bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose
Authors: Strand V , Svartengren M , Rak S , Barck C , Bylin G
Published: November 2002

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.
The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics
Authors: Van Schoor J , Joos GF , Chasson BL , Brouard RJ , Pauwels RA
Published: November 2002

Inhalation of neurokinin (NK) A causes bronchoconstriction in patients with asthma. The NKA-induced bronchoconstriction in isolated human airways is mediated via the NK2 receptor and inhibited by SR 48968, a potent and specific nonpeptide tachykinin NK2 receptor antagonist. In the present study, the effect of orally administered SR 48968 on NKA-induced bronchoconstriction was examined in 12 mild asthmatics. On the screening day and during the study periods, increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol x mL(-1)) were inhaled, until the forced expiratory volume in one second (FEV1) and specific airway conductance (sGaw) decreased by at least 20 and 50%, respectively. During the study periods, 100 mg SR 48968 or matched placebo was ingested in a double-blind, randomized, crossover fashion and NKA provocation was performed at 1.5 and 24 h after dosing. At 1.5 h, the mean (SEM) log10 provocative concentration of NKA causing a 20% fall in FEV1 (PC20 FEV1) was -6.25 (0.20) after SR 48968 and -6.75 (0.17) after placebo (p=0.05); the mean log10 provocative concentration of NKA causing a 35% fall in sGaw (PC35 sGaw) was -7.02 (0.28) after SR 48968 and -7.64 (0.19) after placebo (p=0.05). At 24 h, the mean log10 PC20 FEV1 was -6.21 (0.17) after SR 48968 and -6.65 (0.11) after placebo (p=0.05); the mean log10 PC35 sGaw was -6.85 (0.23) after SR 48968 and -7.17 (0.15) after placebo (nonsignificant). As PC20 FEV1 and/or PC35 sGaw were not reached in up to 4 patients per SR 48968 group, the differences between SR 48968 and placebo were underestimated. In conclusion, oral treatment with 100 mg SR 48968 caused a significant inhibition of neurokinin A-induced bronchoconstriction in asthmatics. This finding constitutes the first evidence of inhibition of sensory neuropeptide-induced bronchoconstriction by a selective tachykinin receptor antagonist in humans.
Effect of chronic theophylline treatment on the methacholine dose-response curve in allergic asthmatic subjects
Authors: Page CP , Cotter T , Kilfeather S , Sullivan P , Spina D , Costello JF
Published: November 2002

Theophylline is a bronchodilator and immunomodulator drug which has recently been demonstrated to attenuate the recruitment and activation of inflammatory cells into lungs of asthmatics. This study investigated the effect of chronic treatment with theophylline for its ability to alter airway responsiveness, as indicated by changes in airway sensitivity and reactivity to inhaled methacholine. The subjects studied were mild asthmatics who relied on beta-agonist medication only and who were randomized into two groups, one receiving theophylline (median dose 250 mg twice daily; range 250-375 mg twice daily) and the other placebo. A number of parameters was measured before and after treatment, including baseline forced expiratory volume in one second (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20; sensitivity), dose-response slope (reactivity) and percentage eosinophils, eosinophil cationic protein and T-cell markers in peripheral blood (by flow cytometry). After 2 months of treatment with theophylline there was a significant lowering of airway reactivity (slope) to methacholine and improvement in methacholine sensitivity (PC20). However, such changes were not associated with any significant change in the number or activation status of eosinophils and lymphocytes in peripheral blood. In conclusion, chronic treatment with theophylline reduces the reactivity of the airways to methacholine, which might be beneficial in the treatment of persistent asthma. The cellular mechanisms of this improvement remain to be clarified.
Quality of life during formoterol treatment: comparison between asthma-specific and generic questionnaires. Canadian and the Dutch Formoterol Investigators
Authors: van der Molen T , Sears MR , de Graaff CS , Postma DS , Meyboom-de Jong B
Published: November 2002

This study aimed to investigate the effect of treating patients with moderate asthma with formoterol on quality of life (QoL) and to compare several questionnaires in their ability to detect changes in QoL. In an eight month multicentre, randomized, placebo-controlled trial, patients with asthma using daily inhaled corticosteroids and beta2-agonists (> or = 5 inhalations x week(-1)) were randomized to 6 months treatment with formoterol 24 microg b.i.d. (by Turbuhaler) or a matching placebo. Patients recorded symptoms (maximal score 21) and peak expiratory flow (PEF) twice daily. QoL was measured with two asthma-specific questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Living with Asthma Questionnaire (LWAQ), and with two generic QoL forms, i.e. the Short Form 36 (SF36) and the Psychological and General Well-Being scale (PGWB) at randomization and after 6 months of treatment. Out of 110 patients studied, 56 received formoterol and 54 placebo. Mean baseline forced expiratory volume in one second was 65% predicted. Mean morning PEF was 369 L x min(-1). Mean total symptom score was 3.6. Morning PEF increased (26.8 L x min(-1), p=0.0001) and symptoms decreased (-1.23, p=0.012) in the formoterol group in contrast to placebo. QoL improvements were measured in the LWAQ total score (baseline 0.61, change -0.05, p=0.048) and the physical construct of the LWAQ (baseline 0.71, change 0.07, p=0.044). The AQLQ and the generic QoL instruments showed no significant changes. In conclusion, the improvement in quality of life reported after 6 months was very small and only reflected by the Living with Asthma Questionnaire.
Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro
Authors: Pennings HJ , Kramer K , Bast A , Buurman WA , Wouters EF
Published: November 2002

Recent studies have implicated a role for tumour necrosis factor-alpha (TNFalpha) in the development of the asthmatic reaction. In this study, we examined the influence of TNFalpha on isotonic contraction of tracheal smooth muscle of the guinea-pig in vitro in response to methacholine. Tracheal rings were incubated with recombinant human (rh)TNFalpha (3x10(-11) M) for 30 min, and concentration-response curves to methacholine before and after incubation with rhTNFalpha were compared with the control. The present study demonstrates that rhTNFalpha increases maximal isotonic contraction of tracheal smooth muscle to methacholine (mean+/-SEM 169.6+/-43%, p<0.005). This effect was observed only after a 30 min delay between incubation and methacholine challenge testing. Experiments with 10(-13) - 10(-10) M rhTNF-alpha yielded similar results at all concentrations used. The effects of rhTNFalpha (10(-11) M) on tracheal hyperreactivity could be completely inhibited by coincubation with dimeric rTNF-receptor-p80 construct (10(-10) M) (p<0.01). In order to analyse secondary mediator release, experiments using coincubation with indomethacin (10(-5) M) and WEB 2086 (10(-6) M), a specific platelet activating factor (PAF) antagonist, demonstrated that the effect of rhTNFalpha on tracheal rings was mediated by PAF, since WEB 2086 completely inhibited rhTNFalpha-induced hyperreactivity (p<0.05). In conclusion, this study demonstrates that recombinant human tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle in vitro, which was shown to be mediated by platelet activating factor. Our study emphasizes the role of tumour necrosis factor-alpha in the pathophysiology of bronchial hyperresponsiveness.
Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells
Authors: Takizawa H , Desaki M , Ohtoshi T , Kawasaki S , Kohyama T , Sato M , Nakajima J , Yanagisawa M , Ito K
Published: November 2002

Erythromycin and its fourteen-member macrolide analogues have attracted attention for their efficacy in bronchial asthma. However, their mechanisms of action remain unclear. We evaluated the effects of the macrolide antibiotics on endothelin-1 (ET-1) expression in normal and transformed human bronchial epithelial cells, one of the sources of this potent bronchoconstrictor important in the pathogenesis of asthma. Human bronchial epithelial cells were obtained from the resected bronchi, and the effect of several antimicrobial and antiasthmatic drugs on the production and messenger ribonucleic acid (mRNA) levels of ET-1 was evaluated. Bronchoepithelial cells were also isolated from the mucosa of asthmatic patients under fibreoptic bronchoscopy, and the modulating effects of the drugs were studied. Erythromycin and clarithromycin uniquely suppressed mRNA levels as well as the release of ET- at therapeutic and non-cytotoxic concentrations (percentage inhibition of ET-1 protein release: 26.4+/-5.22% and 31.2+/-7.45%, respectively, at 10(-6) M). Furthermore, erythromycin and clarithromycin inhibited ET-1 expression in bronchoepithelial cells from patients with chronic, stable asthma. A glucocorticosteroid, dexamethasone, also inhibited ET-1 expression. In contrast, theophylline, salbutamol and FK506 had no effect on ET-1 production. Our findings demonstrated that these fourteen-member macrolide antibiotics had an inhibitory effect on endothelin-1 expression in human bronchial epithelial cells. Moreover, this new mode of action may have some relevance to their clinical efficacy in bronchial asthma.
Relationship between cholinergic airway tone and serum immunoglobulin E in human subjects
Authors: Endoh N , Ichinose M , Takahashi T , Miura M , Kageyama N , Mashito Y , Sugiura H , Ikeda K , Takasaka T , Shirato K
Published: November 2002

It has recently been shown that immunoglobulin (Ig)E facilitates the cholinergic bronchoconstrictor pathway in human tissue in vitro. However, whether this occurs in humans in vivo has not been clarified. In this study, the bronchodilator responses were examined to inhalation of a submaximal dose of the anticholinergic agent oxitropium bromide (600 microg) in normal and allergic subjects with various levels of total serum IgE. Values of the forced expiratory volume in one second (FEV1) for all subjects were greater than 80% of predicted, but were negatively correlated with serum IgE levels (p<0.01). Oxitropium bromide inhalation induced an increase in FEV1 that was significantly greater in allergic rhinitis patients with high serum IgE (155+/-20 mL (mean+/-SEM), p<0.05) than in healthy subjects (64+/-21 mL) or those with allergic rhinitis but low serum IgE (82+/-21 mL, p<0.05). In contrast, the effects of the inhaled beta2-adrenergic agent orciprenaline sulphate (2.25 mg) were not significantly different among the three groups. In conclusion, higher serum immunoglobulin E levels were correlated with lower values of the forced expiratory volume in one second, and anticholinergic agents, but not beta2-adrenergic agents, caused more pronounced bronchodilation in subjects with high than in those with low immunoglobulin E levels. These data suggest that serum immunoglobulin E may be one of the factors that determine the airway tone, possibly via cholinergic mechanisms.
Longitudinal predictors of airway responsiveness to distilled water: the role of atopy and maternal smoke exposure
Authors: Studnicka M , Roithner B , Gartner C , Weiss ST , Neumann M , Frischer T
Published: November 2002

Airway responsiveness is an objectively measurable clinical trait related to the presence of asthma. Although risk factors for this trait have been evaluated cross-sectionally, little is known about its longitudinal predictors. A population cohort of 539 children, aged 8 yrs at the start of follow-up, underwent 3-7 bronchial challenge tests spaced at 3-9 month intervals. Airway responsiveness was assessed by a single-step distilled water challenge. To investigate responsiveness as a continuous trait, the ratio of the postchallenge to prechallenge forced expiratory volume in one second was calculated. A child's repeated ratios were then regressed on the time of follow-up. The resulting child-specific regression coefficient was the outcome variable to assess longitudinal predictors of airway responsiveness (AR). Results were based on 2,267 repeated challenge tests, and indicated an overall decrease in responsiveness. Children with a diagnosis of asthma (mean+/-SD, longitudinal change in AR + yr(-1): -0.060+/-0.149), those with a positive skin-prick test (-0.018+/-0.106) and those with reported exposure to maternal smoking (-0.004+/-0.083) demonstrated increased airway responsiveness over time. All of these changes in airway responsiveness were found to be significant in multiple linear regression analysis (p<0.05). Stratified analysis further indicated that the effect of maternal smoking was observed primarily in nonatopic children and was greatest at an exposure level of > or =10 cigarettes x day(-1). In conclusion, atopy and exposure to maternal smoking can predict longitudinal change in childhood airway responsiveness.
Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung
Authors: Riise GC , Williams A , Kjellstrom C , Schersten H , Andersson BA , Kelly FJ
Published: November 2002

Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.
Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer
Authors: Luporini G , Barni S , Marchi E , Daffonchio L
Published: November 2002

Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine.
Lymphomatoid granulomatosis--a report on four cases: evidence for B phenotype of the tumoral cells
Authors: Taniere P , Thivolet-Bejui F , Vitrey D , Isaac S , Loire R , Cordier JF , Berger F
Published: November 2002

Four cases of lymphomatoid granulomatosis are reported, three of them involving the lung. Histological features included a true angiocentric and angiodestructive polymorphic cellular proliferation. This included histiocytes, plasma cells, many reactive T-cells and rare large, atypical cells which were of the B phenotype. Epstein-Barr virus was detected in the atypical cells by in situ hybridization in three cases, with expression of both latent membrane proteins (LMP)-1 and Epstein-Barr nuclear antigen-2 in two cases and expression of only LMP-1 in the third case. Expression of both of these proteins suggests a defect in the T-cell-mediated immunity and that Epstein-Barr virus is not only a silent passenger but may also be involved in the pathogenesis of the disease. This could have implications for therapy.
Pseudomonas aeruginosa bronchopulmonary infection in patients with AIDS, with emphasis on relapsing infection
Authors: Domingo P , Ferre A , Baraldes MA , Ris J , Sanchez F
Published: November 2002

The aim of this study was to delineate the clinical and therapeutic characteristics of Pseudomonas aeruginosa bronchopulmonary infection in acquired immunodeficiency syndrome (AIDS) patients. Eighteen AIDS patients had 39 episodes of P. aeruginosa bronchopulmonary infection. Their mean CD4 cell count was 0.012+/-0.011 cells x 10(9) x L(-1) and two episodes (5.1%) occurred in neutropenic patients. Ten patients (55.5%) had 21 outbreaks of pseudomonal infection. Relapses were more frequent in patients with chronic bronchitis (80 versus 0%, p=0.03) and in those who received initial oral antibiotic therapy (100 versus 55.6%, p=0.25). Three patients died, but death was directly related to pseudomonal infection in only one patient. In a case-control study, patients with bronchopulmonary P. aeruginosa infection had a survival comparable to patients in the control group. Immunoglobulin prophylaxis was administered to three patients with relapses, without success. The two patients who had P. aeruginosa eradicated were those who began triple antiretroviral therapy and had a CD4 cell increase >0.150 cells x 10(9) x L(-1). Relapsing Pseudomonas aeruginosa bronchopulmonary infection affects patients with advanced human immunodeficiency virus infection, prior underlying lung disease, chronic bronchitis and initial oral antibiotic therapy. Immune reconstitution through triple antiretroviral therapy succeeded in eradicating Pseudomonas aeruginosa respiratory infection in two patients.
Energy intake and energy expenditure in prepubertal males with asthma
Authors: Maffeis C , Chiocca E , Zaffanello M , Golinelli M , Pinelli L , Boner AL
Published: November 2002

This study aimed to measure energy intake (EI) and total energy expenditure (TEE) of asthmatic males and to validate diet history as a method of estimating their energy requirements. EI was assessed by dietary history and TEE by the heart-rate monitoring method in a group of asthmatic and nonasthmatic males. Resting energy expenditure (REE) adjusted for fat-free mass was higher in asthmatic than in nonasthmatic males (5,037 versus 4,839 kJ x day(-1), p<0.05). TEE (93+/-1.8 versus 8.4+/-1.4 MJ x day(-1), respectively; p=NS) and EI (9.2+/-15 versus 8.8+/-15 MJ x day(-1), respectively, p=NS) were not statistically different in asthmatic and nonasthmatic male. EI was not statistically different from TEE in both groups of males. Asthmatic males showed an acceptable agreement between TEE and EI at the individual level (range of agreement: -3.2 to 2.9 MJ x day(-1)), and a good agreement at the group level (95% confidence interval for the bias, - 1.1 to 0.8 MJ x day(-1)). Males with mild-to-moderate asthma have a higher metabolic activity per unit fat-free mass than nonasthmatic males. This increased requirement is apparently well compensated by an adequate energy intake. Diet history is a suitable method for estimating energy requirements in males with mild-to-moderate asthma.
Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause
Authors: Mouloudi E , Katsanoulas K , Anastasaki M , Askitopoulou E , Georgopoulos D
Published: November 2002

The delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer in mechanically ventilated patients has become widespread practice. However, the various ventilator settings that influence the efficacy of MDI are not well established. Application of an end-inspiratory pause (EIP) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy. To test this, the effect of EIP on the bronchodilation induced by beta2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Twelve patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomized to receive six puffs of salbutamol (100 microg x puff(-1)) either with or without EIP of 5 s duration. Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6 h wash-out, patients were crossed over to receive salbutamol by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rmin) and maximum (Rmax) airflow resistance, the difference between Rmax and Rmin (deltaR), static end-inspiratory respiratory system compliance (Cst,rs) and cardiac frequency (fc) were measured before and at 15, 30 and 60 min after salbutamol administration. Salbutamol caused a significant decrease in dynamic and static airway pressures, Rmin and Rmax. These changes were not influenced by application of EIP and were evident at 15, 30 and 60 min after salbutamol. With and without EIP, Cst,rs,deltaR and fc did not change after salbutamol. In conclusion, salbutamol delivered with a metered-dose inhaler and a spacer device induced significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which was not affected by an end-expiratory pause of 5 s. These results do not support the use of end-inspiratory pause when bronchodilators are administered in adequate doses during controlled mechanical ventilation.
Influence of cervical sympathetic nerves on ventilation and upper airway resistance in the rat
Authors: O'Halloran KD , Curran AK , Bradford A
Published: November 2002

The cervical sympathetic trunks innervate the carotid bodies, carotid baroreceptors, thyroid gland and the upper airway mucosa, structures which can influence breathing and upper airway resistance. However, their role in the control of ventilation and upper airway patency is poorly understood. A constant airflow was applied to the upper airway through a high-cervical tracheostomy in anaesthetized rats breathing spontaneously through a low-cervical tracheostomy. The peripheral ends of the cut cervical sympathetic trunks were stimulated electrically and airflow resistance and ventilation were measured. The effects of cervical sympathetic trunk section on ventilation were also measured in conscious rats. In conscious rats, cutting the sympathetic trunks caused a decrease in ventilation during normoxia but only slightly affected ventilatory responses to hypoxia and hypercapnia. In anaesthetized rats, sympathetic trunk stimulation caused an inhibition of breathing which was sometimes followed by excitation. These responses were unaffected by alpha- or beta-adrenoceptor blockade but were abolished by cutting the carotid sinus nerves. Sympathetic stimulation also caused a fall in upper airway resistance which was reduced by bypassing the nose, unaffected by propranolol or carotid sinus nerve section and abolished by phentolamine. It was concluded that the cervical sympathetic nerves exert important influences on ventilation and upper airway resistance.
Accuracy of oxygen delivery by liquid oxygen canisters
Authors: Kampelmacher MJ , Cornelisse PB , Alsbach GP , van Kesteren RG , Melissant CF , Douze JM , Lammers JW
Published: November 2002

The oxygen flow rate delivered by liquid oxygen canisters may be less than intended, owing to inaccuracies of the set flow rates and/or as a result of the outflow resistance caused by the humidifier, oxygen tubing, delivery or conserving device. The aim of this study was to investigate the accuracy of oxygen delivery by liquid oxygen canisters at different flow rates and levels of outflow resistance. Four stationary and 18 portable liquid oxygen canisters from three manufacturers were tested. All flows were measured using a Timemeter RT 200 Calibration Analyser. An adjustable obstruction was used to calculate the effect of the outflow resistance on the delivered flow rate. The measured and set flow rates of both stationary and portable canisters were strongly correlated. Expressed as a percentage of the set flow rate, the measured flow rate of the canisters varied from 36-128%, with the lowest values at flow rates <1 L x min(-1). Sixty-two (26%) of the measured flow rates differed > or =10% from the set flow rate. A difference of 0.5-1.0 L x min(-1) occurred in 16 (7%) of the measurements, but only at set flow rates >2 L x min(-1). Irrespective of the set flow rate, the measured flow rate was hardly affected by the outflow resistance. We conclude that the accuracy of oxygen delivery by liquid oxygen canisters depends on the inaccuracy of the set flow rates rather than on the outflow resistance, even at high flow rates. Although the differences between the measured and set flow rates were mostly small, they may have clinical significance, particularly in patients with chronic obstructive pulmonary disease. To prevent inaccuracy, monthly checks of the canisters by the oxygen provider at the patient's home are more important than yearly maintenance.
Five years' experience of PAS Port intravenous access system in adult cystic fibrosis
Authors: Burdon J , Conway SP , Murchan P , Lansdown M , Kester RC
Published: November 2002

An implantable venous access system provides a reliable and painless entry site for intravenous treatment. This study reports the authors' experience with such a system in adult patients with cystic fibrosis. Sixty five (87%) of 75 PAS Ports were placed successfully in 57 patients with cystic fibrosis. Because of early difficulties in advancing the catheter in patients whose veins had been traumatized by repeated courses of intravenous antibiotics, a technique was developed whereby venous entry was gained by direct subclavian puncture. This catheter insertion method was used in 53 (82%) attempts and the catheter was then passed by subcutaneous tunnelling to the port site on the ventral aspect of the upper arm. Fifty seven (88%) insertions were successful under local anaesthetic. The major early and late complications were iatrogenic pneumothorax (six cases) and infection (five cases), respectively. Late complications were more common when there was coexisting disease, e.g. diabetes mellitus, or an acute severe respiratory exacerbation, or when the Port was used for parenteral feeding. In conclusion, the PAS Port can be inserted safely by direct subclavian puncture. It was well tolerated and universally liked by the patients.
Transcription factors and asthma
Authors: Barnes PJ , Adcock IM
Published: November 2002

Asthma is characterized by the expression of multiple genes for inflammatory proteins, such as cytokines, enzymes, receptors and adhesion molecules. This is orchestrated by transcription factors, which are proteins that bind to the promoter regions of these genes and may be activated by inflammatory stimuli, such as cytokines. Several transcription factors are involved in asthmatic inflammation, including nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), nuclear factor of activated T-cells (NF-AT), cyclic AMP response element binding protein (CREB) and signal transduction-activated transcription factors (STAT). These transcription factors lead to coordinated expression of multiple inflammatory genes. There is increasing evidence that synergistic interaction of these transcription factors (e.g. NF-kappaB and AP-1) results in the optimal expression of particular genes, resulting in the specific inflammatory pattern seen in asthmatic airways. Transcription factors are a target for antiasthma therapy. Corticosteroids activate glucocorticoid receptors, which themselves are transcription factors, and interact with other transcription factors to inhibit their actions. The interaction between transcription factors may be important in amplifying and inhibiting the inflammatory process. Many transcription factors interact with a large co-activator molecule CREB-binding protein (CBP) that coordinates the activation of several transcription factors and controls transcription through the regulation of deoxyribonucleic acid coiling around histone residues in the chromatin structure. Understanding transcription factors in asthma has given new insights into the complex chronic inflammatory process, the mechanism of action of corticosteroids, and may lead to new approaches to therapy in the future.
Use of bilevel positive airway pressure ventilatory support for pathological flail chest complicating multiple myeloma
Authors: Abisheganaden J , Chee CB , Wang YT
Published: November 2002

Multiple myeloma is a common disease that universally involves the skeletal system. Although rib involvement may occur, the development of pathological flail chest is rare. We describe the treatment and course of this condition in an elderly female, and the use of the bilevel positive airway pressure (BiPAP) ventilatory system in providing pneumatic stabilization, while definitive chemotherapy was given to heal the pathological fractures. Our experience with this patient suggests that, despite its dramatic clinical manifestation, the association of flail chest with multiple myeloma may not predict a poor prognosis. We have also found that pneumatic stabilization can be achieved by using the bilevel positive airway pressure ventilatory support through a tracheostomy.
Pathophysiology of changes in absolute lung volumes
Authors: Bancalari E , Clausen J
Published: November 2002

Changes in absolute lung volumes are common in lung disease and result in significant impacts on gas exchange, respiratory muscle function, the sensation of dyspnoea, and limitations to maximal exercise. Though our knowledge regarding the magnitude and determinants of changes in lung volumes in health and disease has increased in the past 20 years, a number of important questions remain unanswered. Consideration of the limitations of specific methods for measuring lung volumes is essential when analysing published studies regarding absolute lung volumes in infants, children and adults. Though functional residual capacity is most commonly measured in children and adults with the subject awake and at rest, increasingly attention is being directed to making these measurements under clinically more relevant conditions (e.g. during exercise, sleep, anesthesia, or mechanical ventilation). The relationships between dynamic changes in functional residual capacity, flow limitation during tidal breaths, sensation of dyspnoea and exercise limitation are important to understand, and are the focus of current and future research. Improved understanding of these relationships may lead to improvements in therapy of patients with acute and chronic lung disease and are likely to be particularly important for evaluating the efficacy of and optimal patient selection for new modes of therapy, such as lung volume reduction surgery.
Opioid switching from morphine to transdermal fentanyl for toxicity reduction in palliative care
Authors: McNamara Paul
Published: November 2002

The study objective was to determine whether switching patients from morphine to transdermal fentanyl resulted in a reduction of morphine-associated side effects, and an improvement in cognitive function and patients' well being while maintaining adequate pain and symptom control. Nineteen patients aged 42– 86 with terminal cancer, maintained on morphine for pain and distressed as a result of morphine toxicity, were given the dose of fentanyl corresponding to their current morphine dose. Pain control was then maintained (mostly fentanyl 50– 100 μg/h) over the 14-day study period. Throughout the study, patients' global assessment of well being (primary efficacy variable) was statistically significantly improved. Sleepiness and drowsiness were significantly less of a problem. There was a trend towards improvement in attention span/ concentration, and in the power and quality of concentration. Cognitive function tests also revealed a significant improvement in working (short term) and speed of memory although not in secondary (long term) memory. Patients did not experience hallucinations or delusions and there was no change in levels of anxiety or depression (Hospital Anxiety Depression Scale). The incidence of dizziness was significantly reduced, and there was a nonsignificant decrease in number of patients who suffered myoclonus and in the severity of this condition over the 14 days. The investigator's overall impression of treatment with transdermal fentanyl was ‘fair’, which was not in agreement with the positive impression expressed by patients (score 74, range: 0 worst, 100 best). Further work is required to determine if the improvement in patients' well being and cognitive function is achieved in larger study populations.
Presacral neurolytic block for relief of pain from pelvic cancer: description and use of a CT-guided lateral approach
Authors: Wilsey C , Ashford N S , Dolin S J
Published: November 2002

A CT guided lateral approach for neurolysis of the presacral plexus is described for treatment of pelvic pain due to advanced cancer. The technique was evaluated in two patients with unrelieved pelvic and perineal pain. Other neurolytic techniques used to treat pelvic pain due to advanced cancer are reviewed with a discussion of benefits and potential side effects of this technique.
Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care
Authors: Bennett Mike , Lucas Viv , Brennan Mary , Hughes Andrew , O'Donnell Valerie , Wee Bee
Published: November 2002

The management of ‘death rattle' was reviewed by a task group on behalf of the Association for Palliative Medicine's Science Committee. Evidence was searched for the effectiveness of various anti-muscarinic drugs in drying oropharyngeal and bronchial secretions in dying patients. Clinical guidelines were constructed based on evidence from volunteer and clinical studies. Death rattle occurs in half of all dying patients and some response occurs in around 80% of treated patients. Clinical studies demonstrate that subcutaneous hyoscine hydrobromide 400 mg is more effective at improving symptoms at 30 min than glycopyrronium 200 mg by the same route. Volunteer studies demonstrate that intramuscular glycopyrronium 400 mg is as effective in drying secretions at 30 min as a dose of 200 mg given intravenously. Duration of response is shortest for hyoscine butylbromide (1 h) and longest for glycopyrronium (more than 6 h). There is insufficient evidence to support the use of one drug over another in a continuous infusion and prescribers should base decisions on different characteristics of each anti-muscarinic drug.
Clinical nurse specialists in palliative care. Part 2. Explaining diversity in the organization and costs of Macmillan nursing services
Authors: Clark David , Seymour Jane , Douglas Hannah-Rose , Bath Peter , Beech Nicola , Corner Jessica , Halliday Deborah , Hughes Philippa , Haviland Jo , Normand Charles , Marples Rachael , Skilbeck Julie , Webb Tom
Published: November 2002

In the UK, the work of Macmillan clinical nurse specialists in palliative care is now well established. There has been little research, however, into the organizational context in which these nurses operate and the implications for the services they deliver. We report on a major evaluation of the service delivery, costs, and outcomes of Macmillan nursing services in hospital and community settings. The study was based on eight weeks of fieldwork in each of 12 selected services. Data are presented from semi-structured interviews, clinical records, and cost analysis. We demonstrate wide variation across several dimensions: location and context of the services; activity levels; management patterns; work organization and content; links with other colleagues; and resource use. We suggest that such variation is likely to indicate the existence of both excellent practice and suboptimal practice. In particular, our study highlights problems in how teamwork is conceptualized and delivered. We draw on recent organizational theories to make sense of the heterogeneous nature of Macmillan nursing services.
Clinical nurse specialists in palliative care. Part 3. Issues for the Macmillan Nurse role
Authors: Seymour Jane , Clark David , Bath Peter , Beech Nicola , Corner Jessica , Douglas Hannah-Rose , Halliday Deborah , Haviland Jo , Marples Rachael , Normand Charles , Skilbeck Julie , Webb Tom
Published: November 2002

The remit and boundaries of the Macmillan Nursing role in the UK have been called into question recently by a number of policy-driven changes. The rapid appointment of tumour site-specific nurses and the development of posts for palliative medicine, stemming originally from the Calman Hine recommendations for reorganizing cancer services, have created unparalleled challenges of adaptation to new working practices and procedures. The extent to which Macmillan Nurses are adapting to these new demands was addressed as part of a major evaluation study of UK Macmillan Nursing in 12 sites commissioned by the UK charity Macmillan Cancer Relief. This paper draws upon semi-structured interviews with Macmillan Nurses (n = 44) and their key colleagues (n = 47). We found that differences of expectation between Macmillan Nurses and their managers about the appropriate focus of their work lead to problems of role ambiguity and role conflict; that Macmillan Nurses lack resources with which to develop an educative and consultative role and yet substitute for inadequacies in skills and knowledge of other health care staff; and that problems are associated in co-working with newly appointed cancer site-specific nurses and palliative medicine colleagues. Macmillan Nursing has a crucial role to play in meeting the objectives in the NHS Cancer Plan. However, in order to ensure that their expertise is used efficiently and effectively, there is an urgent need to clarify the nature and scope of the Macmillan Nurse role, to attend to issues of team working and to improve the skills of nonspecialist staff in palliative care.
Serum hormone levels in humans with low serum concentrations of 2,3,7,8-TCDD
Authors: Johnson ES , Shorter C , Bestervelt LL , Patterson DG , Needham LL , Piper WN , Lucier G , Nolan CJ
Published: November 2002

We measured current serum hormone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 37 men who sprayed 2,4,5- trichlorophenoxyacetic acid (2,4,5-T) in the State of Victoria, Australia. TCDD levels were consistently significantly inversely related to prolactin levels in all analyses. In correlation analyses, TCDD levels were also inversely related to triiodothyronine (T3), thyroid-stimulating hormone (TSH), and testosterone levels, and positively associated with glucagon levels. The mean serum TCDD concentration in these sprayers was between 2.6 and 8.1 parts per trillion (ppt). Since such TCDD levels are commonly found in the general population in countries such as the US, the results could suggest that background levels of TCDD in the general population could have an effect on hormone levels. The findings are preliminary and need to be replicated in order to evaluate their full public health significance.
Validation of exposure estimation for benzene in the Australian petroleum industry
Authors: Glass Deborah C , Gray Christopher N , Adams Geoff G , Manuell Richard W , Bisby John A
Published: November 2002

A nested case-control study was undertaken to investigate whether an excess of lympho-haematopoietic cancers in the Australian petroleum industry was associated with benzene exposure. The benzene exposures of the cases and controls were estimated using a quantitative algorithm based largely on exposures measured in the Australian petroleum industry. The algorithm was used to estimate, for each subject, the benzene exposure in parts per million (ppm) for each job held in the industry, and the cumulative exposure in ppm years. Because of the critical importance of the exposure assessment in this design of epidemiological study, particular attention was paid to the reliability of the inputs to the algorithm. The inputs [base estimates (BEs) of exposure and technology-specific exposure modifiers (EMs)] were compared to data from other sources including the occupational hygiene literature. Where such comparison data were available, they were generally found to confirm the values used in the algorithm, although four input values were changed as a result of the validation exercise. The integrity of the task-based algorithm was validated by employing it to calculate the exposures of the tanker drivers in the study and comparing these with measured daily exposure for tanker drivers in the Australian petroleum industry and exposure values found in the occupational hygiene literature. After adjustment for the mix of products carried by the Australian tanker drivers, the estimates from the algorithm were found to be comparable to the measured and literature values. This exercise provided evidence that the exposure assessment for the epidemiological study was reliable and that the results of the study can be used as the basis for evaluating the relationship between exposure to benzene and the risk of lympho-haematopoietic cancer.
Cognitive performance and cerebrohemodynamics associated with the Persian Gulf Syndrome
Authors: Bunegin Leonid , Mitzel Howard C , Miller Claudia S , Gelineau Jerry F , Tolstykh Gleb P
Published: November 2002

The Persian Gulf Syndrome generally manifests as a set of nonspecific complaints with emphasis on central nervous system impairment. The purpose of this study was to determine if cognitive performance and middle cerebral artery blood flow velocity (MCABFV) were altered in symptomatic Gulf War veterans (sGWVs) and asymptomatic Gulf War veterans (aGWVs) by exposure to low levels of acetone. MCABFV was assessed in male aGWVs (n=8) and sGWVs (n=8) during cognitive challenges while breathing 1) clean air, 2) a clean air placebo, and 3) a mixture of air and 40 parts per million (ppm) acetone. Pulmonary function was also evaluated. Pulmonary function tests showed no statistical differences between aGWVs and sGWVs while breathing clean air or 40 ppm acetone in air. Cognitive performance was similar during the clean air, placebo, and acetone test conditions for sGWVs and aGWVs. Data pooled across test conditions for each group indicated a statistically significant (P <0.05) poorer performance primarily in memory and executive function tasks by sGWVs. sGWVs had a 34.2% higher baseline MCABFV than aGWVs (P <0.05). Increases in MCABFV for aGWVs (averaged over all cognitive tasks for each test condition) ranged between 7.8% and 8.8%, and were not statistically significant. Increases for sGWVs ranged between 0.3% and 4.8%, averaged over all cognitive tasks for each test condition. No significant differences were noted between the clean air and placebo test conditions but both were significantly different compared to the acetone condition. Differences in MCABFV increases for each of the test conditions between aGWVs and sGWVs were also statistically significant. sGWV did not appear to demonstrate pulmonary dysfunction following exposure to acetone. They did, however, appear to have generally lower cognitive function as compared to aGWVs. sGWVs appeared to have a significant degree of autoregulatory disruption in cerebral perfusion, resulting in reduced cognitive reserve capacity and potentially impaired ability to handle complex cognitive tasks.
Asbestos content of omentum and mesentery in nonoccupationally exposed individuals
Authors: Dodson Ronald F , O'Sullivan Michael F , Brooks Dwaina R , Bruce James R
Published: November 2002

Asbestos fibers in occupationally exposed individuals relocate from the lung to extrapulmonary sites. A mechanism for relocation is via the lymphatic circulation. Indeed, asbestos fibers have been found in lymph nodes as well as pleural plaques. Our laboratory has recently shown that asbestos fibers also reach the mesentery and omentum in the peritoneal area where a small percentage of mesotheliomas occurs in exposed individuals. The present study uses light and analytical transmission electron microscopy for defining the asbestos burden in digested lung, omentum, and mesentery tissues from individuals considered as representing the general population in East Texas. The findings, when compared with previous data from occupationally exposed individuals, indicate extreme contrasts as to the level and types of fiber burden between individuals representing the groups.