Search PubMed⌕ Search

Biomedical subjects

R Buhl

Publications and source records attributed to R Buhl.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Onset of action of formoterol in patients with moderate to severe, partially reversible airflow obstruction assessed by bodyplethysmography].

BACKGROUND: Formoterol is a long acting beta2-agonist used for the treatment of obstructive airway diseases. Compared with Salmeterol, Formoterol has a rapid onset of bronchodilation. There are only scant data regarding the comparative onset of action using bodyplethysmography in moderate to severely obstructive patients. METHODS: In a mono-center, single-blinded parallel group study 60 patients (age: 61.9 +/- 12.8 years, 65 % male) with moderate to severe (mean FEV(1) 40.6 +/- 15.3 % of predicted), partially reversible (FEV(1) post bronchodilator > 15 % from baseline) airway obstruction were treated with either formoterol 12 microg bid or salmeterol 50 microg bid over a period of two weeks. Onset of action was measured by airway resistance (sRaw) before and after two weeks of treatment. RESULTS: Compared with Salmeterol, Formoterol had a significantly faster onset of action (10 % decrease of Raw) at baseline (F: 1.4 +/- 0.9 vs. S: 15.1 +/- 34.5 min., p < 0.0001) and after two weeks of treatment (F: 6.2 +/- 21.6 vs. S: 51 +/- 135 min., p < 0.0001). Morning FEV(1) improved similarily during treatment in both study groups, when compared with baseline lung function (F: 1.38 +/- 0.64 vs. 1 +/- 0.41 l; S: 1.43 +/- 0.67 vs. 1 +/- 0.4 l, p < 0.05, both comparisons). Both treatments were well tolerated. CONCLUSION: Formoterol produces a rapid improvement of airway resistance in patients with moderate to severe, partially reversible airway obstruction. The onset of bronchodilation was significantly faster for Formoterol compared with Salmeterol. Both drugs improved lung function similarily after two weeks of treatment. It is important to distinguish beta2-agonists not only into short- and long-acting but also into fast- and slow-acting.

Bronchodilator Agents↗
PubMed2002

The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma.

The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as "excellent/good", compared with approximately 40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.

Administration, Inhalation↗
PubMed2002

Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology. Increased oxidant burden and antioxidant, e.g. glutathione (GSH), deficiency in the lower respiratory tract have been thought to play a role in the progression of IPF. Sputum induction is a safe noninvasive tool to study inflammation in the respiratory tract. The aim of the present study was to evaluate the direct measurement of GSH in induced sputum supernatant. Sixteen IPF patients and 15 healthy, nonsmoking subjects underwent sputum induction. Total GSH in sputum, saliva and plasma was measured spectrophotometrically. Sputum GSH was decreased more then four-fold in IPF patients when compared to healthy subjects (mean GSH 1.4+/-0.34 microM versus 5.8+/-0.98 microM). Salivary GSH was generally low or undetectable in all subjects. Plasma GSH levels were lower in IPF patients (0.26+/-0.1 versus 0.74+/-0.16 microM). In IPF patients, there was a borderline correlation of sputum GSH levels with disease duration and lung-function impairment. These data confirm the established role of oxidant/antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis, and show the potential of induced sputum to directly study inflammatory processes and surrogate markers in interstitial lung diseases like idiopathic pulmonary fibrosis.

Adult↗
PubMed2002

Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma.

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 microg x day(-1)) than in the placebo group (43 microg x day(-1)). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.

Adolescent↗
PubMed2002

The whole story: treatment outcomes with Symbicort.

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physic an education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort is more cost-effective than treatment with budesonide alone.

Administration, Inhalation↗
PubMed2001

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.

Age Factors↗
PubMed2001

Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study.

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m(2), day 1), or regimen B, cisplatin (100 mg/m(2), day 1) plus vinorelbine (25 mg/m(2), days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 x 10(12) particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.

Adenoviridae↗
PubMed2001

[Pathogenesis of bronchial asthma--unveiling new therapeutic prospects].

BACKGROUND: Bronchial asthma is a chronic inflammatory disease of the lower respiratory tract. It is characterized by nonspecific bronchial hyperresponsiveness, which may lead to variable, reversible airflow obstruction in affected patients. Despite therapeutic improvements, the worldwide prevalence and morbidity of asthma have risen during the past decades. An improved understanding of underlying pathological features and mechanisms of asthmatic inflammation is essential to achieve an enhanced asthma symptom control and may lead to prevention in the future. RESULTS: Besides the impact of genetic and environmental factors, scientific interest has especially been focused on the molecular and cellular biology of the asthmatic response. Mucosal inflammation in asthmatics is mainly orchestrated by T cells and derived cytokines. Immunoglobulin E and mast cells play a pivotal role in the initiation and pathogenesis of the early asthmatic reaction, while recruitment and activation of eosinophils seem to be crucial for the persistent asthma phenotype with chronic airflow obstruction. Additionally, smooth muscle cells, parasympathetic nerve fibers, bronchial epithelial cells and a vast amount of mediators may either promote or inhibit the inflammatory pathology of bronchial asthma. CONCLUSION: The recent insights from molecular biology have found their correlate in actual therapeutic guidelines, and have further led to the development of new innovative asthma drugs such as monoclonal antibodies against IgE or IL-5. Hopefully, future progress in revealing pathogenetic mechanisms of asthma may lead to further therapeutic improvement and eventually reverse the trend of rising asthma morbidity in western societies.

Anti-Asthmatic Agents↗
PubMed2001

Nasopharyngeal extension of a craniopharyngioma in a 4 year old girl.

Nasopharyngeal extension of a craniopharyngioma is very rare and usually presents with headache, nasal obstruction and visual disturbances. We present a case of a 4 year old girl, who became symptomatic with visual deterioration. MRI showed a huge supra - and infrasellar cystic craniopharyngioma with extension into the sphenoid sinus. Primary treatment was a transnasal puncture of the cyst followed by a subfrontal approach with removal of the tumour preserving the chiasm and optic nerves. The visual acuity postoperatively improved while she needed hormone replacement due to panhypopituitarism. Follow-up 12 months after the operation showed no recurrence. This is the youngest patient of about 27 patients reported so far in the literature.

Brain Neoplasms↗
PubMed2001

Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature.

BACKGROUND: Though Malignant peripheral nerve sheath tumours (MPNST) are a rare entity accounting for 5-10% of soft-tissue sarcomas they are an important differential diagnosis to benign tumours of the peripheral nervous system regarding treatment and prognosis. METHOD: We present our experience with eight patients who underwent surgery for MPNST at the Department of Neurosurgery between 10/1990 and 9/1999. The median age was 37 years [range: 13-64], the male/female ratio was 1:1. Two patients suffered from Neurofibromatosis type 1. Paraffin embedded tumour specimens were immunohistochemically stained for S-100, p53 and Ki67/MIB-1. FINDINGS: The most frequent initial symptoms were local swelling and pain followed by irritation of cranial nerves and spinal ataxia. Four tumours were localised at the head & neck region, three were found in the extremities and one tumour was located on the trunk. All patients underwent surgery with curative intent, but total resection, defined by negative surgical margins, was achieved in only 3 cases. All of these developed local recurrence with a mean disease free survival time of 10.6 months. In five cases, adjuvant radiation was given. During follow up, three patients developed distant metastases located in the lung, liver and subcutaneous tissue. Five out of eight patients died during follow-up with a mean survival time of 11.6 months after diagnosis. Results of immunohistochemical staining were as followed: S-100 (7/8), p53 (7/8). The Ki67/MIB-1 proliferation index was detectable in all tumour samples, it differed from 10-30%. INTERPRETATION: MPNST is a rare and fatal diagnosis in neurosurgery with high risk of local recurrence and occurence of distant metastases. Though mulitimodal therapy including surgical resection and adjuvant radiotherapy including brachytherapy is available, the prognosis remains dismal. Modern clinical studies and the development of effective chemotherapy is needed in order to gain control of the disease.

Adolescent↗
PubMed2001

Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients: relation to tumor necrosis factor-alpha and interleukin-10.

BACKGROUND: Chronic transplant rejection is characterized by progressive narrowing of small airways caused by matrix remodeling and fibrosis. Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in the turnover of extracellular matrix. METHODS: To clarify the contribution of MMPs and TIMPs to airway inflammation in patients after lung transplantation (LTx), we used enzyme immunoassays to measure induced sputum concentrations of MMP-9, TIMP-1, and controlling cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 of 30 LTx patients and 15 control subjects. RESULTS: Sputum concentrations of MMP-9, TIMP-1, the MMP-9:TIMP-1 ratio, and TNF-alpha were higher in LTx patients than in control subjects (p < 0.04, all comparisons). The MMP-9, MMP-9:TIMP-1, and TNF-alpha levels were also significantly higher in LTx patients with chronic rejection compared with those with stable organ function (p < 0.03, all comparisons), whereas IL-10 levels were higher in the latter group (p = 0.05). In all LTx patients, MMP-9 and the MMP-9:TIMP-1 ratio were negatively correlated with forced expiratory volume in 1 second values (rho = -0.47, p = 0.01, and rho = -0.53, p = 0.003, respectively). We found that MMP-9 positively correlated with sputum neutrophils and TNF-alpha whereas MMP-9 and TIMP-1 did not correlate with IL-10. CONCLUSIONS: These data underline the possible contribution of proteases such as MMP-9 to chronic transplant rejection, and suggest that an imbalance of MMP-9 and TIMP-1 may be involved in the pathogenesis of airway obstruction after LTx. We found that MMP-mediated inflammation seems to be controlled by TNF-alpha whereas IL-10 might elicit anti-inflammatory effects through different pathways.

Adolescent↗
PubMed2001

Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients.

HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different strategies to supplement cysteine supply have been suggested to increase glutathione levels in HIV-infected individuals. The aim of this study was to evaluate the effect of oral supplementation with two different cysteine-rich whey protein formulas on plasma GSH levels and parameters of oxidative stress and immune status in HIV-infected patients. In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (221 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet with a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Bad Hamburg, Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baseline and after therapy. Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.98 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 microM, P = 0.004) while the difference in the Immunocal group did not reach significance (+ 24.5 +/- 59%, 2.51 +/- 1.48 microM, P = 0.43). Spontaneous O2- release by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 +/- 16.1 nmol h-1 10-6 cells, P = 0.52) whereas PMA-induced O2- release decreased in the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h-1 10-6 cells, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and 12 (P > 0.08, all comparisons) as well as routine clinical parameters remained unchanged. Therapy was well tolerated. In glutathione-deficient patients with advanced HIV-infection, short-term oral supplementation with whey proteins increases plasma glutathione levels. A long-term clinical trial is clearly warranted to see if this "biochemical efficacy" of whey proteins translates into a more favourable course of the disease.

Administration, Oral↗
PubMed2001

Brain oedema in secretory meningiomas.

Brain oedema is usually associated with intracranial meningiomas in about 50-66%. As underlying causes, different factors like localisation, vascular supply, angiogenic growth factors and histological subtypes are discussed, and its existence is probably multifactorial. We present 11 patients with the rare subtype of secretory meningiomas. Brain oedema was observed in 82%. These tumours are localised mainly at the frontal convexity and at the sphenoid ridge. All 11 patients were female so that hormonal factors also may play a role in the production of peritumoural oedema. The postoperative outcome was good and no recurrences were seen during follow-up.

Adult↗
PubMed2001

[Treatment of bronchial asthma using a new adjustable combination treatment plan: Asthma Control Plan (ATACO)].

The current guideline of the German Respiratory League (Deutsche Atemwegsliga) recommends the synergistic combination therapy with long acting beta 2-agonists and inhalative corticosteroids only for patients suffering from moderate to severe persistent asthma (step 3 and 4 of the asthma severity scale). Now convenient fixed combinations of these substances are available, which could enhance patient's compliance. A large, randomised, parallel-group study in 8000 mild to moderate asthmatics was designed to compare a flexible asthma control plan with the conventional fixed-dose management with respect to quality of life, symptom control and treatment costs. The fixed combination of 6 micrograms Formoterol and 200 micrograms Budesonide per puff in a new dry powder device was applied either due to a novel flexible asthma control plan "ATACO" (group A) or as a standardised conventional dosing regimen (group B) inhaling two puffs b.i.d. In group A (ATACO) patients reduce the run-in dose after four weeks from two puffs b.i.d. to one puff b.i.d. with the option of doubling the dose immediately, if (pre-defined) asthma deterioration occurs. One week later the dose can be either doubled again or reduced due to the actual asthma symptoms of the patient. After run-in, group B patients continue to take two inhalations b.i.d. In this group, asthma exacerbations will be managed as usual by the physician. In contrast, the ATACO group flexible management plan allows the self-medication: an immediate increase in the dose of the fixed combination will lead to both a fast relief of bronchospasm and an automatically higher dosed corticosteroid treatment for the underlying asthmatic inflammation. Conversely, if later asthma symptoms improve, less reliever and controller medication will be needed and used. The immediate treatment of new onset bronchospasm and asthmatic inflammation by the patient himself could maintain at least the same grade of asthma control, as the conventional group B treatment, improve asthma-related quality of life and decrease treatment costs. If the concept works, fixed combinations of long-acting beta 2 agonists and inhalative corticosteroids could have an impact on future asthma guidelines.

Administration, Inhalation↗
PubMed2001

Cigarette smoking, but not sensitization to Alternaria, is associated with severe asthma in urban patients.

Hereditary susceptibility and allergen exposure have been identified as general risk factors for asthma. However, risk factors for severe asthma still remain to be identified. To further assess and quantify risk factors associated with severe asthma in adult patients apart from clinical exacerbations, 306 randomly selected subjects (mean age 40+/-17 years, 46% males) presenting to an inner city pulmonary practice between 1995 and 1996 were retrospectively investigated. Of these, 117 patients were atopic, 112 had current asthma, and 22 asthmatics had severe asthma. Risk factors associated with atopy were family history of atopy and any domestic pet ownership (OR: 3.1, 95% CI: 1.64-6.1). Asthma was generally associated with atopy (OR: 4.2, CI: 2.4-7.4) and pet ownership (OR: 2.4, CI: 1.2-4.6). Severe asthma was strongly associated with current smoking (OR: 4.8, CI: 1.3-18.3), and lung function was negatively correlated with the amount of consumed cigarettes per day (r = -0.61, p = 0.04). However, no association with sensitization to Alternaria was found in severe asthma. Cigarette smoking is an independent risk factor associated with severe asthma in urban patients, whereas sensitization to Alternaria is of less importance in these patients.

Adult↗