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Biomedical subjects

J L Imbs

Publications and source records attributed to J L Imbs.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

[Theophylline and urinary elimination of lithium in the anesthetized dog].

The effect of theophylline (intrarenal perfusion of 1.2 then of 2.4 mg/kg for two successive 15 minute periods) on urinary lithium elimination was studied in 6 pentobarbital anaesthetized dogs perfused with intravenous lithium chloride. Lithium and inulin clearance and the urinary elimination of sodium, potassium and phosphate were studied. Theophylline increases lithium clearance, glomerular filtration and salidiuresis. This salidiuretic effect partly linked to the inhibition of the proximal reabsorption of sodium attested by the rise in phosphate elimination contrasts with the absence of modifications in the fractional tubular reabsorption of lithium. Under our experimental conditions the increased lithium clearance seems linked to the increased glomerular filtration.

Anesthesia↗
PubMedDate not supplied

[The mechanism of the natriuretic action of dopamine in the anesthetized dogs (author's transl)].

1. The natriuretic effect of increasing doses of dopamine (1.5 to 15 x 10(-8) moles/kg/min intrarenally) was compared in dogs (pentobarbital anesthetized) who were either water restricted or overhydrated. 2. The dopaminergic response to doses larger than 1.5 x 10(-8) moles/kg/min (3 micrograms) was hidden either by important alpha-adrenergic effects or by renal reaction to the modifications in systemic haemodynamics. 3. Renal blood flow was increased by a dose of 1.5 x 10(-8) moles/kg/min of dopamine. At the same dose, natriuresis was increased only in hydrated dogs. Glomerular filtration rate only increased in water restricted animals. 4. The natriuretic effect of dopamine depended on the catecholamine induced variations of renal haemodynamic. 5. In water restricted animals, the absence of natriuretic effect of dopamine goes in hand with an absence of variation in filtration fraction. 6. In hydrated animals, the dopamine-induced natriuretic effect, in the absence of increased glomerular filtration, is tied to a decreased proximal tubular reabsorption of sodium probably secondary to the haemodynamic effects of this catecholamine.

Anesthesia↗
PubMedDate not supplied

[Erythrocyte/plasma ratio of lithium. Determination method and individual stability].

Lithium is a very efficient drug for the treatment of maniac-depressive psychosis, but its therapeutic index is narrow. Moreover, even with lithium plasmatic concentrations in the therapeutic range, some patients showed toxic signs when others seemed not to be efficiently treated. The measurement of erythrocyte lithium concentration might provide a more rational method than the measurement of plasma lithium for monitoring the course of lithium therapy, since the mechanisms of lithium transfer across red blood cells resemble those for neurons. Toxic effects could then be related to high lithium erythrocyte concentrations or a high erythrocyte/plasma lithium ratio (EPR). The intracellular lithium concentration depends mainly on the Li(+)-Na+ countertransport, which is genetically determined. We wondered therefore whether the EPR is a specific characteristic of each patient and how long it requires to stabilise when lithium therapy is started. The EPR was determined by directly measuring the plasma and erythrocyte concentrations with a carefully standardised assay (lithium carbonate administered at 7 pm, blood sample taken at 7 am the next day). Potassium edetate was preferred as anticoagulant to sodium heparinate, which gave an overestimation of EPR. Plasma trapped in the red cell column, with polyfructosan as marker, was found to average 4% in our assay conditions (centrifugation at 3,200 g, 15 min, 4 degrees C). This standardised assay makes it possible to determine the EPR very accurately with an inter-assay variation coefficient of about 2.4%. Following the start of lithium therapy, the EPR stabilised very quickly, mainly within two days (three out of four patients), at a time when lithium erythrocyte and plasma concentrations were still increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[French pharmacovigilance database system: examples of utilisation].

UNLABELLED: The French drug surveillance (pharmacovigilance) system is based on a network of 31 regional centres which receive adverse drug reaction (ADR) reports from health professionals and are drug information centers. Cases are entered into a common database, with causality scores. This database contains large amounts of data, which may be used for pharmaco-epidemiological studies. As an example, all cases in which an antihypertensive drug, suspect or not, was cited were identified. ACE-inhibitor cough was also explored. RESULTS: Since 1985, > 70,000 case reports have been entered into the database. 63 per cent were reported by specialists, 20 per cent by GPs. 54 per cent came from University Hospitals, 21 per cent from private practice. The most numerous age group was 60 to 69. The overall sex ratio (F/M) was 1.28, the female preponderance being most marked at < 39 and > 70 years of age. 43 per cent took only one drug, 20 per cent two drugs, 13.4 per cent three, and 24 per cent > three drugs. The most frequently reported effects concerned the skin and appendages (15 per cent), general status and central nervous system (9.5 per cent each), platelets, liver, and GI systems (6 per cent each). Outcome was favourable in 74 per cent. Dechallenge was positive in 71 per cent, rechallence in 6 per cent. 3.4 per cent of the patients died; in 2.2 per cent death was related to a reaction. Causality assessment indicated close temporal relationship (C2 or C3) in 69 per cent of cases; in 51 per cent of cases, no other obvious cause was found. 66 per cent of the reactions were labelled when reported. The database could also be used to explore drug utilisation: as an example, we studied the age and sex distribution of reports containing antihypertensive drugs, irrespective of their possible causal role in the reaction. Antihypertensives were mentioned in 14 per cent of the reports. The age distribution was skewed towards greater age, with a maximum of 70 years. F/M was 1.57, with more M use < 20 and 30-59, whereas F were more common between 20-29 and 60 years. beta-blockers were more often associated with patients under 70, whereas above 70 diuretics and centrally acting antihypertensive drugs were more often reported. This could be related to greater use or worse tolerance of these drugs. As an example of the exploration of a specific drug-reaction relationship, we explored the relationship between the use of ACE inhibitors (ACEI) and cough. ACE inhibitors were present in 6 per cent of cases, but in 75 per cent of reports of cough. F/M was 1.29 (NS) for all reports concerning ACEI, 1.28 for cough unrelated to ACEI, 2.1 for cough with ACEI (P < 0.05). Cough was present in 12 per cent of all reports concerning ACEI. There was no clear difference between ACEI for cough or sex ratio; women cough more with ACEI. This does not seem related to greater ACEI use by women or to greater sensitivity of women to cough. The reason for this sex difference remains to be explained. There are large amounts of essentially underutilized data in drug surveillance databases. How they can or should be used remains to be validated.

Adult↗
PubMedDate not supplied

[Good practices of publication of clinical cases of pharmacovigilance: comments, Groupe de Travail sur les Bonnes Pratiques de Publication de Cliniques en Pharmacovigilance: commentary].

This paper introduces some comments on the complete text of Good Pharmacovigilance Publishing Practices, which forms appendix number 2 of the Good Pharmacovigilance Practices now published by the French Drug Agency, as was Good Clinical Practices. Each good practice is printed in italic and presented in a frame; the following comments are designed to facilitate its application. The technical terms that are used in this text are presented according to the glossary in Good Pharmacovigilance Practices.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

[Aldosterone antagonists: new pharmacologic prospects].

The pharmacology of the mineralocorticoid receptor antagonist spironolactone and analogues is reviewed in the light of recent discoveries regarding the primary structure of corticosteroid receptors and the different isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase. The type 2 isoform of this enzyme functions in some tissues to keep the aldosterone receptor activation specific, i.e. it allows stimulation by aldosterone while eliminating glucocorticoids such as cortisol and corticosterone. The type 2 isoform has been shown in the colon, hypothalamus, kidney, placenta and salivary gland. New clinical uses of aldosterone antagonists may be derived from these developments. Most prominent in this respect appear to be myocardial fibrosis and specific forms of hypertension with altered mineralocorticoid receptor functioning and deficiencies in the protection system of the receptor against glucocorticoids.

Animals↗