bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-ϵ
Authors: Fang Q. , Liu X. , Abe S. , Kobayashi T. , Wang X.Q. , Kohyama T. , Hashimoto M. , Wyatt T. , Rennard S.I. 
Published: November 2004

The ability of fibroblasts to contract three-dimensional collagen gels has been used as anin vitromodel of the tissue contraction which characterises both normal repair and fibrosis. Among its actions, thrombin can activate the protease-activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The current study evaluated whether thrombin could stimulate fibroblast-mediated collagen gel contraction by activating PAR1 and whether its downstream signalling depends on protein kinase C (PKC)-ϵ.Human foetal lung fibroblasts (HFL-1) were cultured in three-dimensional collagen gels and the area of the gels was measured by image analyser.Both thrombin and TFLLR, a selective PAR1 agonist, stimulated collagen gel contraction mediated by HFL-1. After RNA interference-mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel contraction were partially inhibited (by 22.4±2.2% and 17.6±5.6%, respectively). The gel contraction stimulated by thrombin was also reduced by a nonspecific PKC inhibitor and a calcium-independent PKC-ϵ inhibitor. Both thrombin and TFLLR significantly increased PKC-ϵ activity, and this effect was blocked by PAR1 knockdown.Thrombin stimulates collagen gel contraction at least partially through activation of protease-activated receptor 1 and protein kinase C-ϵ, and may contribute to tissue remodelling in inflammatory airway and lung diseases.
Levofloxacinversusclarithromycin in COPD exacerbation: focus on exacerbation-free interval
Authors: Lode H. , Eller J. , Linnhoff A. , Ioanas M. ,   the Evaluation of Therapy-Free Interval in COPD Patients Study Group
Published: November 2004

Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences.Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacinversus10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for ≥5 days.The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated.In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin.
Adaptation of the diaphragm and the vastus lateralis in mild-to-moderate COPD
Authors: Doucet M. , Debigaré R. , Joanisse D.R. , Côté C. , LeBlanc P. , Grégoire J. , Deslauriers J. , Vaillancourt R. , Maltais F. 
Published: November 2004

The chronology of diaphragm and vastus lateralis adaptation in chronic obstructive pulmonary disease (COPD) has not been studied. The hypothesis of this study was that muscle changes would occur earlier in the diaphragm than in the vastus lateralis in COPD, a finding that would suggest that local factors would be more important than systemic factors in determining the muscle phenotypic expression, at least in mild-to-moderate disease.The adaptation of the vastus lateralis and diaphragm muscles was evaluated in patients with mild-to-moderate COPD and in subjects with normal pulmonary function.In both groups, the oxidative potential and the number of lipofuscin inclusions were higher in the diaphragm than in the vastus lateralis. Compared to control, the diaphragm in COPD had a higher oxidative capacity and a higher proportion of type I fibres, with a reciprocal decrease in type IIA fibres, while there was no difference in diaphragmatic cross sectional areas, capillarisation and lipofuscin inclusions. No significant differences were found in the vastus lateralis from both groups.In conclusion, these data indicate that the diaphragm in controls and in chronic obstructive pulmonary disease has a higher oxidative potential than the vastus lateralis, and that muscle adaptation occurs earlier in the diaphragm than in the vastus lateralis in mild-to-moderate chronic obstructive pulmonary disease.
A prospective study of asthma incidence and its predictors: the RHINE study
Authors: Torén K. , Gislason T. , Omenaas E. , Jögi R. , Forsberg B. , Nyström L. , Olin A-C. , Svanes C. , Janson C. 
Published: November 2004

The objective of this longitudinal study was to estimate the incidence rate of asthma, and to compare the incidence between subjects with or without baseline reporting of certain respiratory symptoms.A follow-up of the random population samples in the European Respiratory Health Survey (ECRHS) in Sweden, Norway, Denmark, Iceland and Estonia was conducted in 1999–2001, in a population aged 30–54 yrs at follow-up (n=14,731). Asthma was defined as reporting either asthma or physician-diagnosed asthma, and a reported year when asthma symptoms were first noticed. Incidence rates, incidence rate ratios and hazard ratios were calculated with 95% confidence intervals.The incidence rate of asthma was 2.2 cases per 1,000 person-yrs. The incidence was higher among females (2.9 cases·1,000 person-yrs−1) than among males (1.5 cases·1,000 person-yrs−1). When subjects with baseline reporting of wheezing were excluded, the incidence rate decreased to 1.7 cases·1,000 person-yrs−1, with a further decrease to 1.5 cases·1,000 person-yrs−1after exclusion of subjects with wheezing, nocturnal dyspnoea, chest tightness and cough. There was a strong association between onset of asthma and wheezing at baseline.In this prospective, population-based study, the incidence rate of asthma in the whole population sample ranged 1.5–2.2·1,000 person-yrs−1, with a higher incidence range among females. The incidence was dependent on the extent to which subjects with respiratory symptoms were excluded from follow-up. Hence, for comparability between studies, the exclusion criteria in the follow-up population must be stated.
Influenza vaccination in asthmatic children: effects on quality of life and symptoms
Authors: Bueving H.J. , van der Wouden J.C. , Raat H. , Bernsen R.M.D. , de Jongste J.C. , van Suijlekom-Smit L.W.A. , Osterhaus A.D.M.E. , Rimmelzwaan G.F. , Mölken M. Rutten-van , Thomas S. 
Published: November 2004

This study aimed to detect the effect of influenza vaccination on quality of life, symptomatology and spirometry in asthmatic children.A randomised double-blind placebo-controlled trial in 696 (296 in 1999–2000 and 400 in 2000–2001) asthmatic children aged 6–18 yrs, which were vaccinated with either vaccine or placebo, was performed. Children participated for only one influenza season. They recorded symptoms in a diary and reported when symptom scores reached a predefined severity level. If this occurred research nurses visited them twice, first to take a pharyngeal swab and spirometry, and a week later to assess quality of life over the past illness week.Compared with placebo, vaccination improved health-related quality of life in the weeks of illness related to influenza-positive swabs. However, no effect was found for respiratory symptoms recorded in the diaries during those weeks. Similarly, no differences were found for quality of life in all weeks of illness or for respiratory symptoms throughout the seasons.Influenza vaccination was found to have a moderately beneficial effect on quality of life in influenza-positive weeks of illness in children with asthma.
Diagnosis and pharmacotherapy of severe acute respiratory syndrome: what have we learnt?
Authors: Tsang K.W. , Ooi G.C. , Ho P.L. 
Published: November 2004

In 2003, the onset of severe acute respiratory syndrome (SARS) caused worldwide chaos. Although SARS was eradicated by isolation towards the end of 2003, sporadic cases have been reported in Singapore, Taiwan and mainland China.In this review, SARS is discussed as a disease, as well as its diagnosis, management and pharmacotherapy.Respiratory physicians and healthcare professionals have to be aware of advances in the understanding of the diagnosis and management of severe acute respiratory syndrome. More research is required in order to prepare for if this respiratory infection recurs, but there are concerns that adequate pharmaceutical support may be lacking for the development of a vaccine.
Lung cancer: clinical presentation and specialist referral time
Authors: Buccheri G. , Ferrigno D. 
Published: November 2004

Many textbooks describe symptoms and signs of lung cancer but refer to old series of patients.To update knowledge about lung cancer presentation, a study was carried out on 1,277 consecutive lung cancer patients, who were seen in a single Institution from January 1989 to October 2002. A set of 33 anthropometric, clinical, physical, laboratory, radiological, pathological and follow-up variables was prospectively recorded for all patients. In addition, information was obtained concerning symptoms of alarm (i.e.potential concern), times to specialist referral and the mix of symptoms at presentation. Patients were carefully followed-up and their subsequent clinical course was recorded.Casual discovery with absence of symptoms occurred more frequently towards the end of the study period and the prevalence of chest pain became less common. No other time-dependent changes were found in the presenting symptoms. Delay in specialist referral was longer when presentation was provoked by cough or by the occurrence of systemic symptoms, such as weight loss, anorexia and asthenia. Referral delay was longer towards the end of the study, perhaps related to an increase in the number of elderly patients with co-morbidities. Both alarm and prevalence symptoms were strong predictors of the clinical outcome, as found in both univariate analysis (favourable: casual discovery and chest infection; unfavourable: chest pain, dyspnoea, systemic symptoms and symptoms of local or systemic dissemination) and in multivariate analysis (favourable: chest infection).Early presentation of lung cancer is characterised by a specific symptomatic pattern. Knowledge of this pattern may help to improve the rate of early diagnosis.
Alveolar antioxidant status in patients with acute respiratory distress syndrome
Authors: Schmidt R. , Luboeinski T. , Markart P. , Ruppert C. , Daum C. , Grimminger F. , Seeger W. , Günther A. 
Published: November 2004

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20).Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), α-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas–liquid chromatography), and F2-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF.GSSG (ARDS: 0.13±0.02 µM; control: 0.03±0.01 µM; mean±sem) and F2-isoprostanes (ARDS: 78±10 pM; control: 26±5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77±15 nM; control: 26±3 nM) and uric acid (ARDS: 11.8±2.2 µM; control: 0.7±0.0 µM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of ∼3 in patients, but plasmalogens showed a significant decrease.In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.
Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study
Authors: Alchanatis M. , Deligiorgis N. , Zias N. , Amfilochiou A. , Gotsis E. , Karakatsani A. , Papadimitriou A. 
Published: November 2004

Patients with obstructive sleep apnoea syndrome frequently have cognitive deficits, especially related to executive functions, which cannot be fully explained by daytime sleepiness and are partial irreversible after nasal continuous positive airway pressure treatment. The causal mechanism of these cognitive deficits is not yet known, but it has been proposed that they are associated with chemical and structural brain cell injury. The aim of this study was to investigate brain metabolism in patients with sleep apnoea syndrome.Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of comparable age were studied using single voxel proton magnetic resonance spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex, parieto-occipital and frontal periventricular white matter.N-acetylaspartate-to-creatine and choline-to-creatine ratios were significantly lower in the frontal white matter of obstructive sleep apnoea patients when compared to controls. Absolute concentrations ofN-acetylaspartate and choline were also significantly reduced in the frontal white matter of patients with sleep apnoea.Frontal lobe white matter lesions are known to be associated with cognitive executive dysfunction. The findings of this study may offer an explanation for the sometimes irreversible cognitive deficits associated with sleep apnoea.
Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects
Authors: Cianchetti S. , Bacci E. , Ruocco L. , Bartoli M.L. , Ricci M. , Pavia T. , Dente F.L. , Di Franco A. , Vagaggini B. , Paggiaro P.L. 
Published: November 2004

The aim of this study was to assess whether hyperosmolarity affects granulocyte mediator levels in induced sputum of asthmatic subjects.A total of 32 mild-to-moderate asthmatics, who inhaled either hypertonic (HS; 4.5% NaCl) or isotonic (IS; 0.9% NaCl) solutions for 15 min, were studied. Selected sputum was used for analysis. Eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and free neutrophil elastase (NE) were measured in sputum supernatant.Sample weight, total and differential cell counts, as well as viability and squamous cell percentage were no different after the two tests. No significant differences in ECP, EPX, MPO or NE levels were observed between HS- and IS-induced sputum. Repeatability of the two tests was good for macrophages, neutrophils, eosinophils, ECP, EPX and NE, but not for lymphocytes and MPO.In conclusion, hyperosmolarity does not affect sputum cell counts and the levels of most granulocyte degranulation markers examined in this study, confirming that both hypertonic and isotonic solutions can be reliably used to induce sputum in asthmatics.
Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma
Authors: Petersen R. , Agertoft L. , Pedersen S. 
Published: November 2004

A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this.A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 µg or 100 µg givenq.d.(QVARTMAutohalerTM; 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5–14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured.Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 µg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 µg: fall in FEV1=20.9%, eNO=8.9 ppb).In conclusion, lowq.d.doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whetherq.d.administration of beclomethasone dipropionate is as effective asb.i.d.administration.
Pramipexole in unipolar and bipolar depression
Authors: Whiskey Eromona , Taylor David 
Published: November 2004

Aims and MethodTo review the evidence for this use of pramipexole in the treatment of unipolar and bipolar depression, a literature search on Embase and Medline was conducted in December 2003. The search was updated in July 2004. The reference sections of retrieved papers were searched for further relevant references.ResultsThere are limited data on the clinical use of pramipexole in affective disorders. Only two double-blind trials in bipolar depression and one in unipolar depression were retrieved. Most information is in the form of case reports and open studies. No dose-response relationships have been established and a wide range of doses has been employed in the reports.Clinical ImplicationsIn view of the fact that the evidence for the use of pramipexole is still limited at the time of writing, its routine clinical use cannot be recommended. The data appear promising, but further research is required to determine its role in affective disorders.
Psychiatry as a career choice compared with other specialties: A survey of medical students
Authors: Rajagopal Sundararajan , Rehill Kamaljit Singh , Godfrey Emma 
Published: November 2004

Aims and MethodThe aim of this study was to determine the attitudes of medical students in the UK towards different specialties as career options and to ascertain the position of psychiatry among these specialties. Students belonging to a London medical school completed a questionnaire.ResultsAmong the 301 students who completed the survey, psychiatry was the least popular clinical specialty. The study revealed that the students had a number of misconceptions about psychiatry. A family history of mental illness was significantly associated with choosing psychiatry as a career.Clinical ImplicationsConsidering the unpopularity of the specialty, it is likely that recruitment of psychiatrists will continue to be a major problem for the foreseeable future. Measures need to be taken to dispel the misconceptions about psychiatry.
Audit of the use of psychotropic medication for challenging behaviour in a community learning disability service
Authors: Marshall Tom 
Published: November 2004

Aims and MethodThe aims of the study were to identify patients in a community learning disability service receiving psychotropic medication for challenging behaviour, to examine prescribing practice and to compare this against local consensus standards. Local consensus standards were agreed by the consultants and the notes were reviewed by the author.ResultsA total of 102 patients were identified as receiving psychotropic medication for challenging behaviour (26.7% of notes examined). The most common additional diagnoses were autism (29%) and epilepsy (28%). The average duration of treatment was 5.3 years, and multiple drugs were used in 34% of these patients. Antipsychotics were the most commonly used drugs (96% of patients). There was rarely a detailed description of the challenging behaviour. There was little regular monitoring of side-effects or warning about potential side-effects when the medication was started.Clinical ImplicationsChallenging behaviour is a common cause of multiple prescribing in learning disability patients, and is often long-term in the absence of a strong evidence base. Other specialties use medication to control disturbed behaviour, particularly in people with dementia or personality disorder, so this audit may also be of interest to old age, adult and forensic psychiatrists.
Experience of stigma among Chinese mental health patients in Hong Kong
Authors: Chung K. F. , Wong M. C. 
Published: November 2004

Aims and MethodThe study was intended to rectify the lack of data on how Chinese people experience the stigma of mental illness. A questionnaire on perceived stigmatisation, experiences of rejection and ways of coping with stigma was completed by 193 persons attending a psychiatric out-patient clinic in Hong Kong.ResultsMost of the participants were aware of the stigma associated with mental illness, but experiences of rejection were relatively less frequent. Eleven per cent of the respondents indicated that they were neglected by health care professionals and 8% had been avoided by family members. The most frequently reported coping method was maintaining secrecy about the illness.Clinical ImplicationsIn China, people with mental health problems experience stigma in various degrees. However, some of the people surveyed expressed feelings of relief that others were supportive and sympathetic towards their illness. Mental health professionals should maintain optimism in helping their patients to cope with the stigma.
Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate With EGFR Expression in Related Metastatic Sites: Implications for Treatment With EGFR-Targeted Monoclonal Antibodies
Authors: Scartozzi Mario , Bearzi Italo , Berardi Rossana , Mandolesi Alessandra , Fabris Guidalberto , Cascinu Stefano 
Published: November 2004

Purpose We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies. Patients and Methods We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was ≥ 1%. Results EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036). Conclusion Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).