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Tobias Welte

Publications and source records attributed to Tobias Welte.

At least 37 records · Page 2Linked to original sources
PubMed2006

Bridge to lung transplantation with the novel pumpless interventional lung assist device NovaLung.

BACKGROUND: Worsening of lung failure in patients awaiting a lung transplantation might lead to ventilation-refractory hypercapnia and respiratory acidosis. Most transplant centers consider pretransplantation extracorporeal membrane oxygenation as a contraindication for lung transplantation because of the poor outcome. We have, for the first time, applied the novel pumpless interventional lung assist NovaLung for bridge to lung transplantation in patients with severe ventilation-refractory hypercapnia. We report on our initial experience. METHODS: Between March 2003 and March 2005, 176 lung transplantations were performed, of which 60% were high-urgency lung transplantations. Twelve of the high-urgency recipients had severe ventilation-refractory hypercapnia and respiratory acidosis. These patients were connected to the novel pumpless interventional lung assist NovaLung for bridge to lung transplantation. RESULTS: The length of interventional lung assist NovaLung support was 15 +/- 8 days (4-32 days). PaO2, pH, and PaCO2 levels in arterial blood prior to interventional lung assist NovaLung implantation were 71 +/- 27 mm Hg, 7.121 +/- 0.1, and 128 +/- 42 mm Hg, respectively. Six hours after interventional lung assist NovaLung implantation, PaO2, pH, and PaCO2 levels had changed to 83 +/- 17 mm Hg (ns), 7.344 +/- 0.1 (P < .05), and 52 +/- 5 mm Hg (P < .05), respectively. Four patients died of multiorgan failure, 2 patients before and 2 after lung transplantation. Thus, 10 out of 12 patients were successfully bridged to lung transplantation, and 8 are still alive (1-year survival, 80%). CONCLUSIONS: This report suggests that interventional lung assist NovaLung implantation is an effective bridge to lung transplantation strategy in patients with ventilation-refractory hypercapnia.

Acidosis, Respiratory↗
PubMed2006

Long-term outcome after pulmonary retransplantation.

OBJECTIVE: Bronchiolitis obliterans syndrome has become the most limiting factor for long-term outcome after lung transplantation. Redo lung transplantation was performed for end-stage bronchiolitis obliterans syndrome. Long-term outcome was compared with that after primary lung transplantation as well as with other indications for retransplantation. METHODS: Of 614 lung transplantation procedures performed at our institution, 54 (8.5%) were redo transplants. These were stratified into different groups according to the indication for redo transplantation, including chronic graft failure/bronchiolitis obliterans syndrome, acute graft failure, and posttransplantation airway complications. Long-term survival was compared with that of the primary lung transplantation cohort, thereby respecting the need for pretransplant mechanical ventilatory support in a subanalysis. In addition, recurrence of bronchiolitis obliterans syndrome after redo lung transplantation was compared with the occurrence of bronchiolitis obliterans after primary transplantation. RESULTS: A 1-year survival of 50% was achieved after redo lung transplantation for acute graft failure and airway complications as well as after primary lung transplantation in patients with pretransplant ventilatory support. Retransplantation for bronchiolitis obliterans syndrome revealed superior 1- (78%) and 5-year (62%) survivals, which were not different from those of first-time lung transplant recipients. In addition, we found a similar incidence of bronchiolitis syndrome after retransplantation for BOS compared with its occurrence after primary lung transplantation. CONCLUSION: Redo lung transplantation for end-stage bronchiolitis obliterans syndrome leads to acceptable long-term outcome in selected patients. Future analyses of redo lung transplantation data should generally stratify bronchiolitis obliterans syndrome from other indications with higher mortality.

Adolescent↗
PubMed2006

Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated protein kinase pathways.

Extracellular nucleotides have a profound role in the regulation of the proliferation of diseased tissue. We studied how extracellular nucleotides regulate the proliferation of LXF-289 cells, the adenocarcinoma-derived cell line from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell proliferation. The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP, UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4-benzoylbenzoyl)-ATP, AMP and UMP were inactive. The nucleotide potency profile and the total blockade of the ATP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 clearly show that P2Y receptors, but not P2X receptors, control LXF-289 cell proliferation. Treatment of proliferating LXF-289 cells with 100 microm ATP or ADP induced significant reduction of cell number and massive accumulation of cells in the S phase. Arrest in S phase is also indicated by the enhancement of the antiproliferative effect of ATP by coapplication of the cytostatic drugs cisplatin, paclitaxel and etoposide. Inhibition of LXF-289 cell proliferation by ATP was completely reversed by inhibitors of extracellular signal related kinase-activating kinase/extracellular signal related kinase 1/2 (PD98059, U0126), p38 mitogen-activated protein kinase (SB203508), phosphatidylinositol-3-kinase (wortmannin), and nuclear factor kappaB1 (SN50). Western blot analysis revealed transient activation of p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, and nuclear factor kappaB1 and possibly new formation of p50 from its precursor p105. ATP-induced attenuation of LXF-289 cell proliferation was accompanied by transient translocation of p50 nuclear factor kappaB1 and extracellular signal-related kinase 1/2 to the nucleus in a similar time period. In summary, inhibition of LXF-289 cell proliferation is mediated via P2Y receptors by activation of multiple mitogen-activated protein kinase pathways and nuclear factor kappaB1, arresting the cells in the S phase.

Adenocarcinoma↗
PubMed2006

Nanoparticle-based diagnosis and therapy.

Nanoparticles are at the leading edge of the rapidly developing field of material science in nanotechnology with many potential applications in clinical medicine and research. Due to their unique size-dependent properties nanoparticles offer the possibility to develop both new therapeutic and diagnostic tools. The ability to incorporate drugs into nanosystems displays a new paradigm in pharmacotherapy that could be used for cell-targeted drug delivery. Nontargeted nanosystems such as nanocarriers that are coated with polymers or albumin and solid lipid particles have been used to transport a large number of compounds. However, nowadays drugs can be coupled to nanocarriers that are specific for cells and/or organs. Thus, drugs that are either trapped within the carriers or deposited in subsurface oil layers could be specifically delivered to organs, tumors and cells. These strategies can be used to concentrate drugs in selected target tissues thus minimizing systemic side effects and toxicity. In addition to these therapeutic options, nanoparticle-based "molecular" imaging displays a field in which this new technology has set the stage for an evolutionary leap in diagnostic imaging. Based on the recent progress in nanobiotechnology, nanoparticles have the potential to become useful tools as therapeutic and diagnostic tools in the near future.

Animals↗
PubMed2006

Proteases and their role in chronic inflammatory lung diseases.

Proteases play an essential role in modulating the turnover of extracellular matrix. Furthermore, they are involved in the processing of various proteins thus regulating fundamental cellular functions such as apoptosis, cells growth and activation, protein secretion and phagocytosis. At the tissue and organ levels, proteases influence mechanisms including cell migration and invasion, cellular interactions and signal transduction as well as tissue formation and stabilization. Proteases are classified based on their catalytic mechanisms into serin, aspartic, metallo, threonin and cysteine proteases and are localized extracellularly, at the cellular surface, in the cytoplasm of cells or within specific subcellular structures such as lysosomes. The present review focuses on the specific functions of lysosomal cysteine proteases and the potential effects of modulators of cysteine protease activity.

Animals↗
PubMed2005

Health-related quality of life in two hundred-eighty lung transplant recipients.

BACKGROUND: Health-related quality of life (HRQoL) has increasingly been accepted as a supplementary outcome measure for patients after lung transplantation (LTx). METHODS: Using a retrospective cross-sectional study design, 280 LTx recipients (3 months to 14 years after LTx) were asked to assess their HRQoL using a generic (Quality of Life Profile for Chronic Diseases) questionnaire, which was previously validated for this specific population. In addition, the questionnaire was also performed by 155 healthy participants. RESULTS: All sub-scale findings ranged from 2.40 to 3.08 (0 to 4) for all patients after LTx. A significantly reduced HRQoL was reported by the sub-cohort of patients living 5 to 6 years with the allograft for all sub-scales (p < 0.006), except for Social Functioning, and was associated with the incidence of bronchiolitis obliterans syndrome (BOS; p < 0.05). Cystic fibrosis patients (p < 0.05), single-lung transplant recipients (p < 0.05) and patients of older age (p < 0.05) showed significantly decreased physical ability ratings. Patients who remained free of infection and late acute rejection episodes scored themselves significantly higher with regard to their Relaxation Capabilities (p < 0.05 for rejection; p < 0.05 for infection) and Social Functioning (p < 0.01 for rejection; p < 0.05 for infection) vs patients who experienced infection or rejection episodes. Comparisons with a normative cohort showed similar HRQoL scales for LTx patients and the healthy population, except with regard to Social Functioning (p < 0.01). CONCLUSIONS: Self-ratings for HRQoL were high for all dimensions for the entire sample, and remained relatively similar even for medium- and long-term survivors. HRQoL was dependent on incidence of infections, rejections and the onset of BOS. Despite differences in life expectancy of LTx patients compared with the healthy population, HRQoL self-ratings were within similar ranges.

Adolescent↗
PubMed2005

Treatment with sequential intravenous or oral moxifloxacin was associated with faster clinical improvement than was standard therapy for hospitalized patients with community-acquired pneumonia who received initial parenteral therapy.

BACKGROUND: Although third-generation cephalosporins, such as ceftriaxone (CTRX), and pneumococcal fluoroquinolones, such as moxifloxacin (MXF), are currently recommended first-line antibiotics for empirical treatment of inpatients with community-acquired pneumonia, CTRX and MXF have never undergone a head-to-head comparison. We therefore compared the efficacy, safety, and speed and quality of defervescence of sequential intravenous or oral MXF and high-dose CTRX with or without erythromycin (CTRX+/-ERY) for patients with community-acquired pneumonia requiring parenteral therapy. METHODS: In this prospective, multicenter, randomized, controlled, nonblinded study, 397 patients were randomly assigned to receive either MXF (400 mg once daily intravenously, possibly followed by oral tablets) or CTRX (2 g intravenously once daily) with or without ERY (1 g intravenously every 6-8 h) for 7-14 days. RESULTS: Among 317 patients evaluable for efficacy and safety, 138 (85.7%) of 161 MXF-treated patients and 135 (86.5%) of 156 CTRX+/-ERY-treated patients (59 [37.8%] of whom received CTRX and ERY) achieved continued clinical resolution. Defervescence and relief of symptoms, such as chest pain, occurred significantly earlier in the MXF-treated group than in the CTRX+/-ERY-treated group. Both regimens were generally well tolerated. CONCLUSIONS: For adult patients hospitalized with community-acquired pneumonia, sequential MXF therapy was clinically equivalent to high-dose CTRX+/-ERY therapy but led to a faster clinical improvement.

Administration, Oral↗
PubMed2005

[Bronchodilators reduce air-trapping in COPD patients].

Expiratory flow limitation, air-trapping and hyperinflation are well-known problems in COPD patients. Due to dyspnea during exercise COPD patients often avoid physical activity, which is one of the most important parameters of quality of life. In studies with long-acting bronchodilators, e.g., the anticholinergic agent tiotropiumbromide, a reduction of expiratory flow limitation, hyperinflation and dyspnea could be demonstrated. This was followed by an increase in physical activity. Increase in inspiratory capacity and reduction of functional residual capacity correlated well with the improvement of exercise capacity. In conclusion, bronchodilators such as tiotropiumbromide are able to reduce hyperinflation in COPD patients.

Bronchodilator Agents↗
PubMed2005

The inflammatory versus constitutive trafficking of mononuclear phagocytes into the alveolar space of mice is associated with drastic changes in their gene expression profiles.

Mononuclear phagocytes enter the lungs both constitutively to maintain alveolar macrophage and dendritic cell homeostasis, as well as during lung inflammation, where the role of these cells is less well defined. We used a transgenic mouse strain (CX3CR1(+/GFP)) that harbors a GFP label in circulating monocytes to identify and sort these cells from the vascular and alveolar compartments under both constitutive and acute lung inflammatory conditions. Using nylon arrays combined with real-time RT-PCR for gene expression profiling, we found that flow-sorted, highly purified mononuclear phagocytes recruited to acutely inflamed mouse lungs showed strongly up-regulated mRNA levels of the neutrophil chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar mononuclear phagocytes that immigrated in steady state. Similar observations were made for the lysosomal cathepsins B, L, and K being strongly up-regulated in mononuclear phagocytes upon recruitment to inflamed lungs but not during constitutive alveolar immigration. Inflammatory elicited mononuclear phagocytes also demonstrated significantly increased mRNA levels of the cytokine TNF-alpha and the PRR-associated molecules CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear phagocytes exhibit strongly increased neutrophil chemoattractants, lysosomal proteases, and LPS signaling mRNA transcripts, suggesting that these cells may play a major role in acute lung inflammatory processes.

Acute Disease↗
PubMed2005

[Bronchodilators in chronic obstructive pulmonary disease (COPD)].

Bronchodilators form the foundation of the pharmacotherapy of patients with chronic obstructive pulmonary disease (COPD). Scores of information from numerous large-scale clinical trials, mechanistic differences between classes of bronchodilators, and anti-inflammatory/bronchodilator fixed combinations make the decision what compound primarily to prefer in COPD treatment a challenge. In this review of large, double-blind, clinical trials with anticholinergic drugs, long- and short-acting beta(2)-agonists, xanthines and different application forms and combination of these compounds will be examined for clinical efficacy. The following practical objectives were accepted to define effective disease management: improvement of lung function, physical parameters such as 6-min walking distance, reduction of exacerbation rate and severity, improvement of quality of life and dyspnea score. Based on this review, inhalation therapy with a long-acting bronchodilator such as tiotropium, formoterol or salmeterol is proposed for early treatment algorithm. The combination of an anticholinergic compound and a long-acting bronchodilator may have an additive effect on bronchodilatation. The addition of inhaled corticosteroids is only recommended in stages III and IV. Besides, pharmacotherapy of COPD should always be flanked by smoking prevention programs, and supportive therapy, if indicated in severe disease stages.

Adrenergic beta-Agonists↗
PubMed2005

Altered expression of membrane-bound and soluble CD95/Fas contributes to the resistance of fibrotic lung fibroblasts to FasL induced apoptosis.

BACKGROUND: An altered susceptibility of lung fibroblasts to Fas-induced apoptosis has been implicated in the pathogenesis of pulmonary fibrosis; however, the underlying mechanism is not completely understood. Here, we studied the susceptibility of lung fibroblasts, obtained from patients with (f-fibs) and without pulmonary fibrosis (n-fibs), to FasL- (CD95L/APO-1) induced apoptosis in relation to the expression and the amounts of membrane-bound and soluble Fas. We also analysed the effects of tumor necrosis factor-beta on FasL-induced cell death. METHODS: Apoptosis was induced with recombinant human FasL, with and without prior stimulation of the fibroblasts with tumor necrosis factor-alpha and measured by a histone fragmentation assay and flow cytometry. The expression of Fas mRNA was determined by quantitative PCR. The expression of cell surface Fas was determined by flow cytometry, and that of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay. RESULTS: When compared to n-fibs, f-fibs were resistant to FasL-induced apoptosis, despite significantly higher levels of Fas mRNA. F-fibs showed lower expression of surface-bound Fas but higher levels of sFas. While TNF-alpha increased the susceptibility to FasL-induced apoptosis in n-fibs, it had no pro-apoptotic effect in f-fibs. CONCLUSIONS: The data suggest that lower expression of surface Fas, but higher levels of apoptosis-inhibiting sFas, contribute to the resistance of fibroblasts in lung fibrosis against apoptosis, to increased cellularity and also to increased formation and deposition of extracellular matrix.

Apoptosis↗
PubMed2005

Treatment and vaccines for severe acute respiratory syndrome.

The causative agent of severe acute respiratory syndrome (SARS), which affected over 8000 individuals worldwide and was responsible for over 700 deaths in the 2002-2003 outbreak, is a coronavirus that was unknown before the outbreak. Although many different treatments were used during the outbreak, none were implemented in a controlled fashion. Thus, the optimal treatment for SARS is unknown. Since the outbreak, much work has been done testing new agents against SARS using in-vitro methods and animal models. In addition, global research efforts have focused on the development of vaccines against SARS. Efforts should be made to evaluate the most promising treatments and vaccines in controlled clinical trials, should another SARS outbreak occur.

Animals↗
PubMed2005

Saccharomyces boulardii induced sepsis: successful therapy with voriconazole after treatment failure with fluconazole.

Saccharomyces boulardii is frequently used for prevention and treatment of all forms of diarrhoea. We report the case of a 19-y-old white male with an underlying severe neurological disease, who developed a fungal sepsis after prophylactic application of a drug containing S. boulardii. Initial treatment with fluconazole was not successful. After the application of voriconazole, the sepsis resolved completely. This is the first clinical report of a successful treatment of Saccharomyces sepsis with voriconazole.

Adult↗
PubMed2005

A case of influenza vaccination induced Guillain Barré syndrome with normal cerebrospinal fluid protein and improvement on treatment with corticosteroids.

We report a case of a 62-y-old male developing an influenza vaccination induced Guillain Barré syndrome (GBS) showing all clinical and neuropathological symptoms of GBS except the characteristic elevation of protein levels in the cerebrospinal fluid. The patient improved under treatment with 100 mg prednisolone. In these cases the administration of corticosteroids might be considered as a treatment option as they might represent a subgroup of GBS with a different immunological response pattern.

Anti-Inflammatory Agents↗