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Biomedical subjects

N G Orie

Publications and source records attributed to N G Orie.

At least 19 recordsLinked to original sources
PubMed1991

The Dutch hypothesis (chronic non-specific lung disease) revisited.

In 1961 the hypothesis (later referred to as the Dutch Hypothesis (DH)) was put forward that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors play a role in the pathogenesis. A hereditary predisposition to develop allergy and bronchial hyperreactivity were considered to be important denominators of disease susceptibility. Complications and complicating diseases would also contribute to the ultimate phenotype of the patient. In the present paper we discuss the relevance of this hypothesis in 1990. Until now it has not been refuted; circumstantial evidence in its favour has accumulated, but formal proof is still lacking. Further research should pay more attention to the genetic aspects of the disease. Arguments are presented against the use of the terms asthma, chronic bronchitis, and emphysema as indicators of disease entities, and in favour of the use of an umbrella-term, e.g. chronic non-specific lung disease (CNSLD), provided that, in addition, every patient is characterized using so-called defining criteria.

Asthma↗
PubMed1987

Pharmacokinetics and pharmacodynamics of thiazinamium in asthmatic patients.

The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction. Disposition after i.v. administration was described by a clearance of 0.54 l.min-1, central compartment volume of 14.8 l, distribution rate constant 0.092 min-1, and an elimination rate constant of 0.0044 min-1. The corresponding estimates after i.m. administration were 0.324 l.min-1, 34.1 l, 0.035 min-1, and 0.0018 min-1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC50 of 12.8 ng.ml-1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng.ml-1, and 9 min. Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats.min-1, with an EC50 of 176 ng.ml-1 and an equilibration half-time of 1.3 min. After i.m. administration the corresponding values were 120 beats.min-1, 250 ng.ml-1, and 3 min. The optimal plasma concentration of thiazinamium was about 100 ng.ml-1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats.min-1.

Adult↗
PubMed1979

First-pass effect after rectal administration of thiazinamium methylsulfate.

The absorption and metabolism of the quaternary ammonium compound thiazinamium methylsulfate were studied in humans using plasma concentration data and urinary excretion measurements. After giving a dose of 150 mg in suppositories, the relative bioavailability was 5.8 +/- 3.2 (SD) % of the dose, comparable to the values obtained following oral administration. The degree of first-pass effect observed after rectal administration was comparable with that after oral administration.

Aged↗
PubMed1978

Purification of specific precipitinogen and extraction of endotoxin from Haemophilus influenzae.

After purifying a Haemophilus influenzae precipitinogen from endotoxic activity by means of ultracentrifugation, column chromatography (Sepharose 6B) and ion exchange chromatography (DEAE Sephadex A25) a fraction was obtained which still contained a specific precipitinogen that was virtually free of endotoxin. Furthermore, during the chromatographic procedures fractions with a high and a low molecular weight endotoxic activity were found. The limulus lysate test was more sensitive in the high molecular weight fractions and the LD50 in mice in the low molecular weight fractions with endotoxic activity.

Animals↗
PubMed1978

The primary immune response of patients with different stages of squamous-cell bronchial carcinoma.

Using the indirect ELISA technique, the IgM, IgG, and IgA antibody response to the primary test immunogen Helix pomatia haemocyanin (HPH) was studied in 30 patients with various clinical stages of primary squamous-cell bronchial carcinoma and compared with values obtained in 15 controls matched for sex, age, smoking habit, and presence of chronic bronchitis. Patients with disseminated disease (stage III) showed a significant decrease in IgG and IgA antibody response (P less than 0.001), but IgM antibodies were relatively high and not different from the controls. Although normal IgG and IgA antibody titres were found at the peak response two weeks after immunisation in patients with localised disease (stage I), these antibody titres showed a significantly more rapid decline after serial investigations at eight and 14 weeks after immunisation compared with the controls (P less than 0.001) despite total removal of the tumour burden at c four weeks after immunisation. In-vitro HPH-induced lymphocyte transformation was considerably decreased in state I patients (P less than 0.01) as well as in stage III patients (P less than 0.001). The results suggest that patients with squamous-cell bronchial carcinoma develop impaired T-cell function, which gives rise to a defective antibody response and in-vitro lymphocyte reactivity to the T-cell dependent primary immunogen HPH.

Aged↗
PubMed1977

Determination of oxyphenonium bromide in plasma and urine by means of ion-pair extraction, derivatization and gas chromatography-electron-capture detection.

A sensitive and selective method for the determination of the quaternary ammonium compound oxyphenonium bromide (Antrenyl), a drug with strong anticholinergic properties, in human plasma and urine is described. The method is based on ion-pair extraction of the cation with perchlorate, a re-extraction according to ion-pair principles with tetrapentylammonium as the counter ion, hydrolysis to cyclohexylphenylglycolic acid, derivatization of this acid to its pentafluorobenzyl ester and determination of the ester by gas chromatography and electron-capture detection. Quantitation is possible down to 2 ng/ml of oxyphenonium bromide using 1 ml of plasma and down to 200 ng/ml using 0.1 ml of urine. The method described can also be applied to other anticholinergic drugs with an ester function.

Animals↗
PubMed1977

Variations in the bioavailability of thiazinamium methylsulfate.

Bioavailability after oral administration of the anticholinergic drug thiazinamium methylsulfate (Multergan), a phenothiazine derivative with a quaternary ammonium group in the molecule, has been studied in patients and volunteers by measuring the drug concentrations in plasma or the excretion of the parent drug in urine. The relative bioavailability as compared to intramuscular injection seems to be of the order of 10%. Much more of the drug is absorbed, however, but is metabolized during the first liver passage. Moreover, there seems to be a substantial interindividual variation in the bioavailability of the drug. Studies in a group of eight volunteers showed that there is also a substantial intraindividual variation, but its magnitude is smaller than that of the interindividual variation.

Administration, Oral↗
PubMed1977

Pulmonary gas transfer 20 years after pneumonectomy for pulmonary tuberculosis.

The changes in pulmonary function after pneumonectomy in 13 patients with pulmonary tuberculosis have been studied. The data at the time of two follow-up studies are compared with those obtained before the pneumonectomy. The first follow-up was carried out between 5 and 30 months postoperatively and the second between 20 and 24 years later. The results of this second follow-up show a relatively normal arterial oxygen saturation and gas transfer factor but an increased residual volume which cannot be explained by increasing age alone.

Adult↗