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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
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↗
PubMed1989

Biochemical reaction of alpha 1 antitrypsin during the substitution therapy of patients with homozygote PI-ZZ deficit.

The homozygote deficit of alpha 1 antitrypsin (alpha 1 PI-ZZ) in patients frequently results in a premature development of emphysema in the lung due to incomplete protection against proteases. An active inhibitor substitution appears to be useful. The presented study proves the biological effect of alpha 1 antitrypsin infused into 8 patients. The results were an activity increase of leukocyte elastase and trypsin inhibition in serum as well as doubling of alpha 1 antitrypsin in sputum. This therapeutical conception (with a dose of 60 mg/kg body weight/week) results in an efficient protection. Inhibitors specific for mucosa are not influenced. An improvement of lung function during 6 weeks of intravenous therapy was not achieved. The progressive destruction of lung parenchyma can be probably prevented, however.

Adult↗
PubMed1989

Controlled prospective study of oral amoxycillin/clavulanate vs ciprofloxacin in acute exacerbations of chronic bronchitis.

This investigation compared the efficacy of oral formulations of amoxycillin/clavulanate and ciprofloxacin in acute exacerbations of chronic bronchitis. Forty patients were randomized to receive either Augmentin (1,000 mg amoxycillin +250 mg clavulanate) tds or ciprofloxacin (500 mg) bd. During and before therapy sputum samples were taken for bacteriology, sputum volume measurement and histamine determination. Lung function was also monitored. From sputum, 143 bacterial isolates and 15 yeast strains were obtained before therapy. During therapy with amoxycillin/clavulanate the incidence of Gram-positive isolates decreased significantly whereas ciprofloxacin left their frequency unchanged. On the other hand, ciprofloxacin more effectively diminished the incidence of Gram-negative isolates. Yeasts were grown from the sputum of several patients before and during therapy. Their number did not increase during amoxycillin/clavulanate therapy while it increased under ciprofloxacin. The groups showed no significant differences with regard to sputum production, histamine concentration or lung function. The majority of patients (28/40) acknowledged improvement of their symptoms. There was no significant difference between the groups. On the basis of these results both amoxycillin/clavulanate and ciprofloxacin appear of similar value for treatment of patients with exacerbations of chronic bronchitis.

Aged↗
PubMed1989

[Changes in the bronchial musculature in chronic obstructive respiratory tract diseases].

Changes in the bronchial musculature in patients with chronic obstructive lung disease, were submitted to a systematic electron-microscopic investigation. A marked interstitial fibrosis with degenerative changes affecting the muscle cells was observed. The formal pathogenetic course of these changes can be reconstructed on the basis of numerous individual findings. The muscle cells are progressively "ensheathed" in a disorderly fine-filamentous basic structure (matrix), and in collagenous fibres. As a result, the contact surfaces between the muscle cells are disturbed, and the nerve endings "displaced" from the muscle cells. This fibrosis is associated with a protracted "shrivelling" of the individual muscle cells. The changes involving the muscles of the bronchial wall are comparable with those seen in the smooth muscles of blood vessels involved in arteriosclerosis. The morphological changes to the muscles of the bronchi described in this paper strongly suggest that protracted fibrosis formation, coupled with the degradation of muscle cells, contribute to a loss of elasticity of the bronchial wall in chronic obstructive lung disease.

Adult↗
PubMed1988

Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease.

In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.

Adult↗