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Biomedical subjects

E W Schmidt

Publications and source records attributed to E W Schmidt.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

[Substitution therapy with alpha-1-Pi in patients with alpha-1-Pi deficiency and progressive pulmonary edema].

In a multi-centre study 20 patients with severe congenital alpha-1-Pi deficiency and progressive pulmonary emphysema received infusions of alpha-1-Pi concentrate from human plasma once weekly for six months, at an initial dosage of 60 mg/kg body-weight, in some instances slightly increased to achieve a minimum serum level above 70 mg/100 ml. The immunologically measured serum level of alpha-1-Pi rose 30 min after start of the infusion by a mean of 130% of normal, at an initial level of 13%. An exponential fall followed this rise. The lowest level occurred at the end of the first week, immediately before the next infusion, to 35% of normal, a serum level which is assumed still to provide an effective protection against elastases in the lung. There was also a definite increase of free inhibitors against both trypsin and leucocyte-elastase in serum of all patients, with a minimal level which for both was many times that of the initial value. There were no side-effects in more than 500 infusions and no dose reduction was necessary. During the entire course there were no significant changes in haematological, coagulation and biochemical test results, and lung function means remained constant. No antibodies against alpha-1-Pi were demonstrated, nor transmission of hepatitis B.

Clinical Trials as Topic↗
PubMed1987

[Anticholinergics as bronchodilators. An action profile].

In 3 test series comprising 107 patients the cholinergic proportion and the proportion of airway obstruction controllable by beta 2-sympathomimetics were determined. A reversible and an irreversible proportion of increased flow resistances in airways are detected. The reversible proportion has to be divided into a section controllable by beta 2-sympathomimetics. Both substance groups have an additive effect extending up to the irreversible proportion. In most cases, the proportion controllable by beta 2-sympathomimetics is larger than that controllable by anticholinergics. The cholinergic proportion of the airway obstruction can be blocked completely by 0.02 mg (0.04 mg) of the controlled dosage aerosol or by 0.125 mg iptratropium bromide (ITB), resp. The cardially recognizable anticholinergic effect is low in this connection. Complete cholinergic cardial block only occurs upon intravenous doses between 0.25 mg and 0.5 mg ITB.

Administration, Oral↗
PubMed1985

The changing concepts of condyloma. A retrospective study of colposcopically directed cervical biopsies.

Human papillomavirus has been implicated in the etiology of cervical intraepithelial neoplasia. A retrospective audit was conducted on all colposcopically directed biopsies performed from June through November, inclusive, in the years 1980 and 1982, a total of 317 cases. In 1980, the misdiagnosis rate for condyloma was 88.9% (69 of 78) and, in 1982, the misdiagnosis rate was reduced to 28.5% (40 of 140). On review, the association of cervical intraepithelial neoplasia with condyloma was 73% (107 of 146), p less than 0.005. The differences in mean ages of patients with condyloma alone, cervical intraepithelial neoplasia with condyloma, and cervical intraepithelial neoplasia alone were significant, p less than 0.02. When condyloma is not recognized, the pathologist tends to overdiagnose grade 3 cervical intraepithelial neoplasia as shown in 28 original cases; 16 of 28 (57.1%) were condyloma alone on review. Fifteen (53.6%) of these 28 patients underwent a cone biopsy or hysterectomy when a less radical procedure would have been acceptable. The morphologic changes indicating cervical condyloma were not fully appreciated by the pathologist, and this resulted in overdiagnosis and later overtreatment by the gynecologist.

Adult↗
PubMed1985

Pharmacokinetics of triamcinolone acetonide and its phosphate ester.

Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.

Adult↗
PubMed1985

Kinetics of methylprednisolone and its hemisuccinate ester.

Methylprednisolone in the form of its hemisuccinate ester was injected intravenously in doses of 10 mg/kg and 63.1 mg. Plasma levels of methylprednisolone and of the ester were measured and their kinetics were calculated. Results indicate dose dependency in the kinetics of both. About 10% of the dose was excreted unchanged as hemisuccinate in the urine, indicating incomplete conversion of the prodrug. When methylprednisolone (80 mg) was also taken by mouth, the relative bioavailability of the tablets was 99%. Saliva levels of methylprednisolone were low but paralleled plasma levels in the postdistribution phase. No methylprednisolone hemisuccinate was found in saliva.

Absorption↗