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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↗
PubMed1986

Sensitivity to hydrocortisone is a relevant factor in the immunoendocrine relationship. I. The cell-mediated immune response in relation to blood levels and in vitro immunosuppressive effects of hydrocortisone in patients with asthma and healthy control subjects.

The role of endogenous hydrocortisone in the regulation of lymphocyte activity was assayed in patients with asthma (patients with chronic nonspecific lung disease, characterized by attacks of dyspnea, alternating with symptom-free periods) and healthy control subjects. After priming, delayed-type hypersensitivity skin reactions were induced with Helix pomatia hemocyanin (HPH). Hydrocortisone blood levels were measured. The effect of hydrocortisone on HPH-induced lymphocyte proliferation was determined in vitro. The results demonstrate that hydrocortisone in low concentrations (100 ng/ml) inhibited in vitro lymphocyte proliferation equally in patients and control subjects. However, both groups demonstrated a large interindividual variation in hydrocortisone sensitivity. Therefore, in order to determine the immunologic effect of hydrocortisone blood levels in vivo, a hydrocortisone suppression index (HSI) was calculated by use of the information on hydrocortisone concentrations in vivo and the biologic effect of hydrocortisone in vitro. This HSI appeared to be inversely related with the in vivo cell-mediated immune response to HPH. This was reflected in an inverse correlation between HSI and delayed-type hypersensitivity skin reactions to HPH, both in patients (R = -0.64), in control subjects (R = -0.69), and in the total group (R = -0.68; p less than 0.001). No differences were observed between patients and control subjects. It is concluded that endogenous hydrocortisone is likely to play an important role in the regulation of lymphocyte activity in patients with asthma and healthy control subjects. This may have important consequences for the clinical expression of asthmatic symptoms, since the role of lymphocyte activity in the pathogenesis of asthma is increasingly recognized.

Adult↗
PubMed1986

Primary cell-mediated immune response in bronchial asthma. Relationship between primary in vitro and in vivo cell-mediated and antibody responses in patients with asthma and healthy controls.

Eleven patients with asthma and ten sex and age matched healthy controls were immunized with the primary immunogen Helix pomatia Haemocyanin (HPH). The amplitude and the kinetics of in vitro cell-mediated immune response were measured by HPH-induced lymphocyte proliferation. Lymphocytes were also challenged in vitro with mitogens and recall antigens. In vivo cell-mediated immunity was determined by inducing delayed type hypersensitivity reactions with HPH. Anti-HPH antibody responses in the IgE, IgG and IgM classes were measured to gain an insight into the relation between cell-mediated and humoral immune responses in patients with asthma and healthy controls. The in vitro and in vivo cell-mediated response and the IgM antibody response did not differ between patients with asthma and controls. The IgE and IgG antibody responses, however, were increased in the patients. IgM antibody response correlated with both the in vitro and in vivo cell-mediated response (R = 0.45, P less than 0.05). IgE and IgG antibody responses however were not correlated with cell-mediated responses. These data suggest that the primary abnormality in immune regulation in patients with asthma concerns the control of the IgE and IgG class antibody responses.

Adult↗
PubMed1986

Bronchial hyperreactivity and bronchial obstruction in respiratory viral infection. An attempt to evaluate the relationship.

The aim of this study was to investigate the relation of viral respiratory infection with bronchial hyperreactivity and bronchial obstruction. A viral infection using a live attenuated influenza virus was induced successfully in 10 of 30 patients with chronic obstructive pulmonary disease (COPD) and in 3 subjects without COPD (non-COPD). No significant change in bronchial reactivity and lung function could be found in comparison with the baseline values.

Administration, Intranasal↗
PubMed1985

The primary immune response in bronchial asthma. I. A kinetic study of Helix pomatia hemocyanin-specific IgE, IgG, IgA, and IgM antibody responses in patients with asthma and in matched controls.

Eleven asthmatic patients with allergy and 10 age- and sex-matched controls were immunized subcutaneously with 1 mg of the primary test immunogen Helix pomatia hemocyanin (HPH). The HPH-specific IgE, IgG, IgA, and IgM antibody response was measured by ELISA. After immunization, not only the IgE but also the IgG antibody response of the patients exceeded that of the controls (p less than 0.01). IgA antibody response also tended to be higher in the asthmatic group (NS). Except for an earlier rise after immunization in the asthmatic group (p less than 0.05), IgM peak responses did not differ significantly between the two groups. There was a high correlation (r = 0.9) between the magnitude of the IgE and the IgG antibody responses. IgM antibody response did not correlate with the response in any of the other antibody classes measured. The total serum immunoglobulin concentration was determined before immunization. Only the IgE level was significantly higher in the asthmatic group (p less than 0.01). No correlation was found between serum immunoglobulin concentrations and the magnitude of the HPH-specific antibody response in the same class. We conclude that the increased humoral responsiveness of asthmatic patients with allergy is not restricted to the IgE class nor to a limited number of commonly encountered antigens (allergens).

Adult↗
PubMed1983

Clinical pharmacokinetics of intramuscular thiazinamium methyl sulfate.

The disposition of the quaternary ammonium compound thiazinamium methyl sulfate is described after intramuscular injection in humans. The plasma concentration-time curves could be resolved into two exponential components, suggesting an open two-compartment model with absorption phase. Absorption was found to be extremely fast. Peak concentrations were always reached within 20 min, but in the majority of cases they were found to be between 6 and 10 min. Occasionally, the first sample (t = 3 min) proved to contain the highest concentration. Apparently the high solubility of the drug in the interstitial fluid is of prime importance for rapid absorption. Injection technique and the injection site seemed to be important for the final profile of the plasma concentration-time curve. Distribution was found to be very fast as well, with a half-life of approximately 20 min, and the apparent volume of distribution for the central compartment was about 40-60 l. Muscle activity and hence increased capillary blood flow during the distribution phase may result in a second peak in the plasma concentration-time curve. The distribution phase is followed by an elimination phase with a much longer half-life (mean value 375 min) and a volume of distribution of approximately 200-400 l. The total body clearance for thiazinamium methyl sulfate was found to be high (mean value about 800 ml/min), suggesting an active excretion process.

Adolescent↗
PubMed1982

Metabolism and excretion of the quaternary ammonium compound thiazinamium methylsulfate (Multergan) in man. I. Parenteral administration.

The quaternary ammonium compound thiazinamium was found to be metabolized by sulfoxidation solely. No ring hydroxylation products, nor demethylation products (e.g. promethazine) could be found. Thiazinamium sulfoxide was found both in urine and bile, but thiazinamium is-after parenteral administration - mainly excreted in the unchanged form. After intravenous injection about 40% of the dose was excreted, unchanged, in the urine. The excretion was very rapid and almost complete within eight hours. About 9% of the dose was excreted in the urine in the form of thiazinamium sulfoxide cations. After intramuscular injection virtually the same figures for urinary excretion were found. No correlation could be observed between urine production or pH and the amount of drug excreted in urine. In a study involving bile-fistula patients it was found that both thiazinamium cations and thiazinamium sulfoxide cations are excreted to a considerable extent in bile. The amount of unchanged drug in bile was almost equal to that in urine, but the amount of sulfoxide was slightly higher.

Bile↗
PubMed1982

Metabolism and excretion of the quaternary ammonium compound thiazinamium methylsulfate (Multergan) in man. II. Oral and rectal administration.

In this study it is shown that biotransformation of thiazinamium, when given orally, does not differ qualitatively from the pattern found after parenteral administration. However, quantitatively both the metabolism and excretion patterns are considerably different from those after intravenous injection. The renal clearance accounted for 256 +/- 136 ml.min-1 (mean +/- SD). This value is higher than glomerular filtration, which may be indicative of an active excretion process. Hepatic clearance (biotransformation and biliary excretion of unchanged cation) was 537 +/- 495 ml.min-1 (mean +/- SD). Hepatic clearance was found to correlate negatively with bioavailability. The ratio between unchanged drug and the only metabolite, the sulfoxide, in urine was about I:0.9. This is substantially different from that found after parenteral administration (ca. I:0.2), which may imply that a 'first-pass effect' occurs. It was estimated that ca. 50% of the absorbed amount was metabolized during the first liver passage. The fate of thiazinamium after rectal administration in Witepsol HI5 suppositories shows several similarities with that after oral administration. The ratio between unchanged drug and metabolite in urine in this case was ca. I:0.8, indicating that also after rectal administration a 'first-pass effect' occurs, now to a degree of ca. 35%.

Administration, Oral↗
PubMed1982

[Treatment of CARA].

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Adrenal Cortex Hormones↗
PubMed1982

Bronchial obstructive reactions after inhalation with endotoxin and precipitinogens of Haemophilus influenzae in patients with chronic non-specific lung disease.

Bronchial obstructive reactions occur after inhalation of Haemophilus influenzae in the absence of proteolytic activity in patients with CNLSD and a lowered histamine threshold in whom specific precipitins are demonstrated. It may be presumed, that the direct bronchial reaction is caused by its content of endotoxin, whereas the late bronchial reaction is the result of a toxic action and a type III allergic reaction. When proteolytic activity is present it lowers the histamine threshold and may influence the endotoxin effect in this way.

Administration, Intranasal↗
PubMed1980

Disposition and clinical pharmacokinetics of microcrystalline theophylline.

Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19 +/- 9 min (mean +/- SD). Maximal serum concentrations reached after 100 +/- 30 min were found to be in a rather narrow range: 9.8 +/- 2.5 mg x 1(-1). The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7 +/- 10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.

Administration, Oral↗
PubMed1980

Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20 SCC patients received no adjuvant treatment. Follow-up studies were done from three to 51 months. Immune reactivity was monitored in vivo with PPD skin tests in 33 treated and in 18 untreated patients. In both the BCG-treated SCC groups recurrence rates decreased statistically significant during follow-up (BCG-A; six to 51 months, p less than 0.001; BCG: 6-9 months, p less than 0.01 and nine to 24 months, p less than 0.001). However, no difference could be demonstrated between systemic and combined systemic and intrapleural treatment. The three BCG-treated AC patients all relapsed within nine months of follow-up. A pronounced increase in skin reactivity to PPD was seen six months after surgery in the BCG-treated patients (BCG-A, p less than 0.001; BCG-B, p less than 0.01), whereas the control patients remained anergic after surgery. This improved immune reactivity went in parallel with a more favourable outcome of the individual patients (BCG-A, p less than 0.02; BCG-B, p less than 0.05). It is concluded that adjuvant BCG immunotherapy used in strongly selected patients with minimal residual squamous cell bronchial carcinoma improves the prognosis. Intrapleural treatment did not improve the prognosis further. A favourable clinical outcome was mirrored by an increase in cellular immune reactivity.

Adenocarcinoma↗