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Biomedical subjects

H R Christensen

Publications and source records attributed to H R Christensen.

At least 19 recordsLinked to original sources

[The synonymous preparation Andion vs. the original preparation becotide in the treatment of steroid-dependent bronchial asthma. A comparative double-blind cross-over trial].

Two different beclomethasone dipropionate inhalation aerosols (Andion and Becotide) were compared in a double-blind, cross-over study in patients with stable, steroid-dependent asthma. Fifty-two patients were included in the study, and 44 completed the two 6-week periods of treatment. The difference in therapeutic efficacy on FEV1 between Andion and Becotide was -0.018 1, and likewise no differences in therapeutic efficacy on FVC and peak expiratory flow were found. There were no significant differences between the two treatment periods regarding peak expiratory flow rates, symptoms, frequency of adverse effects, and amount of salbutamol and beclomethasone dipropionate employed. In conclusion, no significant differences could be demonstrated between Andion and Becotide with regard to pulmonary function, symptoms, and frequency of adverse effects in the treatment of patients with steroid-dependent bronchial asthma.

Adult

[Diurnal blood pressure. Practical, prognostic and therapeutic aspects].

Outpatient blood pressure monitoring is now feasible employing good equipment which is easy to handle. However, some major problems must be solved before outpatient measurement of blood pressure (AMBP) can be employed routinely in the treatment of hypertension. Normal measurements, a satisfactory description of the AMBP curve and more prognostic studies with and without treatment are necessary.

Ambulatory Care

Determination of isradipine and its pyridine metabolite in serum by capillary column gas chromatography with nitrogen-selective detection.

A relatively simple, sensitive and precise gas chromatographic method for the determination of isradipine, a calcium antagonist of the dihydropyridine type, and its main metabolite in serum is described. Using a one-step extraction procedure, a wide-bore column and a nitrogen-phosphorus detector, a limit of quantitation of 0.5 and 2.0 nM for isradipine and the metabolite was found. No interferences from several drugs were observed. The method was successfully used in a pharmacokinetic study in hypertensive women during pregnancy.

Calcium Channel Blockers

Atrial natriuretic peptide (ANP) in chronic obstructive pulmonary disease (COPD): the relationship between plasma ANP and lung function. Effects of exercise and of the calcium antagonist, isradipine, on plasma ANP. A randomised, double-blind, placebo-controlled study.

In patients with severe chronic obstructive pulmonary disease (COPD) an increased pulmonary arterial pressure (PAP), a raised plasma level of atrial natriuretic peptide (ANP) and a correlation between increasing PAP and increasing plasma ANP have been shown. Furthermore, a negative correlation between lung function and PAP has been reported, and calcium antagonists have been claimed to decrease PAP. The purpose of the present study was to investigate whether 1) a negative correlation between lung function and plasma ANP could be demonstrated, whether 2) plasma ANP would increase during exercise in patients with COPD, and whether (3), in a randomised, placebo-controlled, double-blind design, a calcium antagonist was able to decrease plasma ANP at rest and modify the expected increase in plasma ANP during exercise. Eighteen patients with severe COPD were investigated. Plasma ANP was measured at rest and during exercise before and two hours after ingestion of either a single dose of 5 mg of isradipine, or a single dose of placebo. At rest, a correlation between lung function (forced vital capacity) and plasma ANP was found (rho = -0.49, P = 0.05). During the first exercise period, before ingestion of isradipine or placebo, the median level of ANP increased from 74 pg/ml at rest to 97 pg/ml at exhaustion (P less than 0.0002) (all patients). Administration of isradipine did not alter resting levels or exercise induced increases in plasma ANP. It is concluded, that in patients with severe COPD plasma ANP tends to be higher the more severely FVC is reduced. Plasma ANP increases during exercise. The calcium antagonist, isradipine, does not alter resting levels or exercise induced levels of plasma ANP.

Atrial Natriuretic Factor

Interaction between digoxin and indomethacin or ibuprofen.

To study a potential interaction between digoxin and two non-steroid anti-inflammatory drugs, indomethacin (50 mg three times daily) and ibuprofen (600 mg three times daily) were given for 10 days to 10 and 8 patients, respectively, on chronic digoxin treatment. Serum digoxin measured by fluorescence polarisation immunoassay increased significantly (P less than 0.05) during treatment with indomethacin from pre-treatment values of 0.73 +/- 0.34 nmol l-1 (mean +/- s.d.) to a mean value of 1.02 +/- 0.43 nmol l-1, while administration of ibuprofen did not change the steady state serum concentration of digoxin. The result demonstrates that some non-steroidal anti-inflammatory drugs such as indomethacin increase serum digoxin to levels high in the therapeutic range. This should be taken into consideration when co-administering other drugs known to increase the serum concentration of digoxin such as several antiarrhythmics.

Aged

A randomized comparison of isradipine slow release given once daily with isradipine twice daily on 24 hour blood pressure in hypertensive patients.

Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.

Adult

[Physiotherapy and mask treatment of chronic bronchitis and chronic obstructive lung disease].

The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted due to acute exacerbation of chronic bronchitis seems of no help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.

Bronchitis

[Physical therapy and mask treatment of chronic bronchitis and chronic obstructive lung disease (COPD)].

The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted on account of acute exacerbation of chronic bronchitis does not appear to help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast, general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.

Bronchitis

[Peroral terbutaline in the treatment of patients with severe irreversible obstructive pulmonary disease].

This investigation assesses the effect of oral terbutaline in doses of 7.5 mg twice daily as compared with placebo in patients with moderate to severe chronic airflow limitation (CAL) without reversibility. Seventeen patients completed this double-blind randomised cross-over trial. Diaries with reports of dyspnoea during activities of daily living and peak-flow measurements, were obtained. Measurement of pulmonary function, walking distance and various scorings of function after treatment for three and five weeks were assessed. The investigation demonstrates that in patients with CAL treatment with terbutaline tablets may lead to improvement of several subjective effect variables although no real improvement in the majority of objective effect variables is observed. In patients with irreversible obstructive reduction of pulmonary function, in whom no other form of treatment can be considered, oral treatment with beta-2-agonists may be attempted. If no effect is obtained, the treatment should be withdrawn after one to two months.

Administration, Oral

PEEP-masks in patients with severe obstructive pulmonary disease: a negative report.

Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.

Adult

Antitrophic properties of antihypertensive drugs may depend solely on their blood pressure-lowering capability. A comparative study of isradipine, hydralazine, and metoprolol.

The objective of this study was to examine the effect of antihypertensive treatment on the structure of intramyocardial resistance vessels in spontaneously hypertensive rats. The rats were divided into four groups: one was used as control and the other three were treated from the age of four to 24 weeks with isradipine, hydralazine, and metoprolol, respectively. Half of the animals in each group were examined at the end of active treatment and the rest were examined three weeks later. The rats were anesthetized and killed during constant flow perfusion with 1 percent glutaraldehyde. The media index was determined by point counting. The media indices of rats treated with isradipine and hydralazine were significantly smaller than those of age-matched spontaneously hypertensive rat controls, whereas the media indices of rats in the metoprolol group did not differ significantly. Three weeks after treatment withdrawal, the media index tended to increase in all three groups, but the values for the isradipine and hydralazine groups were still significantly reduced. Non-invasive blood pressure measurements taken at the same time demonstrated a significant blood pressure reduction in all groups, although differences within each treatment group were evident. All pressures had stabilized on the level of spontaneously hypertensive rats three weeks after withdrawal. Thus, it is evident that both isradipine and hydralazine were able to prevent hypertrophy of intramyocardial vascular structure and continue to do so even after treatment withdrawal. This finding is consistent with previous findings, suggesting a close relationship between the extent of blood pressure reduction and the degree of prevention of vascular hypertrophy.

Animals

Effect of theophylline and salbutamol on hepatic drug metabolism.

Fifteen otherwise healthy asthmatics with reversible airway obstruction were treated with salbutamol (8 mg slow release twice daily) and theophylline (300 mg twice daily). Each drug was administered for 4 weeks in a double-blind randomized crossover trial. Irrespective of which drug was given first, salbutamol increased antipyrine clearance significantly by a factor of 1.10 and 1.15 after 2 and 4 weeks of treatment, respectively. Theophylline did not change antipyrine clearance. There was no correlation between the extent of change in antipyrine clearance during either of the drug treatments and alterations in lung function as assessed by changes in peak flow, forced vital capacity and forced expiratory volume in first second.

Adult

Influence of rifampicin on thyroid gland volume, thyroid hormones, and antipyrine metabolism.

The influence of rifampicin (450 mg/day for 28 days) on the hepatic microsomal enzymes and thyroid function variables were investigated in 13 healthy male volunteers. After 14 and 28 days of treatment a significant increase in median thyroid volume (determined ultrasonically) was demonstrated (20 ml, range 13-28 before; 26 ml, range 18-48 at day 14, and 24 ml, range 17-40 at day 28) (p less than 0.01). A significant decrease in median serum free T4 index levels was seen (94.1 arbitrary units, range 80.1-123.4 before treatment; 86.8, range 71.7-102.0 at day 14, and 85.3, range 65.5-131.3 at day 28) (p less than 0.01). Serum T4, T3, T3 resin uptake, free T3 index and TSH levels were not significantly altered. Hepatic microsomal enzyme activity assessed by antipyrine clearance was significantly increased (approximately by 85%) at day 14 and 28, whereafter it normalized. The study supports the hypothesis that the increase in thyroid volume after treatment with rifampicin and other hepatic enzyme system inducers (e.g. phenytoin and carbamazepine) is a compensatory mechanism caused by an increased hepatic degradation of thyroid hormones.

Adult

Long-term hypotensive effects of an angiotensin converting enzyme inhibitor in spontaneously hypertensive rats: is there a role for vascular structure?

Male spontaneously hypertensive rats (SHR) were treated from 4 to 24 weeks of age with perindopril, an angiotensin converting enzyme (ACE) inhibitor, in doses of 0.4 and 0.8 mg/kg per day; we investigated the effects of these doses on blood pressure during and after withdrawal of treatment, and on the structural and functional characteristics of the resistance vessels. During treatment, mean blood pressure was maintained close to the level of normotensive control Wistar-Kyoto rats (WKY). At the age of 24 weeks, a resistance vessel segment was taken as a biopsy from the third branch of the superior mesenteric artery, and the structural and functional parameters were determined using an isometric myograph. Taken together with previous results the measurements showed that perindopril had a dose-dependent effect on both blood pressure and resistance vessel media thickness. Treatment was then withdrawn. Twelve weeks later, the mean blood pressure in both groups was still significantly reduced compared to that of age-matched SHR controls, but was no longer dose-related, nor was it related to the resistance vessel media thickness at age 24 weeks. The results suggest that the continuing reduction in blood pressure after withdrawal of treatment with perindopril may not be directly related to the drug's effect on resistance vessel structure.

Angiotensin-Converting Enzyme Inhibitors

Influence of prednisolone on antipyrine elimination in patients with obstructive lung disease.

The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9 +/- 14.8 to 51.7 +/- 14.6 ml/min (mean +/- SD; p less than 0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.

Antipyrine