Biomedical subjects

O Davidsen

Publications and source records attributed to O Davidsen.

17 recordsLinked to original sources

PubMed1995

[Ambulatory coronary arteriography].

Based upon hospital files and a questionnaire we assessed the patient safety of and the patient attitude towards outpatient coronary angiography (CAG). A total of 115 consecutive patients were included in the study. Thirty two of the patients (28%) were admitted following the angiography, while 83 (72%) were discharged to the home as planned. Of those de facto ambulatory patients one (1%) was readmitted because of a groin haematoma. Of those who returned the questionnaire, 93% of the patients admitted and 97% of the de facto ambulatory patients were satisfied with the level of information, and 76% and 99%, respectively, would prefer out-patient CAG to CAG during admission. We conclude that out-patient CAG can be performed with a very low risk and is well accepted by the patients.

Adult↗

PubMed1992

[Bronchial asthma treated with long-acting beta 2 agonist. Comparison between formoterol (12 mu/g) inhaled twice daily and salbutamol (200 mu/g) inhaled 4 times daily].

Forty patients with stable asthma and daily need for inhaled beta 2-agonist, were included in a randomized double-blind study. They were treated for six weeks with inhaled beta 2-agonist, either salbutamol, 4 x 200 micrograms daily, of formoterol, 2 x 12 micrograms and 2 x placebo daily. This was preceded by a run-in period, where all patients received terbutalin-inhalation, 4 x 500 micrograms daily. Twenty patients were given formoterol and 18 salbutamol. One patient in the salbutamol-treated group discontinued treatment after three weeks, because of deterioration of asthma. On a diary card, patients recorded peak expiratory flow rate (PEFR) morning and evening before medication, score of asthma symptoms (scale 0-3; 0 = no symptoms, and 3 = severe symptoms) and use of additional doses of beta 2-agonist. Forced expiratory volume in 1 sec. (FEV1), forced vital capacity (FVC) and PEFR were obtained after 0, three and six weeks of treatment. Blinded global assessment of the treatment was performed by both patient and physician at the end of the study. During run-in the two groups of patients were different. The group subsequently treated with salbutamol had a statistical significant (ss) higher morning-PEFR, ss fewer asthma-symptom scores than one during night and ss less need for additional puffs of beta 2-agonist. During treatment, the formoterol-treated group showed an ss increase in morning-PEFR, as compared to run-in. Furthermore this group had ss fewer nocturnal symptom scores than one and ss less need for extra beta 2-agonist during night, than the salbutamol-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1992

Drug-related illness as a cause of admission to a department of respiratory medicine.

Three hundred and thirteen consecutive admissions to a department of respiratory medicine were evaluated in a prospective high-intensity monitoring scheme concerning adverse drug reactions or dose-related therapeutic failures as the contributing or sole cause of hospital admission. Eleven patients [3.5%, 95% confidence interval (CI) 2.0-6.2] were admitted because of adverse drug reactions. Only 3 of these patients manifested respiratory symptoms, while the remainder had various intercurrent nonpulmonary problems and were well known in the outpatient clinic, e.g. asthma or cancer patients. It is concluded that adverse drug reactions requiring admission rarely present as respiratory symptoms. Fourteen patient (4.5%, CI 2.7-7.4) were admitted because of dose-related therapeutic failures in all cases, except 2 with respiratory symptoms. Half of these were due to noncompliance. Analysis of theophylline samples taken on admission from 46 patients showed 25 (54%) to have concentrations below the therapeutic range of 55-110 microM, but contributed little to the identification of noncompliant patients. Eighty-three percent of the drug events were found to have been unavoidable. Nine patients admitted with acute asthma did not receive corticosteroids prior to admission (2.9%), all of which had therapy prescribed in general practice. The present study showed a comparatively low and hardly affectable prevalence of admissions caused by adverse drug reactions and dose-related therapeutic failure. However, therapeutic failure due to inappropriate choice of asthma medication, which was not included in this estimate, may be an important avoidable cause of admissions.

Adverse Drug Reaction Reporting Systems↗

PubMed1990

Urokinase receptors in human monocytes.

Receptors for the 54 kDa plasminogen activator urokinase were characterized in freshly isolated and 5-14 day cultured human monocytes. The half saturation constant was about 55 pM in freshly isolated monocytes at 4 degrees C and 140 pM at 37 degrees C. Diisopropylfluorophosphate-inactivated urokinase was bound with the same affinity as catalytically active urokinase. Binding per cell of 2-5 pM urokinase increased progressively during cell culture with a concomitant decrease in the apparent affinity. By 14 days, binding had increased 5-7-fold and the half-saturation constant had increased to 500 pM at 4 degrees C, indicating a large increase in the binding capacity. Affinity cross-linking of labelled urokinase to receptors showed a 110 kDa complex in both freshly isolated and cultured monocytes. When cells with labelled urokinase (prebound at 4 degrees C) were incubated at 37 degrees C, about 80% of the urokinase dissociated as the intact molecule, whereas about 20% was degraded to iodide and iodotyrosine. Electron microscopic autoradiography of cultured monocytes incubated at 4 degrees C showed a marked heterogeneity between cells with regard to bound urokinase. Autoradiographic grains were mainly seen over the plasma membrane in areas rich in microvilli and invaginations. Transfer of the cells to 37 degrees C caused no major alteration in the distribution of grains. Thus, freshly prepared monocytes have urokinase receptors (approx. 55 kDa) of high affinity. Development to macrophage-like cells in culture causes a decrease in affinity and a large increase in capacity. The receptors are confined mainly to certain areas of the plasma membrane. Internalization and degradation of the ligand occurs only to a minor extent.

Cross-Linking Reagents↗

PubMed1990

Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes.

Interleukin-6 (IL-6) is a potent stimulator of the hepatic synthesis of acute-phase proteins. 125I-labelled IL-6 disappeared from the blood of rats with an overall half-time of about 1.5 min; 41% of the injected tracer dose was recovered in the liver by 15 min. The clearance was biphasic. The simultaneous injection of tracer and an excess of unlabelled IL-6 eliminated the initial rapid phase, and reduced the hepatic uptake to 14%. Light microscopic autoradiography showed 5% of the grains over non-hepatocytes, and 80% over hepatocytes, accumulating in areas around the bile canaliculi. Thereafter, degradation products accumulated in the bile. At 4 degrees C, isolated rat hepatocytes bound IL-6 with an apparent Kd of 39 pmol l-1 to a uniform class of 4500 receptors per cell with an apparent molar mass of 115-120 kg mol-1. The HepG2 human hepatocellular cell line bound IL-6 with an apparent Kd of 21 pmol l-1 to a uniform class of 1200 receptors per cell with an apparent molar mass of 155-160 kg mol-1. At 37 degrees C, both cell types endocytosed the bound ligand slowly, and degradation products appeared in the medium after a relatively long lag period (40 min in hepatocytes and 1 h in HepG2 cells).

Animals↗

PubMed1990

Cellular targets and receptors for interleukin-6. II. Characterization of IL-6 binding and receptors in peripheral blood cells and macrophages.

Within 15 min, approximately 2.5% of 125I-labelled interleukin-6 (IL-6) injected intravenously into rats was taken up by the spleen. As determined by light microscopic autoradiography, uptake was mainly (60%) accounted for by macrophages in the red pulp. 125I-IL-6 binding in rat peritoneal macrophages was quantitatively similar to that in cultured human monocytes and T-cells. By comparison, IL-6 binding to polymorphonuclear granulocytes and freshly isolated monocytes was low. Stimulation with antigen, but not with mitogen (PWM), induced receptor presentation in B-cells, whereas antigen and mitogen downregulated the binding in T-cells. At 4 degrees C, labelled IL-6 bound to cells with a half-time of about 1.5 h. Binding appeared reversible, but dissociation was slow and incomplete. The apparent Kd for IL-6 binding was about 30 pmol l-1 in most cell types, however, values of approximately 120 pmol l-1 were obtained in polymorphonuclear granulocytes. At 37 degrees C, 125I-IL-6 was rapidly internalized by T-cells and monocyte-macrophages, and after a lag time, TCA-soluble radioactivity was released from the cells following a sigmoidal curve. Polyacrylamide gel electrophoresis of radiolabelled IL-6 cross-linked to its binding sites in T-cells, yielded receptor-ligand complexes with molar masses of 70-80 and 120-140 kg mol-1. This would agree with a dimeric conformation of the IL-6 receptor.

Animals↗

PubMed1989

Characterization, size estimation and solubilization of alpha-macroglobulin complex receptors in liver membranes.

Receptors for alpha 2-macroglobulin-proteinase complexes have been characterized in rat and human liver membranes. The affinity for binding of 125I-labelled alpha 2-macroglobulin.trypsin to rat liver membranes was markedly pH-dependent in the physiological range with maximum binding at pH 7.8-9.0. The half-time for association was about 5 min at 37 degrees C in contrast to about 5 h at 4 degrees C. The half-saturation constant was about 100 pM at 4 degrees C and 1 nM at 37 degrees C (pH 7.8). The binding capacity was approx. 300 pmol per g protein for rat liver membranes and about 100 pmol per g for human membranes. Radiation inactivation studies showed a target size of 466 +/- 71 kDa (S.D., n = 7) for alpha 2-macroglobulin.trypsin binding activity. Affinity cross-linking to rat and human membranes of 125I-labelled rat alpha 1-inhibitor-3.chymotrypsin, a 210 kDa analogue which binds to the alpha 2-macroglobulin receptors in hepatocytes (Gliemann, J. and Sottrup-Jensen, L. (1987) FEBS Lett. 221, 55-60), followed by SDS-polyacrylamide gel electrophoresis, revealed radioactivity in a band not distinguishable from that of cross-linked alpha 2-macroglobulin (720 kDa). This radioactivity was absent when membranes with bound 125I-alpha 1-inhibitor-3 complex were treated with EDTA before cross-linking and when incubation and cross-linking were carried out in the presence of a saturating concentration of unlabelled complex. The saturable binding activity was maintained when membranes were solubilized in the detergent 3-[(3-cholamidopropyl)dimethylammonio]propane sulfonate (CHAPS) and the size of the receptor as estimated by cross-linking experiments was shown to be similar to that determined in the membranes. It is concluded that liver membranes contain high concentrations of an approx. 400-500 kDa alpha 2-macroglobulin receptor soluble in CHAPS. The soluble preparation should provide a suitable material for purification and further characterization of the receptor.

Animals↗

PubMed1988

Cell association and degradation of pregnancy zone protein-chymotrypsin complex in cultured human monocytes.

125I-labelled pregnancy zone protein complexed with chymotrypsin (PZP-ct) bound to freshly isolated and to cultured human monocytes. Binding of uncomplexed 125I-pregnancy zone protein (PZP) was less than 20% of complex binding. At 4 degrees C, labelled PZP-ct complex bound to cultured monocytes with a half-time of about 4 h. Dissociation at 4 degrees C was slow at low receptor occupancies (t 1/2 greater than 24 h). At high receptor occupancies, dissociation was biphasic (initial k-1 = 8 X 10(-3) min-1) and 85% of the cell-associated label had dissociated within 24 h. At near equilibrium, binding of 20 pmol/l 125I-PZP-ct was half maximally inhibited at a ligand concentration of about 450 pmol/l. The Scatchard plot was linear giving an estimated concentration of 2 X 10(4) receptors/cell. Ligand bound at 4 degrees C was rapidly internalized at 37 degrees C (half-time = 0.5 min) and after a 5-10 min lag time, radioactivity comprising monoiodotyrosine was released into the medium following a sigmoidal curve. At 37 degrees C the uptake of 125I-PZP-ct complex was initially linear and within 15 min internalized label accumulated, reaching a steady state at about 85% of the cell-associated radioactivity. Following a lag time of 15 min, radioactivity soluble in trichloroacetic acid appeared in the medium. Similar results were obtained with 125I-alpha 2-macroglobulin-trypsin complex (alpha 2M-T). It is concluded that high affinity receptors mediate binding, uptake and degradation of pregnancy zone protein--and alpha 2-macroglobulin-proteinase complex in human monocyte-macrophages.

Cells, Cultured↗

PubMed1986

Characterization of receptors for alpha 2-macroglobulin-trypsin complex in rat hepatocytes.

High-affinity receptors for alpha 2-macroglobulin-trypsin complex were demonstrated in rat hepatocytes at 4 degrees C. The dissociation rate constant for the labelled complex was very small at low receptor occupancies, approx. 4 X 10(-4) min-1. Dissociation was biphasic at high receptor occupancies with a rate constant for the rapid phase of about 2 X 10(-2) min-1. At near-equilibrium, half of the receptors were saturated at a complex concentration of 150 pM, and the Scatchard plot was concave upwards. Thus, the binding shows complex kinetics with the probable involvement of negative cooperativity. Binding of the labelled complex was not influenced by galactose, mannose, mannose phosphate or fucoidin, whereas it was abolished in the absence of extracellular Ca2+ and inhibited by bacitracin. Approx. 70% of the labelled complex bound at 4 degrees C was rapidly internalized (kint about 3 X 10(-1) min-1) after being warmed to 37 degrees C. Radioactivity released from the cells at 37 degrees C comprised intact labelled complex and iodide. The complex was initially released at a rapid rate (k-1 about 1 X 10(-1) min-1) from about 25% of the cell-bound pool. This probably represents dissociation from the receptors. A slow phase of release followed, so that half of the bound pool was finally released as intact complex. Iodide release followed a sigmoidal curve after a 20 min lag period. Thus, specific high-affinity receptors mediate the internalization and eventual degradation of alpha 2-macroglobulin-proteinase complex into hepatocytes.

Animals↗

PubMed1985

Uptake of rat and human alpha 2-macroglobulin-trypsin complexes into rat and human cells.

Uptake of rat and human alpha 2-macroglobulin-trypsin complexes was measured in rat hepatocytes, rat and human adipocytes and human fibroblasts. Uptake and degradation of 125I-labelled rat complex were about one-third of that of the human complex in the various isolated cell types. In rat hepatocytes, the apparent Km for cell association of the rat complex was about 16 nM as compared to about 6 nM for the human complex. The Vmax values were similar, about 1 X 10(4) molecules X cell-1 X min-1. Thus, rat alpha 2-macroglobulin (an acute-phase protein) complexed with trypsin follows the same pathways of uptake as the human homologue, although with a somewhat lower affinity for the uptake system.

Adipose Tissue↗

PubMed1985

The plasma clearance of human alpha 2-macroglobulin-trypsin complex in the rat is mainly accounted for by uptake into hepatocytes.

Rats were given intravenous injections of 125I-labelled human alpha 2-macroglobulin X trypsin. The half-time of disappearance of radioactivity from arterial blood was 2 min. External counting showed that radioactivity in the liver was maximal by 10 min and then decreased slowly. 87% of the injected dose was recovered in the liver by 10 min. Light- and electron microscopic autoradiography carried out on samples of liver fixed with glutaraldehyde 3 min or 30 min after the injection showed that 85-90% of the grains were over the hepatocytes and 4-9% were over the Kupffer cells. Thus, uptake into hepatocytes, and not into Kupffer cells as believed previously, appears to account for the major part of the uptake of alpha 2-macroglobulin X trypsin by the liver and thereby for its rapid removal from the blood.

Animals↗

PubMed1979

Analgesic treatment with levomepromazine in acute myocardial infarction. A randomized clinical trial.

The efficacy of a non-narcotic analgesic is evaluated in a double-blind randomized series of patients with acute myocardial infarction (AMI). Levomepromazine or pethidine were given in 328 consecutive cases to 316 patients within 24 hours after the onset of symptoms. Levomepromazine, 12.5 mg, appeared as effective as pethidine, 50 mg, in the alleviation of pain, though the initial dose had to be higher. Nausea and vomiting were half as frequent in the levomepromazine group as in the pethidine group (p less than 0.001). The incidences of arrhythmias, lung oedema, hypotension and thromboembolic complications did not differ between the groups. The mortality rate in the first 4 weeks was 22% in the levomepromazine group and 37% in the pethidine group (p less than 0.005), and after one year 39 and 50% (p less than 0.05), respectively. It is concluded that levomepromazine is better tolerated than pethidine in AMI. This suggests that the present management of pain in AMI should be reconsidered.

Acute Disease↗

PubMed1978