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Biomedical subjects

R J Royer

Publications and source records attributed to R J Royer.

At least 55 records · Page 3Linked to original sources

[Acute effects of ethanol on the performance and metabolism of the isolated working heart, both normal and failing].

The direct effects of ethanol on cardiac contractility are controversial, probably because of methodological reasons in relation to the choice of appropriate experimental models. We studied the direct effects of 1, 2, 5 and 10 g/l ethanol on myocardial performance and metabolism in the isolated perfused working guinea-pig heart. In the normal heart ethanol induced a dose-dependent, fully reversible depression of cardiac contractility without significant changes of heart rate or cardiac metabolism. In the post-anoxic failing heart this effect was more pronounced. Ethanol had no arrhythmogenic effect even at high concentrations. Finally, it had no measurable effect on anoxic-induced alterations or post-anoxic recovery after a period of 20 minutes of anoxic perfusion. However anoxic-induced lactate production was decreased in hearts pretreated with 10 g/l ethanol. These results demonstrate the direct negative inotropic effect and the lack of chronotropic effect of ethanol. They suggest the lack of effect on excitability. The mechanism of the negative inotropic effect does not seem to be metabolically related since cardiac oxygen consumption and lactate production remained unaltered.

Animals↗

[Drug monitoring].

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Drug Information Services↗

Experimental synovitis induced by aluminium phosphate in rabbits. Comparison of the changes produced in synovial tissue and in articular cartilage by aluminium phosphate, carrageenin, calcium hydrogen phosphate dihydrate, and natural diamond powder.

The goal of this experimental study was to examine the effect on articular tissue of tribasic aluminium phosphate (crystalline and amorphous forms) after intraarticular injection in rabbit and to compare it with that of various phlogistic compounds such as carrageenin, calcium hydrogen phosphate dihydrate and diamond powder, as a control. Synovium and cartilage were studied with light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive micro-analysis (EDM). Crystalline and amorphous aluminium phosphate could induce a synovitis with articular effusion in rabbits. With TEM, lysosomal inclusions of phagocytosed material were observed. Through SEM coupled with EDM, aluminium associated with phosphate was found in cellular elements.

Aluminum Compounds↗

[Passage of nonsteroidal anti-inflammatory agents across the synovial membrane].

The therapeutic effectiveness of non-steroid anti-inflammatory (NSAI) drugs is partly determined by their passage across the synovial membrane. The synovium can be compared to a double barrier the permeability of which to NSAI drugs depends on the degree of inflammation of the joint and on the pharmacokinetic properties of the drugs (lipophilia, pka, protein-binding). A few hours after one single systemic dose, concentrations in the synovial fluid are higher than in serum. During chronic administration, concentrations of NSAI drugs with a short half-life vary less in synovial fluid than in serum. During steady state, free fractions of NSAI drugs with prolonged half-life may be similar in both compartments.

Anti-Inflammatory Agents↗

The effects of amrinone on cardiac function, oxygen consumption and lactate production of an isolated, perfused, working guinea-pig heart.

Compared with isolated heart muscle and Langendorff preparations, the isolated, working heart preparation allows a more complete analysis of cardiac function and metabolism. We have studied the effects of amrinone 20 micrograms/ml and 200 micrograms/ml on the isolated perfused working guinea-pig heart. We have measured: heart rate (HR), mean systolic aortic pressure (SP), aortic flow (AF), coronary flow (CF), total cardiac output (CO), and calculated the stroke volume (SV) and the rate of external work (W). The rates of oxygen consumption (VO2) and lactate production (Lact) were also measured and the external efficiency (Eff) calculated. Hearts were allowed to fail spontaneously after work for 90 min. Amrinone was then added at the required concentration to the perfusion medium. Amrinone 20 micrograms/ml, increased AF, CF, CO, SV, W and VO2. HR was slightly but significantly increased. Lact and Eff were not altered. Amrinone 200 micrograms/ml substantially increased CF and VO2, but it increased slightly and not significantly AF, CO, SV and W, suggesting the predominance of the coronary vasodilating effect of amrinone at higher doses. Lact and Eff remained unchanged. The positive chronotropic effect was of the same magnitude than that observed with the lower dose. No arrhythmias occurred with either concentration. These results would suggest that amrinone is a positive inotropic drug with vasodilating properties at higher doses, and weak positive chronotropic effect. It stimulates aerobic but not anaerobic metabolism of the heart.

Aminopyridines↗

Cation transport in erythrocytes of patients with renal failure.

Na+, K+-ATPase activity in erythrocytes (RBC) has been assessed indirectly by the 86Rb uptake method in 10 patients with acute renal failure (ARF), 11 patients with chronic renal failure (CRF) on haemodialysis and 13 patients treated by kidney transplantation, and compared to age-matched healthy controls. In each patients, the sensitivity of 86Rb uptake to digoxin (IC50) has been measured. Na+, K+-ATPase activity was decreased in patients with ARF and in patients with CRF but not in transplanted patients. IC50 was lowered in transplanted patients. The implications of these findings are discussed in terms of possible mechanisms of the changes in Na+, K+-ATPase activity in RBC of patients with renal failure.

Acute Kidney Injury↗

Inflammatory effect of aluminium phosphate on rat paws.

The aim of this experiment was to determine the inflammatory effect of aluminium phosphate on the rat paw and to compare it with those of carrageenan, calcium hydrogen phosphate dihydrate and natural diamond powder. At the probability threshold of the various tests used there was a significant increase in volume of the treated paw relative to the control paw for all the substances at all times, except for the two concentrations of diamond (effect no longer significant from 30 min on), of calcium phosphate (not significant from 2 h), and of aluminium phosphate (not significant from 24 h). The effects were not significantly different between diamond and calcium phosphate (both concentrations). The effects of aluminium phosphate were significantly different from those of the two until at least 2 h after the injection ; there was no significant difference between the two doses of this substance. The kinetics of the effects produced by carrageenan differed from the kinetics of the other materials, its effects were not significantly different from those produced by aluminium phosphate until 2 h and later. The inflammatory effect that we have demonstrated in this study is added information suggesting that in addition to apatite, calcium pyrophosphate dihydrate, and sodium monourate, aluminium compounds can play a role in the unexpected appearance of inflammatory manifestations in haemodialysed patients with chronic renal insufficiency treated with aluminium gels.

Aluminum Compounds↗

[Protein binding of salicylates in rheumatoid arthritis].

Protein binding of salicylates was determined in 16 control subjects and 27 patients suffering from rheumatoid arthritis. Results obtained after separation of the free and bound fractions by dialysis to equilibrium and measured by spectrofluorometry were analyzed using a new mathematical model. In correlation with the decrease in plasma albumin concentrations, a decrease was found in the protein binding of salicylates in patients with rheumatoid arthritis. This phenomenon was less marked in therapeutic zones and was related to the degree of severity of the inflammatory syndrome. The binding capacity per albumin molecule at saturation was decreased in patients suffering from advanced forms, suggesting that the changes seen were not due solely to quantitative variations in serum albumin levels. This study confirms the value of the determination of free salicylate levels in patients suffering from inflammatory rheumatic disorders.

Adolescent↗

Respiratory acidemia and theophylline pharmacokinetics in the awake dog.

Recently, respiratory acidemia has been shown to be associated with an altered volume of distribution (Vd) of theophylline in patients during an acute exacerbation of chronic obstructive pulmonary disease. However, many factors other than acidemia could have altered the pharmacokinetics. Our purpose was to study the effects of respiratory acidemia alone. Six awake dogs had normocapnia and hypercapnia induced in a conditioned chamber. After intravenous injection (8 mg/kg), plasma theophylline concentrations were measured for 8 hours by means of quantitative enzyme immunoassay technique. There were no statistically significant effects of respiratory acidosis on Vd and total theophylline clearance. There was no significant correlation between these variables and pH, PCO2, PO2. We conclude that respiratory acidosis, per se, does not effect theophylline pharmacokinetics in dogs.

Acidosis, Respiratory↗

Changes in 86-rubidium uptake in erythrocytes of digoxin-treated patients, in heart failure with sinus rhythm. Relationship to clinical effects.

Previous studies have shown a significant relationship between the clinical effect of digoxin and a tissue response, namely the inhibition of 86Rb uptake by the patients' erythrocytes. In the present study, this relationship is confirmed in patients, in heart failure with sinus rhythm. The slowing of the heart rate but not the QS2 index changes correlates significantly with the 86Rb uptake inhibition.

Adult↗

Digoxin in the elderly and in renal failure. Contribution of erythrocyte 86-rubidium uptake tests.

Na+,K+-ATPase activity was assessed indirectly in three groups of subjects of differing age, and in a group of patients with renal failure, by measuring the 86-rubidium uptake in the patients' own erythrocytes. The inhibiting action of digoxin on this activity was also measured in vitro. Erythrocyte 86Rb uptake was found to be lower in the elderly as was the calculated volume of distribution of digoxin. Sensitivity to the inhibiting action of digoxin increased with age. In the renal failure group 86Rb uptake was diminished and the sensitivity to digoxin was variable. This suggested that Na+,K+-ATPase activity could be one determinant of the volume of distribution of digoxin and that quantitative and qualitative changes of this enzyme could explain features of the pharmacokinetics of digoxin in renal failure and in old age.

Adult↗

Study of the sensitivity of neonates to digoxin: contribution of erythrocyte 86rubidium uptake test.

In general, there is little agreement how digoxin should be used in newborn, and the results of studies in this field seem contradictory. This study attempts a quantitative assessment of the number and the sensitivity of cellular receptors for digoxin in the organism, by the in vitro measurement of erythrocyte 86Rubidium uptake in neonates compared with adults and old people. Red blood cells are first incubated with differing concentrations of digoxin, and then incubated with 86Rb. The initial level of 86Rb uptake (Rbi) is that observed in the absence of digoxin. The 50% index of captation (IC50) is the digoxin concentration in nanograms per ml at which 86Rb uptake is half Rbi. Three groups of patients were studied: Group I: 12 neonates, less than 5 days old; Group II: 11 adults (26 to 57 years old); Group III: 9 elderly people (71 to 82 years old). Rbi was significantly lower in neonates (Mean +/- SD: 25.8% +/- 3.5, P less than 0.001) and in the elderly (29.9% +/- 3.1) than in adults (36.8% +/- 4.6). IC50 was significantly lower in the elderly (12.1 ng/ml +/- 2.4) than in the adult patients (20.5 ng/ml +/- 5.5, P less than 0.001). In the newborns, values of IC50 were widely scattered (16.2 ng/ml +/- 7.2). The authors suggest that since Rbi reflects Na+, K+-ATPase activity, this activity is diminished in newborn and old people, and indicates that they have fewer cellular receptors for digoxin than adults. In the elderly, the low IC50 would imply increased sensitivity to digoxin. In neonates, the wide range of values for IC50 suggests considerable individual variation in sensitivity to digoxin. The results are consistent with the recently recommended lower dosages of digoxin in neonates.

Adult↗

[Peripheral haemodynamic disturbances of the limbs in Raynaud's phenomenon (author's transl)].

Study of 36 cases of Raynaud's phenomenon by Doppler effect (radial artery and digital pulp at rest and during hyperhaemia) showed that measurement of peripheral resistance is an excellent method for differentiating idiopathic Raynaud's disease (index higher than 5) from syndromes to obliterative disease of the digital arteries or scleroderma (index less than 4). Capillaroscopy offers additional information concerning the validity of the distal bed, stasis and sludging phenomena and is a diagnostic aid in early scleroderma.

Adult↗