in forced expiratory flow, which suggests that, at least in essential hyperhidrosis patients, airway bronchomotor tone is influenced by sympathetic innervation.
Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis
Authors: Riise GC , Andersson B , Ahlstedt S , Enander I , Soderberg M , Lowhagen O , Larsson S
Published: May 2003

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.
Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study
Authors: Finnerty JP , Lee C , Wilson S , Madden J , Djukanovic R , Holgate ST
Published: May 2003

The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies of symptomatic atopic asthmatic subjects were investigated. Following a 2 week run-in period, asthmatic subjects were randomly assigned to either placebo (n=11) or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy at the beginning and end of a 6 week period, during which subjects took placebo or theophylline medication at a dose intended to produce therapeutic concentrations. Nine of the placebo subjects and 12 of the theophylline subjects completed the study. Improvement in asthma control was seen in the theophylline-treated group. The mean (SD) theophylline blood level at the end of the study was 10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from 1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline-treated group compared with placebo, although there was no change in mast cell numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from 2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti-inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers and in the expression of IL-4, believed to be an important cytokine in the pathophysiology of asthmatic inflammation. We speculate that theophylline induces downregulation in vivo of cytokine production, accounting for the known inhibitory effect of theophylline on the late asthmatic reaction.
A dose-response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients
Authors: Schreurs AJ , Sinninghe Damste HE , de Graaff CS , Greefhorst AP
Published: May 2003

The aim of this randomized, double-blind, parallel group study was to determine the lowest effective dose of 6, 12 and 24 microg formoterol fumarate dihydrate Turbuhaler b.i.d. compared with placebo. The 4 week treatment was preceded by a 1 week run-in period. Morning peak expiratory flow (PEF) before intake of the study drug was the primary variable. Patients recorded PEF, prior to and 15 min after intake of the study drug (immediate response), asthma symptoms, and use of rescue medication morning and evening. Of 221 patients (71 females and 150 males), 194 were included in the efficacy per protocol (PP) analysis; mean age 47 yrs, mean forced expiratory volume in one second (FEV1) 2.01 L (58% of predicted), mean FEV1 reversibility 27% at entry. Ninety percent used inhaled steroids. Compared with placebo, 6 microg formoterol b.i.d was found to be the lowest effective dose in the morning (p=0.008) and evening p=0.0041) PEF. The mean increases in PEF were 22 and 23 L x min-1 respectively, compared with placebo. After 6 microg formoterol, the mean immediate increase in morning PEF was 42 L x min-1 compared to an increase of only 9 L x min-1 after placebo (<0.0001). All doses produced a statistically significant decrease in asthma symptoms, day and night, and the need for rescue medication at night. All doses were well-tolerated. In conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6 microg b.i.d.
Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action
Authors: van Noord JA , Smeets JJ , Raaijmakers JA , Bommer AM , Maesen FP
Published: May 2003

We evaluated the profile of the bronchodilatory effect of three inhaled beta2-agonists, 24 microg formoterol, 50 microg salmeterol and 200 microg salbutamol, in patients with stable, moderately severe asthma. Thirty asthmatics (mean+/-SD age 54+/-8 yrs; forced expiratory volume in one second (FEV1) 58+/-12% predicted; reversibility of FEV1 21+/-8% from baseline) participated in a single-centre, double-blind, randomized, single-dose, cross-over study. FEV1 was obtained in baseline condition and 10, 20, 30, 60 min, and every hour up to 12 h after inhalation of the trial drug. Specific airway conductance (sGaw) was measured at baseline condition and 1, 3, 5, 7, 10, 20, 30, 60 min, and every hour up to 12 h after inhalation. Formoterol produced a mean increase in sGaw (as % of baseline) of 44% after 1 min, maximal (135%) after 2 h, and 56% after 12 h. The mean increase in FEV1 was maximal (27%) after 2h, and 10% after 12 h. After salmeterol, mean increase in sGaw amounted to 16% after 3 min, maximal (111%) after 2-4 h, and 58% after 12 h. The mean increase in FEV1 was maximally 25% after 3h, being 11% after 12 h. After salbutamol, mean increase in sGaw was 44% after 1 min and maximal (100%) after 30 min. The peak increase in FEV1 was 25%. We conclude that formoterol (24 microg) and salmeterol (50 microg) had an equal bronchodilatory capacity, which was similar to that of 200 microg salbutamol and lasted for at least 12 h in patients with asthma. However, formoterol had a more rapid onset of action than salmeterol, equal to that of salbutamol.
Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group
Authors: Paggiaro PL , Giannini D , Di Franco A , Testi R
Published: May 2003

The aim of this study was to compare the clinical efficacy of salmeterol versus theophylline in the treatment of moderate-to-severe asthma. One hundred and eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) >50% of predicted) were randomized to receive either salmeterol dry powder, 50 microg b.i.d. via a Diskhaler (n=92) or dose-titrated slow-release theophylline capsules ("Theo-Dur") b.i.d. (n=97), in a double-blind, double-dummy, parallel group study for 4 weeks. Patients had previously been titrated with theophylline to a serum theophylline level of 10-20 microg x mL-1. The median percentage of nights with no asthma symptoms rose from 14% in both groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044). There was also a significant increase for salmeterol in the median percentage of nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L x min-1 in the salmeterol group and 332 L x min-1 in the theophylline group to 372 and 357 L x min-1, respectively. No significant difference between the two treatments was observed for PEF, symptoms or additional salbutamol medication during the day. The incidence of gastrointestinal symptoms (gastric irritation, nausea and vomiting) was greater among patients receiving theophylline (11%) than with salmeterol (3%). These findings suggest that inhaled salmeterol is more effective in relieving symptoms of asthma, and better tolerated than theophylline in patients with moderate-to-severe asthma.
Increased bronchial responsiveness to exercise as a risk factor for symptomatic asthma: findings from a longitudinal population study of children and adolescents
Authors: Ulrik CS , Backer V
Published: May 2003

The prevalence of asthma seems to be on the increase and risk factors are not well-established. To investigate the relationship between asymptomatic increased bronchial responsiveness to exercise (BRE) and subsequent development of asthma, we studied a population sample of children and adolescents, aged 7-17 yrs at enrollment, examined twice 6 yrs apart (54 and 68%, respectively, of the original sample participated in the two examinations). Complete information was available for 383 subjects (191 males and 192 females). Case history and questionnaire data were obtained and were used to assess the presence or absence of symptomatic asthma. Exercise testing, performed at enrolment only, consisted of steady running on a 10% sloping treadmill for 6 min in a climate chamber. BRE was recorded as percentage fall in forced expiratory volume in one second (FEV1) from pre-exercise FEV1, within 15 min after exercise. Twenty subjects (5%) had asthma at enrolment, whereas 58 subjects (15%) had current asthma (i.e. symptoms within the preceding 12 months) at the time of follow-up, of whom 40 were asymptomatic at enrolment (new asthma). In general, increased BRE at enrolment was significantly associated with symptomatic asthma at follow-up. Analysing the data for subjects who were asymptomatic at enrolment (n=363), showed that new asthma at follow-up was not predicted by increased BRE at enrolment, whether BRE was evaluated as a continuous (R2=0.06, p=0.13) or dichotomous (cut-off: BRE =10% decline in FEV1; odds ratio (OR) 0.8 (0.4-1.2); p=0.11) variable. However, the data do not exclude the possibility that asymptomatic subjects with BRE >15% have an increased risk for subsequent development of asthma. The findings of the present study suggest that increased bronchial responsiveness to exercise in asymptomatic children and adolescents is not a strong predictor for subsequent development of symptomatic asthma. Further studies, preferably of larger samples, are needed to confirm these findings.
Early and late allergic reaction in the nose assessed by whole body plethysmography
Authors: de Bruin-Weller MS , Weller FR , Scholte A , Rijssenbeek LH , van der Baan S , Bogaard JM , de Monchy JG
Published: May 2003

Physiological changes during late phase nasal responses after allergen challenge are difficult to establish and different criteria are used for the definition of a positive late phase nasal reaction. The objective of this study was to assess the value of whole body plethysmography in detecting changes in nasal airway resistance after allergen challenge and to suggest criteria for the definition of early and late phase nasal reactions. Nasal challenge with allergen was performed in 15 allergic patients. Nasal resistance was followed until 10 h after allergen challenge and on a control day using whole body plethysmography. The mean percentage changes in the inspiratory nasal resistance during the early phase period (0.25-2 h) and the late phase period (4-10 h) were significantly higher on the allergen challenge day than on the control day (p=0.001 and p=0.01, respectively). The mean percentage change in the inspiratory nasal resistance during the early and late phase period on the control day plus 2 times the standard deviation served as cut-off point for a positive reaction. Using this definition, all patients had early reactions and 7 of the 15 patients (47%) also had late reactions. We conclude that whole body plethysmography is a useful, noninvasive method for the measurement of the physiological changes in the nose following allergen challenge.
Hormonal treatment in advanced non-small cell lung cancer: fact or fiction?
Authors: Vansteenkiste JF , Simons JP , Wouters EF , Demedts MG
Published: May 2003

In patients with advanced non-small cell lung cancer, cachexia is an important cause of morbidity and mortality. The pathogenic mechanism of this finding, usually referred to as "cancer anorexia and cachexia syndrome" (CACS), is complex and far from completely understood, but a disturbed equilibrium between possible food intake and metabolic needs seems to be fundamental. The literature data on the treatment options in advanced non-small cell lung cancer (NSCLC) with cachexia are reviewed. Based on the clinical studies on cancer cachexia, some recommendations for the therapeutic approach of this disorder in patients with advanced NSCLC can be given. Metoclopramide is easily administered, can alleviate gastric disturbances, but probably does not correct the catabolic spiral of CACS. There are not enough data to advise the use of parenteral nutritional support, hydrazine, cyproheptadine, tetrahydrocannabinol or nandrolone decanoate. Corticosteroids are useful in additional analgesia and fast palliation of very weak and debilitated patients in the final episode of their disease. Recent data in non-small cell lung cancer patients are in favour of the use of high-dose progestagens to improve both appetite and weight.
The role of the epithelial cell in Escherichia coli induced neutrophil migration into the urinary tract
Authors: Agace WW
Published: May 2003

Neutrophil influx to mucosal surfaces represents one of the earliest inflammatory responses to mucosal infection. We have been studying external interactions with urinary tract epithelial cells in an attempt to understand the molecular mechanisms behind this process. Uropathogenic Escherichia coli induced urinary tract epithelial cells to secrete the neutrophil chemoattractant interleukin-8 (IL-8). IL-8 secretion was higher in response to isogenic strains expressing type 1 or P fimbriae that adhered to the epithelial surface. Deliberate colonization of the human urinary tract with E. coli induced the local production of IL-8 and levels correlated with urinary neutrophil numbers suggesting a role for IL-8 in neutrophil migration. E. coli induced neutrophil migration across urinary tract epithelial layers in vitro, and this process was blocked with anti-IL-8 antibody. IL-8's activity was localized to the epithelial surface. Furthermore, these cells were shown to constitutively express IL-8 receptor A and B messenger ribonucleic acid (mRNA), suggesting a possible role for IL-8 on epithelial cell function. E. coli enhanced the expression of intercellular adhesion molecule-1 (ICAM-1) on urinary tract epithelial cells, and neutrophil migration across urinary tract epithelial layers in vitro was dependent on epithelial ICAM-1 and neutrophil Mac-1 (CD11b/CD18) expression. These results suggest that bacterial/epithelial cell interactions play a key role in the induction of neutrophil migration during mucosal infection, and show the necessity for host-derived chemotactic factors and cell adhesion events in E. coli induced transuroepithelial migration in vitro.
Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia
Authors: Torres A , El-Ebiary M , Soler N , Monton C , Fabregas N , Hernandez C
Published: May 2003

The aetiopathogenesis of ventilator-associated pneumonia (VAP) requires abnormal oropharyngeal and gastric colonization and the further aspiration of their contents to the lower airways. VAP develops easily if aspiration or inoculation of microorganisms occur in patients with artificial airways, in whom mechanical, cellular and/or humoral defences are altered. Well-known risk factors for gastric colonization include: alterations in gastric juice secretion; alkalinization of gastric contents; administration of enteral nutrition; and the presence of bilirubin. However, the role of the colonized gastric reservoir in the development of VAP remains debatable. Evidence in favour of the role of the stomach in the development of VAP comes mainly from randomized, controlled trials of selective gut decontamination and stress ulcer prophylaxis in the intensive care unit (ICU), in which reducing the bacterial burden of the stomach decreases the incidence of nosocomial respiratory infections. However, at least three studies of flora have found an absence of stomach origin of pneumonia occurring during mechanical ventilation. Prophylactic measures suggested to prevent VAP in relation to the gastric reservoir include: treatment for stress ulcers with sucralfate; prevention of duodenal reflux with metoclopramide; reduction of gastric burden and bacterial translocation by selective digestive decontamination; acidification of enteral feeding; and jejunal feeding. Gastro-oesophageal reflux can be prevented by using small bore nasogastric tubes and jejunal feeding. The aspiration of gastric contents can be reduced by positioning patients in a semirecumbent position, checking the patency of the tube cuff, and aspiration of subglottic secretions. The role of the stomach as a reservoir for microorganisms causing ventilator-associated pneumonia is still controversial but despite the debate, there is major evidence in the literature in favour of the gastric origin of part of these pulmonary infections.
Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation
Authors: Drent M , Cobben NA , Henderson RF , Wouters EF , van Dieijen-Visser M
Published: May 2003

This review describes the usefulness of monitoring the activity level of lactate dehydrogenase (LDH) and its isoenzyme pattern as indicators of pathological conditions in the lungs, such as cell damage or inflammation. Cytoplasmatic cellular enzymes, like LDH, in the extracellular space, although of no further metabolic function in this space, are still of benefit because they serve as indicators suggestive of disturbances of the cellular integrity induced by pathological conditions. Since LDH is an enzyme present in essentially all major organ systems, serum LDH activity is abnormal in a large number of disorders. Although the increase in total serum LDH activity is rather nonspecific, it is proposed that measurement of LDH activity levels and its isoenzyme pattern in pleural effusion and, more recently, in bronchoalveolar lavage fluid may provide additional information about lung and pulmonary endothelial cell injury.
Detection of herpesvirus-like DNA in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma
Authors: Cathomas G , Tamm M , McGandy CE , Perruchoud AP , Mihatsch MJ , Dalquen P
Published: May 2003

Pulmonary involvement is a clinically important form of visceral Kaposi's sarcoma in immunocompromised patients. Recently, herpesvirus-like deoxyribonucleic acid (DNA) sequences, defining a new herpesvirus termed "human herpesvirus 8" (HHV8) or "Kaposi's sarcoma-associated herpesvirus" (KSHV), were detected in Kaposi's sarcoma of acquired immune deficiency syndrome (AIDS) and non-AIDS patients. We describe the successful detection of HHV8 DNA in the bronchoalveolar lavage (BAL) fluid of patients with pulmonary Kaposi's sarcoma. Three immunocompromised patients, two HIV seropositive and one after kidney transplantation, suffered from respiratory symptoms and showed pulmonary infiltrates on chest radiography after development of biopsy proven Kaposi's sarcoma of the skin. Bronchoscopy revealed the typical Kaposi like livid endobronchial lesions. BAL fluid was analysed for the presence of HHV8 DNA using a nested polymerase chain reaction (PCR) assay. HHV8 DNA was detected in the BAL fluid of all three patients. In addition, HHV8 DNA could be detected in the skin biopsy tissue, lymph node, and peripheral blood mononuclear cells of these patients. Our data show that human herpesvirus 8 deoxyribonucleic acid can be detected in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma. If further studies reveal a high specificity for human herpesvirus 8 deoxyribonucleic acid detection, this test will improve the tools for the diagnosis of pulmonary Kaposi's sarcoma without further need of biopsies.
Frequency dependence of specific airway resistance in a commercialized plethysmograph
Authors: Peslin R , Duvivier C , Malvestio P , Benis AR , Polu JM
Published: May 2003

Specific airway resistance (sRaw) measured by body plethysmography has been shown to decrease markedly with decreasing breathing frequency when the inspired air is not conditioned to body temperature, atmospheric pressure and saturation with water vapour (BTPS). The phenomenon has been attributed to noninstantaneous gas warming and wetting in the airways. The aim of this investigation was to assess whether the phenomenon was also present in a commercialized plethysmograph featuring an "electronic BTPS correction". Airway resistance (Raw) and sRaw were measured in 15 healthy subjects at six breathing frequencies ranging 0.25-3 Hz, using a constant volume plethysmograph in which a correction for non-BTPS gas conditions was applied by electronically flattening the box pressure-airway flow loop (Jaeger Masterscreen Body, version 4.0). The temperature and water vapour saturations in the box averaged 26.5 +/- 1.3 degrees C and 59 +/- 6%, respectively. Raw and sRaw exhibited a clear positive frequency dependence in all but one subject. From 0.25 to 3 Hz Raw increased from (mean+/-SD) 0.62 +/- 0.55 to 1.71 +/- 0.76 hPa x s x L-1 (p<0.001), and sRaw from 2.34 +/- 1.90 to 7.55 +/- 3.08 hPa x s (p<0.001). The data are consistent with a simple model, in which gas conditioning in the airways and external dead space occurred with a time constant of 0.39 s. We conclude that the electronic BTPS correction of the instrument was inadequate, probably because it is assumed that gas conditioning in the airways is instantaneous. We recommend that, with similar instruments, airway resistance be measured using as high a panting frequency as feasible.
Disseminated mucormycosis presenting with lower extremity weakness
Authors: von Pohle WR
Published: May 2003

Mucormycosis is an uncommon, but important opportunistic fungal infection. The most commonly reported areas of infection are pulmonary, rhinocerebral and cutaneous. It has only rarely been reported to cause peripheral neurological symptoms. This report presents the case of a patient who presented with ascending paralysis due to pulmonary mucormycosis. The presentation is believed to be due to a lesion which abutted the vertebral column and caused infarction of the spinal cord.
M. Kansasii pulmonary disease in idiopathic CD4+ T-lymphocytopenia
Authors: Anzalone G , Cei M , Vizzaccaro A , Tramma B , Bisetti A
Published: May 2003

Cases of patients with markedly depressed CD4+ T-lymphocyte counts, with or without opportunistic infections, in the absence of any evidence of human immunodeficiency virus (HIV) have been described in recent years. In 1992, the definition of "idiopathic CD4+ T-lymphocytopenia" was formulated by the Centers for Disease Control and Prevention (CDC) of Atlanta (USA). The present case illustrates the occurrence of an unexplained Mycobacterium kansasii pneumonia in a white HIV-negative subject with a persistent depletion of CD4+ T-lymphocytes and suppression of cell-mediated immunity. To our knowledge, this is the first observation of idiopathic CD4+ T-lymphocytopenia with pulmonary mycobacteriosis due to Mycobacterium kansasii, and the sixth case of this kind of immunodeficiency described in Italy.
Atypical mycobacteriosis as a complication of talc pneumoconiosis
Authors: De Coster C , Verstraeten JM , Dumortier P , De Vuyst P
Published: May 2003

A 57 year old man, receiving compensation for talc pneumoconiosis since 1977, was admitted to hospital for the first time in 1987, with symptoms of weight loss, fever, dyspnoea and productive cough. A chest roentgenogram showed bilateral cavitation. Two years later, Mycobacterium xenopi was found in sputum cultures. Despite specific oral antibiotherapy, the patient's health deteriorated and he died in 1990. To the best of our knowledge, this is the first reported case of an association of talcosis with a M. xenopi pneumonia. The relative timing of the two diseases suggests that talc pneumoconiosis predisposed to the infection by M. xenopi.
Pulmonary hypertension associated with POEMS syndrome
Authors: Ribadeau-Dumas S , Tillie-Leblond I , Rose C , Saulnier F , Wemeau JL , Hatron PY , Wallaert B
Published: May 2003

Pulmonary hypertension (PH) is an uncommon but lethal complication of some connective tissue diseases. We describe two cases of PH associated with plasma cell dyscrasia, with polyneuropathy (P), organomegaly (O), endocrinopathy (E), M protein (P) and skin changes (S) described as POEMS syndrome. Two patients, one female and one male, were hospitalized for dyspnoea. Both had a history of POEMS syndrome a few years previously. PH was diagnosed from cardiac catherization, and complete investigations did not reveal other underlying disease. In Case No. 1, mean pulmonary artery pressure was 40 mmHg and pulmonary vascular resistance was 775 dyne x s x cm-5 x m2, with a significant reversibility to vasodilators. Nifedipine and fluindrone treatment was initiated. The patient was still alive 18 months later. In Case No. 2, mean pulmonary artery pressure was 28 mmHg and pulmonary vascular resistance was 243 dyne x s x cm-5x m2, with a slight reversibility to vasodilators. The patient died 6 months later. Our observations suggest that pulmonary hypertension (PH) may be associated with the POEMS syndrome, and that patients suffering from the POEMS syndrome and dyspnoea should be tested for PH.
Auditory cues can modify the gait of persons with early-stage Parkinson's disease: a method for enhancing parkinsonian walking performance?
Authors: Howe T E , Lövgreen B , Cody F WJ , Ashton V J , Oldham J A
Published: May 2003

Objective: To investigate whether systematically adjusting the rate of auditory cues induces corresponding modulations of the temporal and spatial parameters of gait of patients with early-stage Parkinson's disease.

Design: Subjects performed a series of 15 9-metre walks along a level floor under uncued and four cued conditions; the order of cued conditions was randomized.

Setting: A physiotherapy gymnasium, Manchester, UK.

Subjects: Eleven subjects with early-stage idiopathic Parkinson's disease.

Interventions: Preferred pace was established from the initial three uncued walks. The rate of auditory cues delivered throughout subsequent walks was systematically adjusted for each subject, representing 85, 92.5, 107.5 and 115% of their mean cadence at preferred walking pace.

Main outcome measures: Mean cadence, mean stride length and mean velocity.

Results: Repeated measures ANOVA indicated that the mean velocity and mean cadence of subjects' gait significantly ( p ≤ 0.01) increased relative to baseline values at cue rates of 115 and 107.5% of cadence at preferred pace and decreased at cue rate of 85%. Mean stride length was unaffected by variations in cue rate.

Conclusion: The rate of auditory cues, within the range tested, can modulate cadence and thus velocity of gait of subjects with early-stage Parkinson's disease. The provision of auditory cues provides a potential strategy for enhancing walking performance in these patients.
Interpreting change scores on the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
Authors: Jenkinson C , Peto V , Jones G , Fitzpatrick R
Published: May 2003

Objectives: To determine the amount of change over time on the five dimensions of the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) that are subjectively meaningful to patients. Minimally important differences (MID), effect sizes (ES) and standardized response means (SRM) are calculated for respondents who indicate only a little change over the time of the study whilst mean change scores, ES and SRM statistics are calculated for those who indicated much change.

Design: Postal survey. Copies of the ALSAQ-40 were completed on two occasions three months apart. Respondents were also asked to indicate how much change they had experienced since baseline on each of the five domains of the questionnaire.

Setting: All patient members of the Motor Neurone Disease Association for England, Wales and Northern Ireland.

Subjects: Seven hundred and sixty-four patient members returned questionnaires at baseline and follow-up.

Results: For those reporting minor change since baseline results varied across dimensions. For example a MID was reflected in a change of 6.67 (SD 16.52) points for the Communication dimension, whilst for the Emotional functioning dimension the change was 2.67 (SD 15.45) points. Similarly ESs and SRMs varied considerably across dimensions. Mean change over time, ES and SRM statistics for those who reported that their health was much worse at follow-up were substantially larger: for example, mean changes ranged from 6.87 (SD 15.87) to 13.79 (SD 22.60).

Conclusions: Results indicate the minimum magnitude of change that is subjectively meaningful to patients. Results indicate that smaller changes than have been suggested previously as significant have a subjectively meaningful adverse effect upon patients.
Modelling terrestrial vegetation dynamics and carbon cycling for an abrupt climatic change event
Authors: Scholze Marko , Knorr Wolfgang , Heimann Martin
Published: May 2003

Abrupt climatic changes have occurred several times in the past, leading to large-scale modifications of vegetation patterns with important consequences for the global carbon cycle. Dynamic global vegetation models (DGVM) constitute an advanced tool for reconstructing past or predicting future shifts in vegetation distributions in response to climatic change on a global scale. The Lund-Potsdam-Jena (LPJ) model is a DGVM that also includes a complete description of terrestrial-vegetation carbon cycling. Here, it is used for a long-time integration simulating terrestrial ecosystem responses to an abrupt climatic change event. Climate data from an 850-year-long coupled ocean-atmosphere model (ECHAM3/LSG) experiment representing a highly idealized Younger Dryas (c. 12 ka BP) like event are used to study the reactions of the vegetation distribution and changes in terrestrial carbon storage. The main feature of the Younger Dryas simulation experiment is the suppression of the Atlantic thermohaline circulation leading to a significant cooling of the Northern Hemisphere accompanied by a large-scale precipitation decrease. The simulation exhibits a significant shift of the vegetation distribution in the Northern Hemisphere during the cold period in conjunction with a change in global total terrestrial carbon stocks of 180 X 1012 kg C as a consequence of the climatic change event. The response time of the terrestrial biosphere lags the climatic changes by about 250 years for vegetation and 400 years for soil-carbon pools.
Holocene glacier variability: three case studies using an intermediate-complexity climate model
Authors: Weber S. L. , Oerlemans J.
Published: May 2003

Synthetic glacier length records are generated for the Holocene epoch using a process-based glacier model coupled to the intermediate-complexity climate model ECBilt. The glacier model consists of a mass-balance component and an ice-flow component. The climate model is forced by the insolation change due to variations in the Earth's orbital parameters. We consider three glaciers, ranging from maritime to continental. At Nigardsbreen (southern Norway), the simulated long-term trend in the annual mass-balance is primarily determined by summer temperature, with a smaller contribution from winter precipitation. In the early Holocene, summers were warmer and winters wetter than today in the ECBilt simulation. Both signals seems consistent with proxy data. The simulated glacier length shows a phase of rapid expansion during the mid-Holocene, followed by more gradual growth. At Rhonegletscher (the Swiss Alps), ECBilt simulates warmer and wetter summers in the early Holocene. The temperature signal seemns realistic, but proxy data and earlier modelling results are not conclusive with respect to the precipitation signal. The implied glacier length shows a maximum extent at 3-5 kyr BP, which seems unlikely. This suggests that the simulated precipitation response is not realistic. The simulated early-Holocene climate at Abramov glacier (Kirghizia) is characterized by high summer precipitation, associated with a northward extension of the Asian monsoon. The precipitation signal reaches its maximum around 6 kyr BP, which is consistent with the timing of the maximum in lake-level data. The simulated glacier length shows a pronounced postglacial maximum at the time of maximum monsoon intensity. There is considerable centennial-timescale variability in the simulated glacier length records. These length variations are generated by internal climatic variability. They are typically asynchronous among the three different glaciers. ECBilt has reasonable skill in simulating the relative importance of temperature and precipitation as well as the seasonality of the forcing, although the overall level of variability is underestimated. Length variations are shown to behave as a lagged moving-average process, with a glacier-specific memory.
A theoretical approach to glacier equilibrium-line altitudes using meteorological data and glacier mass-balance records from southern Norway
Authors: Lie Øyvind , Dahl Svein Olaf , Nesje Atle
Published: May 2003

Based on a close exponential relationship between mean ablation-season temperature and winter precipitation at the equilibrium-line altitude (ELA) of 10 Norwegian glaciers, three equations are derived. The first equation enables calculation of the minimum altitude of areas climatically suited for glacier formation, and is termed the altitude of instantaneous glacierization (AIG). Equation (2) is derived based on the ‘principle of terrain adaptation’, enabling quantification of the glacial buildup sensitivity (GBS) in presently non-glaciated areas. The theoretical climatic temperature-precipitation ELA (CTP-ELA) in presently non-glaciated areas is calculated in equation three by combining GBS with terrain altitude. Mass-balance records from four modern glaciers (Ålfotbreen, Nigardsbreen, Storbreen and GrÅsubreen) situated in maritime to continental climate regimes in southern Norway are used to test these equations. Correlation between AIG and net balance measurements (bn) yielded correlation coefficients of r=-0.80 to r=-0.84. Calculated AIGs correspond well with observed ELAs on Ålfotbreen, Nigardsbreen and GrÅsubreen, while it deviates from the observed ELA on Storbreen; the latter is probably due to leeward accumulation of wind-blown snow on this cirque glacier. Based on this approach, regional representative climatic ELAs can be calculated for non-glaciated areas with instrumental records of ablation-season temperature and winter precipitation.