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Biomedical subjects

E W Schmidt

Publications and source records attributed to E W Schmidt.

At least 19 recordsLinked to original sources
PubMed1998

[Submaximal spiroergometric stress study in patients with mixed dust pneumoconiosis].

Disabilities of patients with coal-workers' pneumoconiosis (CWP) are currently estimated by changes in lung function at rest and the degree of dust equivalents in chest x-ray (ILO-classification 1980). Functional disturbances during exercise are not taken into consideration on a regular basis. We assumed that standardised sub-maximal exercise tests might be useful even in disabled patients to give additional information on functional disabilities of patients with CWP. The impact of low-grade anthracosilicosis on ventilation and gas exchange during exercise was assessed in 20 patients (all male, age 64.55 +/- 3.78 years) and 24 healthy volunteers (all male, age 58.13 +/- 4.68 years, never dust exposed). Data were also analysed according to ILO classification subgroups (group 1: ILO-classification 1/0 to 1/2, n = 11; group 2: ILO-classification 2/1 to 2/2, n = 9). Heart rate (HR), minute ventilation (VE), ventilatory equivalent for O2 (VE/VO2), ventilatory equivalent for CO2 (VE/VCO2), O2 uptake (VO2)CO2 output (VCO2), end-tidal oxygen partial pressure (PetO2), end-tidal carbon dioxide partial pressure (petCO2) and estimated dead space to tidal volume ratio (VD/VT) were determined breath-by-breath during a 50 watts constant work load protocol on an exercise bicycle. The VE/VO2 (patients: 32.9 +/- 4.2; controls: 25.7 +/- 2.9; p < 0.001), the VE/CO2 (patients: 39.4 +/- 4.6; controls; 31.0 +/- 3.9), the VE (patients: 30.1 +/- 5.6, controls: 23.5 +/- 3.0; p < 0.001) and the PetO2 (patients 115.6 +/- 4.8; controls: 99.1 +/- 27.4; p < 0.05) at an exercise of 50 watts were significantly higher in the patients' group, the PetCO2 (patients: 38.4 +/- 4.5; controls: 44.0 +/- 4.1) were significantly lower in the patients' group. The comparison of patients subgroups did not reveal any significant differences between group 1 and group 2. A higher VE/VO2 during 50 watts of exercise is attributable to an increased ventilation/perfusion mismatch. There was no correlation between the radiological grade of the CWP (ILO classification) and the ventilation and gas exchange during exercise. We conclude that a sub-maximal spiroergometry with a 50 watts constant work load might serve as a sensitive and easy to apply procedure add information about the functional impairment in CWP. The exercise test should be included in the evaluation for disability benefits.

Adult↗
PubMed1998

Pharmacokinetics of beta2-sympathomimetics at the example of fenoterol and conclusion for the administration.

The pharmacokinetics of fenoterol (salbutamol, terbutaline) after systemic administration (i.v., infusion, nasal administration) can be best described by a three-compartmental model. Nasal administration causes an effect-time profile between that of infusion and inhalation. The effects of nasal administration on the lung function and the heart rate depend on the plasma levels of the beta2-agonist. The absorption rate after inhalation differs individually in a large variability (1-27% of the dosage). After inhalation the effect on the lung function does not depend on the absorption rate nor on the plasma levels of the beta2-agonist. After inhalation the effect on the lung function is three- to fivefold more expressed than predictable from the plasma level. From the pk/pd data it can be assumed, that there are 10-20 fold higher concentrations in the airways than in the plasma. It is assumed that there are structures nearby the beta2-receptor responsible for the long-lasting effect observed after inhalation. These depot structures cannot be reached from the plasma in concentrations needed for bronchodilation under in vivo conditions. In respect to the effect/side effect relations, there is no doubt that inhalation is the optimal solution for administering beta2-agonists. In respect to the effect/side effect relations more frequent administration of small doses seems to be more favourable than high doses inhaled in long periods.

Absorption↗
PubMed1998

[Dyspnea and lung function. Results of a multicenter study].

UNLABELLED: In seven pneumological centres 266 patients with different pneumological diseases were investigated. After having clarified several questions regarding the severity of the dyspnoea, cough intensity and the volume of sputum, as well as basic clinical investigation and after an x-ray of the thorax, the diagnosis was arrived at. Subsequently the lung function investigation with the flow-volume curve (including IVC, FVC, PEF, FEV1, MEF50%) and the body plethysmographic Rt and IGV were carried out. Different quality control procedures at and between the different centres ensured comparable results. All centres agreed to using methods well compatible with each other. The question as to which kind of parameters of lung function would agree best with the amount of the dyspnoea, was resolved. The causes for the large scatter of the results are described. Cough and sputum exercise an influence even on the degree of dyspnoea, but not by deteriorating the lung function. The results are shown for the entire collective (Part I) in respect of the different diagnoses (Part II). With different diagnosis the same significant correlations exist but the curves are positioned at different levels of the coordinate system. CONCLUSION: Significant correlations exist between the dyspnoea scale and function parameters. There are individual differences between the dyspnoea scale and disturbances of the function parameters. Carefully performed lung function analyse definitely important in any case.

Adult↗
PubMed1997

The flow-volume curve in patients with obstructive airway diseases partial analysis and functional importance.

Flow-volume curves in patients with obstructive airway disease differs from that observed in healthy subjects. Two types of pathological curves can be differentiated: these with clear sharp bend and intermediate forms characterised by the different grade of concavity of the descending segments plotted against X-axis. The aim of our present investigation is to elucidate the mechanisms which determines the forced expiratory airflow course in patients with obstructive airway diseases. Patients with sharp bend curves show changes of the several lung function data which are more advanced than in subjects with the intermediate forms of the flow-volume curves. In cases of bend curves the volume of the forced expiration can be differentiated on the two parts: circumferential and serial. Circumferential volume exhaled on the very beginning of the expiration (above the bend) amounts 0.118L in average. This volume depends on the expiratory narrowing of the bronchi from the 1-st to 9-th generation. The serial volume contained between the bend and the end of expiration amounts about 95% of the expired volume. Flow limitation occurs in 5-th to 9-th generations which is manifested by the strong increase of the flow resistance. The intermediate types of the flow-volume curves is caused by the inhomogenous emptying of the lung together with corresponding volume dependent narrowing of the bronchi. The same mechanisms can be detected even on the bodypletysmographic tidal breathing resistance curves. The concave and particularly bend flow-volume curves has been attributed to the pulmonary emphysema. This is not entirely truth. Other conditions leading to inhomogenic emptying of the lung due to airway and parenchymal changes (such as lung cicatrisation) can influence expiratory flow course resulting in concave or even bend flow-volume relationships.

Adult↗
PubMed1997

[Correlation of radiologic and pathologic-anatomical findings in dust-induced pneumoconiosis in former coal miners].

The ILO classification of small and large opacities is the basis for the compensation of patients with pneumoconiosis. In order to validate the radiological findings, we compared the ILO classification with the gradings of pneumoconiosis in the post mortem investigation (n = 126). An ILO classification of 1/0 used as the threshold value for accepting the diagnosis of a pneumoconiosis was 100% sensitive with a specificity of 2%. With a value of 2/3 the sensitivity decreased to 60% and specificity increased to 74%. The grading of large opacities in the radiograph correlated well with the post mortem findings (rs = 0.71; p < 0.001). For accepting the diagnosis pneumoconiosis from the radiograph alone a threshold value of 1/0 is not specific. The ROC-plot revealed that specificity reached acceptable levels with an ILO classification of at least 2/3.

Coal↗
PubMed1996

[Chronic bronchitis and its sequelae. Therapy--prognosis--insurance medicine aspects].

Chronic bronchitis is of enormous epidemiological, socio-medical and economical importance. The main cause of chronic bronchitis is active but also passive cigarette smoking. Other etiologic factors are: viral or bacterial infections, chronic dust exposure in occupational settings and air pollution. Cease of cigarette smoking is considered the most valuable action in the treatment of the chronic bronchitis. In addition to drug therapy, physical therapy and other measures of rehabilitation may be a supportive benefit. ABout 10-20% of all patients with chronic bronchitis develop airway obstruction and/or lung emphysema. Obstructive bronchitis with or without lung emphysema should be treated with corticosteroids, beta 2-agonists and/or theophylline. Evidence for the socio-economical burden of chronic bronchitis and its complications are the enormous costs for the social economy (direct costs: in- and outpatient treatment; indirect costs: premature pensions, sick leave).

Bronchitis↗
PubMed1995

Makaluvamines H-M and damirone C from the pohnpeian sponge Zyzzya fuliginosa.

Seven new pyrroloiminoquinone alkaloids, makaluvamines H-M [19-24] and damirone C[25], together with the known compounds, makaluvamines C[13], D[14], and G[17], were isolated from the sponge Zyzzya fuliginosa collected at Nahpali Island, Pohnpei, Micronesia. The structures of the new compounds were elucidated by interpretation of spectral data. The chemotaxonomic relationships involving the makaluvamines and related pyrroloiminoquinone alkaloids are discussed.

Animals↗
PubMed1995

Pharmacokinetics and pharmacodynamics of beta 2-agonists (in the light of fenoterol).

As an example of beta 2-agonists fenoterol was used in this study on 27 patients with chronic obstructive airways diseases (COAD). After refraining from any kind of bronchodilator during 12 h the patients were given the drug in a crossover design in three groups. Using aerosol inhalation, intravenous route and nasal instillation we measured the response of airway resistance, intrathoracic gas volume and fenoterol plasma concentrations. The plethysmographic measurement of airways resistance (Rt) and intrathoracic gas volume showed comparable results of bronchodilation (at different dosages) for each of the routes. Even the onset of action was nearly the same with all the different routes. The amount of bronchodilatation was in the range of 59% of the initial Rt values. The duration of bronchodilatation was much longer after metered dose inhalers (MDI) inhalation ( > 4 h) than after intravenous routes. The duration after nasal administration was in between. The infusion maintains its effect only as long as the infusion is given. The bronchodilation response induced by fenoterol reaches the same values with different routes of administration and depends on the amount of decrease of airway obstruction. The highest plasma concentrations were reached with the intravenous boluses. Immediately after injection the concentration decreased rapidly. The maximum plasma concentrations after MDI were around 20% of that after the intravenous route for the same bronchodilatation. The heart rate is a function of the plasma concentration. At low concentrations such as after aerosol inhalation of 200 micrograms the influence on the heart rate is not significant. After aerosol inhalation the effect at the receptor can be calculated to be > 7 times stronger than seen from any plasma concentration after intravenous administration. It is assumed that there are structures near the beta 2-bronchodilator receptor which are responsible for the long-lasting effect that is observed only after aerosol inhalation. These depot structures cannot be reached from the plasma in concentrations needed under in vivo conditions. Loss of these structures shortens the duration of the bronchodilator effect. In respect to effect/side effect relationship, more frequent administration of smaller doses may be the best method for administering beta 2-agonists as aerosols in patients with COAD. For many patients with severe forms of this disease, individual optimal dosage with MDI has to be defined following repeated measurements of the airway obstruction so as to achieve the best possible bronchodilatation.

Administration, Intranasal↗
PubMed1995

[Effect duration and treatment effectiveness of salmeterol, fenoterol and salbutamol in severe forms of respiratory tract obstruction].

Duration and intensity of bronchodilator action of 0.2 mg Fenoterol, 0.2 mg Salbutamol, and 0.05 mg Salmeterol were investigated in 15 subjects with COPD over a period of 12 hours. Airway resistance and FEV1 were measured and subjective side effects noted. Salbutamol MDI was used as rescue medication. Airway resistance and FEV1 demonstrated significant bronchodilation with all bronchodilator drugs after 15 min and maximum bronchodilation between 1 and 2 hrs. After 3 to 5 hrs. bronchodilator effects of fenoterol and salbutamol are lost by at least 50%, whereas this effect is only seen after 8 to 9.5 hrs. with salmeterol. There were considerable individual differences of the efficacy of all three drugs. However, salmeterol was equally efficaceous, compared to fenoterol and salbutamol, but its duration was at least twice as long. Consequently, rescue medication was used in only about 50% of the cases. Side effects of all substances were comparable. From these data it may be concluded that the efficacy of beta2-adrenergic agonists is comparable, irrespective of the duration of action of a single administration, if repeated administrations are used with short acting substances. In addition, this study confirmed that in individual patients a) the response to beta2-adrenergic agonists is variable and b) that different lung function parameters such as airway resistance and FEV1 may give different results.

Adult↗
PubMed1995

[Responder and non-responder in the bronchodilator test?].

In 15 patients with chronic airflow obstruction 0.2 mg salbutamol was administered to determine reversibility within 15 minutes ("test effect"). Subsequently, maximum 24-hour effects of three beta 2-agonists (fenoterol 0.2 mg, salbutamol 0.2 mg, salmeterol 0.05 mg, each by MDI) were determined in random order ("best effect"). Airways obstruction was measured by FEV1, MEF50, MEF25, airway resistance Raw and thoracic gas volume TGV. "Best effects" were compared with "test effects". As a whole test effects were significantly smaller than best effects, often not reaching a 15% change, normally achieved during the 24-hour observation. Significant correlations existed between FEV1 and the corresponding values of Raw, MEF50 and MEF25, although there were considerable individual differences between test results. The reduction of TGV after a beta 2-agonist was significantly related to TGV-baseline values. We conclude in line with other authors that tests of acute reversibility of airways obstruction cannot reliably differentiate between "responders" and "non-responders" and that such tests may mislead if used for the differentiation of asthma and COPD.

Administration, Inhalation↗
PubMed1994

Orbital myositis as a paraneoplastic syndrome.

We describe a patient with bilateral orbital myositis, multiple cranial neuropathies, a sensory polyneuropathy, serum and cerebrospinal fluid paraproteins, and high-grade non-Hodgkin's lymphoma. Neurologic symptoms began more than 1 year before diagnosis of the lymphoma. Results of extraocular muscle biopsy showed extensive destruction of myofibers and granulomatous features, with no evidence of direct tumor involvement. The cranial neuropathies and orbital myositis improved with immunosuppressive therapy, while the patient's tumor progressed. We believe the orbital myositis and the multiple neurologic abnormalities were paraneoplastic effects of the lymphoma. To our knowledge, this is the first case of orbital myositis identified as a paraneoplastic syndrome.

Adult↗
PubMed1994

Immunogenetic studies on HLA-DR in German coal miners with and without coal worker's pneumoconiosis.

Coal worker's pneumoconiosis is caused by the pulmonary deposition of coal dust, including silica particles. Several factors such as chemical composition and physical properties of silica-containing dust, particle size distribution, intensity, and duration of exposure influence the disease development. Genetic factors may also be involved. To define whether HLA-DRB may function as a genetic factor for predisposition to coal worker's pneumoconiosis, we determined DRB1, 3, 4, 5 alleles. For this purpose, DRB typing with sequence-specific oligonucleotide probes in 204 German miners with pneumoconiosis and in 52 German miners without pneumoconiosis was used. The miners had worked under comparable conditions. The frequency of DR8 (1*0801-0804) was increased in patients developing pneumoconiosis during the first 15 years of mining (p = 0.047). The frequency of DR1 (1*0101-0103) was elevated (p = 0.022) and that of DR52 (3*0101, 3*0201, 3*0202, and 3*0301) was reduced (p = 0.026) in miners without pneumoconiosis. Our data show that the presence of DR1 and the absence of DR52 support the resistance to coal worker's pneumoconiosis. Furthermore, DR8 may be involved in the rapid development of coal worker's pneumoconiosis.

Adult↗
PubMed1993

[Lung function and normal values].

Interindividual derived predicted values of lung function are not suitable for detection of early changes of lung function. Intraindividual values show variability, which should be considered. Many of the very common obstructive lung diseases start with small variations of the individual values of lung function, long time before clinical manifestation takes place. Followup of the most useful measurements (FEV1, MEF 50%, Rt und IGV%) show reliable early changes, important for preventive therapeutic intervention. Strong variability of the individual values argue for hyperreagibility of the airways, even as a risk factor for manifestation of obstructive airway diseases.

Adult↗
PubMed1992

Pharmacokinetic/dynamic correlation of pulmonary and cardiac effects of fenoterol in asthmatic patients after different routes of administration.

Pulmonary and cardiac effects of the beta 2-adrenergic drug fenoterol were studied in 27 asthmatic patients using an integrated pharmacokinetic/dynamic (PK/PD) approach. Airway resistance (Rf), intrathoracic gas volume (IGV), heart rate, and plasma levels were monitored after placebo, injection (12.5 and 25 micrograms), nasal instillation (400 micrograms), inhalation (200 and 400 micrograms), and infusion (200 micrograms/180 min with or without loading dose). The pharmacokinetics were best described by an open three-compartment model with a terminal half-life of 200 min (gamma = 0.23 +/- 0.08 L/hr), a volume of distribution at steady state of 1.9 +/- 0.8 L/kg, and a clearance of 0.86 +/- 0.32 L/hr/kg, with 14 and 9% absorbed after nasal and pulmonary administration, respectively. For the noninhalation regimens, a PK/PD correlation linked the concentration in the shallow pharmacokinetic compartment to the investigated effects via an Emax relationship, resulting in three to five times higher EC50 values (concentration necessary to achieve half-maximal effect) for the heart rate than for the beta 2-mediated effects on IGV and Rf. In contrast, pulmonary effects after inhalation could not be incorporated into the correlation, indicating that these effects are induced locally after inhalation. Intrapatient variability for EC50 and Emax was approximately 90%.

Administration, Intranasal↗
PubMed1990

Long term effect on lung function of alpha 1-protease inhibitor substitution therapy in COPD patients with Pi ZZ phenotype.

Eight patients suffering from alpha 1-protease inhibitor (alpha 1-PI) deficiency (Pi ZZ phenotype) and chronic obstructive lung disease received substitution therapy (60 mg.kg-1 weekly) for a period of up to 30 months. Intrathoracic gas volume, airway resistance and arterial oxygen tension were followed once every three months. There was no trend for these indices to deteriorate or improve over the period of observation.

Airway Resistance↗
PubMed1989

[Pulmonary emphysema. Clinical aspects and open questions].

The development of airway obstruction is decisively influenced by the formation of emphysemata. Preventing the formation of emphysemata will have a substantial influence on the progression of obstructive airway diseases. Absolute as well as relative protease excess can be regarded as essential cause for emphysemata. Alpha 1-antitrypsine as significant protease inhibitor in alveolar regions is capable of compensating for a protease imbalance. Processes accompanied by an excess of proteases in the alveolar region should be influenced by adequate alpha 1-antitrypsine substitution to prevent the development of emphysemata. This promising preventive as well as therapeutic principle is apt to be extended and specified.

Humans↗