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Biomedical subjects

G Fruhmann

Publications and source records attributed to G Fruhmann.

At least 37 records · Page 2Linked to original sources
PubMed1994

Respiratory and other hazards of isocyanates.

Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1% of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.

Air Pollutants, Occupational↗
PubMed1994

Urinary platinum in hospital personnel occupationally exposed to platinum-containing antineoplastic drugs.

Urinary platinum levels of 21 nurses and hospital pharmacy personnel occupationally exposed to platinum containing antineoplastic drugs were determined in 24-h urine by voltammetric analysis after UV photolysis. All study participants applied standard safety measures, including a vertical laminar air-flow cabinet and latex gloves. The amount of platinum-containing drugs prepared for intravenous application ranged from 40-3260 mg/day. Urinary platinum was detected in 9 of 52 urine samples collected on days when platinum-containing drugs were mixed (limit of determination 4 ng/l). In comparison with a non-exposed control group, elevated urinary platinum levels were found in one pharmacist (35 ng/g creatinine) and one pharmacy technician (28 ng/g creatinine). The pharmacist's urinary platinum remained elevated after 2 days without occupational exposure to antineoplastic drugs. The urinary platinum level of the pharmacy technician dropped considerably after several weeks without handling cytostatic drugs. Voltammetric detection of urinary platinum is a highly sensitive method suitable for biological and environmental monitoring.

Adult↗
PubMed1994

Allergens causing bird fancier's asthma.

The study investigates to what extent bird feathers contain relevant allergens/antigens involved in bird fancier's asthma. The study group consisted of two budgerigar fanciers, two parrot fanciers and one canary fancier. All subjects complained of asthmatic symptoms, caused by contact with their birds, and they showed a significant bronchial hyperreactivity to acetylcholine. Positive IgE antibody reactions to bird sera as well as to extracts of feathers were observed in RAST. Well-defined major allergenic bands could be detected and identified in the IgE immunoblots with feather extracts as well as with serum proteins of budgerigar, parrot, pigeon, canary, and hen (mol. mass 20-30 kDa and 67 kDa). The most pronounced bands appeared with the extracts of species to which an exposure had taken place. Weaker IgG-binding patterns were also observed. Our results show that inhalable feather dust contains several allergenic components which cross-react with serum allergens/antigens of the same as well as of other bird species. This emphasizes the significance of bird feathers for immediate-type allergic reactions.

Adult↗
PubMed1994

Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs.

The occupational exposure of 21 nurses and pharmacy personnel from eight hospitals to cyclophosphamide and ifosfamide was determined by quantifying the amount of the drugs handled and by measuring the urinary excretion of the unmetabolised substances. Preparing antineoplastic drugs for intravenous treatment was the major task of all study participants. Twenty four hour urine was collected on days when cyclophosphamide and/or ifosfamide were mixed, on average 3900 mg cyclophosphamide and/or 5900 mg ifosfamide. The analyses were performed by gas chromatography with electron capture, detection limit 2.5 micrograms/24 hour urine. Despite standard safety precautions, including a vertical laminar air flow safety cabinet and gloves, cyclophosphamide was detected in 12 of 31 and ifosfamide in four of 21 urine samples on days when the drugs were handled. Excretion of cyclophosphamide ranged from 3.5 to 38 micrograms/24 h (mean 11.4 micrograms/24 h) urine, ifosfamide from 5 to 12.7 micrograms/24 h (mean 9 micrograms/24 h) urine. Based on an excretion rate of 11.3% unmetabolised cyclophosphamide, the average amount excreted corresponded to an uptake of 101 micrograms cyclophosphamide. For ifosfamide the mean quantity incorporated was 20 micrograms assuming that 45% of the drug was excreted. Pertaining to the doses handled, the uptake of cyclophosphamide and ifosfamide was estimated to be approximately 0.0025% and 0.0004% respectively. Despite time-consuming purification procedures, gas chromatographic analysis is a suitable method for monitoring personnel occupationally exposed to cyclophosphamide and ifosfamide and is a major contribution to the evaluation of potential health risks of exposed personnel.

Adult↗
PubMed1994

[Ergospirometry in sarcoidosis patients].

Our investigation should clarify the question of whether cardiopulmonary exercise testing (CPX) offers additional information of clinical relevance in patients with pulmonary sarcoidosis. We investigated the relationship between changes of lung function including the diffusing capacity and the changes of gas exchange. Furthermore, we determined the correlation of functional and morphological lung changes on the basis of radiological parameters and on the influence of a steroid therapy over the gas exchange. Forty-seven patients with histologically diagnosed pulmonary sarcoidosis were examined. The lung function test includes the measurement of lung volumes with spirometry and the diffusing capacity of carbon monoxide in the single breath technique. Minute ventilation, oxygen uptake at maximum, oxygen pulse, functional dead space/tidal volume ratio, anaerobic threshold, and alveolar-arterial oxygen difference were measured continuously during exercise. We found significant correlations between the lung volumes and the CPX data. An increased relative minute ventilation and an increased alveolar-arterial oxygen difference with exercise allows a more objective differentiation in radiological stages I and II than does the lung function at rest. A steroid therapy improves the effectivity of alveolar ventilation and an improvement of the ventilation-perfusion-match. The CPX detects early changes of pathological gas-exchange, before the lung function at rest is evident pathologically. It offers additional information on the pathophysiology of sarcoidosis, and is useful in reviewing steroid therapy.

Adult↗
PubMed1993

Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid from patients with fibrosing alveolitis.

BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the decisive event in the pathogenetic sequence leading to pulmonary fibrosis. Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL) fluid to assess its relationship to the activity of fibrosing alveolitis. METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five patients received immunosuppressive therapy and 15 refused. At the beginning of follow up BAL was performed and, as a possible indicator of fibroblast stimulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet derived growth factor. The procollagen III peptide level in BAL fluid served as a marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen III peptide concentrations in BAL fluid and chemoattractant activity were not significantly correlated. For further evaluation chemoattractant activity of 36% (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated (> or = 36%) activity. At the end of follow up, untreated patients with high chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC, and TLCO and a small increase of exercise PaO2 occurred in treated patients with high chemoattractant activity. Patients with low chemoattractant activity (< 36%) showed no consistent change in lung function measurements, irrespective of treatment. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. CONCLUSIONS: In patients with fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and may help to improve the clinical management of these patients.

Adult↗
PubMed1993

Activation of blood neutrophils in acute episodes of farmer's lung.

Farmer's lung often presents clinically as recurring acute episodes several hours after exposure to moldy hay. During these episodes the blood neutrophil count increases. Because activated neutrophils release toxic oxygen metabolites and proteinases, we hypothesized that the pulmonary reaction in farmer's lung may be induced by the secretory products of activated neutrophils. To evaluate this concept, we quantified the respiratory burst of separated blood neutrophils from patients with farmer's lung (n = 12) during standardized exposure tests with moldy hay. The respiratory burst of these cells was evaluated by measuring zymosan-stimulated and lucigenin-amplified chemiluminescence (CL). Asymptomatic farmers (n = 12) and normal volunteers with no prior exposure to moldy hay (n = 15) were used as control subjects. As expected, following exposure in the group of patients with farmer's lung, striking changes in VC, TLCO, and PaO2 were observed, whereas there were only minor changes in these parameters in both control groups. In all three groups a considerable increase in the blood leukocyte count was observed. The CL response of the blood neutrophils from patients with farmer's lung 6 h after exposure was significantly higher than before or 1 h after exposure (p < 0.05 for both comparisons), whereas there was no significant change in the CL response in either control group during the observation period. Our results indicate that antigen inhalation induces an increase in the number of circulating neutrophils in patients and controls, but in patients with an acute episode of farmer's lung the neutrophils are primed for an enhanced respiratory burst and may thereby damage the lung.

Acridines↗
PubMed1991

Isocyanate-induced asthma: results of inhalation tests with TDI, MDI and methacholine.

We performed diisocyanate inhalation tests (maximal concentration, 20 ppb; exposure time, 1-2 h) using toluene diisocyanate (TDI, n = 15) and diphenylmethane diisocyanate (MDI, n = 7) as well as methacholine challenges in 19 workers who had a clinical history of TDI/MDI-induced asthma. Additionally we tested volunteers who had no previous contact with diisocyanates: 10 healthy individuals with a negative methacholine test and 14 patients with asthma and a positive methacholine test were exposed to TDI. In all, 1 of the normal volunteers and 3 of the patients with asthma unrelated to diisocyanates showed a positive airway reaction to TDI, and 13 of the 19 diisocyanate workers displayed a positive result in the TDI/MDI inhalation test; however, only 6 of these 13 individuals reacted to methacholine. Furthermore, 3 of the 6 patients with a negative TDI/MDI challenge test demonstrated a significant response to methacholine. We conclude that bronchial hyperreactivity as evaluated by the methacholine challenge test is not closely related to isocyanate-induced bronchoconstriction and, therefore, the metacholine challenge is only of limited diagnostic value in patients with suspected isocyanate-induced asthma.

Asthma↗
PubMed1991

Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations.

To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.

Adult↗
PubMed1991

[Diagnosis of humidifier lung--comparison of various serologic procedures].

Humidifier lung is a form of exogenous-allergic alveolitis caused by microbial growth in humidifiers and air conditioners. It was the aim of the present study to employ and test the ELISA method as an alternative to antibody determination. 134 employees in a large printhouse equipped with air conditioning plant were examined by us. Specific IgG antibodies against contaminated humidifier fluid were determined by means of a solid-phase radioimmunoassay (protein A RAST) that we had developed further. Alternatively we examined a commercially available ELISA method (Pharmacia IgG-RAST 40; enzyme: beta-galactosidase) and an assay based on protein A peroxidase. The influence of different test conditions was studied. All the methods examined proved suitable for determining the specific IgG antibodies. The commercial beta-galactosidase assay could be adapted to application on microtitre plates in a slightly modified form. In the peroxidase assay it is recommended to use very low serum and enzyme concentrations on account of its high sensitivity. Examination of all the 134 serum samples yielded a high correlation between the results of these two non-radioactive methods and those obtained with the protein-A RAST.

Air Microbiology↗
PubMed1991

[Correlation of parameters of the flow-volume curve for the assessment of bronchial hyperreactivity].

The association of maximal expiratory flow-volume curve and the response of nonspecific bronchial responsiveness was studied in 265 normal and asthmatic subjects. Bronchial hyperresponsiveness to acetylcholine was found in 143 subjects. These hyperreactive persons had already significantly reduced maximal expiratory flow rate at 75%, 50% and 25% vital capacity before the test started. Besides, we found a significant correlation between the provocative dose and the flow-volume parameters, although resistance was in the normal range. We concluded that the flow rates at middle and low lung volumes may be an important determinant of bronchial sensitivity to acetylcholine.

Acetylcholine↗
PubMed1990

[Bronchial asthma in a hairdresser caused by hair bleach].

Three years after starting to work as a hairdresser a 33-year-old woman developed urticaria on contact with hairbleach. After a further four years rhinoconjunctivitis set in and later also bronchial asthma on contact with such bleaches. Extensive tests revealed hypersensitivity to widely used persulphate-containing bleaching liquids which ultimately forced the patient to give up her profession. The causative role of this group of chemicals was proven by positive skin tests and specific workplace-related provocation tests. But specific IgE antibodies could not be demonstrated. The findings suggest a pseudoallergic reaction.

Adult↗
PubMed1990

Tuberous sclerosis with pulmonary involvement.

Pulmonary involvement in tuberous sclerosis (pTS) is very rare and seems to be associated with a more benign course, compared to tuberous sclerosis without pulmonary manifestation (TS). Furthermore, pTS seems to be related to lymphangiomyomatosis (LAM). We present the case of a 33-year-old woman in whom the overlap of TS, pTS and LAM is demonstrated. Treatment with medroxyprogesterone was initiated, but without success.

Adult↗
PubMed1990

Beta 2-adrenoceptors in human lung and peripheral mononuclear leukocytes of untreated and terbutaline-treated patients.

Beta 2-adrenoceptor agonists act against bronchoconstriction by stimulating beta 2-adrenoceptors in bronchial smooth muscle. However, tachyphylaxis has been argued to occur because of beta 2-adrenoceptor down-regulation following therapy with beta 2-adrenergic agents. To investigate receptor alterations, human peripheral mononuclear leukocytes are frequently used, since human lung tissue is not easily available. In order to study whether beta 2-adrenoceptors in MNL reliably reflect the conditions in the human lung tissue, we compared MNL and human lung tissue of 18 patients who had to undergo lung resection. Ten patients were untreated, and eight had bronchodilator therapy prior to therapy with terbutaline because of bronchoconstriction. Both in human lung and MNL, the beta 2-adrenoceptor subpopulation was characterized by competition experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist ICI 118.551. In MNL, a significant decrease in the density of beta 2-adrenoceptors was found in treated but not in untreated patients, while the antagonist affinity of the beta 2-adrenoceptors remained unchanged. However, in lung parenchyma, which was obtained at the very same time from the same patients, no down-regulation of the total amount of beta 2-adrenoceptors could be measured. It is concluded that MNLs are a reliable model for studying properties of beta 2-adrenoceptor regulation. However, the hereby obtained results show that MNLs do not reflect the conditions of beta 2-adrenoceptors in human lung tissue. Human lung tissue is found to be less susceptible than human MNL for beta 2-adrenoceptor down-regulation by terbutaline treatment at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

[Diagnosis of irritative-toxic isocyanate asthma with the isocyanate exposure test].

We investigated 10 healthy control subjects, 15 asthmatics without occupational exposure to isocyanate, and 45 "isocyanate workers" with workplace-related respiratory symptoms. In none of the cases did the skin test or the IgE-RAST reveal a type I sensitisation to isocyanate. The investigation programme included a lung function test, provocation with metacholine or acetylcholine, and an isocyanate challenge test under controlled clinical conditions. A total of 17 "isocyanate workers", and 1 asthma patient with no occupational exposure to isocyanate revealed a positive bronchial obstructive reaction to the isocyanate challenge test. In 10 of the patients, the MCH (ACH) test was positive; 2 were chronically obstructive, but 6 patients showed no signs of bronchial hyperreactivity. No significant differences in the severity of the bronchial obstructive reaction induced by isocyanate exposure were observed between patients with and those without bronchial hyperreactivity. In the group of "isocyanate workers", the isocyanate challenge test was observed to be superior to the MCH (ACH) provocation test in terms of sensitivity (0.68 versus 0.62) and specificity (1.0 versus 0.61), this difference being more obvious in the overall group (sensitivity 0.71 versus 0.62; specificity 0.98 versus 0.49).

Airway Resistance↗