bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of chronic respiratory failure in kyphoscoliosis: oxygen or ventilation?
Authors: Buyse B. , Meersseman W. , Demedts M. 
Published: August 2003

Patients with kyphoscoliosis and chronic respiratory insufficiency are treated either with home oxygen therapy or ventilation. Kyphoscoliotic patients demonstrate impaired ventilatory mechanics, consequently ventilation seems to be the treatment of choice. Yet, no randomised controlled trials (CRT) exist to prove it.Most investigators find it difficult to ethically justify a CRT. Therefore, the current authors performed the following retrospective study: survival and pulmonary function were analysed in all consecutive kyphoscoliotic patients who started long-term oxygen therapy (LTO group; n=15, aged 62±11 yrs (mean±sd)) or LTO plus nocturnal nasal intermittent positive pressure ventilation (nNIPPV group; n=18, aged 61±7 yrs) in the Dept of Pulmonology (University Hospital Gasthuisberg, Leuven) between 1990–2002.Prior to treatment partial pressure of oxygen (PO2) was lower, partial pressure of carbon dioxide (PCO2) tended to be higher and vital capacity (VC) tended to be lower in the nNIPPV group than in the LTO group (PO25.9±1versus6.7±0.9 kPa (44±8versus50±7 mmHg),PCO28±1versus7.3±0.9 kPa (60±8versus55±7 mmHg), VC 32±12versus40±16% predicted, or 645±244versus970±387 mL). In the nNIPPV group the 1‐yr survival was higher (100%versus66%). nNIPPV patients demonstrated an improvement inPO2(breathing air) +54%,PCO2(breathing air) −21%, VC +47% and maximal static inspiratory mouth pressure +33%; these improvements were absent in the LTO group.In conclusion, nocturnal nasal intermittent positive pressure ventilation, plus long-term oxygen therapy results in more favourable survival and changes in blood gases and respiratory function than long-term oxygen therapy alone.
The occupational burden of chronic obstructive pulmonary disease
Authors: Trupin L. , Earnest G. , San Pedro M. , Balmes J.R. , Eisner M.D. , Yelin E. , Katz P.P. , Blanc P.D. 
Published: August 2003

Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need.A randomly selected sample of 2,061 US residents aged 55–75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis.After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (CI) 1.6–2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% CI 13–27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% CI 1.1–2.5) for high and 1.4 (95% CI 1.1–1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% CI 3–15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% CI 19–41%).Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.
Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation
Authors: Abramowicz M.J. , Van Haecke P. , Demedts M. , Delcroix M. 
Published: August 2003

Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite‐suppressant drugs.The authors identified a BMPR2 gene mutation in a 27‐yr‐old female who developed PAH after a short course of the appetite‐suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine‐related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant‐related PPH.The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.
Do GOLD stages of COPD severity really correspond to differences in health status?
Authors: Antonelli-Incalzi R. , Imperiale C. , Bellia V. , Catalano F. , Scichilone N. , Pistelli R. , Rengo F. ,   the SaRA investigators
Published: August 2003

The purpose of this study was to assess whether different stages of chronic obstructive pulmonary disease (COPD) severity defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria correlate with meaningful differences in health status.A total of 381 COPD patients, aged 73±6 yrs, were classified in the five GOLD stages. Disease-specific (St George Respiratory Questionnaire (SGRQ)) and generic indexes of health status were measured in all patients. Multivariate analysis of covariance or Kruskal Wallis tests were used to compare health status indexes across the spectrum of GOLD stages of COPD severity.GOLD stages of COPD severity significantly differed in SGRQ components and Barthel's index, but not in the indexes assessing cognitive and affective status and quality of sleep. The largest variation in health status was observed at the transition from stage IIa to stage IIb, while there were no other significant differences between consecutive stages. Both female sex and comorbidity were associated with a greater impact of COPD on the health status.In conclusion, the upper limit of stage IIb (forced expiratory volume in one second of 49%) marks a threshold for dramatic worsening of health status. Progression of chronic obstructive pulmonary disease severity from stage 0 to stage IIa does not correspond to any meaningful difference in health status.
Upregulation of MCAM in primary bronchial epithelial cells from patients with COPD
Authors: Schulz C. , Petrig V. , Wolf K. , Krätzel K. , Köhler M. , Becker B. , Pfeifer M. 
Published: August 2003

An increasing body of evidence indicates that the bronchial epithelium plays a crucial role in the pathophysiology of chronic obstructive pulmonary disease (COPD). The aim of this study was to identify new genes whose bronchoepithelial expression is specifically altered in COPD patients.Primary bronchial epithelial cell (PBEC) cultures were established from exsmokers with stable airflow limitation and never smokers. Complementary deoxyribonucleic acid array technology was used to investigate the differential expression of 847 cytokine and cytokine-related genes between the two groups. Statistical analysis was performed by means of significance analysis of microarrays and Bonferroni-corrected analysis of variance on ranks. Discriminant analysis and light cycler measurements as well as flow cytometry and Western blotting were used to confirm the significance of the array results at both the messenger ribonucleic acid (mRNA) and protein expression levels.With respect to array experiments, melanoma cell adhesion molecule (MCAM) was identified as the sole gene showing highly significant upregulation in PBECs from COPD patients compared to never smokers. Light cycler measurements confirmed these results, revealing a 2.9‐fold and 2.0‐fold increase in MCAM mRNA expression in COPD patients compared to nonsmokers and smokers, respectively. In addition, these differences are associated with higher median protein expression levels.These results strongly suggest involvement of melanoma cell adhesion molecule in the pathophysiology of the chronic airway inflammation seen in patients with chronic obstructive pulmonary disease.
Carcinoembryonic antigen mRNA analysis detects micrometastatic cells in blood from lung cancer patients: Table 1
Authors: Castaldo G. , Tomaiuolo R. , Sanduzzi A. , Ponticiello A. , Marchetiello I. , Salvatore F. 
Published: August 2003

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells.CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months.Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases.Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.
Cathepsins in bleomycin-induced lung injury in rat
Authors: Koslowski R. , Knoch K. , Kuhlisch E. , Seidel D. , Kasper M. 
Published: August 2003

Endogenous inhibitors tightly control the activity of proteinases in the extracellular space. Proteinase/antiproteinase imbalance may be caused by predominance of proteinases, resulting in severe tissue damage or abundance of proteinase inhibitors, leading to a shift in the balance of synthesis and degradation of extracellular matrix proteins and accumulation of these matrix components. Lung fibrosis is characterised by accumulation of fibrous matrix proteins in the alveolar interstitium.The activity of cathepsin D and amounts of cathepsins D and B in bleomycin-injured rat lung tissue and alveolar macrophages were examined. In addition, the activities of cathepsins and cysteine proteinase inhibitors (CPIs) in bronchoalveolar lavage fluid (BALF) were determined.No cathepsin but high CPI activity and large amounts of procathepsin B were detected in the BALF. In the alveolar lumen, the disturbed proteinase/antiproteinase balance for cysteine proteinases was clearly dominated by CPIs. In alveolar macrophages, the main source of increased cathepsin levels, large changes in cathepsin B and D content were observed during the inflammatory phase, corresponding to the occurrence of procathepsin B in BALF. With the end of the phase of tissue remodelling, imbalances in cathepsin and CPI activities were largely eliminated. Immunoblot data, revealing an increase in cathepsin D levels in myofibroblast-like cells compared to fibroblasts and in resting fibroblasts compared to proliferating cells, implicate this proteinase in the differentiation and conversion processes occurring at the beginning of the fibrotic phase of lung injury.The results show that cathepsin amounts and activities are increased transiently in lung tissue during regeneration processes in bleomycin-induced lung injury. Imbalances of cathepsin and cysteine proteinase inhibitors activities are also a phenomenon of the phase of tissue remodelling initiated by lung injury.
Evidence of mast cell activation and leukotriene release after mannitol inhalation
Authors: Brannan J.D. , Gulliksson M. , Anderson S.D. , Chew N. , Kumlin M. 
Published: August 2003

The aim of this study was to investigate if mannitol inhalation, as a model of exercise-induced bronchoconstriction (EIB), causes mast cell activation and release of mediators of bronchoconstriction.Urinary excretion of previously identified mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before andfor90 min after challenge. The urinary concentrations of leukotriene (LT)E4, the prostaglandin (PG)D2metabolite and the mast cell marker 9α,11β‐PGF2weremeasured by enzyme immunoassay. Nτ‐methylhistamine was measured by radioimmunoassay.In asthmatic subjects, inhalation of a mean±sem dose of 272±56 mg mannitol induced a reduction in forced expiratory volume in one second (FEV1) of 34.5±2.1%. This was associated with increases in urinary 9α,11β‐PGF2(91.9±8.2versus66.9±6.6 ng·mmol creatinine−1, peakversusbaseline) and LTE4(51.3±7.5versus32.9±4.7). In nonasthmatic subjects, the reduction in FEV1was 1.0±0.5% after inhaling 635 mg of mannitol. Although smaller than in the asthmatics, significant increases of urinary 9α,11β‐PGF2(68.4±6.9versus56.0±5.8 ng·mmol creatinine−1) and LTE4(58.5±5.3versus43.0±3.3 ng·mmol creatinine−1) were observed in the nonasthmatic subjects. There was also a small increase in urinary excretion of Nτ‐methylhistamine in the nonasthmatics, but not in the asthmatics.The increased urinary levels of 9α,11β‐prostaglandin F2support mast cell activation with release of mediators following inhalation of mannitol. Increased bronchial responsiveness to the released mediators could explain the exclusive bronchoconstriction in asthmatic subjects.
Chronic cough and phlegm in young adults
Authors: Cerveri I. , Accordini S. , Corsico A. , Zoia M.C. , Carrozzi L. , Cazzoletti L. , Beccaria M. , Marinoni A. , Viegi G. , de Marco R. 
Published: August 2003

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines underline that the presence of chronic cough and sputum production before airflow obstruction offers a unique opportunity to identify subjects at risk of chronic obstructive pulmonary disease for an early intervention. Current epidemiological data on these subjects are scant.Between 1998–2000, the authors evaluated the prevalence and characteristics of these symptoms by a multicentre cross-sectional survey of Italian people aged between 20–44 yrs from the general population (Italian Study on Asthma in Young Adults (ISAYA)). Besides the questions on asthma, more than 18,000 subjects answered the question: “Have you had cough and phlegm on most days for as much as 3 months per year and for at least two successive years?”The adjusted prevalence of subjects with chronic cough and phlegm was 11.9%, being 11.8% in males and 12.0% in females. From these subjects ∼20% reported coexisting asthma and ∼30%, predominately females, were nonsmokers. The survey showed thatsex (female), smoking and low socioeconomic status were significantly and independently associated with chronic cough and phlegm, current smoking playing the major role.The prevalence of subjects with chronic cough and phlegm is startlingly high among young adults. Further follow-up studies are needed to establish how many of them will go on to develop chronic obstructive pulmonary disease.
The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma
Authors:   The ENFUMOSA Study Group
Published: August 2003

Since severe asthma is a poorly understood, major health problem, 12 clinical specialist centres in nine European countries formed a European Network For Understanding Mechanisms Of Severe Asthma (ENFUMOSA).In a cross-sectional observational study, a total of 163 subjects with severe asthma were compared with 158 subjects whose asthma was controlled by low doses of inhaled corticosteroids (median dose of beclomethasone equivalents 666 µg). Despite being treated with higher doses of inhaled corticosteroids (median dose 1773 µg) and for a third of the severe asthmatics also being treated with regular, oral-steroid therapy (median daily dose 19 mg), the subjects with severe asthma met the inclusion criteria. The criteria required subjects to have undergone at least one asthma exacerbation in the past year requiring oral steroid treatment. Females dominated the severe asthma group (female/male ratio 4.4:1versus1.6:1 in the controlled asthmatics), and compared with controlled asthmatics, they had a predominantly neutrophilic inflammation (sputum neutrophils, 36versus28%) and evidence of ongoing mediator release but less atopy.From these findings and other physiological and clinical data reported in this paper, it is suggested that severe asthma might be a different form of asthma rather than an increase in asthma symptoms. The findings prompt for longitudinal studies and interventions to define the mechanisms in severe asthma.
Older Age Is an Adverse Prognostic Factor in Stage I, Favorable Histology Wilms’ Tumor Treated With Vincristine Monochemotherapy: A Study by the United Kingdom Children’s Cancer Study Group, Wilm’s Tumor Working Group
Authors: Pritchard-Jones K. , Kelsey A. , Vujanic G. , Imeson J. , Hutton C. , Mitchell C. 
Published: August 2003

Purpose: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms’ tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. Patients and Methods: During two consecutive trials of the United Kingdom Children’s Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms’ tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. Results: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P = .001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P = .01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P = .66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). Conclusion: Treatment for stage I FH Wilms’ tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms’ tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.
Phase II Study of Temozolomide Plus Thalidomide for the Treatment of Metastatic Melanoma
Authors: Hwu Wen-Jen , Krown Susan E. , Menell Jennifer H. , Panageas Katherine S. , Merrell Janene , Lamb Lynne A. , Williams Linda J. , Quinn Carolyn J. , Foster Theresa , Chapman Paul B. , Livingston Philip O. , Wolchok Jedd D. , Houghton Alan N. 
Published: August 2003

Purpose: To further investigate the efficacy and safety of temozolomide plus thalidomide in patients with metastatic melanoma without brain metastases. Patients and Methods: Patients with histologically confirmed advanced-stage metastatic melanoma were enrolled in an open-label, phase II study. The primary end point was response rate. Patients received temozolomide (75 mg/m2/d × 6 weeks with a 2-week rest between cycles) plus concomitant thalidomide (200 mg/d with dose escalation to 400 mg/d for patients < 70 years old, or 100 mg/d with dose escalation to 250 mg/d for patients ≥ 70 years old). Treatment was continued until unacceptable toxicity or disease progression occurred. Results: Thirty-eight patients (median age, 62 years) with stage IV (three patients with M1a, eight with M1b, and 26 with M1c) or stage IIIc (one patient) melanoma and a median of four metastatic sites were enrolled, and received a median of two cycles of therapy. Twelve patients (32%) had an objective tumor response, including one with an ongoing complete response of 25+ months’ duration and 11 with partial responses. Five patients achieving partial response with a more than 90% reduction of disease were converted to a complete response with surgery. Treatment was generally well tolerated. Median survival was 9.5 months (95% confidence interval, 6.05 to 19.38 months), with a median follow-up among survivors of 24.3 months. Conclusion: The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.
Comparison of Gemcitabine Versus the Matrix Metalloproteinase Inhibitor BAY 12-9566 in Patients With Advanced or Metastatic Adenocarcinoma of the Pancreas: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group
Authors: Moore M.J. , Hamm J. , Dancey J. , Eisenberg P.D. , Dagenais M. , Fields A. , Hagan K. , Greenberg B. , Colwell B. , Zee B. , Tu D. , Ottaway J. , Humphrey R. , Seymour L. 
Published: August 2003

Purpose: To compare the selective matrix metalloproteinase inhibitor BAY 12-9566 with the nucleoside analog gemcitabine in the treatment of advanced pancreatic cancer. Methods: Patients with advanced pancreatic adenocarcinoma who had not previously received chemotherapy were randomly assigned to receive BAY 12-9566 800 mg orally bid continuously or gemcitabine 1,000 mg/m2 administered intravenously on days 1, 8, 15, 22, 29, 36, and 43 for the first 8 weeks, and then days 1, 8, and 15 of each subsequent 28-day cycle. The primary end point was overall survival; secondary end points were progression-free survival, tumor response, quality of life, and clinical benefit. The planned sample size of the study was 350 patients. Two formal interim analyses were planned. Results: The study was closed to accrual after the second interim analysis on the basis of the recommendation of the National Cancer Institute of Canada Clinical Trials Group Data Safety Monitoring Committee. There were 277 patients enrolled onto the study, 138 in the BAY 12-9566 arm and 139 in the gemcitabine arm. The rates of serious toxicity were low in both arms. The median survival for the BAY 12-9566 arm and the gemcitabine arm was 3.74 months and 6.59 months, respectively (P < .001; stratified log-rank test). The median progression-free survival for the BAY 12-9566 and gemcitabine arms was 1.68 and 3.5 months, respectively (P < .001). Quality-of-life analysis also favored gemcitabine. Conclusion: Gemcitabine is significantly superior to BAY 12-9566 in advanced pancreatic cancer.