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Biomedical subjects

Tobias Welte

Publications and source records attributed to Tobias Welte.

66 records · Page 4Linked to original sources
PubMed2003

[Noninvasive ventilation in the intensive care unit -- is it still negligible?].

Non-invasive positive pressure ventilation (NIPPV) has been discussed comprehensively in the last years, but usage of non-invasive ventilation in Intensive Care Units is rare. The reasons may be uncertainty in indications and difficulties in handling the masks and ventilators. In the last years the introduction of full face masks and respiratory helmets has made it possible to ventilate patients with unusual facial forms and to avoid problems of pressure necrosis. Software components designed for NIPPV are available for standard respirators. Indications for NIPPV (neuromuscular diseases, spinal abnormalities, chest wall malformations, COPD, cardiogenic pulmonary edema) have been ensured in clinical trials. No sufficient data are available for the application of NIPPV in weaning and respiratory failure following extubation. Indication for NIPPV becomes apparent when therapy starts in early stage with sufficient ventilation pressure. Compared to standard therapy, no reliable advantage has been seen for NIPPV in hypoxic hypercapnia respiratory failure except for malignant diseases. However, prophylactic use in patients with high risk might be conceivable. For these patients strict criteria of termination are required to avoid missing the time point for intubation. Gas exchange disturbances in advanced lung fibrosis, pneumonia and ARDS are not amenable to NIPPV. Contraindications for NIPPV are non-compliant patients, absence of cough- and pharyngeal reflexes as well as retention of secretions and malignant ventricular arrhythmia. Relative contraindications are catecholamine-dependent circulatory collapse and acute myocardial infarction, since sufficient data for NIPPV are missing.

Acute Disease↗
PubMed2003

Mercury contamination of rat amylin mimics vasoactivity and cytotoxic effects.

Rat amylin differs from human amylin (hIAPP) in that it lacks a fibril-forming capacity. As a consequence, toxic effects have been reported for human but not for rat amylin. This report demonstrates how a mercury contamination of commercial rat amylin imitates peptide-related vasoactive and cytotoxic effects on preparations of isolated blood vessels. The source of mercury contamination was believed related to the peptide synthesis. Thiol groups of cysteine-containing peptides are often protected by acetamidomethyl (Acm) which is cleaved by mercuric acetate.

Acetylcholine↗
PubMed2003

Beau's lines in a patient treated with moxifloxacin for anaerobic pulmonary infection.

Onychotoxicity of fluoroquinolones is a rare event. Previously described cases of fluoroquinolone-related nail disorders were due to onychophototoxicity. This report presents a case of nail toxicity after treatment with moxifloxacin for anaerobic pulmonary infection, which has not been described previously. The appearance and circumstances of this nail disorder were consistent with the diagnosis of Beau's lines.

Anti-Infective Agents↗
PubMed2003

Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis.

OBJECTIVES: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study, we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis (AECB). METHODS: Eighty-one patients (56 males, 25 females, age 65.3 +/- 10.1 years) with AECB were included. A subgroup of 21 patients underwent pharmacokinetic and pharmacodynamic examination. The patients received either ceftazidime 2 g every 8 h (C3 x 2) or ceftazidime 2 g as a loading dose, followed by ceftazidime 2 g over 7 h every 12 h (C2 x 2) for 8-14 days. Clinical and bacteriological responses were monitored at day 8 or 9, and 72 h after the end of therapy (EOT). RESULTS: At EOT, clinical success was recorded in 90% and 90.2% of clinically evaluable patients receiving C3 x 2 and C2 x 2, respectively. Bacteriological success at EOT was achieved in 87.5% and 90.2% of evaluable patients treated with C3 x 2 and C2 x 2, respectively. C(max) (mg/L) varied between 168.9 +/- 34.1 and 144.0 +/- 9.8 in the C3 x 2 group, and between 60.1 +/- 34.1 and 54.2 +/- 30.4 at steady-state in the C2 x 2 group. Minimal concentrations were between 9.1 and 13.4 mg/L in the C3 x 2 group, and between 16.6 and 17.7 mg/L in the C2 x 2 group. Concentrations >4-5 x MIC were seen in all pathogens, except Staphylococcus aureus, during 100% of infusion time. CONCLUSION: The 2 x 7 h infusion of ceftazidime 2 g (C2 x 2) was clinically and bacteriologically as effective as the usual 3 x 2 g ceftazidime short-term infusion in the treatment of AECB, and demonstrated advantages in terms of pharmacodynamic parameters compared with the C3 x 2 regimen.

Acute Disease↗
PubMed2003

Cystic fibrosis: cost of illness and considerations for the economic evaluation of potential therapies.

Cystic fibrosis (CF) is the most common life-shortening inherited disease of the Caucasian race, with a prevalence of around 1 in 2500 live births. Advances in the treatment and management of respiratory and pancreatic disorders have dramatically increased the life expectancy of patients with CF. This article presents an overview of cost-of-illness studies of CF, identifies deficits in the available health economic analyses of CF and discusses which specific factors are essential for the economic evaluation of potential therapies, based on a critical review of the health economic literature on two main therapeutic strategies. Cost-of-illness studies of CF have predominantly been restricted to direct costs. According to the literature, direct costs amount to between 6200- 16300 US dollars (1996 values) per patient per year. As most studies likely underestimated the actual costs (e.g. by disregarding provision of certain healthcare services), real healthcare costs tend to be at the upper end of the cost range. Healthcare costs depend on the patient's age (for adults, costs are approximately twice as high as for children), the grade of severity (the cost relationship of severe to mild CF is between 4.5 and 7.1) and other factors. Lifetime direct costs of CF are estimated at 200 000-300000 US dollars (at 1996 values and a discount rate of 5%). Home intravenous (IV) antibacterial therapy and recombinant human DNase (rhDNase; dornase alfa) treatment are the two main therapeutic strategies most often evaluated in health economic studies of CF. While home IV antibacterial therapy (compared with inpatient IV antibacterial therapy) is assumed to be cost saving, rhDNase treatment is a very cost-intensive therapy intended to efficiently achieve health improvements. Health economic analyses of future CF therapeutic technologies should present explicit data regarding healthcare services provision, resource consumption and unit costs. Indirect costs and patient costs should be considered more often than they have to date, particularly when they are significantly influenced by novel CF technologies. The perspective of health economic studies should be stated explicitly and always include the societal perspective. More economic studies should be based on a controlled, and preferably randomised, design. The observation period must be long enough to identify long-term effects of interventions. A greater number of effectiveness studies should be performed to determine costs and outcomes of therapies applied under everyday life conditions for patients with CF. Finally, international comparison studies should identify the influence of different healthcare systems on the costs and outcomes of interventions.

Anti-Infective Agents↗
PubMed2002

[State of the art of the inhalation therapy of asthma].

The current concept of asthma pathogenesis is that a characteristic chronic inflammatory process involving the airway wall causes the development of airflow limitation and increased responsiveness, thereby predisposing the airways to narrow in response to a variety of specific (allergic) or unspecific stimuli. Medications for asthma are used to reverse and prevent symptoms and airflow limitation and include controllers and relievers. The major advantage of delivering drugs directly into the airways via inhalation is that high concentrations can be delivered more effectively to the airways, and systemic side effects are avoided or minimized. Bronchodilators with or without anti-inflammatory substances are used as basic therapeutic approach in these patients. The stepwise approach to therapy recommends that the number/type and frequency of medications are increased with increasing asthma severity by adding systemic medications to existing inhalation therapy (step III-IV in asthma management guidelines). Combination therapy using a long acting beta 2-agonist and a glucocorticosteroid resulted in higher lung function improvement, and was superior in reduction of exacerbation rates compared with an inhaled glucocorticosteroid alone. Hence, the development of a fixed combination containing both substances in one device is a logic consequence, and thus, simplifying asthma therapy.

Administration, Inhalation↗
PubMed2002

[Do we need inhalative steroids in chronic COPD patients?].

The use of inhaled steroids in the management of chronic obstructive pulmonary disease (COPD) is controversially discussed. Neither the optimistic view of the 90s nor the current pessimistic view on these substances seems to be justified. It becomes apparent that a more differentiated approach, depending on the clinical situation and the cellular composition in the airways, is necessary. Patients with severe inflammation, poor lung function, and frequent exacerbations seem to benefit more from inhaled steroids. Patients in early stages of the disease with occasional symptoms only, and patients predominantly suffering from emphysema than from bronchitis seem to have no benefit from this treatment option. Special attention should be turned to mixed types with asthma-like symptoms. The combination of inhaled long-acting beta 2-mimetics and steroids seems to be of advantage; for a final judgment, however, the results of ongoing clinical trials have to be awaited.

Administration, Inhalation↗
PubMed2002

Floating aortic thrombus in systemic aspergillosis and detection by transesophageal echocardiography.

After immunosuppressive treatment for a colitis ulcerosa, a 49-yr-old man developed signs of systemic aspergillosis with subsequent septic shock and encephalitis. For recurrent signs of thromboembolism, transesophageal echocardiography was performed and revealed a large floating thrombus of the aortic arch. Despite appropriate antibiotic treatment, the patient died a few days later suffering from adult respiratory distress syndrome. The appearance of aortic thrombi concomitant to systemic fungal infection rarely has been reported. The present case is the first report of in vivo detection of large vessel involvement in systemic aspergillosis by transesophageal echocardiography. In our opinion, transesophageal echocardiography is the method of choice for bedside diagnosis of this rare complication in critically ill patients.

Aorta, Thoracic↗
PubMed2002

Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.

Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin.

Bronchi↗
PubMed2002

Anticholinergics in the treatment of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in the world. In the majority of cases, the disease is the result of years of cigarette smoking. Contributing factors leading to bronchial obstruction in COPD include mucus hypersecretion and an increase in bronchial muscle tone, which is triggered mainly by cholinergic mechanisms. Anticholinergic bronchodilators reduce vagal cholinergic tone, the main reversible component of COPD; hence they are the first-line treatment for bronchial obstruction in COPD. In addition to improving lung function, anticholinergics improve dyspnea, quality of life and exercise tolerance, and they reduce exacerbations. When compared with other bronchodilators, anticholinergics show at least equivalent bronchodilator potency, but with fewer side effects. In addition, due to their unique site of action, anticholinergics can be effectively combined with other bronchodilators. The introduction of new, long-acting anticholinergics is a promising addition to the treatment of COPD and is expected to lead to improved treatment outcomes and improved patient compliance.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Functional consequences of cathepsin L deficiency in human lung epithelial cells.

Cathepsin L is a cysteine protease of the papain family. Lung epithelial cells play an important role in host defence. The aim of the present study was to investigate the functional role of cathepsin L in the human lung carcinoma cell line A549. Cathepsin L-deficient A549 clones were generated. They showed a significant lower proliferation and secreted 5- to 8-fold more IL-8 than the control cells. The production of IL-6, IL-18, and TGF-beta1/2 was not affected significantly. It was shown that the cells upregulate IL-8 transcription and that IL-8 in the culture supernatant is necessary for the containment of cellular proliferation. In conclusion, the data show that suppression of cathepsin L expression in A549 cells leads to a growth inhibition which is partially compensated by an upregulation of IL-8 production.

Cathepsin L↗