Biomedical subjects

R Breuer

Publications and source records attributed to R Breuer.

At least 19 recordsLinked to original sources

PubMed2005

Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests.

BACKGROUND: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5'-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. METHODS: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. RESULTS: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO > 7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: deltaFEV1 > or = 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: < or = 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: < or = 150 mg/ml (sensitivity 89.5%, specificity 95.6%). CONCLUSIONS: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.

Adenosine Monophosphate↗

PubMed2004

Tube thoracostomy during allogeneic stem cell transplantation does not carry an increased risk for infections or bleeding.

BACKGROUND: Candidates for stem cell transplantation may occasionally suffer from massive pleural effusions related to their disease and require tube thoracostomy. The additional risk of this procedure during allogeneic transplantation procedure is not known. METHODS: Four high-risk patients transplanted in our institution during a 2-yr period had chest drainage by tube thoracostomy. The characteristics of the fluid, the clinical course, and the outcome were assessed. RESULTS: A total of nine chest drains were inserted (range 1-5). No bleeding complications related to the procedure were noted. None of the patients developed any clinical signs of local infection at the tube insertion site or within the pleural fluid. All cultures taken from the drained fluid or from the insertion wound were negative. CONCLUSIONS: Tube thoracostomy in itself does not seem to pose additional risks in the transplant procedure, despite all patients in this series being considered to be at high-risk for complications.

Adult↗

PubMed2004

Low incidence of pulmonary complications following nonmyeloablative stem cell transplantation.

Bone marrow transplantation is associated with pulmonary opportunistic infections and immune-mediated pulmonary processes such as idiopathic pneumonia syndrome and bronchiolitis obliterans. The aim of the present study was to test the hypothesis that nonmyeloablative stem cell transplantation (NST) has less adverse effects on the lungs. A review was undertaken of the pulmonary complications occurring in 53 patients with various haematological malignancies, some of whom were considered high-risk patients with chemoresistant disease, who underwent fludarabine-based irradiation-free conditioning for NST performed between March 1996 and October 1998. All data related to transplant procedure, disease outcome, graft-versus-host disease (GVHD), chest imaging, microbial cultures and lung biopsies, were retrieved from information collected prospectively at the time of transplantation. The median follow-up period after transplantation was 45 months, with 35 patients surviving > 100 days. Approximately half of the patients displayed some form of GVHD, with 11% developing severe chronic GVHD. In 17 (32%) patients, the lungs were somehow adversely affected. Only two (3.8%) patients developed a clinical picture consistent with idiopathic pneumonia syndrome and none developed diffuse alveolar haemorrhage or bronchiolitis obliterans. Dose-reduced conditioning is associated with a low rate of pulmonary toxicity and side-effects. These findings may extend understanding of significant immune-mediated complications occurring after bone marrow transplantation.

Adult↗

PubMed2002

Invasive airway aspergillosis with new airflow obstruction mimicking post-BMT bronchiolitis obliterans.

A 52-year-old male with severe gastrointestinal graft-versus-host disease (GVHD), developed dyspnea and irreversible airflow obstruction, 11 weeks post-allogeneic bone marrow stem cell transplantation. Based on the clinical picture and presence of 'mosaic attenuation' pattern on chest high-resolution computerized tomography (HRCT), he was presumed to have bone marrow transplantation-related bronchiolitis obliterans. Post-mortem examination revealed invasive airway aspergillosis with no evidence of bronchiolitis obliterans.

Airway Obstruction↗

PubMed2002

Time course of bleomycin-induced lung fibrosis.

Intratracheal instillation (IT) of bleomycin is a widely used experimental model for lung fibrosis. In this study we describe the time-course of bleomycin-induced lung fibrosis in mice using computer-assisted morphometry. C57Bl/6J mice were treated with a single IT dose of bleomycin or control saline. Animals were killed 3, 6, 14 and 21 days post-IT. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, hydroxyproline concentration in the lung, routine light microscopic examination resulting in a semiquantitative morphological index (SMI) of lung injury, and quantitative morphological measurements (fibrosis fraction and alveolar wall area fraction) aided by optimas image analysis software. Changes in BAL fluid attributed to bleomycin treatment include increased total cell count (days 14 and 21), and increased percentage of neutrophils (days 3 and 6) followed by a sustained increase in lymphocytes (days 6, 14 and 21). Hydroxyproline levels increased in bleomycin-treated mice on days 14 and 21. Median SMI grades were significantly elevated on days 3, 14 and 21. Computer-assisted morphometry demonstrated a 3-fold increase in fibrosis fraction and a 1.3-fold increase in wall area fraction in bleomycin-treated mice on day 14, with no further increase on day 21. These data also demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days after IT instillation of bleomycin, based on the observation that at 14 days the animals developed extensive fibrosis, but had less variability in the fibrotic response and lower mortality than later at 21 days. Computer-assisted morphometry provides objective and quantitative measurements that are a useful tool for the evaluation of bleomycin-induced lung injury.

Animals↗

PubMed2002

Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters.

OBJECTIVE: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated. DESIGN: A retrospective analysis. SETTING: The Institute of Pulmonology, Hadassah University Hospital. PATIENTS AND METHODS: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared. RESULTS: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%). CONCLUSIONS: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.

Adult↗

PubMed2001

All-trans-retinoic acid (ATRA) is of no benefit in bleomycin-induced lung injury.

All-trans-retinoic acid (ATRA) has anti-fibrotic and antiinflammatory properties, and may be useful as a therapeutic agent in lung fibrosis. To test this hypothesis we investigated the effect of ATRA on bleomycin-induced lung fibrosis in Sprague-Dawley rats. Treatment groups included: (1) a single intratracheal (i.t.) instillation of bleomycin and daily intraperitoneal (i.p.) injection of 0.5 mg/kg per day ATRA; (2) i.t. bleomycin and i.p. ATRA, 2 mg/kg per day, (3) i.t. bleomycin and i.p. diluent (cottonseed oil); (4) i.t. saline and i.p. ATRA, 0.5 mg/kg per day, (5) i.t. saline and i.p. ATRA, 2 mg/kg per day; and (6) i.t. saline and i.p. diluent. Animals were studied 14 days after i.t. instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semi-quantitative morphological index of lung injury, and by biochemical analysis of lung hydroxyproline content. Overt signs of lung injury were apparent in bleomycin-treated rats by all measures. These changes were not affected by treatment with ATRA at either dose. This study does not support the use of ATRA to prevent or ameliorate lung fibrosis.

Animals↗

PubMed2001

Human recombinant interferon-alpha2a and interferon-alphaA/D have different effects on bleomycin-induced lung injury.

BACKGROUND: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis. OBJECTIVE: To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice. METHODS: Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content. RESULTS: In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury. CONCLUSION: IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.

Animals↗

PubMed2001

Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge.

Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/microg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/microg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/microg, 95% CI; 0.08 to 1.72 versus 2.97 pg/microg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/microg, 95% CI; 0.74 to 3.92 versus 4.62 pg/microg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.

Adult↗

PubMed2001

[Contribution of PET using FDG in the diagnosis of lung cancer--first results].

Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells. Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use. We performed 135 FDG-PET studies between July '97-April '99 and present our preliminary results with examples of the main indications for PET in lung cancer.

Adult↗

PubMed2000

The effect of suramin on bleomycin-induced lung injury.

Since transforming growth factor beta (TGF-beta) is presumed to play a role in lung fibrosis, we evaluated the effect of suramin (Sur), a substance with an anti-TGF-beta effect, in vivo on bleomycin (Bleo)-induced pulmonary injury in mice and in vitro on human lung fibroblasts. Four groups of C57BL/6 mice each received one of four treatments: (1) intratracheal (i.t.) instillation of Bleo and intraperitoneal (i.p.) injections of Sur, every other day, starting one day before i.t. instillation of Bleo (Bleo-Sur); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. Sur (Sal-Sur); and (4) i.t. and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, histologically by the semiquantitative morphological index, and biochemically by analysis of lung hydroxyproline content. In vitro, Sur did not affect TGF-beta induced increase of alpha1 (I) collagen mRNA in human lung fibroblasts. In vivo treatment of mice with Sur did not affect Bleo-induced lung injury. These results indicate that despite its potential anti TGF-beta and lymphocytotoxic effects, Sur is not a therapeutic candidate drug for rescue of lung fibrosis.

Animals↗

PubMed2000

Cerebrospinal fluid lactate dehydrogenase isoenzyme analysis for the diagnosis of central nervous system involvement in hematooncologic patients.

BACKGROUND: Central nervous system (CNS) involvement is common in hematooncologic diseases. The aim of the current study was to determine the diagnostic value of cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) isoenzyme analysis for the diagnosis of CNS involvement in hematooncologic patients. METHODS: The study was comprised of 63 consecutive hematooncologic patients without previous CNS disease who underwent CSF examination as an integral part of their initial staging procedures (44 patients) or for the evaluation of neurologic symptoms (19 patients). Fifteen of these patients had CNS involvement by leukemia or lymphoma. The LDH isoenzyme pattern was established in the CSF of all patients and analyzed by the classification and regression trees (CART) method to construct a decision tree for the prediction of CNS involvement. An additional group of 30 consecutive patients comprised a validation set that was used for cross-validation of the CART-derived decision tree. RESULTS: A decision tree, with a single split at LDH5 >/= 2.8% for the prediction of CNS involvement, was constructed and validated by data from a validation set of patients. The decision tree had a sensitivity of 93% and a negative predictive value of 98%. One patient (1.6%) and 2 patients (6.6%) were misclassified in the derivation and validation sets, respectively. Overall, in the combined derivation and validation patient population, the decision tree misclassified 3.2% of patients, whereas CSF cytologic examination misclassified 4.3% of patients. CONCLUSIONS: Analysis of the LDH isoenzyme pattern in CSF fluid may be helpful in the evaluation of CNS involvement in patients with hematologic malignancies. The combination of CSF cytology and LDH isoenzyme analysis may improve the sensitivity of CSF cytology significantly.

Central Nervous System Neoplasms↗

PubMed2000

Gender-specific effects of NAT2 and GSTM1 in bladder cancer.

One approach for risk assessment of cancer is the evaluation of polymorphic enzymes involved in cancer using molecular tools. Phase II enzymes are involved in the detoxification of several drugs, environmental substances and carcinogenic compounds. Here, we analyzed enzymes for their putative relevance in urinary bladder cancer. The hereditable enzyme polymorphism of arylamine N-acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) was studied in 157 hospital-based patients and in 223 control subjects. Slow acetylation was not observed to be a significant risk factor of developing bladder cancer (OR: 1.33; 95% CI 0.85-2.09). One genotype responsible for slow acetylation (NAT2*5B/*6A) was observed significantly more frequently in bladder cancer patients compared with control subjects (OR: 1.63; 95% CI 1.03-2.58). Gender-specific effects were observed when patients were divided into subgroups. In male patients, slow acetylators were identified as carrying a significant increased risk of developing bladder cancer, in particular when the genotype NAT2*5B/*6A was combined with the GSTM1 null genotype (OR: 4.39; 95% CI 1.98-9.74). By contrast, the same genotype combination significantly protected female patients from bladder cancer (OR: 0.21; 95% CI 0.06-0.80).

Adult↗

PubMed2000

Susceptibility genes: GSTM1 and GSTM3 as genetic risk factors in bladder cancer.

Glutathione S-transferase (GST, E.C. 2.5.1.18) comprises a family of isoenzymes that play a key role in the detoxification of such exogenous substrates as xenobiotics, environmental substances, and carcinogenic compounds. At least five mammalian GST gene families have been identified to be polymorphic, and mutations or deletions of these genes contribute to the predisposition for several diseases, including cancer. The gene cluster of GSTM1-GSTM5 has been reported to be localized on chromosome 1p and spans a length of nearly 100 kb. One mutation of the GSTM3 gene generates a recognition site for the transcription factor yin yang 1. As a result of this mutation, the expression of GSTM3 can be influenced. The mutated GSTM3 gene has been reported to be involved in increased susceptibility for the development of cancer, but no information is available concerning its role in bladder cancer. We have identified patients with a heterozygous GSTM3 geno- type who carry a significantly increased risk for the development of bladder cancer. Here we report that the mutation of intron 6 of GSTM3 increases the risk for bladder cancer (odds ratio: 2.31; 95% confidence interval [CI], 1.79-2.82). We developed a procedure to identify heterozygous or homozygous carriers of the GSTM1 alleles. Heterozygous carriers of the GSTM1 null genotype have a significantly elevated risk of developing bladder cancer. We calculated an odds ratio of 3.54 (95% CI, 2.99-4.11) for this genotype. These observations lead to the assumption that the lack of detoxification by glutathione conjugation predispose to bladder cancer when at least one of two alleles is affected. Furthermore, individuals presenting the homozygous wild type of GSTM1 and GSTM3 are significantly protected against bladder cancer.

Aged↗

PubMed2000

The role of BAL in the diagnosis of pulmonary mucormycosis.

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.

Adult↗

PubMed1999

Lactate dehydrogenase isoenzyme analysis for the diagnosis of pleural effusion in haemato-oncological patients.

This study aimed to evaluate the utility of the pleural fluid lactate dehydrogenase (LDH) isoenzyme algorithm for the differential diagnosis of pleural fluid in patients with haematological malignancies. Twenty consecutive haemato-oncological patients with pleural effusion, hospitalized in the Haematology Department during a 2.75-year period, were prospectively and independently evaluated for the cause of effusion by standard methods for the LDH isoenzyme algorithm. The causes of the pleural effusions established during the standard evaluations were compared to the results obtained from the LDH isoenzyme algorithm. Following the standard evaluation, the pleural effusion was attributed to congestive heart failure in one patient, to infection in six, to the underlying malignancy in 12 and to concomitant congestive heart failure and malignancy in one. LDH isoenzyme analysis correctly predicted the cause of pleural effusion in 18 patients (positive predictive value 90%). In haemato-oncological patients, the pleural fluid LDH isoenzyme pattern may be helpful in the differential diagnosis of the most common causes of pleural effusion.

Biomarkers↗

PubMed1999

The effect of enoxaparin on bleomycin-induced lung injury in mice.

We have evaluated the effect of enoxaparin, a potent antithrombotic drug, on bleomycin (Bleo)-induced pulmonary inflammation in mice. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of female C57BL/6 mice, each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of enoxaparin (EN) starting one day before i.t. instillation of Bleo (Bleo-EN); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. enoxaparin (Sal-EN); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage fluid and histologically by an overall semiquantitative index of lung injury and a quantitative image analysis assessing alveolar wall area fraction and fibrosis fraction. Treatment of mice with enoxaparin did not ameliorate Bleo-induced lung injury. Our study does not establish a critical role of procoagulant activity in the evolution of Bleo-induced lung injury and does not support the use of antithrombotic therapy for the prevention of pulmonary fibrosis.

Animals↗

PubMed1999

Effect of immunomodulators on bleomycin-induced lung injury.

BACKGROUND: The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear. OBJECTIVE: To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline. METHODS: C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content. RESULTS: Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose. CONCLUSION: This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.

Adjuvants, Immunologic↗