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Biomedical subjects

W R Pohl

Publications and source records attributed to W R Pohl.

11 recordsLinked to original sources
PubMed2005

Adjustable maintenance dosing with budesonide/formoterol or budesonide: double-blind study.

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.

Administration, Inhalation↗
PubMed1996

Alveolar macrophages of patients with adult respiratory distress syndrome express high levels of heat shock protein 72 mRNA.

Adult respiratory distress syndrome (ARDS), a multifactorial disease with poor prognosis, is characterized by an accumulation of inflammatory cells within the airspaces of the lungs. There is evidence that alveolar macrophages (AM) are involved in the pathogenesis of this pulmonary disease. It has been demonstrated that AM synthesize heat shock proteins (HSPs) after exposure to certain stress factors. Increasing evidence suggests that HSPs could confer protection against oxidative injury, noxious molecules, and bacterial toxins. In stressed cells HSP 72 appears to be essential for survival during and after exposure to cellular injury. The aim of this study was to evaluate the magnitude of HSP 72 expression by human AM of patients with ARDS and correlate that with respiratory burst activity. Bronchoalveolar lavage was performed in six ARDS patients, 10 patients with high risk for developing ARDS, and two patients who underwent bronchoscopy for other reasons. Spontaneous ex vivo expression of HSP 72 in AM could be demonstrated by immunocytochemistry. Total RNA as well as poly(A)-rich mRNA were extracted from recovered AM and analyzed by Northern blot and slot blot using a human HSP 72-specific probe. Signals of slot blot were analyzed by densitometry and expressed as relative levels of HSP 72 mRNA of stressed (42 degrees C) HT 1080 control cells. Significantly (p < .001) higher levels of HSP 72 mRNA were measured in patients with ARDS (96.2 +/- 9.5 relative levels) in comparison to those not developing this syndrome (46.0 +/- 4.2). With regard to respiratory burst activity of AM in patients with ARDS, there was a negative correlation between HSP 72 expression and reactive oxygen species production. The AM of patients with ARDS with high relative levels of HSP 72 expression showed low respiratory burst activity. A predictive value for disease severity of high level of HSP 72 mRNA in AM in patients at risk for ARDS has to be evaluated by future studies. This demonstration of HSP 72 expression ex vivo suggests a protective role of HSP response against endo/exogenously generated stress factors in AM.

Adult↗
PubMed1996

[Practicability, effectiveness and tolerance of a standardized prepared theophylline infusion].

The practicality, efficacy, and tolerance of a standardized, ready-to-use theophylline solution (Eloasthmin, Leopold Pharma, Graz) was studied on 33 patients with bronchial asthma and/or chronic obstructive bronchitis (COPD) (19 males, 14 females) aged 19 to 79 (median 50) years. Eloasthmin a ready-to-use pure theophylline solution containing no auxilliary substances, contains one gram theophyllin per liter in a hypotonic (2/3) NaCl solution. The infusion therapy was carried out in patients in an acute stage of their chronic obstructive ventilation dysfunction. The therapy was carried out for 2 to 4 days at a dose of 400 to 1000 mg theophylline per day, so that theophylline blood levels remained within the therapeutic range of 8 to 20 mg/ml. A highly significant improvement (p < 0.001) of lung function parameters was seen during treatment: VC before therapy = 2.46 l, after therapy = 3.36 l; FEV 1 before therapy = 1.34 l, after therapy = 2.04 l; and PEF before therapy = 3.48 l/s after therapy = 5.13 l/s. Since most patients also received concomittant medication (beta 2-sympathomimetica and/or glucocorticoids), it was difficult to differentiate the specific efficacy of the theophylline.

Adult↗
PubMed1993

Elevated levels of bronchoalveolar lavage vitronectin in hypersensitivity pneumonitis.

Vitronectin is an adhesive glycoprotein that is present in plasma and the extracellular matrix. Hypersensitivity pneumonitis (HP) is characterized by pulmonary inflammation and damage to the extracellular matrix. Perhaps reflecting this, fibronectin has been found to be elevated in the lower respiratory tract of subjects with HP. Vitronectin, like fibronectin, binds to both extracellular matrix components and cells and may mediate tissue remodeling. Thus, it was investigated whether vitronectin might be increased in bronchoalveolar lavage (BAL) fluid of patients with HP. Vitronectin and, for comparison, fibronectin were measured in BAL fluid from 16 patients with HP and nine healthy control subjects by enzyme-linked immunosorbent assay. Vitronectin was significantly increased in the HP group (658.4 +/- 121.8 ng/ml) compared with the controls (58.4 +/- 11.1 ng/ml, p < 0.001) and was found to be positively correlated with fibronectin. Patients whose last antigenic exposure was 4 or fewer days before the BAL had statistically significantly higher BAL vitronectin and fibronectin than did patients whose last exposure was 5 or more days before the BAL. The serum vitronectin levels did not differ. There was no significant relationship between the lavage fluid vitronectin and fibronectin levels and the BAL cell profile in HP. This study confirms that vitronectin, like fibronectin, is a normal constituent of the lower respiratory tract, and demonstrates that vitronectin is elevated in the lower respiratory tract of patients with HP and may play a role in tissue remodeling and fibrosis in this disease.

Adult↗
PubMed1993

[Interferon therapy of the lung and locoregional therapy in pulmology].

The constant increase of lung cancer incidence is confronted with the relatively low efficacy of drug therapy in patients with advanced stages of this disease. According to results of phase II studies interferon-alpha (IFN-alpha) monotherapy used as palliative measure is ineffective in all histological types of lung cancer. However, in certain therapy settings IFN-alpha has some efficacy. In small cell lung cancer IFN-alpha therapy, when given as maintenance following chemo- and/or radiation therapy-induced remissions, has shown some clinical benefit as documented by a prolongation of remission-free intervals. In patients with advanced non-small cell lung cancer and especially of the squamous cell type the combination of IFN-alpha with cisplatinum achieved remissions in about 45%. The efficacy of locoregional administration, i.e. intrapleural, in patients with malignant effusions is currently under investigation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components.

Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.

Adult↗
PubMed1993

[Vitronectin in bronchoalveolar lavage--a parameter of disease activity in sarcoidosis].

Vitronectin is a multifunctional glycoprotein which is involved in several of the processes of inflammation and repair. In previous studies we demonstrated that increased concentrations of vitronectin can be detected in bronchoalveolar lavage fluids (BAL) of patients with interstitial lung disease (e.g. sarcoidosis). The outcome of sarcoidosis is generally favorable, however, some patients progress to pulmonary fibrosis. There is a need for markers indicating early fibrotic changes in the lung in patients with sarcoidosis. The present study was designed to evaluate the potential of BAL-vitronectin measurements for the assessment of disease activity in subjects with sarcoidosis. BAL-vitronectin concentrations were determined in 19 patients with biopsy proven sarcoidosis and sequential analysis of BAL-vitronectin levels were performed in 11 patients before and after therapy. Patients with active sarcoidosis had higher BAL-vitronectin concentrations (1.56 +/- 0.89 microgram/ml) than patients with inactive disease (0.68 +/- 0.33 microgram/ml; p < 0.01). Patients with active sarcoidosis received high-dose glucocorticoid treatment for four weeks followed by low-dose glucocorticoid therapy for eleven months. After high-dose medication BAL-vitronectin concentrations fell significantly (1.08 +/- 0.9 microgram/ml; p < 0.01). A further decrease in vitronectin levels resulted when therapy was continued for a year (0.75 +/- 0.48 micrograms/ml). Clinical deterioration correlated with an increase in BAL-vitronectin concentrations. Thus, measurement of BAL-vitronectin levels might be a useful marker for assessing disease activity and response to therapy in patients with sarcoidosis, but does not provide prognostic information.

Adult↗
PubMed1993

[Diagnostic value of secretory products of eosinophils and neutrophils in bronchoalveolar lavage in patients with idiopathic lung fibrosis].

Idiopathic pulmonary fibrosis (IPF) is characterized by a chronic inflammatory process in the lower respiratory tract of unknown etiology and poor prognosis. There is evidence that cytotoxic mediators released by neutrophils and eosinophils, such as myeloperoxidase (MPO) and eosinophil cationic protein (ECP) play a central role in the pathogenesis of this disease. The aim of this study was to assess disease activity in patients with IPF by measuring MPO and ECP concentrations in bronchoalveolar lavage (BAL). 14 patients with IPF had significantly higher concentrations of BAL-MPO and ECP (median = 117.2 micrograms/l, range: 4-217 micrograms/l and median = 16 micrograms/l, range: 4-34 micrograms/l, respectively) than patients with sarcoidosis (n = 9) (median = 6.5 micrograms/l, range: 4-12 micrograms/l and median = 7.1 micrograms/l, range: 2-13 micrograms/l, respectively) or pneumonia (n = 13) (median = 10.8 micrograms/l, range: 5-14 micrograms/l and median = 7.6 micrograms/l, range: 3-10 micrograms/l, respectively) (p < 0.01). Follow-up of MPO and ECP concentrations in BAL was performed in 8 patients with IPF before and after 4 weeks high-dose and 12 months low-dose corticosteroid therapy. Changes in MPO and ECP levels paralleled the clinical course and successful treatment resulted in a significant decrease of both MPO and ECP concentrations (p < 0.05), while clinical deterioration or treatment failure was associated with an increase of BAL-MPO and ECP levels. Increased MPO and ECP concentrations in BAL seem to reflect ongoing disease activity and may be useful prognostic markers in the management of patients with IPF.

Adrenal Cortex Hormones↗
PubMed1992

Serum procollagen III peptide levels in subjects with sarcoidosis. A 5-year follow-up study.

In a prospective study, Type III procollagen N-terminal peptide was measured in the sera of 38 subjects with biopsy-proven pulmonary sarcoidosis at 6-month intervals over a period of 5 yr. The subjects were divided into four groups according to their radiologic presentation and clinical course: Group A (n = 10) subjects with sarcoidosis Type I without radiologic progression over 5 yr; Group B (n = 5) subjects with sarcoidosis Type I with radiologic progression to Stage II or III; Group C (n = 9) subjects with sarcoidosis Types II and III without progression over 5 yr; and Group D (n = 14) subjects with sarcoidosis Types II and III with radiologic progression. Lung function tests (FVC, FEV1, and DLCO), chest roentgenograms, and measurements of serum angiotensin converting enzyme (S-ACE) were performed concurrently with the S-PCP-III levels. Significantly higher levels of S-PCP-III were found in group B (Type I, progressive) (18.2 +/- 1.09 ng/ml) and in group D (Type II/III, progressive) (13.9 +/- 1.2 ng/ml) compared with those of Group A (Type I, stable) (9.1 +/- 1.09 ng/ml) and Group C (Type II/III, stable) (7.6 +/- 1.1 ng/ml) or normal volunteers (9.4 +/- 4 ng/ml) (p less than 0.001 for all comparisons). Changes in S-PCP-III levels tended to parallel the clinical course, and steroid treatment resulted in a significant decrease in S-PCP-III concentrations (p less than 0.001). In contrast, serum angiotensin converting enzyme (S-ACE) levels did not correlate with either the clinical course or radiologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Vitronectin in bronchoalveolar lavage fluid is increased in patients with interstitial lung disease.

Vitronectin, also known as S-protein, is a 75,000-dalton serum glycoprotein that has a variety of functions, including the capacity to interact with the terminal components of the complement cascade, the coagulation system, and cell surfaces. By virtue of its ability to interact with cells, vitronectin is capable of mediating cell-spreading and adhesion and may also influence cell differentiation and cell growth. To investigate the possibility that vitronectin might contribute to the pathogenesis of interstitial lung disease, vitronectin was measured in bronchoalveolar lavage fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis, and, for comparison, normal volunteers. Vitronectin was detected in lavage fluid and serum of all study subjects. Increased lavage fluid concentrations were found in patients with interstitial lung disease when compared with normal subjects (p less than 0.005), and glucocorticoid-treated patients with interstitial lung disease had lower vitronectin levels than did untreated patients. Furthermore, on SDS-PAGE and Western blot analysis lavage fluid vitronectin comigrated with serum vitronectin, suggesting similar molecular size. Thus, vitronectin is a normal constituent of the epithelial lining fluid, and lavage fluid vitronectin is similar to serum vitronectin. The increase of vitronectin concentrations in the epithelial lining fluid of patients with interstitial lung disease suggests that vitronectin may contribute to the pathogenesis of interstitial lung disease.

Blood Proteins↗