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R Buhl

Publications and source records attributed to R Buhl.

At least 73 records · Page 4Linked to original sources
PubMed2001

Secretory meningiomas: clinical and immunohistochemical observations.

OBJECTIVE: Secretory meningiomas are a rare histological subtype of these benign intracranial tumors. Few reports have been published regarding their tendency to develop peritumoral edema. METHODS: Between July 1994 and February 1999, 11 patients with secretory meningiomas underwent operations in the Department of Neurosurgery, University of Kiel, Kiel, Germany. The clinical notes and radiological data (computed tomographic and magnetic resonance imaging scans) were reviewed. Immunohistochemistry was used to examine the expression of carcinoembryonic antigen and epithelial membrane antigen as well as progesterone and estrogen receptors. RESULTS: Secretory meningiomas were found in 11 (5%) of 214 patients with intracranial meningiomas who were operated on in that period. All 11 patients were women. These patients' mean age was 65 years (range, 51-87 yr). The localization of these tumors was at the convexity in seven patients, at the sphenoid ridge in two patients, and in the olfactory groove and petroclival region in one patient each. Two meningiomas had no edema surrounding them, two meningiomas had a small amount of edema, two had moderate edema, and five had severe edema. No recurrences were observed during the mean follow-up period of 26 months (range, 8-65 mo). Immunohistochemically, all tumors contained pseudopsammoma bodies and reacted with epithelial membrane antigen and carcinoembryonic antigen. The MIB-1 antibody staining index showed a mean of 2% (range, 0-7%). CONCLUSION: Secretory meningiomas are rare tumors, and they are mainly localized at the frontal convexity and the sphenoid ridge. They are surrounded by more edema than usual. The preponderance of female patients with this presentation is striking. The expression of carcinoembryonic antigen and epithelial membrane antigen is a characteristic feature of secretory meningiomas. These meningiomas are also positive for progesterone receptors, which has been shown to be a good prognostic factor.

Aged↗
PubMed2001

Glutathione in induced sputum of healthy individuals and patients with asthma.

BACKGROUND: Glutathione is central to the antioxidant defences of the lung. The aim of this study was to determine whether sputum induction can be used for the measurement of glutathione in the respiratory tract. METHODS: Saliva and induced sputum (3% NaCl, 20 minutes) samples were collected from 10 healthy individuals and 10 patients with stable asthma receiving treatment with inhaled corticosteroids. Samples were chilled on ice and dispersed by dilution with ice cold phosphate buffered saline and pipetting. Cell-free supernatants were obtained by centrifugation of samples and filtration of supernatants and analysed for total glutathione, glutathione disulfide, and albumin content. The cells were treated with dithiothreitol and cell numbers, cell viability, and differential cell patterns were determined. RESULTS: As judged by cell viability and percentage of non-squamous cells, adequate sputum samples were obtained from nine healthy and nine asthmatic subjects. The salivary total glutathione content was low (median concentration 1.2 microM (range 0.8-1.5) in healthy subjects and 0.9 microM (0.7-1. 2) in asthmatic subjects). The sputum total glutathione content of both healthy and asthmatic subjects was within the same range (3.9 (1.0-12.3) microM and 6.4 (1.3-19.2) microM, respectively; p=0.35). Surprisingly, and in marked contrast to results obtained with bronchoalveolar lavage, sputum levels of glutathione disulfide represented more than 50% of the total glutathione in both groups (50.9% (range 24.6-83.1) and 72.3% (range 36.5-97.4), respectively; p=0.2). CONCLUSIONS: The results of this study indicate that sputum induction can be used to measure the glutathione content of bronchial secretions. Sputum glutathione levels of stable asthmatic patients did not differ significantly from healthy controls.

Adolescent↗
PubMed2001

Induced sputum cell profiles in lung transplant recipients with or without chronic rejection: correlation with lung function.

BACKGROUND: Sputum induction is a non-invasive procedure for measuring inflammatory processes of the lower respiratory tract. The aim of this study was to establish sputum cell counts and differentials in patients after lung transplantation (LTx), with or without chronic transplant rejection. METHODS: Sputum induction was performed in 41 LTx patients (25 single LTx (sLTx), 16 double LTx (dLTx) and 15 healthy non-smoking volunteers. Sputum was processed according to standard protocols. Total cell count was calculated as mean (SE) cells x 10(6)/ml sputum and cell differential (%) was evaluated after staining. Cellular profiles were correlated with lung function. RESULTS: Total sputum cell counts were increased in sLTx (9 (1.9) cells x 10(6)/ml, p=0.01) and dLTx patients (7.2 (1.5) x 10(6)/ml, p=0.01) compared with healthy controls (2.6 (0.6) x 10(6)/ml). There was also a marked sputum neutrophilia in both patient groups (59 (6)% and 62 (6)%, respectively, p<0.001 v controls). Moreover, in both sLTx and dLTx patients with chronic transplant rejection there was an increased number of sputum neutrophils compared with patients with normal graft function (p<0.05 both comparisons), and neutrophils were inversely correlated with lung function (forced expiratory volume in one second (FEV(1)) % predicted): sLTx, r=-0.61, p=0.001; dLTx, r=-0.75, p=0.001, respectively). Sputum lymphocytes and eosinophils were similar in both groups. No relevant side effects occurred during sputum induction. CONCLUSIONS: Sputum induction is a safe and non-invasive tool for monitoring lower respiratory tract inflammation in LTx patients. Both sLTx and dLTx patients with chronic rejection had increased sputum neutrophils compared with patients with normal transplant function. These data support findings of other authors highlighting a possible role for neutrophils in the pathogenesis of chronic transplant rejection.

Adolescent↗
PubMed2001

Stroke pattern interpretation: the variability of hypertensive versus amyloid angiopathy hemorrhage.

INTRODUCTION: It is commonly felt that cerebral amyloid angiopathy (CAA) related intracerebral hemorrhage (ICH) can be distinguished from hypertension (HTN)-related ICH by certain typical features on computerized tomography (CT) and magnetic resonance imaging (MRI). The purpose of this study was to investigate the performance of clinicians who were asked to differentiate between CAA and HTN based on hemorrhage pattern interpretation and to assess the feasibility of such classification. METHODS: The admission scans from 83 patients who were admitted to our service with an acute ICH were presented to 5 clinicians in a randomized and blinded fashion (1 junior, and 1 senior neurosurgical resident, 1 attending neurosurgeon, and 2 neurosurgeon-neuroradiologists). There were no patients who received oral anticoagulants other than low-dose aspirin, or who suffered from vascular malformations or tumors. Scans from 41 patients with a histologically proven diagnosis of CAA and from 42 patients with a clear history of HTN were investigated. Hematoma evacuation was done in all CAA patients and in 59% of HTN patients (n = 25). RESULTS: The overall average classification accuracy was 66.8% (range: 62.7-69.9). For correct HTN classification it was 69.5% (range: 64.3-81), and 63.9% for CAA, respectively (range: 48.9-75.6). There were negligible differences in classification accuracy among all observers. Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74 vs. 66.5 years, p < 0.05). There was a significantly higher number of hematomas >30 ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglionic hemorrhage was seen in CAA, but in 40.5% in HTN. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Two patients (4.9%) with CAA, and 7 patients with HTN (16.7%) presented with cerebellar hematomas. CONCLUSIONS: Three of 10 scans were not correctly diagnosed regardless of the examiner's level of training. This calls into question the reliability of classifying the underlying pathological condition based on hemorrhage pattern interpretation on CT or MRI. The definite diagnosis of CAA- versus HTN-related hemorrhage requires a histopathological confirmation and should not be based solely on hemorrhage pattern interpretation.

Adult↗
PubMed2001

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

Administration, Inhalation↗
PubMed2001

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics.

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

Acute Disease↗
PubMed2000

[Anticholinergic drugs in therapy of chronic obstructive lung disease (COPD)].

Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder responsible for a significant morbidity and mortality in western societies. In the vast majority of patients, COPD is caused by tobacco smoke. Contributing factors leading to airway obstruction and lung hyperinflation in COPD differ from those observed in asthma, with a major role of hypersecretion and peripheral airway obstruction due to increased cholinergic airway smooth muscle tone. Therefore, anticholinergics are considered the firstline therapy to improve airway obstruction in COPD. In addition to effects on lung function, anticholinergics may also improve exercise tolerance, quality of life and sleep quality in these patients. When compared with other classes of bronchodilators, anticholinergics show an equal potency of bronchodilation, with a favorable safety profile. Due to their unique mechanism of action, anticholinergics can also be combined with different types of bronchodilators. Novel, long-acting anticholinergics may hold a future potential for further improvement of therapy in COPD, particularly in terms of user friendliness and compliance.

Airway Resistance↗
PubMed2000

Giant cystic craniopharyngiomas with extension into the posterior fossa.

Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT). A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach. For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.

Adolescent↗
PubMed2000

Spontaneous intracranial haematomas caused by neoplasms.

We report about 50 patients with spontaneous intracerebral haematomas (ICH) caused by intracranial neoplasms to assess the underlying histological condition, their presentation on admission, diagnostic work-up, treatment, histological diagnosis, and clinical outcome. These patients were identified in a prospective series of 2041 patients with intracranial neoplasms and 692 patients with spontaneous ICH, which were both consecutively collected over a nine-year-period. The frequency of ICH in patients with intracranial neoplasms was 2.4%. The frequency of tumour related ICH in the ICH group was 7.2%. The leading cause of tumour related ICH were metastases of extracranial origin (n = 18; 36%), followed by glioblastoma multiforme (n = 15; 30%). Nine patients (18%) had benign primary intracranial neoplasms. On admission 18 patients were somnolent (36%) and 14 patients (28%) were comatose. In 29 cases (58%) ICH was the first clinical sign of neoplastic disease, while in 21 patients (42%) a malignant tumour was already known. We operated on 45 patients (90%), four patients (8%) were not operated on because of poor clinical condition and died, one patient refused surgical treatment. Six patients (12%) died despite surgery. This series confirms the importance of a proper neuroradiological and clinical work-up of patients with suspected tumour related ICH followed by operative treatment and histological confirmation of the diagnosis. This is supported by the fact that 18% of patients had prognostically favourable intracranial tumours which would not otherwise have been adequately treated.

Acute Disease↗
PubMed2000

Results in the operative treatment of elderly patients with intracranial meningioma.

With life expectancy in the industrial nations increasing during recent years, the number of patients older than 70 years with intracranial tumours and, especially, meningiomas is rising. To evaluate the indications for operative treatment, we reviewed 66 patients older than 70 years who were operated upon for intracranial meningioma in our department between 1991 and 1997. The mean age was 75 years. The oldest patients were 86 years old. Thirteen patients with recurrent meningiomas were operated upon. The mortality rate was 7.6%. Neurological symptoms improved in 38 patients (57.6%), were unchanged in 11 (16.6%), and deteriorated in 12 (18.2%). Patients with recurrent meningiomas seem to have a higher operative risk and their outcome is worse than after a primary operation. In general, there were good postoperative results in patients with few concomitant diseases, small meningiomas, small edema, short time of operation, and accessible location (convexity rather than skull base). Age in general is not a contraindication for operation. In cases of incidental findings of small meningiomas, we recommend observation and MRI follow-up. Symptomatic meningiomas should be removed whenever there is an acceptable risk from an internal or anaesthesiological point of view.

Aged↗
PubMed2000

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals.

Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U x mL(-1) were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics. Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1)% predicted (66+20% versus 83+/-17%; p<0.001), FEV1% forced vital capacity (FVC) (70+/-14% versus 81+/-8%; p<0.001) and forced mid expiratory flow (FEF25-75) (1.7+/-0.9 L x s(-1) versus 2.8+/-0.9 L x s(-1); p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEVI % pred: r=-0.5, p<0.001; FEV1% FVC: r=-0.53, p<0.001; FEF25-75: r=-0.52, p<0.001). In the whole study population, multivariate analysis showed a greater than fivefold asthma risk for nonallergic individuals with serum IgE>150 U x mL(-1). These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity.

Adult↗
PubMed2000

[efficacy and safety of salmeterol in long-term therapy in patients with chronic obstructive airway diseases].

BACKGROUND: Salmeterol is a long-acting inhaled beta 2-agonist with a bronchodilating effect lasting over 10 to 12 hours. METHODS: A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of inhaled salmeterol (50 micrograms BID) over a mean treatment period of 29 months (range: 4-1145 days) in 634 patients (54% male, age 45 +/- 15 years) with mild to moderate asthma or chronic obstructive pulmonary disease (COPD). Peak expiratory flow rates, rescue use of short acting beta 2-agonists and safety were study objectives. Patients were critically monitored for a possible loss of bronchodilator efficacy of salmeterol during long-term treatment. RESULTS: During the first month of salmeterol therapy, morning peak flow improved from 384 +/- 104 l/min to 413 +/- 112 l/min (p < 0.001), and use of rescue salbutamol was significantly reduced (21 +/- 21 to 8 +/- 14 puffs/week during daytime and 9 +/- 12 to 4.5 +/- 9 puffs/week during nighttime, p < 0.001 both comparisons). Peak flow improvement and reduction of short-acting beta 2-agonist use was maintained during the whole study period. Frequent adverse events were exacerbations of the underlying airway disease (24%) and infections (12%), while typical pharmacological side-effects like tremor or tachycardia where reported in less than 1% of all patients. CONCLUSIONS: These results confirm the persistent efficacy and favourable safety profile of salmeterol during long-term therapy over more than two years. No clinical signs of a decreasing bronchodilator potency indicating tachyphylaxis were observed. Salmeterol treatment provides a therapeutic option to further improve the management and care of patients with moderate obstructive airway diseases.

Administration, Inhalation↗
PubMed2000

[Correlation of plasma glutathione and total IgE level: evidence for a regulatory role of antipxodants in vivo].

BACKGROUND: Atopy is characterized by increased levels of circulating immunoglobulin E (IgE). Moreover, elevated IgE levels are frequently observed in HIV-infected individuals and are of prognostic significance in these patients. Several In vitro studies have established an association of intracellular antioxidants like glutathione with IgE production by B-lymphocytes, suggesting a regulatory role of these substances in IgE synthesis. However, in vivo data consistent with these findings have not been reported. METHODS: Total IgE levels, CD4(+)-lymphocyte count and plasma glutathione were determined in non-atopic, HIV-positive individuals. RESULTS: 27 HIV-positive subjects (mean age Alter +/- SD: 43 +/- 11 years, 85% males) were studied. Mean CD4(+)-lymphocyte count was 250 +/- 136/microliter. The median serum IgE level was 85.3 U/ml (Range: 3-1298 U/ml), and the mean plasma glutathione concentration was 2.08 +/- 0.7 muMol. Plasma glutathione was significantly correlated with CD4(+)-lymphocyte count (r = 0.37; p = 0.05), and was inversely related to total IgE (r = -0.46; p = 0.01). CONCLUSIONS: Plasma glutathione and total IgE levels are negatively correlated in HIV-positive individuals. This observation supports the concept of a regulatory role of antioxidants and IgE synthesis in vivo. Further studies aiming at the possible significance of these mechanisms in atopic patients are clearly warranted.

Adult↗
PubMed2000

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.

BACKGROUND: Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. OBJECTIVES: The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. METHODS: To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 microg/10(6) cells. Inflammatory cytokine mRNA and protein concentrations were quantified in BEAS-2B mono- and BEAS-2B-BM cocultures by RT-PCR and ELISA following exposure to soot for 1 and 8 h. RESULTS: No inflammatory cytokine mRNA expression was observed in unstimulated BEAS-2B cells. IL-6 and IL-8 mRNA and protein levels showed a dose-dependent elevation in FR 101-exposed blood monocytes. In addition, both IL-6 and IL-8 mRNA expression was upregulated in cocultured BEAS-2B cells while cytokine concentrations in the blood monocyte-BEAS-2B coculture medium were significantly increased. This upregulation was likely due to a synergism of two cell populations. CONCLUSIONS: Exposure to soot particles induces an autocrine stimulation of inflammatory cytokine release by blood monocytes and BEAS-2B cells. Since IL-6 and IL-8 play a major role in the pathogenesis and persistence of bronchial inflammation, these findings may serve as a partial explanation for the aggravation of asthmatic and bronchitic symptoms after exposure to soot.

Adult↗
PubMed2000

Nasal continuous positive airway pressure: A method to avoid endotracheal reintubation in postoperative high-risk patients with severe nonhypercapnic oxygenation failure.

OBJECTIVES: To study whether nasal continuous positive airway pressure (nCPAP) improves pulmonary oxygen transfer and avoids reintubation in patients with severe nonhypercapnic oxygenation failure after major cardiac, vascular, or abdominal surgery. DESIGN: Prospective interventional study. SETTING: Surgical ICU of a university hospital. PATIENTS: Twenty consecutive patients after thoracic, abdominal, or combined thoracoabdominal operations, in whom pulmonary oxygen transfer deteriorated continuously following elective extubation after initial mechanical ventilation. Respiratory failure was due to atelectasis and/or left heart failure, and all patients met predefined criteria for reintubation. INTERVENTIONS: nCPAP therapy (8 to 10 cm H(2)O) was initiated if PaO(2) had decreased to < 80 mm Hg despite application of 100% oxygen (flow, 25 L/min), intermittent mask continuous positive airway pressure, and maximum conventional therapy. MEASUREMENTS AND RESULTS: nCPAP treatment was started 24.1 +/- 3.4 h after elective extubation. PaO(2) was < 80 mm Hg in all patients, in 13 patients it was < 60 mm Hg, and in 3 patients it was < 50 mm Hg. Mean PaO(2)/fraction of inspired oxygen (FIO(2)) ratio had decreased to 60 +/- 2.6, and increased within the first hour of nCPAP to 136 +/- 12 (p < 0.001). The clinical condition in all patients improved further, and after 35.2 +/- 6.3 h, all patients were well oxygenated by face mask at ambient pressure (PaO(2)/FIO(2) ratio, 146 +/- 14). Two patients were reintubated for reasons unrelated to oxygenation or ventilation (data are presented as mean +/- SEM). CONCLUSIONS: nCPAP is safe, easy to apply, and effective to improve arterial blood oxygenation in < 1 h in postoperative patients with severe nonhypercapnic oxygenation failure. In these patients, who otherwise would have been reintubated, nCPAP can avoid endotracheal reintubation and mechanical ventilation.

Blood Gas Analysis↗
PubMed2000

Asbestos-exposed blood monocytes--deoxyribonucleic acid strand lesions in co-cultured bronchial epithelial cells.

OBJECTIVES: In lungs of asbestos-exposed persons alveolar and interstitial macrophages are able to release genotoxic substances such as reactive oxygen intermediates. It is unknown whether reactive oxygen intermediates released by macrophages are able to induce DNA (deoxyribonucleic acid) strand lesions in neighboring bronchial epithelial cells. METHODS: A co-culture (transwell) system was established which allows exposure of human blood monocytes cultured on a polycarbonate membrane within a distance of 1 mm of a monolayer of the bronchial epithelial cell line BEAS-2B. RESULTS: Exposure of blood monocytes to chrysotile B (100 microg/10(6)cells) caused an up to 2.8-fold increase in DNA strand lesions in co-cultured BEAS-2B cells measured by alkaline elution when compared with the levels of control cells after 1, 3, 24, and 48 hours. The main DNA damage thus occurred as early as within 1 hour of incubation, corresponding to the time course of the release of reactive oxygen intermediates by blood monocytes determined by chemiluminescence. The maximum release of reactive oxygen intermediates (3.2-fold increase over control values) was measured after 30 minutes of exposure of blood monocytes to chrysotile B. The addition of catalase (200 U/ml) or desferoxamine (100 microM) to the culture medium blocked almost completely the induction of DNA strand lesions in this system (maximum 85%). CONCLUSIONS: Exposure of blood monocytes to chrysotile B results in an increase in the release of reactive oxygen intermediates and induces DNA strand lesions in neighboring bronchial epithelial cells.

Adult↗
PubMed1999

Additional NO2 exposure induces a decrease in cytokine specific mRNA expression and cytokine release of particle and fibre exposed human alveolar macrophages.

Soot particles, asbestos fibres and irritant gas are common air pollutants which are able to induce lung and airway pulmonary injury. The aim of this study was to investigate the effect of a simultaneous NO2 and particle or fibre exposure on the proinflammatory specific mRNA expression and protein secretion of human alveolar macrophages (AM) in comparison to only particle or fibre exposed AM. AM were simultaneously exposed to FR 101, P 90, TiO2 or Chrysotile B at a concentration of 100 microg/10(6) cells and to NO2 at a concentration of 1.0 ppm for 30 min. Particle or fibre exposure of the AM was continued in humidified air at 5% CO2 and 37 degrees C for an additional hour (harvesting of total RNA) or additional 7 hrs (harvesting of culture supernatant). The mRNA expression of the proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha of NO2-particle/fibre co-exposed AM and only particle or fibre exposed AM was detected using specific RT-PCR. IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific protein secretion was measured by ELISA. Cytotoxicity was detected by lactatedehydrogenase quantification in the culture supernatant. We observed an increased IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific mRNA expression of particle or fibre exposed AM, which was decreased after an additional NO2 exposure. Also the particle or fibre exposure induced significant increase in IL-1beta-, IL-6-, IL-8 and TNF-alpha-release of AM which was decreased after an additional NO2 exposure (p <0.031). The relative cytotoxicity of the NO2-particle/fibre co-exposure was higher than the particle or fibre induced cytotoxicity, but mostly <10%. Therefore it is concluded that particle or fibre exposure may result in an increase in proinflammatory cytokine release by AM, which may be decreased by toxic NO2 due to the oxidative potential (e.g. lipidperoxydation) of this irritant gas. Particle, asbestos fibre and irritant gas exposure may induce airway and pulmonary injury by the activation of AM and consecutive proinflammatory cytokine release.

Aged↗