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Biomedical subjects

K F Rabe

Publications and source records attributed to K F Rabe.

At least 37 records · Page 2Linked to original sources
PubMed2005

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis.

The objective of the current study was to assess the yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for the diagnosis of sarcoidosis in a large patient group. Bronchoscopy with transbronchial lung biopsy (TBLB) is nondiagnostic in 30% of patients with suspected sarcoidosis and has a risk of pneumothorax and haemoptysis. In order to obtain a diagnosis, mediastinoscopy is often performed as the next diagnostic procedure. EUS-FNA provides a nonsurgical alternative for the demonstration of noncaseating granulomas by aspirating mediastinal lymph nodes from the oesophagus. In total, 51 patients with suspected sarcoidosis stage I and II underwent EUS-FNA. Thirty-six patients (71%) previously underwent a nondiagnostic bronchoscopy. All patients were clinically followed (median 18 months) and surgical-pathological verification occurred in those patients with EUS aspirates that contained unrepresentative material. EUS-FNA demonstrated noncaseating granulomas without necrosis in 41 of 50 patients (82%) with the final diagnosis of sarcoidosis. Specific ultrasound features of clustered, well-demarcated iso-echoic lymph nodes were observed in 64% of patients with sarcoidosis. No complications occurred. Endoscopic ultrasound-guided fine-needle aspiration has a high yield in diagnosing sarcoidosis and qualifies as the next diagnostic step after a nondiagnostic bronchoscopy. The current authors expect that endoscopic ultrasound-guided fine-needle aspiration will reduce the number of mediastinoscopies for the diagnosis of sarcoidosis dramatically.

Adult↗
PubMed2004

Human neutrophil defensins and secretory leukocyte proteinase inhibitor in squamous metaplastic epithelium of bronchial airways.

OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the number of proliferating (Ki-67-positive) epithelial cells was analyzed by immunohistochemistry in bronchial epithelium from subjects with (n = 15) or without (n = 14) chronic obstructive pulmonary disease (COPD). RESULTS: Our data demonstrate higher numbers of defensin-positive (p = 0.0001), elastase-positive (p = 0.0001) and Ki-67-positive (p = 0.0001) cells in areas with squamous cell metaplasia as compared to areas with intact or damaged epithelium, while the reverse was observed for SLPI expression (p = 0.002). No differences were observed between subjects with or without COPD, nor between current smokers and those that had stopped smoking. CONCLUSIONS: These data are in line with a role of defensins in the hyperproliferative phenotype of squamous metaplastic lesions in the airways. This role does not seem to be restricted to patients with COPD.

Adult↗
PubMed2004

Towards a minimally invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA.

STUDY OBJECTIVE: To asses the value of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in the nodal staging of patients with (suspected) non-small cell lung cancer (NSCLC) and a (18)FDG positron emission tomography (PET) scan suspect for N2/N3 mediastinal lymph node (MLN) metastases. BACKGROUND: Due to the imperfect specificity of positron emission tomography, PET positive MLN should be biopsied in order to confirm or rule out metastasis. Currently, invasive surgical diagnostic techniques such as mediastinoscopy/-tomy are standard procedures to obtain MLN tissue. The minimally invasive technique of EUS-FNA has a high diagnostic accuracy (90-94%) for the analysis of MLN in patients with enlarged MLN on computed tomography of the chest (CT). DESIGN AND PATIENTS: Thirty-six patients with proven n=26 or suspected n=10 non-small cell lung cancer and a PET scan suspect for N2/N3 lymph node metastases underwent EUS-FNA. When EUS-FNA did not confirm metastasis and the PET lesion was within reach of mediastinoscopy, a mediastinoscopy was performed. EUS-FNA negative patients with PET lesions beyond the reach of mediastinoscopy or those with a negative mediastinoscopy were referred for surgical resection of the tumour and MLN sampling or dissection. RESULTS: EUS-FNA confirmed N2/N3 disease in 25 of the 36 patients (69%) and was highly suspicious in one. In the remaining 10 patients, one PET positive and one PET negative N2 metastasis was detected at thoracotomy. The PPV, NPV, sensitivity, specificity and accuracy of EUS-FNA in analysing PET positive MLN were 100%, 80%, 93%, 100% and 94%, respectively. No complications of EUS-FNA were recorded. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA yields minimally invasive confirmation of MLN metastases in 69% of the patients with potential mediastinal involvement at FDG PET. The combination of PET and EUS-FNA might qualify as a minimally invasive staging strategy for NSCLC.

Adult↗
PubMed2004

[Vasoactive intestinal polypeptide in the respiratory tract: physiology and pathophysiology].

Peptidergic neuromediators have gained importance in the field of respiratory physiology and pathophysiology due to the characterisation of numerous pulmonary effects in the past years. With regard to the multitude of mediators, the neuropeptide vasoactive intestinale polypeptide (VIP) plays a special role as it exerts potent anti-inflammatory and immunomodulatory effects. Neurophysiologically the peptide has been attributed to the family of the inhibitory non-adrenergic non-cholinergic (i-NANC) neuromediators of the pulmonary innervation. VIP-containing nerve fibres are localized in the airway and vascular smooth muscle layers of trachea and bronchi in the human respiratory tract. Apart from strong vasodilatory effects, the peptide also shows a high bronchodilatory potency. In a large number of respiratory diseases VIP may play a pathophysiological role. In this respect, increased levels of VIP have been demonstrated for inflammatory diseases of the upper and lower airways and the peptide may also play a role in pulmonary hypertension. Due to its fast enzymatic cleavage, VIP-based therapies have not been used in routine therapy so far. Also, the use of synthetic VIP-agonists did not lead to an improved outcome in patients with bronchial asthma if compared to classical drugs. However, recent data from animal experiments indicate potent immunomodulatory effects which suggest a future use of this mediator and its agonists in the therapy of immune diseases.

Anti-Inflammatory Agents↗
PubMed2004

[Endoscopic ultrasound-guided fine-needle aspiration in pulmonary medicine].

Endoscopic ultrasound-guided fine-needle aspiration has significantly increased the capacity of pulmonary diagnostic procedures. Since this method was introduced, 1212 examinations have been performed at two centres of pulmonary medicine. Data on indications, procedures, findings, diagnostic yield and complications have been recorded. This paper describes the experiences thus gained regarding the possibilities and limitations of the method and assesses the current significance of the technique in pulmonary medicine according to previous studies. In primary diagnosis of mediastinal tissue alterations and in staging of malignant diseases the method offers a low-complication diagnostic measure which has a seminal impact on therapy in many cases, even though in daily practise the diagnostic accuracy of published studies is not always attained.

Biopsy, Fine-Needle↗
PubMed2003

Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease?

Maintenance treatment with PDE(4) inhibitor cilomilast improves FEV(1) in chronic obstructive pulmonary disease (COPD) patients. We investigated the acute bronchodilating effects of a single dose of cilomilast with or without concomitant administration of inhaled salbutamol and/or ipratropium bromide in 21 patients with COPD (mean (SD) age 64 (8.1) y, post-salbutamol FEV(1) 47.7 (13.2) %predicted). FEV(1) was measured before and up to 8 hourly intervals after intake of placebo, cilomilast, or cilomilast in combination with inhaled salbutamol 400 microg and/or ipratropium bromide 80 microg. Maximum increase in FEV(1) from pre-dose baseline was calculated after each treatment and differences between treatment arms were analyzed by ANOVA. The mean (SEM) maximum increase in FEV(1) was 139.6 (18.5) ml following cilomilast and 151.5 (18.5) ml following placebo (95% C.I. for mean difference between cilomilast and placebo: -67.3, 43.6 ml). Furthermore, combined treatment of cilomilast with salbutamol or ipratropium resulted in a maximum increase in FEV(1) of 280.7 (25.6) and 297.0 (25.9) ml, respectively, while this was 379.0 (24.6) ml following cilomilast with both salbutamol and ipratropium (p < 0.01). We conclude that a single dose of cilomilast does not produce acute bronchodilation in patients with COPD who otherwise respond to inhaled bronchodilators. Our results implicate that the change in lung function seen after long-term treatment with cilomilast is not the result of acute bronchodilation in patients with COPD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD).

Selective inhibitors of phosphodiesterase-4 (PDE4) inhibit the hydrolysis of intracellular cAMP, which may result in bronchodilation and suppression of inflammation. We examined the effect of 1 week treatment with BAY 19-8004 (5 mg once daily), a novel orally administered PDE4 inhibitor, on trough FEV1 and markers of inflammation in induced sputum in patients with asthma or chronic obstructive pulmonary disease (COPD). Seven patients with asthma (mean [SD] FEV1 69.5 [9.3]% predicted; reversibility in FEV1 26.2 [10.1]%; all non-smokers) and 11 patients with COPD (FEV1 58.6 [8.3]% predicted; reversibility in FEV1 6.5 [4.7]%; median [range] 44 [21-90] pack years of smoking) were included in this randomized, double-blind, placebo-controlled trial. FEV1 was measured before and after 1 week of treatment; sputum was induced by 4.5% saline inhalation on the last day of treatment. FEV1 did not improve during either treatment in both patient groups (p>0.2). Sputum cell counts were not different following placebo and BAY 19-8004 treatment in asthma and COPD patients (p>0.2). However, only in patients with COPD, small but significant reductions in sputum levels of albumin and eosinophil cationic protein were observed (p<0.05). In conclusion, 1 week of treatment with the selective PDE4 inhibitor BAY 19-8004 does not affect FEV1 and sputum cell numbers in patients with asthma or COPD. However, such treatment does seem to reduce levels of albumin and eosinophil cationic protein in sputum samples obtained from patients with COPD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics.

BACKGROUND: The mechanisms that regulate epithelial integrity and repair in asthma are poorly understood. We hypothesized that allergen exposure could alter epithelial inflammation, damage and proliferation in atopic asthma. OBJECTIVE: We studied epithelial cell infiltration, shedding, expression of the proliferation marker Ki-67 and the epithelial cell-cell adhesion molecules Ep-CAM and E-cadherin in bronchial biopsies of 10 atopic mild asthmatics 48 h after experimental diluent (D) and allergen (A) challenge in a cross-over design. METHODS: Epithelial shedding, expressed as percentage of not intact epithelium, Ki-67+, eosinophil/EG-2+, CD4+ and CD8+ cells were quantified by image analysis in bronchial epithelium, and adhesion molecules were analysed semi-quantitatively. RESULTS: Epithelial shedding was not altered by A (D: 88.1+/-3.1% vs. A: 89.2+/-3.7%; P=0.63). The numbers of Ki-67+ epithelial (D: 10.2+/-0.2 vs. A: 19.9+/-0.3 cells/mm; P=0.03), EG-2+ (D: 4.3+/-0.5 vs. A: 27+/-0.3 cells/mm; P=0.04) and CD4+ cells (D: 1.7+/-1.2 vs. A: 12.3+/-0.6 cells/mm; P=0.04) were significantly increased after A, whilst CD8+ numbers were not significantly changed (P>0.05). E-cadherin and Ep-CAM epithelial staining showed a similar intensity after D and A (P>0.05). We found a positive correlation between EG-2+ and Ki-67+ cells in the epithelium (Rs: 0.63; P=0.02). CONCLUSION: Our study indicates that allergen challenge increases epithelial proliferation in conjunction with inflammation at 2 days after exposure. This favours the hypothesis that long-lasting epithelial restitution is involved in the pathogenesis of asthma.

Adult↗
PubMed2003

Mediastinitis caused by EUS-FNA of a bronchogenic cyst.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and minimally invasive diagnostic technique for the analysis of mediastinal lesions. This case report describes a patient who developed a life-threatening mediastinitis after EUS-FNA of a mediastinal lesion, which (based on computed tomography of the thorax) had been suspected to be a lymph-node metastasis, but proved to be a bronchogenic cyst.

Abscess↗
PubMed2003

Correlation between annual change in health status and computer tomography derived lung density in subjects with alpha1-antitrypsin deficiency.

BACKGROUND: There is increasing recognition that questionnaires of health status and lung density measurements are more sensitive tools for assessing progression of emphysema than forced expiratory volume in 1 second (FEV(1)) and transfer coefficient (KCO). A study was undertaken to investigate prospectively the correlation between annual change in health status and computer tomography (CT) derived lung density in subjects with alpha(1)-antitrypsin deficiency. METHODS: Twenty two patients of mean (SD) age 40.7 (9.2) years with ZZ type alpha(1)-antitrypsin deficiency were investigated at baseline and 30 months later by FEV(1) and KCO, St George Respiratory Questionnaire (SGRQ), and by a spiral CT scan of the chest. CT data of chest images were analysed using software designed for automated lung contour detection and lung density measurements. The density data were corrected for changes in inspiration levels. RESULTS: Changes in lung density, expressed as 15th percentile point or relative area below -950 HU, correlated well with changes in health status (SGRQ total score): R = -0.56, p = 0.007 or R = 0.6, p = 0.003. Neither changes in health status nor changes in lung density correlated significantly with changes in FEV(1) or changes in KCO. CONCLUSIONS: The SGRQ total score (which is a global measure in COPD) and lung density (a specific measure of emphysema) are sensitive to deterioration in patients with alpha(1)-antitrypsin deficiency. This finding may facilitate future studies with new drugs specific for emphysema, a frequently occurring component of COPD.

Adult↗
PubMed2003

State of the art in beta2-agonist therapy: a safety review of long-acting agents.

Despite concerns in the 1970s and 1980s about the safety of short-acting beta2-agonists, it is now generally accepted that these agents, used at appropriate doses, provide safe and effective treatment for asthma symptoms. After their introduction, beta2-agonists with a long duration of action--formoterol and salmeterol--became widely used as maintenance therapy with inhaled corticosteroids (ICS). Both beta2-agonists are well tolerated in long-term studies, with no reduction in lung function observed over time, indicating a lack of clinically relevant tolerance development in patients with asthma and COPD. High-dose studies have indicated that formoterol produces systemic effects of similar duration to, but less pronounced than, salbutamol and terbutaline. Formoterol produces long-lasting bronchoprotection against exercise-induced bronchoconstriction, even in patients receiving regular maintenance therapy; its fast onset of effect (similar to salbutamol) allows formoterol to be used as a reliever. Clinically the safety of formoterol and salmeterol has been demonstrated in several studies, both with ICS and alone.

Adrenergic beta-Agonists↗
PubMed2002

Asthma control and differences in management practices across seven European countries.

Failure to follow asthma management guidelines may result in poor asthma control for many patients. The Asthma Insights and Reality in Europe (AIRE) survey, a multi-national survey assessing the level of asthma control from the patients perspective in seven Western European countries, previously demonstrated that the Global Initiative for Asthma (GINA) guideline goals were not achieved in Western Europe and that both adults and children with asthma were poorly controlled. Using additional data on asthma management practices from each of the seven countries in the AIRE survey, we compared variations in asthma morbidity and asthma management practices across countries to provide insight into the reasons for poor asthma control. Asthma management practices and asthma control among adults and children with current asthma were suboptimal in each of seven countries surveyed. Among patients with symptoms of severe persistent asthma, over 40% reported their asthma was well or completely controlled. School absence due to asthma was reported by upto 52.7% of children and up to 27.6% of adult reported work absence due to asthma. Lung function testing in the past year was uncommon: ranging from 13.5% of children in the U.K. to 68.8% of adults in Germany. Written asthma management plans were used by less than 50% of adults and less than 61% of children in all seven countries. Most adults (49.5-73.0%) and a large proportion of children (38.4-70.6%) had follow-up visits for their asthma only when problems developed. The ratio of recent inhaled corticosteroid use to recent short-acting beta-agonist use was inappropriate (<1) among patients with symptoms of severe asthma in all countries. This disparity was greatest among adults in Italy and France, where recent inhaled corticosteroid use was reported by less than one in nine patients reporting recent use of short-acting bronchodialators (IS:SAB <0.11). Management practices differ between countries and additional public health interventions and resources may be necessary to reduce patient suffering. Further efforts to fully implement asthma management guidelines are required to improve asthma control in Europe.

Adolescent↗
PubMed2002

Studying human airway pharmacology in microsections: application of videomicrometry.

The influence of endogenously-released mediators and activated eosinophils on the airway lumen and the effect of passive sensitization on anti-immunoglobulin (Ig)-E-induced contractile responses was investigated by videomicrometry. Human bronchial sections of 2-3 mm internal diameter, placed in 250 microL Hank's balanced salt solution on microtitre plates, were monitored and recorded by digitized image analysis. Airway preparations exhibited a spontaneous narrowing (mean+/-SEM -33+/-5% of the luminal area). Removal of the bronchial epithelium almost completely prevented the development of spontaneuous narrowing (-6+/-3%; p<0.001). The addition of platelet-activating factor stimulated human eosinophils to the bronchial sections led to significant narrowing of the airway lumen (-39+/-9%; p<0.05). Passive sensitization induced hyperresponsiveness to polyclonal anti-IgE (-35+/-8%; p<0.01). It is concluded that videomicrometry is suitable for studying interactions between human airways and inflammatory cells, as well as the effect of passive sensitization on smooth muscle reactivity in vitro, without the imposition of preload. Under these conditions, human airways exhibited a spontaneous decrease of the airway lumen over time suggesting a role for epithelium-derived mediators because the development of spontaneous tone was epithelium dependent.

Antibodies, Anti-Idiotypic↗