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Biomedical subjects

J Brugmans

Publications and source records attributed to J Brugmans.

At least 19 recordsLinked to original sources
PubMed1983

Site of action of low dose ketoconazole on androgen biosynthesis in men.

Ketoconazole inhibits testosterone biosynthesis in men, but the exact site of its action on the androgen pathway remains to be established. To examine this question, we measured several steroids in the androgen and glucocorticoid pathways in normal men before and after receiving either a single dose of 200 mg ketoconazole or placebo in a cross-over randomized trial. Total and free plasma testosterone fell to levels 60% below basal within 4-8 h (P less than 0.02 in all) and then returned to control concentrations by 24 h after drug administration. The transient alterations of plasma testosterone correlated well with ketoconazole blood levels, which peaked at 2 h and fell exponentially thereafter. A compensatory increase in plasma LH at 24 h in the drug but not placebo group was consistent with the decrease in plasma testosterone. The levels of plasma androstenedione paralleled those of testosterone in the ketoconazole-treated subjects. In marked contrast, plasma 17 alpha-hydroxyprogesterone increased at 4-8 h (all P less than 0.02) before returning to basal values at 24 h. This rise in precursor with fall in product steroid implicated an effect of ketoconazole on the C17-20 lyase enzyme. This conclusion was supported by the highly significant increase in the ratio of plasma 17 alpha-hydroxyprogesterone to androstenedione observed between 2 and 24 h after drug administration. The effect of ketoconazole at this dose level appeared relatively specific, since no decrements in plasma cortisol or 11-desoxycortisol were found. During chronic administration of 200 mg ketoconazole daily, decrements of plasma testosterone 2-4 h after drug administration were minimal and documented only by paired comparisons within subjects but not by unpaired tests between normal men and men receiving drug. The lack of major effects on testosterone levels long term at this dosage probably explain why few androgen-related side effects with this drug were previously reported. Ketoconazole, therefore, represents another compound with relatively selective effects on a cytochrome P-450-mediated steroid hydroxylation step, namely that involved with C17-20 lyase.

Adult↗
PubMed1981

Endocrine effects of domperidone: a peripheral dopamine blocking agent.

In the present study, effects of domperidone, a peripheral dopamine blocking agent, on prolactin and growth hormone were examined to determine whether dopamine regulation of these hormones involved structures external to the blood-brain barrier. A clearcut elevation in prolactin was produced by domperidone. GH response to apomorphine was partially blocked by domperidone.

Adult↗
PubMed1980

Reactive hyperemia in patients with intermittent claudication, and correlation with other diagnostic methods.

The value of blood flow measurements was evaluated in 16 patients with intermittent claudication and in 17 healthy sex and age-matched volunteers. Limb volume was recorded with an ECG-triggered venous occlusion plethysmograph (Periflow, Janssen), and the flow values were automatically plotted on a second channel. Resting blood flow was similar in both groups, but all the parameters from the reactive hyperemia curve in the claudication group were significantly different from those in the control group. The present data are preliminary in this respect. In most patients visual inspection of the curve allows differentiation of normal and abnormal. Variability of the flow parameters is found to be small; the time-to-peak flow varies the most, but gives at the same time the largest different results in both groups. Finally, there is a positive correlation between resting blood flow, peak blood flow, and walking distance. The present results suggest that flow measurements provide valuable and objective information about the degree of functional distress caused by obliterative vascular diseases in the limbs.

Aged↗
PubMed1980

Postoperative pain relief by demand analgesia.

Postoperative pain relief is only apparently an easy task. A brief survey of literature investigating the discomfort experienced in the postoperative phase is all but encouraging. One can identify four basic problems in obtaining adequate results by delivery of analgesic drugs: a) the biological variability among individual patients, b) the unpredictable uptake of the drug administered intramuscularly, c) the time lag involved between request by the patient and the subsequent administration of a single dose and d) the lack of knowledge about the nature of the discomfort and its remedies. An alternative strategy introducing "On-Demand" analgesia administering prescribed doses at the right moment is presented and analysed a) as an operant conditioning process implementing a particular reinforcement schedule (behavioural sciences), as well as b) a negative feedback control loop that entrust the central judgement to the patient (system theory). Both approaches give insight into the results: the technique copes with biological variability; anticipating pain induced by fear disappears; the feedback strategy works well and patients adapt to a wide range in prescriptions; intermittent administration makes more efficient use of the analgesic; an optimal result is demonstrated in studies comparing on-demand analgesia with the normal IM-regime and epidural analgesia; continuity in pain relief can be obtained in routine clinical practice.

Analgesics↗
PubMed1978

Levamisole in infectious diseases--a review of the literature.

Levamisole is toxic to a range of nematodes with gastrointestinal and systemic localization. Since nematodes are characterized by an immunologically determined pattern of predilections for hosts and tissues, pharmacological, biochemical, and immunological properties must be considered when the mechanism of action of levamisole is discussed. Levamisole causes a reversible stimulation of ganglia and neuromuscular inhibition of the depolarizing type, inhibits nematode-specific succinate dehydrogenase and increases delayed hypersensitivity reactions. The latter effect is mediated by immune cells and may explain why levamisole alleviates chronic and recurrent infections, particularly in patients with immunodeficiency syndromes.

Animals↗
PubMed1978

Multinational evaluation of etomidate for anesthesia induction. Conclusions and consequences.

An overall analysis was made of 4763 case report forms from 45 anesthesiologists who used etomidate (Hypnomidate) routinely as an induction hypnotic in a total of 4127 surgical cases or compared it to thiopental in a series of controlled studies (325 on etomidate, 311 on thiopental). Premedication was standardized only in the controlled studies, and there were no restrictions on the use of anesthetic agents or techniques. Etomidate proved to be a safe and effective induction hypnotic. Sleep was deep and long enough to allow the normal induction and maintenance procedures. Blood pressure and heart rate remained remarkably stable in the 3 study groups. The incidence of respiratory depression was higher for thiopental; anesthesiologists' acceptance of etomidate was, however, reduced by the occurrence of venous pain during injection and of associated involuntary muscle movements. It is expected that these adverse effects will be largely eliminated by using the recently introduced new formulation of etomidate shortly after fentanyl.

Adolescent↗
PubMed1976

Levamisole treatment of a child with severe aphthous stomatitis and neutropenia.

The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed.

Agranulocytosis↗