bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality in asthmatics over 15 yrs: a dynamic cohort study from 1983–1998
Authors: Connolly C.K. , Alcock S.M. , Prescott R.J.
Published: July 2002

The Darlington and Northallerton long-term asthma study observes outcome in asthmatics in the light of potential explanatory variables recorded prospectively. This paper reports changes in mortality during the study, and assesses the relevant risk factors.

All asthmatics attending secondary care were recruited at 5‐yr intervals from 1983 and reviewed 5 yrs later. Demographic and functional variables, including a formal estimate of best function were recorded prospectively.

The dynamic cohort comprised 1,148 asthmatics with 95% follow-up, enabling 612 observations in the period 1983/1988, 774 in 1988/93 and 823 in 1993/98, with 101, 111 and 100 deaths respectively. Principal risk factors for mortality were lower social class and best forced vital capacity. Mortality relative to 1983 halved by 1993/98 and was reduced against the Darlington population, despite an entry forced expiratory volume in one second of 84.7%. There was no change in predictive value of risk factors during the study period, or with date of entry.

This study demonstrates a consistent reduction in mortality, which was not entirely a survivor effect, but may be associated with changes in management. By 1993/98 mortality approximated to that of the local reference population despite a lower than predicted forced expiratory volume in one second.
Individual allergens as risk factors for asthma and bronchial hyperresponsiveness in Chinese children
Authors: Wong G.W.K. , Li S.T. , Hui D.S.C. , Fok T.F. , Zhong N.S. , Chen Y.Z. , Lai C.K.W.
Published: July 2002

The role of allergen sensitization in the development of asthma in the Chinese is not clear. This study aims to determine the relationship of sensitization to individual allergens, and the development of asthma and bronchial hyperresponsiveness (BHR) in schoolchildren from three Chinese cities: Hong Kong, Beijing and Guangzhou.

Community-based random samples of 10-yr-old schoolchildren from three Chinese cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n=10,902), skin-prick tests (n=3,479), and methacholine challenge tests (n=608).

The prevalence rates of wheeze in the past 12 months (Hong Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) and atopy (Hong Kong, 41.2%; Beijing, 23.9%; Guangzhou, 30.8%) were highest in schoolchildren from Hong Kong. Multivariate logistic regression analyses revealed that sensitization toDermatophagoides pteronyssinus(odds ratio (OR)=4.48; 95% confidence interval (CI): 3.02–6.66), cat (2.59; 1.67–4.03),Dermatophagoides farinae(2.41; 1.65–3.51) and mixed grass pollen (2.85; 1.24–6.50) were significantly associated with current wheeze. Atopy, defined as having ⩾1 positive skin-prick tests, was not an independent risk factor for current wheeze in children from any of the three cities. Furthermore, atopy (OR=2.53; 95% CI: 1.07–5.97), sensitization to cat (3.01; 1.39–6.52) andD. farinae(3.67; 1.93–6.97) were significantly associated with BHR.

The authors confirmed that sensitization to house dust mite and cat was significantly associated with current wheeze and bronchial hyperresponsiveness in Chinese schoolchildren. However, the difference in the prevalence rate of atopic sensitization cannot explain the higher prevalence of childhood asthma in Hong Kong, when compared with those children from Beijing and Guangzhou.
Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium
Authors: Vincken W. , van Noord J.A. , Greefhorst A.P.M. , Bantje Th.A. , Kesten S. , Korducki L. , Cornelissen P.J.G.
Published: July 2002

Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients.

Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18µg once daily (n=356) compared with ipratropium 40µgq.i.d.(n=179).

Screening forced expiratory volume in one second (FEV1) were 1.25±0.43 L (41.9±12.7% of the predicted value) (tiotropium) and 1.18±0.37 L (39.4±10.7% pred) (ipratropium). Trough FEV1at 1 yr improved by 0.12±0.01 L with tiotropium and declined by 0.03±0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments.

Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.
The effect of air pollution on inner-city children with asthma
Authors: Mortimer K.M. , Neas L.M. , Dockery D.W. , Redline S. , Tager I.B.
Published: July 2002

The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City Asthma Study.

Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SO2), nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4–9 yrs).

None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning % PEFR (0.59% decline (95% confidence interval (CI) 0.13–1.05%) per interquartile range (IQR) increase in 5‐day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95% CI 1.02–1.30) per IQR increase in 4‐day average ozone, OR=1.32 (95% CI 1.03–1.70) per IQR increase in 2‐day average SO2, OR=1.48 (95% CI 1.02–2.16) per IQR increase in 6‐day average NO2and OR=1.26 (95% CI 1.0–1.59) per IQR increase in 2‐day average PM10.

This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.
Chemokines, innate and adaptive immunity, and respiratory disease: Table 1—
Authors: Sabroe I. , Lloyd C.M. , Whyte M.K.B. , Dower S.K. , Williams T.J. , Pease J.E.
Published: July 2002

Selective leukocyte trafficking and recruitment is primarily regulated by a specific family of small proteins called “chemokines”. This extended family shepherds and guides leukocytes through their lives, facilitating their development, regulating their interactions with other leukocyte types, and guiding their recruitment to sites of inflammation.

Through the actions of chemokines, allergen sensitization is regulated in atopic asthma, through the controlled migration of dendritic cells, T- and B-lymphocytes, mast cells and basophils. Subsequently, atopic inflammation is driven by chemokine-directed recruitment of eosinophils, basophils and lymphocytes. Diseases from cancer to chronic obstructive pulmonary disease to interstitial fibrosis are all potential targets for chemokine receptor antagonism.

Innate immunity (the early pattern-recognition responses to stimuli such as lipopolysaccharide, viral proteins and bacterial DNA) needs to bridge the gap to specific immunity and antibody production and immunological memory. Again, chemokines are likely to be fundamental mediators of these responses.

Chemokines are fundamental regulators of leukocyte homeostasis and inflammation, and their antagonism by small molecule chemokine receptor antagonists may be of enormous importance in the future treatment of human respiratory disease.
Serological evidence ofLegionellaspecies infection in acute exacerbation of COPD
Authors: Lieberman D. , Lieberman D. , Shmarkov O. , Gelfer Y. , Ben-Yaakov M. , Lazarovich Z. , Boldur I.
Published: July 2002

A prospective study was conducted to identify and characterize hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with serological evidence of infection withLegionellaspp. (Lsp).

Two-hundred and forty hospital admissions for AECOPD of 213 patients were included in the study. Paired sera were obtained for each of the admissions and were tested for 41 different serogroups of Lsp, using microimmunofluorescence-serology. Only a significant change in immunoglobulin‐G and/or immunoglobulin‐M antibody titres was considered diagnostic.

In 40 admissions (16.7%) there was serological evidence of infection with Lsp (LspH).Legionella pneumophila1 was identified in nine admissions,L. pneumophila3–15 in 19 and nonpneumophila in 22. In 26 LspH (65%) there was serological evidence of infection with at least one other respiratory pathogen. Compared to the 200 admissions without Lsp (NLspH), the LspH patients were younger (p<0.05) and more hypoxaemic (p<0.04). None of the cases in the LspH group had an abrupt onset of disease, compared to 58 (29.0%) in the NLspH group (p<0.0001). The incidence of myalgia/arthralgia was 55% for LspH compared to 37% for NLspH (p<0.03).

To conclude, serological evidence of infection withLegionellaspp. is common among patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease. In most hospital admissions with serological evidence of infection withLegionellaspp. an additional respiratory pathogen can be identified. Acute exacerbation develops gradually in these patients and is characterized clinically by more systemic manifestations than hospital admissions without serological evidence of infection withLegionellaspp. The true interpretation and practical relevance of these findings should be determined in further studies.
Achilles tendon disease in lung transplant recipients: association with ciprofloxacin
Authors: Chhajed P.N. , Plit M.L. , Hopkins P.M. , Malouf M.A. , Glanville A.R.
Published: July 2002

Achilles tendonitis or rupture are uncommon complications following the use of fluoroquinolones, with a reported incidence in the general population of 0.4%. The aims of the current study were to determine the incidence of Achilles tendon disease (ATD) in lung transplant recipients (LTR) and to identify risk factors.

Questionnaires were sent to 150 LTR of whom 101 responded (67%). Twenty-two LTR (21.8%) experienced ATD (tendonitis 16, rupture six). The mean age of LTR who developed ATD was 52.9±6.1 yrs (range: 19–63.5 yrs).

Only the use of ciprofloxacin was significantly associated with ATD (p<0.05). Age, sex, underlying disease necessitating transplantation, serum creatinine and cyclosporine levels were not associated with ATD. The association between ciprofloxacin and ATD was not dose related. Of the 72 LTR who had received ciprofloxacin, 20 (28%) developed ATD (tendonitis 15, rupture five). In patients receiving ciprofloxacin, there was no association between the mean cumulative dose of prednisolone and ATD. Tendon rupture occurred with a lower ciprofloxacin dosage than tendonitis and the mean recovery duration was significantly longer.

To conclude, lung transplant recipients receiving ciprofloxacin are at significant risk of developing Achilles tendon disease. The association between ciprofloxacin and Achilles tendon disease appears to be idiosyncratic rather than dose-related.
Determinants ofFi,O2with oxygen supplementation during noninvasive two-level positive pressure ventilation
Authors: Thys F. , Liistro G. , Dozin O. , Marion E. , Rodenstein D.O.
Published: July 2002

To maintain arterial oxygen saturation (Sa,O2) above 90% in patients with acute respiratory failure, oxygen (O2) is often added to the circuit of two-level noninvasive positive pressure ventilation (NPPV). However, the final inspiratory oxygen fraction (Fi,O2) is not known.

To clarify this issue, the effect of different inspiratory positive airway pressures (IPAP) of the oxygen tubing connection site and the flow rate of O2, onFi,O2was assessed. The effects of the tidal volume (VT) and the respiratory rate on theFi,O2were then clarified in a model study.

TheFi,O2varied depending on the point where O2was added to the circuit. When all other variables were constant, the connection closest to the exhaust port (ventilator side) gave the highestFi,O2. Increases in IPAP led to decreases inFi,O2. Finally,Fi,O2increased with O2flow, although it was difficult to obtain anFi,O2>0.30 unless very high O2flows were used. Paradoxically, NPPV with low IPAP values and without O2supplementation led to aFi,O2<0.21 at the circuit-patient interface.VTand respiratory rate did not appear to influenceFi,O2.

To conclude, when using noninvasive positive pressure ventilation with two-level respirators, oxygen should be added close to the exhaust port (ventilator side) of the circuit. If inspiratory airway pressure levels are >12 cmH2O, oxygen flows should be at least 4 L·min−1.
Sulphasalazine and lung toxicity
Authors: Parry S.D. , Barbatzas C. , Peel E.T. , Barton J.R.
Published: July 2002

Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here.

All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms “sulphasalazine” and “sulfasalazine” were combined with the terms “lung”, “pulmonary disease”, “pneumonitis” and “pleuritis” using Medline and PubMed databases.

Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids.

In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.
A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease
Authors: Casaburi R. , Mahler D.A. , Jones P.W. , Wanner A. , San Pedro G. , ZuWallack R.L. , Menjoge S.S. , Serby C.W. , Witek T.
Published: July 2002

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD.

Patients with stable COPD (age 65.2±8.7 yrs (mean±sd), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 µg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01versus0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1(i.e.FEV1prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded.

Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1response (∼12% over baseline) (p<0.01) and mean response during the 3 h following dosing (∼22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0%versusplacebo 2.7%, p<0.05).

Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.
Lung cGMP release subsequent to NO inhalation in pulmonary hypertension: respondersversusnonresponders
Authors: Ghofrani H.A. , Wiedemann R. , Rose F. , Weissmann N. , Schermuly R.T. , Quanz K. , Grimminger F. , Seeger W. , Olschewski H.
Published: July 2002

Inhalation of nitric oxide (NO) is widely employed for the assessment of pulmonary vasoresponsiveness in pulmonary hypertension (PH). However, the reasons for the huge differences in vascular reactivity to NO between patients are unknown, and the role of NO-induced cyclic guanosine monophosphate (cGMP) is unclear.

Twenty patients with severe precapillary PH were investigated. Thirty-six Swan-Ganz catheter investigations were performed and the study subjects were tested for responses to NO inhalation. This included an assessment of pulmonary and systemic arterial plasma cGMP and atrial natriuretic peptide (ANP) levels.

A significant NO response (pulmonary vascular resistance (PVR) decrease >20%) was noted in nine of 20 patients (45%) during the first catheterization. A highly significant correlation between baseline plasma cGMP and ANP levels with PVR was observed (r=0.62 and r=0.66, respectively; p<0.0001). In response to NO, systemic and mixed venous cGMP levels increased from 13.9±1.28 nM and 12.75±0.99 nM to 79.23±4.99 nM and 55.25±4.41 nM (p<0.001), respectively, accompanied by the appearance of a marked transpulmonary cGMP gradient. Although in the responder group ANP levels were significantly reduced after NO inhalation, no significant correlation was observed to the extent of PVR reduction. The magnitude of the NO-elicited cGMP response did not discriminate between haemodynamic responders and nonresponders.

This study concludes that plasma cyclic guanosine monophosphate levels are significantly correlated with the severity of disease in pulmonary arterial hypertension. Nitric oxide inhalation provokes a prompt increase in cyclic guanosine monophosphate secretion, but the magnitude of this release is not linked with a decrease in pulmonary vascular resistance.
Perception of bronchoconstriction in asthma patients measured during histamine challenge test
Authors: Bijl-Hofland ID , Folgering HT , van den Hoogen H , Cloosterman SG , Van Weel C , Donkers JM , van Schayck CP
Published: July 2002

This study investigated two aspects of the perception of bronchoconstriction ("sensitivity" and "absolute perceptual magnitude") in asthmatic patients and identified which clinical characteristics are related to these two aspects of perception of bronchoconstriction. The perception of histamine induced bronchoconstriction was measured in 128 asthmatic patients. Subjects quantified their breathlessness on a Visual Analogue Scale (VAS) before forced expiratory volume in one second (FEV1 was measured after each inhalation of histamine. The perceptive "sensitivity" for changes in FEV1 was analysed by the "VAS percentage fall in FEV1" slope. The "absolute perceptual magnitude" was determined by the VAS value at a 20% fall in FEV1. Spearman correlations were used for analysis between the two aspects of perception and asthma symptoms, peak flow variability, bronchial responsiveness and FEV1 % predicted. Patients with a low "sensitivity" for changes in FEV1 were more likely to show a frequent peak flow variability (Rs=-0.21; p<0.05), a high bronchial responsiveness (Rs= 0.37; p<0.001) and a low baseline FEV1 % pred (Rs=0.22; p<0.05). Patient's "absolute perceptual magnitude" correlated positively with symptoms during daily life (significant correlations varied 0.21-0.32) but not with the lung function parameters. The severity of asthma reflected by a low lung function and a high bronchial responsiveness, is associated with a low "sensitivity" for changes in forced expiratory volume in one second. A patient's "absolute perceptual magnitude" is positively related with asthma symptoms during daily life.
Effects of respiratory syncytial virus persistence on airway responsiveness and inflammation in guinea-pigs
Authors: Bramley AM , Vitalis TZ , Wiggs BR , Hegele RG
Published: July 2002

Recurrent wheezing and asthma often develop after acute respiratory syncytial virus (RSV) bronchiolitis, but the mechanisms of these sequelae are poorly understood. Using a guinea-pig model of human RSV lung infection, the effects of long-term viral persistence on three hallmarks of asthma: nonspecific airway responsiveness, airway inflammation and airway remodelling were examined. Guinea-pigs were studied 100 days after intranasal instillation of either human RSV or uninfected vehicle, using: 1) acetylcholine challenge to test for airway hyperresponsiveness (AHR); 2) lung histology to quantify the numbers of airway eosinophils and metachromatic cells (mast cells/basophils); 3) airway morphometry of the areas of the airway subepithelial connective tissue, smooth muscle and adventitia, to test for airway remodelling; and 4) immunohistochemistry to identify lung cells containing RSV antigens. The RSV-inoculated group had significantly elevated AHR and airway eosinophils compared to uninfected control animals (p<0.05). There were no significant differences between the two groups in terms of numbers of airway metachromatic cells, or the areas of subepithelial connective tissue, smooth muscle or adventitia. Viral proteins were identified by immunohistochemistry within several types of lung cells. In conclusion, long-term persistence of respiratory syncytial virus in the guinea-pig lung is associated with airway hyperresponsiveness and airway eosinophilia, and these changes may be pertinent to the pathogenesis of postbronchiolitis wheezing and asthma in children.
Adrenomedullin inhibits ovalbumin-induced bronchoconstriction and airway microvascular leakage in guinea-pigs
Authors: Ohbayashi H , Suito H , Yoshida N , Ilto Y , Kume H , Yamaki K
Published: July 2002

Human adrenomedullin is a potent vasodilator with bronchodilation properties. The effects of adrenomedullin on antigen-induced bronchoconstriction and airway microvascular leakage in guinea-pigs was investigated. The portion of the adrenomedullin molecule possessing these pulmonary active profiles was also examined, using two truncated adrenomedullin molecules: adrenomedullin (1-25) and adrenomedullin (22-52). Four weeks after sensitization with ovalbumin (0.1 mg x k(-1)), the guinea-pigs were anaesthetized and mechanically ventilated. Respiratory resistance, dynamic compliance and arterial blood pressure were monitored. Airway microvascular leakage was evaluated by extravasation of 20 mg x kg(-1) Evans blue into airway interstitial tissue. In order to enhance the pulmonary effects of adrenomedullin, the active production of endogenous nitric oxide was inhibited by coadministration of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methethyl ester (10 mg x kg(-1)). Intravenous pretreatment with adrenomedullin (10, 30 and 100 microg x mL(-1)) dose-dependently inhibited ovalbumin-induced bronchoconstriction and airway microvascular leakage in all airway segments. Inhaled adrenomedullin (100 microg.mL(-1), 1 min) also significantly inhibited pulmonary changes induced by ovalbumin inhalation (3 mg x mL (-1) , 3 min). These pulmonary profiles of adrenomedullin were enhanced by inhibiting the active production of endogenous nitric oxide. In conclusion, adrenomedullin has inhibitory effects on antigen-induced microvascular leakage and bronchoconstriction in guinea-pigs. These beneficial effects strongly related to its unique ring structure and N-terminal segment, making it a potential anti-asthma.
Role of neutrophil elastase in ozone-induced airway responses in guinea-pigs
Authors: Matsumoto K , Aizawa H , Inoue H , Koto H , Nakano H , Hara N
Published: July 2002

Ozone-induced airway hyperresponsiveness occurs concurrently with neutrophilic inflammation and epithelial injury in various species including humans. The mechanism of neutrophil-induced airway hyperresponsiveness, however, has not yet been fully clarified. Neutrophil elastase (NE) is a multipotent protease released from activated neutrophils, which may play a role in ozone-induced airway hyperresponsiveness. In order to address this issue, the effects of ONO-5046, a specific NE inhibitor, were investigated in ozone-exposed guinea-pigs. Awake animals were exposed to ozone at 3 parts per million for 2 h, airway responsiveness to acetylcholine (ACh) measured and examination of bronchoalveolar lavage fluid (BALF) performed. Ozone exposure increased airway responsiveness to both inhaled and intravenous ACh, the concentration of NE in BALF and the number of neutrophils and airway epithelial cells in BALF. Although pretreatment with ONO-5046 (200 mg x kg(-1), i.p.) had no effect on these changes immediately after the exposure, it significantly inhibited airway hyperresponsiveness to inhaled ACh, whilst decreasing the number of neutrophils and epithelial cells in BALF 3-5 h after the exposure. In contrast, ONO-5046 showed no significant effect on airway hyperresponsiveness to intravenous ACh at any time. These results suggest that neutrophil elastase contributes to ozone-induced airway hyperresponsiveness developing during the hours after exposure, presumably by means of inducing epithelial injury.
Effects of theophylline, dexamethasone and salbutamol on cytokine gene expression in human peripheral blood CD4+ T-cells
Authors: Choy DK , Ko F , Li ST , lp LS , Leung R , Hui D , Lai KN , Lai CK
Published: July 2002

CD4+ T-cells are considered as pivotal in orchestrating the airway inflammation in asthma through the actions of their cytokines. Current hypothesis suggests that the anti-asthma effect of theophylline may be due to its anti-inflammatory actions, although the exact mechanisms remain unclear. The in vitro effect of theophylline on cytokine gene expression in peripheral blood CD4+ T-cells in normal subjects was compared with that of dexamethasone and salbutamol. CD4+ T-cells were cultured with phytohaemagglutin and phorbol myristate acetate in the presence of different concentrations of theophylline (10(-8)-10(-3) M or 0.0018-180 microg x mL(-1)) in one group of subjects (n=8), dexamethasone (10(-9)-10(-6) M or 0.39-390 ng x mL(-1)) in a second group (n=8) and salbutamol (10(-9)-10(-4) M or 0.00058-58 microg x mL(-1)) in a third group (n=8). Gene expression of interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-gamma was semiquantified by reverse transcription-polymerase chain reaction. Suppressed expression of IL-3 (36.9%), IL4 (38.8%), GM-CSF (24.6%) and IFN-gamma (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10(-3) M (180 microg x mL(-1)) (p<0.05) and not at lower concentrations. In contrast, dexamethasone caused a dose-dependent suppression of transcription of all cytokines, with 39.5% for IL-3, 84.4% for IL-4, 40.6% for IL-5, 50.9% for GM-CSF and 31.8% for IFN-gamma at 10(-6) M (390 ng x mL(-1)) (p<0.05-0.001). Salbutamol did not suppress gene expression of any of the cytokines at the concentrations examined. These data suggest that cytokine gene expression of CD4+ T-cells is not affected at therapeutic concentrations of theophylline and salbutamol, but its suppression is likely to be an important mechanism underlying the therapeutic effect of corticosteroids in asthma.
The importance of genetic influences in asthma
Authors: Los H , Koppelman GH , Postma DS
Published: July 2002

Asthma is a complex genetic disorder in which the mode of inheritance is not known. Many segregation studies suggest that a major gene could be involved in asthma, but until now different genetic models have been obtained. Twin studies, too, have shown evidence for genetic influences in asthma, but have also revealed substantial evidence for environmental influences, in which nonshared environmental influences appeared to be important. Linkage, association studies and genome-wide screening suggest that multiple genes are involved in the pathogenesis of asthma. At least four regions of the human genome, chromosomes 5q31-33, 6p21.3, 11q13 and 12q14.3-24.1, contain genes consistently found to be associated with asthma and associated phenotypes. Not only genes associated with asthma but also genes which are involved in the development and outcome of asthma will be found in the future. This will probably provide greater insight into the identification of individuals at risk of asthma and early prevention and greater understanding for guiding therapeutic intervention in asthma. Exchange of information between researchers involved in the genetics of asthma is important because of mandatory agreement on phenotypes and analytical approaches. Genetics will contribute to the a better understanding and management of asthma in the future.
The effects of platelet inhibitors on blood use in cardiac surgery
Authors: Lee Leonard Y , DeBois William , Krieger Karl H , Girardi Leonard N , Russo Laura , McVey James , Ko Wilson , Altorki Nasser K , Brodman Richard A , Isom O Wayne
Published: July 2002

Platelet inhibition via glycoprotein (GP) IIb/IIIa receptor antagonists has greatly reduced the need for emergent cardiac surgery. However, this change has come at a cost to both the patient and the cardiac surgical team in terms of increased bleeding risk. Current guidelines for patients requiring coronary artery bypass surgery include: 1) cessation of GP IIb/IIIa inhibitor; 2) delay of surgery for up to 12 h if abciximab, tirofiban, or eptafibitide is used; 3) utilization of ultrafiltration via zero balance technique; 4) maintenance of standard heparin dosing despite elevated bleeding times; and 5) transfusion of platelets as needed, rather than prophylactically. These agents present cardiac surgery teams with increased risk during CABG, although overall risk may be diminished by the substantial benefits to patients with acute coronary syndromes and percutaneous interventions, i.e., reduced infarction rates and improved vessel patency. With judicious planning, urgent coronary artery bypass can be safely performed on patients who have been treated with GP IIb/IIIa receptor inhibitors.
Early intervention for acute back injury: can we finally develop an evidence-based approach?
Authors: Smith Daphne , McMurray Nancy , Disler Peter
Published: July 2002

Objective: Several reviews of the treatment of acute low back pain have been published in the past and have formed the basis of clinical guidelines. However, these lack consistency in some areas and valid data in others. As the literature in this field has continued to expand, the present review was undertaken to establish whether the guidelines in current use are supported by more recently published, scientifically rigorous research, and whether additional consensus regarding treatment of acute low back injury has been forthcoming in recent years.

Design: A review, and critical analysis, of literature relating to the treatment of acute low back pain that has been published since the production of the currently used clinical guidelines. The guidelines have been reviewed to assess whether their recommendations remain supportable.

Conclusions: Recent research appears to support current clinical guidelines i.e. exercise may have a positive effect while bed rest is ineffective and may be harmful, simple analgesics and nonsteroidal anti-in‘ammatory drugs (NSAIDs) have short-term benefits, and spinal manipulation may be effective in the first four weeks; no evidence was found for traction or back schools. However, we need more randomized controlled trials of treatments shown to be successful with the chronic population, e.g. focused on understanding psychological determinants, and using a multidisciplinary biopsychosocial approach. In the future this may help us to prevent acute low back progressing to the chronic state.
Evaluation of the effectiveness of professionally guided self-care for people with multiple sclerosis living in the community: A randomized controlled trial
Authors: O'Hara Louise , Cadbury Heather , De Souza Lorraine , Ide Lorely
Published: July 2002

Objective: The aim of the study was to assess the ef”cacy of a patient-focused professionally guided self-care programme for the management of multiple sclerosis (MS) in the community.

Design: This was a single-blind randomized controlled trial.

Setting: The study was conducted with people with MS living in the community.

Participants: Two hundred and seventy-eight people with MS were invited to take part in the study. One hundred and eighty-nine people consented to take part (68%). Of these 183 began the study and 169 (92.3%) completed it. Seventy-three individuals were in the intervention group and 96 were in the control group.

Intervention: The intervention comprised discussion of self-care based on client priorities, using an information booklet about self-care.

Main outcome measures: These included the Barthel Index, a measure of mobility, the SF-36, and the Standard Day Dependency Record (SDDR) which measures the need for assistance with daily activities. Assessments were conducted at baseline and again six months later.

Results: Changes in health status were small. However, at follow-up the intervention group had better SF-36 health scores, in mental health ( p = 0.04), and vitality ( p = 0.05) and considered help with daily activities to be less essential, as measured by the SDDR ( p = 0.04), than the control group. Participants in the intervention group had maintained levels of independence at follow-up ( p = 0.62) while the control group showed a signi”cant decrease in independence ( p = 0.001).

Conclusion: This intervention could be a useful aid for health professionals who are supporting people with MS living in the community.
Placing social capital
Authors: Mohan Giles , Mohan John
Published: July 2002

This paper reviews the contribution that the concept of social capital might make to geography, and the contribution geography might make to the analysis of social capital. We begin by summarizing the conceptual origins and dimensions of social capital, in the process of which we distinguish it from several other social properties (human and cultural capital; social networks). We then summarize key criticisms of the concept, especially those levelled at the work of Robert Putnam. The core of the paper is a discussion of the issue of whether there might be a geography of social capital. We consider links between geographical debates and the concept of social capital, and we assess the difficulties of deriving spatially disaggregated measures of social capital. We illustrate this discussion with reference to literature on three sets of issues: the question of ‘institutional tissue’ and its effects on regional development; the understanding of health inequalities; and the analysis of comparative government performance. In conclusion, we argue that the popularity of the concept reflects a combination of academic and political developments, notably the search for ostensibly ‘costless’ policies of redistribution on the part of centrist governments. We therefore conclude with a discussion of the practical applications of the concept in different contexts.
Oxidants and antioxidative defense
Authors: Grune T
Published: July 2002

The role of oxygen free radicals and other oxidants in several diseases has been well established over the past decade. Whereas it was long known that high doses of oxidants may damage or kill cells, the effect of low doses or long-time exposure to small flux rates of oxidants have been the focus of the free radical research until now. Here one has to take into account that most physiological and pathophysiological actions of oxidants and free radicals are based on the permanent action of small doses and flux rates. This includes effects of oxidants on signal transduction pathways and gene expression patterns. Therefore, only a few answers can be given today on the relevance of the effects of low doses of oxidants.
Disaster on the Drina: The Austro-Hungarian Army in Serbia, 1914
Authors: Schindler John R.
Published: July 2002

Serbia’s defeat of the Austro-Hungarian invasion of 1914 counts among the major upset victories of the last century. This article, which examines Austro-Hungarian tactical performance in Serbia in that campaign, offers unique insights into the causes of the Habsburg debacle. Analysis of the battlefield performance of the Austro-Hungarian 21st division, which fought and lost the first Habsburg engagement in August 1914, reveals much about the operational shortcomings of Vienna’s field forces that summer and autumn; in particular, this article details the impact of the controversial nationalities issue on Habsburg battlefield effectiveness, offering a revisionist perspective about the realities and liabilities of a multinational army.
A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients
Authors: Frank J A , Richert N , Lewis B , Bash C , Howard T , Civil R , Stone R , Eaton J , McFarland H , Leist T
Published: July 2002

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-1 (rhIGF-1) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sclerosis (MS) patients. Monthly clinical and MRI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-1. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included clinical and MRI measures of disease activity including: white matter lesion load (WMLL), magnetization transfer ratio (MTR), T1-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-1 (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-1 was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-1 did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-1 alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination.
A double-blind pilot study of the effect of Prokarin™ on fatigue in multiple sclerosis
Authors: Gillson G , Richards T L , Smith R B , Wright J V
Published: July 2002

In this 12-week study with 29 subjects, the effect of Prokarin™ (n=22), a proprietary blend of histamine and caffeine, was compared to placebo group (n=7) for the following outcomes: 1) fatigue as measured by the Modified Fatigue Impact Scale (MFIS); 2) lower limb function as measured by timed walk test; 3) upper limb function as measured by the pegboard test; 4) cognitive function as measured by the Paced Auditory Serial Additions Test (PASAT); 5) serum caffeine level; 6) change in brain chemistry as measured by quantitative magnetic resonance spectroscopy assay of N-acetyl aspartate (NAA); and 7) safety as measured by routine blood chemistry, TSH and urinalysis. Data were acquired at baseline, 4, 8 and 12 weeks. The Prokarin™ group MFIS mean was significantly different from the mean of the placebo group at 12 weeks (df=24, t=2.08, P=<0.02), with respective means of 37.40, SD=15.18, for the Prokarin™ group and 53.2, SD=11.39 for the controls. For the secondary endpoints (PASAT, 25 foot timed walk, peg test, and magnetic resonance spectroscopy [MRS]), there were no significant differences between the Prokarin™ -treated group and the placebo group. However, there were significant improvements within the Prokarin™ group for each of these measures for the pre-versus posttreatment comparison at 12 weeks. Serum caffeine data indicated that caffeine exerted no independent effect on performance. No laboratory abnormalities were seen, and the treatment was well tolerated. Conclusion: There was a modest-size statistical effect of Prokarin™ on fatigue in multiple sclerosis (MS) compared with the placebo group. A larger trial is warranted, based on this pilot study.
APOE genotypes and disease severity in multiple sclerosis
Authors: Masterman T , Zhang Z , Hellgren D , Salter H , Anvret M , Lilius L , Lannfelt L , Hillert J
Published: July 2002

Apolipoprotein E (apoE) is involved in the transport of lipids necessary for membrane repair and is encoded by a gene on chromosome 19q13, a region positive for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE e4 allele confers susceptibility to both familial and sporadic Alzheimer’s disease (AD). Carriage of e4 is associated with defective dendritic remodeling in AD, and with unfavorable clinical outcome in head trauma and cerebrovascular disease. According to the results of previous studies, APOE e4 does not increase the risk of developing MS, but it may influence disease progression and ultimate disability. From a total cohort of over 900 MS patients, we compared APOE e2-4 genotypes in, roughly, the cohort’s least disabled and most disabled septiles. ‘Benign MS’ (n=124) was defined as an Expanded Disability Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease duration, and ‘severe MS’ (n=140) as the attainment of an EDSS score of 6.0 within 8 years of disease onset. We found no significant differences in genotype or phenotype frequencies between the benign-MS and severe-MS septiles; however, the risk conferred by e4 rose progressively upon comparison of carriage rates in more narrowly defined anti-podal quantiles.
A ‘civilized’ commerce: gender, ‘race’, and empire at the 1893 Chicago Exposition
Authors: Domosh Mona
Published: July 2002

The 1893 World’s Columbian Exposition held in Chicago represents a turning point in American history, a point when the United States moved from an era of nation-building to one of empire-building. This paper examines the links between these eras through an analysis of the ideologies that underpinned two types of exhibits at the Exposition - depictions of Native-Americans, and commercial displays of American products sold overseas. I argue that the turn-of-the-century discourse of civilization that helped legitimize American economic imperialism was formulated from within, and built upon, the discursive construction of Anglo-American/Native-American relationships.
Urine Dipstick as a Screening Test for Serum Creatinine Elevation in Emergency Department Patients with Severe Hypertension
Authors: Karras David J. , Heilpern Katherine L. , Riley Louis J. , Hughes Lynn , Gaughan John P.
Published: July 2002

Objective: Patients presenting to the emergency department (ED) with severe hypertension require assessment for acute end‐organ damage. Serum creatinine (SCr) measurement is routinely recommended to detect renal dysfunction. The authors assessed the utility of the urine dipstick test in screening for acute SCr elevation in this population. Methods: The authors performed a prospective study of adult ED patients with diastolic blood pressures ≥115 mm Hg that persisted for ≥30 minutes or necessitated emergent treatment. Excluded were menstruating and pregnant women and patients with urinary infection, trauma, or dialysis dependence. Patients reporting a history of renal disease were excluded if the SCr was abnormal and no baseline value was available. Each subject had an SCr and urine dipstick test. The authors examined the performance of the dipstick in identifying an elevated SCr, defined as SCr >1.2 mg/dL or >25% above baseline. Results: Of 143 patients, 42 had SCr >1.2 mg/dL. Eighteen reported prior renal disease but had an SCr that was normal or ≤25% above baseline. The remaining 24 subjects comprised the elevated SCr group. The presence of either proteinuria or hematuria on dipstick identified these patients with 100% sensitivity and 29.7% specificity. Specificity rose to 42.4% without loss of sensitivity when an abnormal dipstick was defined as hematuria or ≥1+ proteinuria. Conclusions: The urine dipstick may be an effective screening test for SCr elevation in patients with severe hypertension. A restrictive definition of an abnormal dipstick would identify all patients with elevated SCr and substantially reduce the number of SCr assays necessary.
Tissue Harmonic Imaging Improves Organ Visualization in Trauma Ultrasound When Compared with Standard Ultrasound Mode
Authors: Blaivas Michael , DeBehnke Daniel , Sierzenski Paul R. , Phelan Mary Beth
Published: July 2002

The focused abdominal sonography for trauma (FAST) examination is complicated by brightly lit trauma bays, limited time, and body habitus. Recently, new ultrasound (US) technology has become available that improves organ visualization in abdominal scans. Objective: The hypothesis was that a new US mode, tissue harmonic (TH) imaging, improves visualization of critical organ relationships in the FAST examination by making use of previously unused frequencies. The authors performed a blind, prospective observational study to compare the images obtained in typical FAST views with those obtained in standard US and TH modes. Methods: Blunt trauma patients presenting to a level I trauma center between April and September 2000 were enrolled on a convenience basis. Typical FAST views were obtained in standard and TH modes. The emergency ultrasonographer (EU) switched between modes for each view, optimizing the gain each time. Multiple digital still images were made with all indications of the mode used disguised. For each view on a patient, the best image in each mode was selected in a blinded fashion. Three experienced EUs, blinded to the mode used, rated each image pair for resolution, detail, and total image quality as previously defined on a ten‐point Likert scale, 10 being the best for each category. Wilcoxon signed‐ranks test, 95% confidence intervals (95% CIs), and interobserver correlation were calculated. Results: A total of 76 image groups (39 of Morison's pouch, 20 splenorenal, and 17 bladder) from 52 patients were rated. Tissue harmonics produced improved resolution, detail, and quality when compared with the standard US mode, with median scores of 6.7 vs. 6.0, 6.7 vs. 6.0, and 6.3 vs. 6.0, respectively. The differences of 0.7 (95% CI = 0.4 to 0.93), 0.7 (95% CI = 0.4 to 0.93), and 0.33 (95% CI = 0.17 to 0.67) were statistically significant, with p = 0.0001, 0.0001, and 0.0003, respectively. There was good interobserver agreement (kappa = 0.74; 95% CI = 0.68 to 0.79). Conslusions: Tissue harmonics produced FAST images higher in detail, resolution, and total image quality than standard‐mode US images.