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Martin H Brutsche

Publications and source records attributed to Martin H Brutsche.

At least 19 recordsLinked to original sources
PubMed2006

Analysis with respect to instrumental variables for the exploration of microarray data structures.

BACKGROUND: Evaluating the importance of the different sources of variations is essential in microarray data experiments. Complex experimental designs generally include various factors structuring the data which should be taken into account. The objective of these experiments is the exploration of some given factors while controlling other factors. RESULTS: We present here a family of methods, the analyses with respect to instrumental variables, which can be easily applied to the particular case of microarray data. An illustrative example of analysis with instrumental variables is given in the case of microarray data investigating the effect of beverage intake on peripheral blood gene expression. This approach is compared to an ANOVA-based gene-by-gene statistical method. CONCLUSION: Instrumental variables analyses provide a simple way to control several sources of variation in a multivariate analysis of microarray data. Due to their flexibility, these methods can be associated with a large range of ordination techniques combined with one or several qualitative and/or quantitative descriptive variables.

Algorithms↗
PubMed2006

Sarcoidosis is a multisystem disorder with variable prognosis--information for treating physicians.

Sarcoidosis is a chronic granulomatous inflammatory disorder of unknown origin with heterogeneous outcome. In most cases the disease is self-limited, others progress or die from organ involvement, which is often associated with extensive scarring. Although often the primarily affected sites are the lungs and thoracic lymph nodes patients with sarcoidosis must be staged for multiorgan involvement. Modern treatment strategies appraise a critical awareness for the side-effect-ratio of long-term medication. A main interest of research is to identify those patients with unfavourable outcome.

Biomedical Research↗
PubMed2006

Feasibility of mobile cardiopulmonary exercise testing.

QUESTIONS UNDER STUDY: Evaluation of cardiopulmonary capacity and work ability is often done by cardiopulmonary exercise testing under laboratory conditions. Mobile CPET devices allow measurements under specific real-life conditions, i.e.: at the patient's workplace. We investigated the feasibility and validity of mobile CPET in healthy controls. METHOD: We compared oxygen uptake measured by mobile CPET (MCPET) with that by standard CPET (LCPET), and we compared oxygen uptake with markers of self-reported physical exhaustion. Twenty-two healthy subjects (15 male, 21-49 years) underwent LCPET and 6 outdoors 12-min running tests (MCPETs) at different intensities. Physical exhaustion and the time they could continue exercising (T(EX)) was reported for each level. Standard descriptive statistics were applied. RESULTS: Of 132 MCPETs, performed in 22 subjects, 128 (97%) were of suitable quality. The facemask was well tolerated and nobody felt uncomfortable at any time. On average VO2 [peak] was 21% (SD 9%) higher with MCPET compared to LCPET (median 3.60, range [2.22, 5.14] versus median 2.63, range [1.67, 4.16] L*min(-1)), but showed a strong correlation (r2 = 0.90). MCPET-VO2 at steady state correlated with subjectively rated physical exhaustion, and with TEX. CONCLUSIONS: Out-of-laboratory MCPET was feasible, correlated with parameters of standard CPET, and correlated with markers of physical exhaustion. After validation in patients, MCPET could be used for a rational evaluation of cardiopulmonary capacity and work ability in selected patients.

Adult↗
PubMed2006

Therapeutic bronchoscopy interventions before surgical resection of lung cancer.

BACKGROUND: Therapeutic bronchoscopy is used for endobronchial staging of lung cancer and symptomatic relief of central airway obstruction or postobstructive pneumonia. The aim of this study was to assess the utility of therapeutic bronchoscopy as a complementary tool in the combined bronchoscopic and surgical management of malignant airway lesions before curative lung surgery. METHODS: Seventy-four consecutive patients with nonsmall cell lung carcinoma undergoing a therapeutic bronchoscopy procedure followed by surgery with a curative intent were included. RESULTS: A single interventional bronchoscopic method was used in 27 patients (36%) and a combination of methods in 47 patients (64%). Median forced expiratory volume in 1 second (FEV1) before and after bronchoscopy were 1.7 L and 2.2 L, respectively, and forced vital capacity (FVC) was 2.5 L and 3.3 L, respectively. Sleeve upper lobectomy was performed in 22 patients (30%), sleeve upper bilobectomy in 16 patients (22%), lower bilobectomy in 2 patients (3%), pneumonectomy with sleeve resection in 2 patients (3%), and pneumonectomy in 28 patients (38%). The following surgeries were performed in 1 patient each: sleeve middle lobectomy, sleeve lower lobectomy, carina resection and complex reconstruction, and exploratory thoracotomy. Overall, parenchyma-sparing surgery (lobectomy or bilobectomy) could be performed in 57% patients after therapeutic bronchoscopy. There were no in-hospital deaths or deaths in the first 30 days after surgery. CONCLUSIONS: Therapeutic bronchoscopy can be used as a complementary tool in the combined bronchoscopic and surgical management of malignant airway obstruction before curative lung surgery. Therapeutic bronchoscopy might permit parenchyma-sparing surgery in patients with lung cancer.

Adenocarcinoma↗
PubMed2006

Outcome of treated advanced non-small cell lung cancer with and without central airway obstruction.

OBJECTIVE: In patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy, we compared survival in patients with treated central airway obstruction to those who did not have central airway obstruction. METHODS: One hundred forty-four patients with advanced and inoperable NSCLC were included. These consisted of 52 consecutive patients treated with therapeutic bronchoscopy plus chemotherapy with or without radiotherapy (group A) and 92 consecutive patients who did not have central airway obstruction treated with chemotherapy alone (group B). Chemotherapy consisted of cisplatin or carboplatin, and one third-generation chemotherapy agent. RESULTS: There was no significant difference in the survival of patients with and without central airway obstruction (p = 0.395). There was no influence of the histologic subtype on survival in both groups combined and also in each group separately. Median survival in patients belonging to group A was 8.4 months and those in group B was 8.2 months; 3-, 6-, and 12-month survival rates in patients in group A were 90%, 71%, and 40%, respectively, and those in group B were 82%, 63%, and 34%. CONCLUSION: Patients having advanced NSCLC with locally treated malignant central airway obstruction in combination with chemotherapy do not have a worse survival compared to those with advanced NSCLC without central airway obstruction. Therapeutic bronchoscopy should be offered to patients with NSCLC and central airway obstruction.

Adenocarcinoma↗
PubMed2006

Progressive pulmonary sarcoidosis--a fibroproliferative process potentially triggered by EGR-1 and IL-6.

BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a chronic granulomatous disorder of unknown etiology. In most patients the disease is self-limited, although for reasons unclear, others progress or die from progressive organ fibrosis. Growth factors have been implicated in the pathogenesis of other fibrotic lung conditions. We have, therefore, examined the relationship between growth factor expression and disease phenotype in sarcoidosis. METHODS: Adopting a target gene approach utilizing gene expression arrays, growth factor gene expression profile was analyzed in the peripheral blood of 12 patients and 12 healthy controls. Expression, functional activity and the effect of oligonucleotide antisense treatment on selected proteins differentially expressed in progressive sarcoidosis were then tested in vitro on primary human lung fibroblasts. RESULTS: Genes regulating angiogenesis were preferentially upregulated in the self-limited form of disease, while early growth response-1 and interleukin-6 were predominantly activated in progressive sarcoidosis. Increased expression of early growth response-1 in sarcoid lung was confirmed by immunohistochemistry. Stimulated human fibroblasts also rapidly expressed interleukin-6 and early growth response-1 and these proteins were found to mediate serum-induced fibroblast proliferation as proliferation could be significantly abrogated with interleukin-6 and early growth response-1 antisense oligonucelotides. CONCLUSION: We conclude that progressive pulmonary sarcoidosis is characterized by a fibroproliferative dysregulation potentially triggered by early growth response-1 and interleukin-6. Our disease model underlines the inability of steroids to prevent ongoing fibroproliferation in the lung.

Case-Control Studies↗
PubMed2005

Optimized between-group classification: a new jackknife-based gene selection procedure for genome-wide expression data.

BACKGROUND: A recent publication described a supervised classification method for microarray data: Between Group Analysis (BGA). This method which is based on performing multivariate ordination of groups proved to be very efficient for both classification of samples into pre-defined groups and disease class prediction of new unknown samples. Classification and prediction with BGA are classically performed using the whole set of genes and no variable selection is required. We hypothesize that an optimized selection of highly discriminating genes might improve the prediction power of BGA. RESULTS: We propose an optimized between-group classification (OBC) which uses a jackknife-based gene selection procedure. OBC emphasizes classification accuracy rather than feature selection. OBC is a backward optimization procedure that maximizes the percentage of between group inertia by removing the least influential genes one by one from the analysis. This selects a subset of highly discriminative genes which optimize disease class prediction. We apply OBC to four datasets and compared it to other classification methods. CONCLUSION: OBC considerably improved the classification and predictive accuracy of BGA, when assessed using independent data sets and leave-one-out cross-validation. AVAILABILITY: The R code is freely available [see Additional file 1] as well as supplementary information [see Additional file 2].

Algorithms↗
PubMed2005

Treatment of sonographically stratified multiloculated thoracic empyema by medical thoracoscopy.

INTRODUCTION: In cases of empyema, some form of intervention, either chest tube drainage, thoracoscopy, video-assisted thoracic surgery (VATS), or thoracotomy, with or without pleural fibrinolysis, is required. What the best approach is and when and how to intervene is a matter of debate. STUDY OBJECTIVE: To analyze the safety and outcome of medical thoracoscopy in the treatment of multiloculated empyema. METHODS: We report a retrospective series of 127 patients with thoracic empyema treated with medical thoracoscopy from 1989 to 2003 in three hospitals in Switzerland and Italy. All patients had multiloculated empyema as identified by chest ultrasonography. In the absence of multiloculation, or in case of fibrothorax, simple chest tube drainage or surgical VATS/thoracotomy were performed, respectively. RESULTS: Mean age +/- SD was 58 +/- 18 years (range, 9 to 93 years). In 47%, a microbiological diagnosis was made. Complications occurred in 9% of patients (subcutaneous emphysema, n = 3; air leak of 3 to 7 days, n = 9). No mortality was observed. Forty-nine percent of patients received postinterventional intrapleural fibrinolysis. Medical thoracoscopy was primarily successful in 91% of cases. In four patients, the insertion of an additional chest tube or a second medical thoracoscopy was required. Finally, 94% of patients were cured by nonsurgical means. Six percent of patients required surgical pleurectomy, mostly through thoracotomy. CONCLUSION: Multiloculated empyema as stratified by ultrasonography can safely and successfully be treated by medical thoracoscopy.

Adolescent↗
PubMed2004

Prediction of treatment-response to inhaled corticosteroids by mannitol-challenge test in COPD. A proof of concept.

BACKGROUND: There are no predictors known that can identify COPD patients who will respond to treatment with ICS. METHOD: We investigated 30 patients (median age 65 (range 44-83, 12 females) with mild to moderately severe COPD. All patients had post bronchodilator FEV1/forced vital capacity ratio of less than 70% and a reversibility of less than 12% and 200 ml from baseline. We wanted to determine if airway responsiveness (AHR) to histamine and mannitol could predict who would respond to a 3-month course of ICS. RESULTS: At baseline, all patients had AHR to histamine, but only 7 (23%) patients to mannitol. After 3 months of treatment with ICS, there was no significant change in spirometry or the quality of life when analysing all individuals together. However, FEV1% predicted improved from 67% (IQR12) to 79% (IQR16) in mannitol positive patients; whereas it was unchanged in the mannitol negative patients. The difference in the mean change of FEV1% predicted between the two groups was 12 (IQR13.5) and this was highly significant (p=0.001). The improvement in quality of life (SGRQ 30 (IQR10.5) to 21 (IQR12; p=0.01) was only significant in the patients positive to mannitol. CONCLUSION: We propose that AHR to mannitol could predict ICS-responsiveness in mild to moderately severe COPD patients.

Administration, Inhalation↗
PubMed2004

Systemic Th1- and Th2-gene signals in atopy and asthma.

BACKGROUND: Atopic disorders have been associated with a Th-2 cytokine predominance. This study investigated Th1- and Th2-related gene expression in asthmatics, atopics and healthy individuals. METHODS: We compared Th1- and Th2-related in vivo-signals using gene expression arrays in 18 atopic asthmatics, 8 atopic non-asthmatic and 14 healthy control subjects. Purified mRNA from peripheral blood mononuclear cells was reverse-transcribed and hybridised to cDNA membranes. Group differences were assessed after standardisation with Mann-Whitney U-test. RESULTS: Atopic individuals had upregulated lymphotoxin-alpha and downregulated IFNGR1. On the other hand, they had particularly high IL-4, IL-5 and IL4R levels, together with significantly upregulated IL10. Asthmatic individuals had normal Th1-gene expression, but an upregulation og Th-2 genes. Atopic individuals had high, asthmatic individuals excessively high IL12RB1-levels. No Th-2 gene was downregulated in both atopic phenotypes. The expression of IL6R correlated with the daily dose of inhaled corticosteroids. CONCLUSIONS: Atopic individuals had a down regulation of key TH1- and Th2-genes, resulting in a balanced upregulation of Th-specific genes. In contrast, asthmatic subjects had normal Th1-gene expression but a constant upregulation of Th2-specific genes, leading to Th2-predominance.

Adolescent↗
PubMed2004

Prevalence of coeliac disease in patients with sarcoidosis.

OBJECTIVE: Susceptibility to sarcoidosis and coeliac disease has been linked to the class II haplotype HLA-DR3, DQ2, and an association between the two disorders has been suggested. As a pilot study, we have sought to determine the prevalence of coeliac disease in a cohort of Irish patients with sarcoidosis. DESIGN: Prospective, case-controlled study. METHODS: One hundred and two sarcoid patients (47 males, 55 females) from the west of Ireland and 105 (52 males, 53 females) healthy, ethnically matched, controls underwent interview and screening for coeliac disease and human leucocyte antigen typing by serology. Those with elevated anti-gliadin IgA (AGA) and/or positive endomysial antibody (EMA) were offered small intestinal biopsy. RESULTS: Three (3%) sarcoid patients had a prior diagnosis of coeliac disease. A further 12 (12%) patients and four (4%) controls had elevated AGA (P = 0.047), of whom three and one, respectively, had positive EMA. Small intestinal biopsy in 11 patients and three controls confirmed coeliac disease in one individual each, giving a prevalence of coeliac disease in patients compared with controls of 4/102 (4%) versus 1/105 (1%) (P = 0.21). Sensitivity and specificity of EMA and elevated AGA in sarcoid patients was 100% and 50%, and 50% and 9%, respectively. Of the four affected sarcoid patients, three carried HLA-DR3, DQ2 and one carried DR5 (12), DR7, DQ2. CONCLUSION: We have demonstrated a moderately increased prevalence of coeliac disease in Irish patients with sarcoidosis, which we feel justifies future screening of our sarcoid population. Estimation of EMA is recommended and should be restricted to those with susceptible haplotypes.

Adult↗
PubMed2004

Complementary and alternative medicine for bronchial asthma: is there new evidence?

PURPOSE OF REVIEW: Complementary and alternative medicine is widely used in bronchial asthma. Data on efficacy of these treatment modalities are lacking. RECENT FINDINGS: Studies published since June 2002 on complementary and alternative medicine in bronchial asthma were systematically reviewed. SUMMARY: Studies do not support the use of homeopathy, air ionizers, manual therapy, or acupuncture for asthma. These methods bear some risks to patients related to undertreatment and side effects. There might be a possible, but so far not clearly established, role for antioxidant dietary supplementation, and some natural antiinflammatory and immunomodulatory remedies. However, their effect size compared with the classical treatment and side-effect profile is not clearly established. Strategies influencing breathing technique or perception, such as breathing or retraining exercises, need to be studied over the next few years to establish their additive role in the treatment of asthma. Breathing exercises could improve lung function and quality of life in different studies. Psychotherapy-related methods such as relaxation, hypnosis, autogenic training, speleotherapy, and biofeedback might have a small effect in selected cases, but have not proven to be superior to placebo. Nevertheless, more randomized controlled trials of good methodological quality are required to allow firm conclusions.

Acupuncture Therapy↗
PubMed2004

Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.

BACKGROUND: Sarcoidosis is a systemic disorder of unknown cause, highly variable phenotype and unpredictable outcome. Antigen processing, inflammatory response and immunomodulation appear critical to development and prognosis of the disease. METHODS: We performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HUG95A, Affymetrix Inc.) for gene expression profiling from peripheral blood of patients with acute pulmonary sarcoidosis (n = 12) and matched healthy controls (n = 12), mean age 36 +/- 12 and 33 +/- 10 years respectively. RESULTS: At follow-up (18 [15-24] months), 7 patients had self-limited disease and 5 had persistent disease. Significantly different expression comparing patients and controls was identified for 1,860 (14.9%) and 729 (5.8%) gene products at p = 0.05 and p = 0.01 levels respectively. Genes closely associated with persistent disease included HLA-DRB1*1501 DQB1*0602, TNFA, NFKB, cyclic AMP-responsive element modulator (CREM) and T-cell activation marker CD69. IL1B, IL8, growth related (GRO)-beta/-gamma and CCR 2,5,6 were closely associated with self-limited disease. CONCLUSION: We hypothesize that, in self-limited disease, greater effector cell activation leads to successful antigen elimination/tolerance, whereas HLA-DRB1*1501 DQBI*0602-mediated, probably defective/partial T-lymphocyte activation results in an inefficient primary immune response, antigen intolerance and persistent disease.

Adult↗
PubMed2004

HLA-DR2 predicts susceptibility and disease chronicity in Irish sarcoidosis patients.

BACKGROUND: HLA-DR2 (15) and 14 (6) have been recently proposed as susceptibility alleles for the development of sarcoidosis and HLA-DR15 as a marker of poor outcome, but validation in other populations is necessary. METHODS: Employing serological techniques, we HLA-typed 103 Irish sarcoidosis patients and 105 ethnically-matched healthy controls for class I A and B and II DR and DQ alleles. RESULTS: HLA-B5 (10% vs. 2%, p = 0.018) and DR2 (45% vs. 27%, p = 0.007) were positively associated and B15 (0% vs. 7%, p = 0.01) negatively associated with sarcoidosis compared to control subjects. Seventy-five patients were followed > 2 years and 47 (63%) had chronic and 28 (37%) non-chronic disease. HLA-DR2 (55% vs. 27%, p = 0.001) and DR11 (26% vs. 5%, p<0.0001) were significantly more frequent in chronic disease vs. controls, in contrast to HLA-DR3 (13% vs. 38%, p = 0.002), which had a significant negative association. HLA-B5 (11% vs. 2%, p = 0.029) and DR3 (64% vs. 38%, p = 0.005) were significantly more frequent in non-chronic disease. Of the 29 patients achieving spontaneous remission, 24 (83%) were HLA-DR3 -positive and DR3-positivity was associated with significantly greater carbon monoxide diffusion at follow-up compared to DR3-negative patients (90% vs. 82% predicted, p = 0.027). CONCLUSIONS: This study supports the role of HLA-DR2 (15) as both a susceptibility and poor prognostic marker in sarcoidosis and DR2 positive patients may particularly benefit from close follow-up and early treatment. In contrast, DR3 positive patients are at a much lesser risk of chronic disease. Studies for long-term treatment effects require stratification for HLA-DR2 and DR3 status.

Adult↗
PubMed2003

An individualized, adjustable maintenance regimen of budesonide/formoterol provides effective asthma symptom control at a lower overall dose than fixed dosing.

PRINCIPLES: Current asthma management employing inhaled corticosteroids (ICS) and longacting b2-agonists (LABA) aims to rapidly achieve and then maintain overall asthma control including symptoms with minimal medication. This study compared self-guided adjustable maintenance dosing with budesonide/formoterol in a single inhaler with fixed dosing. METHODS: In an open-label, parallel-group, multicentre study, 127 asthmatic patients, well controlled on ICS and LABA, were treated with budesonide/formoterol (Symbicort) Turbuhaler) 200/6 mg (equivalent to 160/4.5 mg delivered dose) 2 inhalations bid for 4 weeks, and were then randomised to budesonide/formoterol adjustable dosing (n = 69) (guided self-adjustment of dose: 1 inhalation bid or 2 inhalations at night with interim step ups to 2 inhalations bid and if not sufficient up to 4 inhalations bid for 14 days) or fixed dosing (2 inhalations bid) (n = 58) for 12 weeks. RESULTS: Patients used adjustable dosing effectively; >50% used a decreased maintenance dose on >50% of the days. Seventy-two percent (50/69) from the adjustable-dosing group reduced their maintenance dose within the first 2 treatment weeks. Thirteen adjustable-dose patients (18.8%) never reduced their dose and 4 (5.8%) stepped up their dose. Symptom severity (NHLBI severity grade) decreased in both groups; however, the decrease was only statistically significant (p = 0.004) in the adjustable-dosing group. Treatment failures occurred in 17% and 24% of patients (adjustable and fixed dosing, respectively p = 0.35). Nocturnal awakenings (0.057 vs. 0.067/night, p = 0.006) and rescue medication use (0.15 vs. 0.23 inhalations/day, p <0.0001) were significantly less frequent with adjustable dosing, and the average daily medication dose was significantly reduced (3.0 vs. 3.9, p <0.0001) compared with fixed dosing. Lung function measurements (FEV1 and PEF) were not significantly different between groups during the study. There were no asthma-related hospital admissions. CONCLUSION: Asthma patients on adjustable maintenance dosing with budesonide/ formoterol maintained control of symptoms using significantly less medication overall than fixed dosing. Thus, adjustable maintenance dosing achieved guideline goals of effective asthma control at an appropriately low maintenance dose. However, larger studies on adjustable maintenance dosing are needed.

Adolescent↗
PubMed2003

Functional genomics and gene microarrays--the use in research and clinical medicine.

In the year 2000, the Human Genome Project Consortium presented the first complete draft of the human genome together with Celera Genetics. Since then, the so-called "post-genome era" has started. Microarrays are capable of profiling gene expression patterns of tens of thousands of genes in a single experiment and thus allow a systematic analysis of DNA and RNA variation. They seem likely to become a standard tool of both molecular biology research and clinical diagnostics. These prospects have attracted great interest and investment from both the public and private sectors. This review introduces the principle of microarray technology and gives an overview of its current and future potential in clinical medicine.

Animals↗
PubMed2003

Accuracy of pleural puncture sites: a prospective comparison of clinical examination with ultrasound.

STUDY OBJECTIVE: To assess the value of chest ultrasonography vs clinical examination for planning of diagnostic pleurocentesis (DPC). DESIGN: Prospective comparative study. SETTING: Pulmonary unit of a tertiary teaching hospital. PATIENTS AND PARTICIPANTS: Sixty-seven consecutive patients referred to 30 physicians of varying degrees of experience for DPC. INTERVENTIONS: Based on clinical data and examination, physicians determined whether and where a DPC should be performed. Selected puncture sites were evaluated with ultrasound and considered accurate when > or = 10 mm fluid perpendicular to the skin were present. MEASUREMENTS AND RESULTS: In 172 of 255 cases (67%), a puncture site was proposed. Twenty-five sites (15%) were found to be inaccurate on ultrasound examination, and a different, accurate site was established in 20 of these cases. Physicians were unable to locate a puncture site in 83 cases (33%). Among these, ultrasound demonstrated an accurate site in 45 cases (54%), while a safe tap was truly impossible in 38 cases (46%). Overall, ultrasound prevented possible accidental organ puncture in 10% of all cases and increased the rate of accurate sites by 26%. The sensitivity and specificity for identifying a proper puncture site with clinical examination compared to ultrasound as the "gold standard" were 76.6% and 60.3% (positive and negative predictive values, 85.5% and 45.8%, respectively). Risk factors associated with inaccurate clinical site selection were as follows: small effusion (p < 0.001), evidence of fluid loculation on chest radiography (p = 0.01; relative risk, 7.8; 95% confidence interval, 1.9 to 32.9), and sharp costodiaphragmatic angle on chest radiography (p < 0.001; relative risk, 7.0; 95% confidence interval, 2.3 to 15.2). Experienced physicians did not perform better than physicians in training. CONCLUSIONS: Puncture site selection with bedside ultrasonography increases the yield of and potentially reduces complication rate in DPC. Physician experience does not predict the accuracy of selected puncture sites.

Adult↗