[Dysphagia in Parkinson's disease].
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Deglutition Disorders↗
Biomedical subjects
H Allain
Publications and source records attributed to H Allain.
Comparison of the influence of dihydroergotoxine on cerebral oxygenation in the normoxic and hypercapnic hypoxic dog.
50 bastard dogs are anesthetized by chloralose (100 mg/kg) and mebubarbital (5 mg/kg) and then perfused by three-different dosages of dihydroergotoxine (DHET) (1.25; 2.5; 5 micrograms/kg/min). The effect of DHET on cerebral oxygenation is analyzed under two conditions: normoxia and hypercapnic hypoxia. The following biochemical and physiological parameters are studied: mean vertebral flow (MVF), aortic arterial pressure (AP), heart rate (HR); pO2, pCO2, total CO2, pH, haemoglobin saturation ratio, both in arteries and veins. Other parameters are calculated: O2 arterio-venous difference, CMRO2, O2 extraction coefficient, cerebral O2 supply, vertebral resistance. Under normoxia, DHET, whatever the dosage, induces a decrease of the MVF associated with an inconstant decrease of oxygen supply. At 2.5 micrograms/kg/min, a permanent and significant increase of CMRO2 is obtained. At 5 micrograms/kg/min, similar results are obtained although the decrease of HR and AP is more pronounced. Under hypoxia, the arterio-venous oxygen content difference and the CMRO2 are increased by DHET (2.5 micrograms/kg/min) without any repercussions on AP and MVF (hypothetical role of the blood pH decrease). In conclusion, DHET doubles the CMRO2, as a consequence of an increase of the oxygen extraction ratio. A 2.5 micrograms/kg/min dosage is by itself able to give this maximum effect without any major consequences on HR, AP and MVF. This effect is still obtained in hypoxia without any peripheral vascular effect.
Animals↗
Impairment of acquired temporal response regulation of rats under normobaric hypoxia.
Effects of hypoxia on learning involving temporal regulation of behaviour was investigated. Under 10% hypoxia there was a decrease in the number of conditioned responses, and the 'efficiency' of reinforcement, but no modification of temporal discrimination. Normobaric hypoxia may be a useful model for studying certain behavioural and pharmacological effects of cerebral circulatory insufficiency, and their implications at the level of the central nervous system, but it would be incorrect to use such a model to study factors that might prevent the loss of acquired knowledge.
Animals↗
Experimental hepatic iron overload in the baboon: results of a two-year study. Evolution of biological and morphologic hepatic parameters of iron overload.
Four baboons receiving intramuscular iron for 15 months were compared with two control baboons. From the overall two-year observation period the following data emerge: (1) The baboon is a suitable animal for obtaining a massive and chronic iron overload. Liver iron concentrations reached very high levels (ranging from 41.3 to 180.6 mumol/100 mg dry weight vs 1.7 +/- 0.5, mean +/- SEM, in controls), and a major liver iron overload (ie, with concentration values greater than or equal to 18) was present in all four animals for an average period of 16.5 months (range 14-19). (2) When compared with human hepatic iron-overload disorders, iron distribution was similar to that observed in secondary (transfusional) hepatic siderosis since iron deposits were found primarily in sinusoidal cells. However, a marked parenchymal siderosis was also obtained close to that observed in primary (genetic) siderosis. Iron toxicity was present biologically as indicated by an increase in serum transaminases. Histologically, a slight fibrosis was observed in the most heavily iron-overloaded baboon. On the whole, this study of subhuman primates brings new evidence that iron per se has only a minor hepatic damaging effect. It also suggests that the iron-overloaded baboon liver provides a promising tool for the study of liver cell disturbances in human iron overload.
Animals↗
[Epidural anesthesia using the bupivacaine-fentanyl combination for cesarean section].
This prospective study was designed to evaluate the benefit of a bupivacaine-fentanyl mixture vs bupivacaine alone in epidural anaesthesia for caesarean section. In 10 women, 0.5% bupivacaine (1.18 ml per metamer) was injected in the epidural space. In 20 women, 0.5% bupivacaine (1.06 ml per metamer) was injected by the same route together with fentanyl (1.70 +/- 0.09 micrograms X kg-1). The bupivacaine-fentanyl group showed a significantly shortened onset of analgesia (p less than 0.001), as well as a significant reinforcement of this analgesia graduated from 0 to 4 (p less than 0.01 at 25 min, p less than 0.001 at 75 min and at the maximum of pain, for the two sets of scores). All the Apgar scores were maximal at 5 min. No clinical respiratory depression was observed in either the mothers or the neonates. Fetal and maternal blood concentrations were in favour of respiratory innocuousness of the method (peak fentanyl concentrations: in mothers 1.5 ng X ml-1, in neonates 0.8 ng X ml-1). Fentanyl never induced any significant haemodynamic variations. Pruritus and nausea respectively occurred in six and two patients respectively in the bupivacaine-fentanyl group. In conclusion, in caesarean section, the adjunction of fentanyl to bupivacaine significantly improved analgesia without any clinical respiratory depression both in the mother and the neonate.
Adult↗
[Pharmacokinetics of intravenous ranitidine and its effect on gastric acid secretion stimulated by pentagastrin in the cirrhotic].
The pharmacokinetics of 50 mg intravenous ranitidine and the consequences on pentagastrin (2 micrograms/kg/h)-stimulated gastric acid secretion were studied in ten cirrhotic patients. Group I (n = 5) included patients without ascite; group II (n = 5) was characterized by the presence of ascites. Blood creatinine was normal in all the subjects. In non-ascitic cirrhotic patients, pharmacokinetic parameters are similar to those published in healthy subjects. In group II ascitic cirrhotic patients, the half-life is significantly increased by 50 p. 100 (P less than 0.05), as compared to group I, due to a 38 p. 100 decrease of total clearance and to a 45 p. 100 decrease of renal clearance (P less than 0.05). Hepatic clearance and volume of distribution are similar in both groups. The percentage of the inhibition by ranitidine of pentagastrin-stimulated acid out-put, in 6 cirrhotic patients, is 95 +/- 4 p. 100 (SD) when measured at the maximal inhibition peak, and 71 +/- 4 p. 100 (SEM) on the average, during the 3 h following the injection. In conclusion, ranitidine may be considered as an effective anti-secretory drug in cirrhotic patients; the pharmacokinetic variations observed in ascitic cirrhotic patients are the result of the decrease of ranitidine renal clearance.
Aged↗
[Undesirable dermatologic results of drugs. Result of a drug monitoring survey].
A prospective survey of drug-induced diseases has been performed along a one year period in a department of dermatology. Among the 550 patients hospitalized during this period for a cutaneomucous event, a drug-induced disease is pointed out in 30 of them (5.6 p. cent). The use of algorithm allows the establishment of the cause-effect relationship; the relative value of literature data and the role of three main predisposing factors (age, allergic antecedents, polymedication) are insisted upon. Three categories of drugs are primarily implicated: cardiovascular, antiinflammatory and antiinfectious drugs. The most commonly observed events are erythrodermia and allergic phenomena. If favorable evolution is usual, one fatal adverse drug reaction is firmly established in our series. Such a survey would lead to preventive attitudes.
Adult↗
[Hemodynamic and biological effects of bromocriptine in essential hypertension].
Central dopaminergic dysfunction has been suggested as the cause of essential hypertension. Agonist dopaminergic substances (AD) possess documented anti-hypertensive properties. We studied the cardiovascular effects of a single oral dose of 10 mg of Bromocriptine (Br) in untreated subjects with essential hypertension. A number of hemodynamic and biological parameters (direct blood pressure, pulmonary arterial and capillary pressures, cardiac index, heart rate, right ventricular and left ventricular work indices, systemic arterial and pulmonary vascular resistance, plasma renin activity, prolactin, and circulating Br levels) were measured before and after ingestion of the drug (at I, 1,5, 2, 3, 4, 5, 6, 8, 10 and 12 hours). Despite great individual variability, under the experimental conditions, Br displayed a strong anti-hypertensive action. The fall in blood pressure was early (Ist our) progressive, stabilising between the 3rd and 6th hour and prolonged (12 hour). This response was independent of the basal blood pressure with basal plasma renin activity (R = 0.64; p less than 0.05) but not with the prolactin level. The left ventricular work index underwent a similar change. Systemic arterial resistance fell, but this occurred after the fall in blood pressure. There was an independent and significant fall in pulmonary arterial pressure and pulmonary vascular resistance. The prolactin level fell very quickly and remained low throughout the 12 hours. There was an excellent correlation between the direct blood pressure and prolactin level (r = 0.97; p less than 0.01). Plasma renin activity rose after the third hour to reach a maximum at the 8th hour. There was a weak correlation between the blood pressure and plasma renin activity (r = 0.65, p less than 0.05). The serum Br level varied from patient to patient but reached a maximum at 1 hour, remaining stable until the 6th hour before decreasing. There was a correlation between the plasma renin activity and prolactin levels at each dosage (r = 0.66; p less than 0.005). The hemodynamic effects of Br are similar to those of central anti-hypertensive agents. The changes in plasma renin activity are comparable to those observed in central dopaminergic dysfunction. The excellent chronological correlation between the change in blood pressure and prolactin level is compatible with the hypothesis of this type of dysfunction in essential hypertension, if the inhibition of prolactin is accepted as a central dopaminergic effect of bromocriptine.
Adult↗
[Study of three biocides (dimethoate, parathion ethyl and zineb) on female rat neuro endocrinological balance (author's transl)].
The authors studied the neuro endocrinological effects of three pesticides. Two of them were organophosphorus compounds (ethyl parathion and dimethoate) and one was a carbamate (zineb). Mature female rats have been orally administered these compounds for 16 days at respectively 1/25, 1/10 and 1/10 of the LD50. The parameters recorded are: the gonadotropins, the length of estrous cycle and the weight of the anterior pituitary gland, the ovaries and the uterus. In contradistinction with the organochlorine compounds the organophosphorus did not induce any disturbances in the neuro endocrinological system, whereas the carbamate compound decreased the pituitary gonadotropins.
Animals↗
[Does bromocriptine act through the autonomic nervous system?].
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Autonomic Nervous System↗
The use of bromocriptine for testing central dopaminergic reactivity.
A single oral intake of 10 mg of Bromocriptine can modify both plasma renin activity (PRA) and arterial blood pressure (BP). The changes in both variables depend on the integrity of the central dopaminergic systems. The parkinsonians whose extrapyramidal symptoms are markedly improved by L-Dopa in association with a decarboxylase inhibitor (IDC) and the untreated parkinsonians are the only patients whose PRA and BP are lowered 1 h after Bromocriptine ingestion. The results obtained in the L-dopa-induced dyskinetic parkinsonians are similar to those obtained in the group of L-Dopa-resistant patients. This points to the paradoxical hypothesis of dopaminergic hyposensitivity in the dyskinetic patients. In spite of the absence of correlation between PRA and BP, it is possible that lowering of BP by Bromocriptine is linked to the parallel decrease of PRA. An increase of the BP may be obtained in the dyskinetic and L-Dopa-resistant groups. These data point to a possible involvement of central dopaminergic systems in some aspects of hypertension.
Blood Pressure↗
[Hyperparathyroidism secondary to cirrhosis. Arguments supplied by ionized calcium, urinary cyclic AMP and blood N-terminal parathyroid hormone].
A laboratory study including estimation of 25 OH vitamin D, terminal parathormone (PTH) C and N fractions, urinary cyclic AMP (AMP cU) and ionised calcium, was carried out in 25 patients, 10 cases of alcoholic cirrhosis without decompensation (group 1) and 15 cases of decompensated cirrhosis (group 2) in order to seek evidence in favour of hyperparathyroidism secondary to cirrhosis. The results show: 1) The existence of hypovitaminosis D which seems to be independent of the liver failure. 2) A very definite increase in terminal PTH N in group 2 compared with group 1 (p < 0.01), without any increase in terminal C fraction. 3) An insignificant increase in urinary cyclic AMP in group 2 compared with group 1. 4) A low serum ionised calcium in group 2 compared with 14 controls (p < 0.05). The terminal N PTH was correlated significantly with urinary cyclic AMP and ionised calcium. The evidence is in favour of secondary hyperparathyroidism where the ionised calcium plays a role, but one wonders whether other factors do not intervene, e.g. serum iron, owing to the discovery of a significant link between serum iron and terminal N PTH levels.
Adult↗
[Effect of ascorbic acid during acute iterative anoxia, hypothesis of an anti-oxidizing mechanism of action in comparison with the effect of hydroquinone].
Some of the problems which appear during senescence, are said to be caused by cerebral oxygen deficiency and various experiments have been set up to try to imitate this particular aspect of the ageing process. We have already studied the action of many drugs with regard to acute repeated anoxia. Our work has given us clear evidence of the activity of ascorbic acid, which delays the moment of electroencephalographic silence in rats and decreases the latent period up to the reappearance of electrical activity. In order to pinpoint the mechanism of action, we compared the influence of lysine aceto-salicylate with that of hydroquinone. Very small doses of the latter drug produce a marked effect and lead us to put forward the hypothesis that it may be anti-oxydising. However, although all the drugs which proved effective in these experiments may be grouped together (despite their varying pharmacological profiles) and described as "anabiotic" drugs, it is not possible to revert to a single mechanism of action for the group as a whole.
Animals↗
[Shy and Drager syndrome. Physiopathological and pharmacological approach based upon one case (author's transl)].
The authors report a new case of Shy and Drager syndrome characterized by the severity of the extrapyramidal signs as well as that of orthostatic hypotension and urinary dysfunction. Peripheral adrenergic disturbance was proven, associated with an abnormality of the renin-angiotensin system. The authors describe the various drugs tried experimentally in treatment of the three main symptoms of the disease. A combination of Trihexyphenidyl and Dibenzepine finally appeared to be the most effective. Six months later, there remained a marked improvement in extrapyramidal signs and orthostatic hypotension. By contrast there was no improvement in urological symptoms.
Basal Ganglia Diseases↗
Plasmatic renin activity in patients treated with L-dopa and inhibitor of dopa decarboxylase (IDC).
Plasmatic renin activity (PRA) was studied in patients receiving L-dopa, together with a decarboxylase inhibitor, at rest times and after periods of physical exertion. Although we can superimpose the results from unrelated Parkinson's disease patients on those of the control group, the results are inversed in stabilized patients (lowered PRA) and dyskinetic patients (increased PRA). There is a definite correlation between the increase in PRA and intensity of the dyskinesia. Dosage is the only other factor differentiating the two groups of Parkinsonians treated. The figures relative to arterial pressure are studied in the various groups.
Adult↗
[Neuropharmacological data on the striatum].
The striatum constitutes the most voluminous basal ganglia in man. It is issued from ganglionic eminences which are very early bound by limbic kernels. If the cortical and reticulo-spinal projections have been first described the existence of anatomical connexions with the limbic system offers a large number of functional possibilities. The knowledge of the distribution of the different chemical substances which are present within this structure as well as the enzymes necessary for their synthesis and destruction permits to establish a chemical mapping, the dopaminergic one being the best known. The dopaminergic synaptic function in the striatum helps to understand the respective roles of the pre and post-synaptic receptors as well as the mechanisms by which the other neuromediators can modulate the dopaminergic activity, the cyclic nucleotides being often necessary for this action. These fundamental data subtend the mechanism of action of most of the drugs which are involved in extrapyramidal phenomenons (neuroleptics, dopaminergic agonists) and allows to put forth physiopathological hypothesis on Parkinson disease, Huntington chorea, as well as certain induced or spontaneous dyskinetic states. The functions of the striatum are then evoked: if the role of this structure in motor control is critical, its involvement in complex behaviours is strongly suggested.
Animals↗
Activity of some drugs on the electroencephalogram of curarized rats during acute and iterative hypercapnic anoxia Hypotheses on mechanisms of action.
The present study is related to the activity of some drugs in a test of acute and iterative hypercapnic anoxia in curarized rats. The interpretation of the results is based on the values of cerebral resistance to anoxia and on the duration of post-anoxic recovery and cerebral electric silence, i.e. the duration of "nul" electroencephalogram. Results obtained allow us to put forward some hypotheses about mechanisms of action. Cerebral or systemic vasodilation or vasoconstriction both seem to be excluded. Membrane activity as well as an increase in cerebral blood perfusion pressure or an impact at the level of the brain neurotransmitters may be taken into consideration. Furthermore, it is possible that extracerebral phenomena (cardiovascular, respiratory, within the blood cells for example) could interact with cerebral phenomena. It would be necessary to undertake further, more extensive studies if we wish to evaluate the potential interest of the experimental model used and the way in which the drugs proposed as treatment for cerebrovascular diseases or ageing processes work.
Animals↗
[Familial dystonia transformed by the bromocriptine].
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Adolescent↗