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T Welte

Publications and source records attributed to T Welte.

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

[Recommendations for the treatment of respiratory complications in case of a viruspandemic].

In case of a viral pandemic without availability of effective vaccination, one can expect to be faced with additional 250 to 300 new admissions per hospital per week given the worst case scenario. Major complications are expected to occur in the respiratory system with the focus on viral pneumonia often complicated by bacterial superinfection. Frequently these patients will require artificial ventilation. The present infrastructure will not be capable of dealing sufficiently with such high numbers of casualties. These recommendations of the German Society for Pneumonology are based on the successful application of non-invasive ventilation for acute respiratory failure in recent years. It is of importance to achieve effective treatment by the use of relative simple means. The recommendation proposes to use a separate building in order to realize quarantine. In terms of diagnostic tools, a simple x-ray apparatus should be available. To monitor patients pulsoxymetry and ECG devices should be sufficient in most cases. For the treatment of acute respiratory insufficiency a sufficient number of ventilators, masks, tubing systems and filters should be kept in stock. In terms of medical treatment antibiotics to treat superinfections are of major importance. Analgesics, sedatives and intravenous fluids will also be needed. Oxygen should be available for every single patient. The recommendation gives detailed advise for the enforcement of hygiene control, diagnostic as well as therapeutic steps for in hospital treatment of high numbers of casualties of a viral pandemic.

Disease Outbreaks↗
PubMed2005

Goal-oriented treatment and combination therapy for pulmonary arterial hypertension.

Combination therapy may improve outcome in patients with severe pulmonary arterial hypertension (PAH). PAH patients were treated according to a goal-oriented therapeutic strategy. Patients who did not reach the treatment goals with monotherapy received combination treatment according to a predefined strategy, including bosentan, sildenafil and inhaled iloprost. Intravenous iloprost and lung transplantation were reserved for treatment failures. End points were overall survival, transplantation-free survival, and survival free from transplantation and intravenous prostanoid treatment. Between January 2002 and December 2004, 123 consecutive patients with PAH were treated according to the novel approach. Survival at 1, 2 and 3 yrs was 93.0, 83.1 and 79.9%, respectively, which was significantly better than the survival of a historical control group, as well as the expected survival. Compared to the historical control group, the use of combination treatment also significantly improved the combined end point of death, lung transplantation and need for intravenous iloprost treatment. In conclusion, a therapeutic approach utilising combinations of bosentan, sildenafil and inhaled iloprost in conjunction with a goal-oriented treatment strategy provides acceptable long-term results in patients with severe pulmonary arterial hypertension, and reduces the need for intravenous prostaglandin treatment and lung transplantation.

Administration, Inhalation↗
PubMed2005

Pulmonary arterial hypertension: pathobiology, diagnosis and treatment.

Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure. It includes a variety of pulmonary hypertensive diseases with different etiologies but similar clinical presentation. PAH is a disease of the small pulmonary arteries, characterized by progressive obliteration of the pulmonary vascular bed. Vasoconstriction, remodeling of the pulmonary vessel wall and thrombosis contribute to an increased pulmonary vascular resistance. Major advances in our understanding of the mechanism of disease development have been achieved over the past decade. Several of these new insights have led to the development and clinical application of novel treatments that includes new classes of drugs such as prostanoids, endothelin receptor antagonists and type 5 phosphodiesterase inhibitors.

Humans↗
PubMed2004

[Sepsis management -- antibiotic therapy].

Sepsis is one of the most frequent infectious problems at Intensive Care Units, and sepsis is associated with significant mortality. The latter could not be markedly reduced in the last years, despite a number of advances in the field of volume substitution, catecholamines, and endocrinologic therapy. The reason might be that important steps towards overcoming of sepsis are the surgical resection of infectious foci and an adequate antibiotic treatment. A critical role plays the growing resistance of pathogens against the common antibiotics. Since no major progress in the development of new antibiotics can be expected for the next years, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad and high dose initial treatment, a de-escalation strategy according to the clinical course, and -with exceptions- a limitation of treatment to 7 to 10 days. Rotation of antibiotics should be performed, if problems with resistances exist or no specialist for infectious diseases is available on the Intensive Care Unit.

Anti-Bacterial Agents↗
PubMed2004

Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group.

PURPOSE: To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 + cisplatin 75 mg/m(2) on day 2 every 3 weeks). Primary end point of the study was overall survival. RESULTS: Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P =.73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P =.35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P =.004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. CONCLUSION: In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.

Adolescent↗
PubMed2004

[Competence network "community acquired pneumonia" (CAPNETZ). A first interim report].

Community acquired pneumonia (CAP) is a disease with high morbidity and mortality in Germany. However, no reliable data are available about spectrum and resistance of pathogens, course of the disease, evidence based guidelines for treatment, and pathogen-host interactions. The German Ministry of Education and Research recognized these deficits and therefore decided to fund CAPNETZ, a network of competence for community acquired pneumonia. CAPNETZ integrates components of health research as well as clinical and basic research (horizontal network) on one hand and supports cooperation among general practitioners, community hospitals and universities (vertical network). Since October 2002, 1547 patients with CAP have been recruited within the network. First results indicate, that new observations made in terms of symptoms, spectrum of pathogens involved, and treatment modalities will impact on the formulation of new guidelines for the management of community acquired pneumonia.

Biomedical Research↗
PubMed2004

[Lung transplantation. Possibilities and limitations].

Lung transplantation is an option for patients with endstage pulmonary diseases without contraindications. Recent European studies showed a survival benefit for patients with cystic fibrosis, fibrosis and emphysema after lung transplantation. Early mortality has been reduced recently by surgical improvements. Life expectancy after lung transplantation has improved in recent years but is still lower than in patients with other solid organ transplantations. Quality of life is consistently improved but exercise tolerance keeps reduced in comparison to the normal population. Specific problems described in detail are frequent organ rejections and infections, airway problems and a high incidence of malignant diseases. 5-year survival after lung transplantation is in average 60%.

Comorbidity↗
PubMed2004

Diagnostics of Helicobacter pylori infection in patients with peptic ulcer bleeding.

BACKGROUND: In peptic ulcer bleeding, the sensitivity of H. pylori tests, in particular of the rapid urease test (RUT), has been reported to be insufficient. AIM: To validate the RUT, serology and the urea breath test were carried out in patients with bleeding peptic ulcers, and to study the influence of H. pylori suppressive treatment (HpSuT), i. e., antibiotics and proton pump inhibitors. PATIENTS AND METHODS: 123 consecutive patients (mean age 65.5 years) with a relevant bleeding from gastric or duodenal ulcers were prospectively tested for H. pylori infection by directs tests (RUT, histology, culture, urea breath test) and by IgG serology as an indirect test. Positive H. pylori status was defined by positive histology or culture. RESULTS: In patients without HpSuT during the preceding four weeks (N = 83), the sensitivity and specificity of RUT was 94 and 84 %, that of serology 83 and 68 % respectively. The sensitivity of urea breath test decreased from 82 to 60 % after even one day of HpSuT. In the overall group, the duration of HpSuT and preceding hospitalization were independent factors linked with negative results of all direct tests. CONCLUSIONS: In peptic ulcer bleeding, RUT combined with histology is an adequate diagnostic approach. However, false negative results have to be considered following even short-term HpSuT or hospitalization. Non-invasive diagnosis based on serology alone is inaccurate and should be complemented by the urea breath test prior to starting HpSuT.

Adult↗
PubMed2004

[Multicenter study on "non-invasive ventilation in patients with severe chronic obstructive pulmonary disease and emphysema(COPD)"].

Non-invasive ventilation is applied with increasing frequency in patients with chronic hypercapnic COPD and insufficiency of the ventilatory pump. In the few existing clinical trials on long-term use of NIV, no significant improvement on survival could be proven, mainly due to methodical reasons. The "National Task Force for Non-invasive ventilation and weaning" plans to study patients with severe COPD and hypercapnic ventilatory pump insufficiency in a prospective, randomised, multicentre clinical trial over one year. In the intervention group, NIV will be applied for at least six hours per day in addition to standard COPD-treatment. The target of mechanical ventilation is a reduction of PCO (2) during spontaneous breathing by at least 20 %, or into the normal range. The main outcome parameter is all-cause mortality, secondary outcome parameters are course of the disease, exercise capacity, quality of life and consumption of medical resources. The sample size is estimated on 300 patients (150 control group, 150 intervention group). The whole study will take approximately three years.

Emphysema↗
PubMed2004

Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension.

It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy. This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET). The 6MWD at baseline was 346+/-66 m and improved to 403+/-80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11+/-5 months, the walk distance had declined to 277+/-80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392+/-61 m and the patients remained stable throughout the median follow-up of 9 months (range 6-12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients. These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.

Adult↗
PubMed2004

Pulmonary infiltrates in Costello Syndrome.

This paper reports on a patient with diffuse pulmonary infiltrates directly related to Costello Syndrome. This congenital disorder is characterised by multiple congenital abnormalities, such as psychomotor retardation, short stature, redundant skin, papillomata, curly hair, relative macroencephaly, distinctive face and various defects of internal organs. This study is the first to document the histopathological findings in the lungs. Most conspicuous was the depositing of abnormal collagen and elastic fibres and the development of endogenous lipid pneumonia.

Abnormalities, Multiple↗
PubMed2004

Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells.

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.

Analysis of Variance↗
PubMed2004

Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation.

Lysosomal cysteine proteases are a family comprising > 10 enzymes. For many years it was believed that these enzymes catalyse protein breakdown unselectively, are highly redundant in their substrate specificity and are also expressed ubiquitously. This view has changed dramatically since a number of new lysosomal cysteine proteases with restricted expression and outstanding enzymatic activity have been described. In addition, knockout mice and selective protease inhibitors have been used to characterise specific functions of single proteases. In this review, some of these functions are discussed in relation to the lungs, especially the role of lysosomal cysteine proteases in matrix remodelling, immunoregulation and surfactant protein processing.

Animals↗
PubMed2004

Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.

BACKGROUND: Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms. OBJECTIVES: This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. METHODS: Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW). RESULTS: The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011). CONCLUSIONS: Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

Adolescent↗
PubMed2003

[Diagnosis of multiple myeloma by demonstrating plasma cells in bronchoalveolar lavage].

HISTORY AND CLINICAL FINDINGS: A 61-year-old man was transferred from a peripheral hospital with the diagnosis of interstitial lung disease and an unclear mediastinal tumour. At the time of admission the patient had congestive heart disease NYHA class IV. INVESTIGATIONS: The echocardiogram showed a small left ventricle with concentric hypertrophy and a left ventricular ejection fraction of 35 %. The myocardium was relatively echo-rich with solid structures inside. Chest X-ray showed a massive rightsided pleural effusion. The abdominal ultrasound demonstrated ascites and hepatomegaly. The bronchoalveolar lavage showed an increased part of CD3 negative and CD16/CD56 positive cells, which were identified as plasma cells by light and electron microscopy. Aspiration and investigation of the bone marrow verified the diagnosis of a IgG multiple myeloma, highly differentiated characterised by monoclonal expression of light-lambda chains. Additionally Bence-Jones-proteins were found in the urine and osteolysis in the x-ray of the skull and the humerus. DIAGNOSIS: Multiple myeloma, IgG-lambda, stage IIA. THERAPY AND CLINICAL COURSE: Chemotherapy with prednisolone and melphalan was initiated. His general condition increased after administration of the first cycle of chemotherapy. CONCLUSION: Cardiopulmonary involvement is seldom seen in multiple myeloma but should be excluded when clinical symptoms are present.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Community-acquired and nosocomial pneumonia].

Mortality of pneumonia is low in the outside setting (1%) but rises up to 20% in hospital admitted patients. Early diagnosis and standardized therapy improve patient's prognosis. For community acquired pneumonia age, comorbidity and the setting of therapy (outside department, normal ward or intensive care unit) are the most important variables to choose an adequate antibiotic treatment. For nosocomial pneumonia risk stratification is according to severity of illness, length of hospital stay and antibiotic pretreatment. In the outpatient setting a 7-day monotherapy is mostly successful. In severe illness the combination of a betalactam antibiotic with a new fluorchinolon seems to be superior to an aminoglycosid therapy. Antibiotic resistance due to mistakes in antibiotic therapy is an increasing problem in the intensive care unit. Therefore, pneumonia preventive measures like influenza and pneumococcal vaccination become more important. Standardized hygienical procedures help to reduce nosocomial, mainly ventilator associated pneumonia.

Anti-Bacterial Agents↗