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Biomedical subjects

P Bédard

Publications and source records attributed to P Bédard.

At least 19 recordsLinked to original sources

On the role of static and dynamic visual afferent information in goal-directed aiming movements.

Movement planning has been shown to be optimized when the participant is permitted to see his or her hand resting on the starting base prior to movement initiation. However, this proposition is opposed by contradictory results. In the present study, we wanted to determine whether these conflicting results were caused by procedural differences. The results showed that seeing one's hand on the starting base did not result in more accurate aiming movement than when this information was not available. However, lower aiming errors were found when one was asked to foveate the starting base and then the target prior to movement initiation, but only when no dynamic visual information was available during movement. When an aiming movement was performed while one's hand was visible in visual periphery, foveating the starting base or not prior to movement initiation did not modify aiming accuracy. These results suggest that gazing at the starting base and then at the target provides an eye-based representation of the movement to be performed that can be used by the CNS to plan a manual aiming movement. Information for better planning of the direction--but not the extent--dimension of an upcoming movement can also be derived from dynamic visual information available in peripheral vision.

Adult↗

Clinical patterns and trends of outcome of elderly patients with bronchogenic carcinoma.

OBJECTIVE: To investigate the clinical characteristics and determinants of operative mortality and long-term survival of elderly patients submitted to pulmonary resection for intended cure of lung cancer. METHODS: Retrospective analysis of 500 consecutive pulmonary resections performed in patients aged over 70 years from 1975 to 1996. Predictors of in-hospital mortality were identified by univariate and multivariate analyses. Determinants of long-term outcome were investigated in all survivors, with no patient being lost to follow-up. RESULTS: Mean age was 74 +/- 3 years (maximum: 90), and 36 patients were octogenarians. The sex-ratio M:F was 5:3. History of combined cardiovascular or previous neoplastic disease was noted in 193 and 63 patients, respectively. The predominant histology was squamous cell carcinoma (n = 243), with a significantly higher incidence in male than in female. Most patients received standard procedures, while 103 patients underwent extended resections for tumors involving the mediastinum (n = 44), the chest wall (n = 33), the carina (n = 2) or had a sleeve resection of the main bronchus (n = 24). Procedures were considered to be complete and curative in 459 patients, among whom 294 had a stage I disease. There were 37 (7.4%) in-hospital deaths. Mortality rates following pneumonectomy, bilobectomy, lobectomy and lesser resection were 11:136, 4:34, 22:291, and 0:39, respectively. Age, male gender, hypertension, low FEV1 and extended procedure were identified as independent predictors of early mortality. Overall survival rates were 33.7 and 12% at 5 and 10 years, respectively. Multivariate analysis demonstrated that the disease stage was the main prognosticator. During the follow-up period, cancer recurrence (n = 183; 39.5%) or second primary lung cancer (n = 20; 4.3%) occurred in 203 patients, among whom 18 (9%) had a second lung resection. Carcinoma in other systems occurred in 25 patients (5.3%), and major cardiovascular event in 51 (11%). CONCLUSIONS: Male and squamous cell carcinoma are characteristic of elderly patients with resected lung cancer. Operative mortality is acceptable for standard resection, and survival figures are concordant with those reported in other series which include younger patients.

Aged↗

The dopaminergic nigropallidal projection in primates: distinct cellular origin and relative sparing in MPTP-treated monkeys.

In summary, our findings revealed the existence in primates of a dopaminergic pallidal projection that arises from neurons of the substantia nigra-ventral tegmental area complex and terminates preferentially in the internal pallidum. This projection is largely distinct from the nigrostriatal dopaminergic pathway and appears to be relatively spared in parkinsonian monkeys. Thus, in addition to their potent influence at striatal levels, the midbrain dopaminergic neurons may directly modulate the activity of basal ganglia output neurons at pallidal levels.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Repeated stimulation of D-1 dopamine receptors increases the circling response to bromocriptine in rats with a 6-OHDA lesion.

We have studied the effect of repeated injections of a specific D-1 agonist, (SKF 38393), on circling behaviour in response to a specific D-2 agonist (bromocriptine) and on striatal D-2 DA receptors in rats with a unilateral lesion of the nigrostriatal pathway. Two groups of rats were formed on the basis of their circling response to a first injection of SKF 38393: clear contralateral circling (SKF-positive) and no (or ipsiversive) circling (SKF-negative). A few days later, these rats were tested once for bromocriptine-induced circling. A repeated treatment of 8 injections of SKF 38393 over 4 days was started the next day. The animals were tested again for bromocriptine-induced circling at the end of the repeated treatment with the D-1 agonist. A third group of rats received only the 2 test injections of bromocriptine and a fourth group included intact control animals. During the repeated treatment, the D-1 agonist induced an increase of the circling response up to the fourth injection and a decrease thereafter in the SKF-positive group. This was followed by a pronounced increase of circling in response to the second injection of bromocriptine. This increased sensitivity appears to be due to the chronic treatment with SKF 38393 since animals that did not respond initially to the D-1 agonist (SKF-negative group) and those that received only 2 injections of bromocriptine showed no increase of their circling response. The treatments did not increase the affinity of [3H]spiperone binding for the striatal D-2 dopamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Neurotensin receptor binding sites in monkey and human brain: autoradiographic distribution and effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.

Neurotensin (NT) receptor binding sites were characterized and localized by using membrane binding assay and in vitro receptor autoradiography in monkey and human brain. Additionally, the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment on NT binding sites were investigated in monkey. [125I]Tyr3-NT ([125I]NT) apparently binds to a single class of high-affinity sites (Kd in nanomolar range) in both species. Ligand selectivity patterns strongly suggest that the structural requirements of both monkey and human brain NT receptors are very similar to those previously reported in other tissues, such as those of the rat brain and rat stomach. In monkey brain, [125I]NT binding sites are discretely distributed with high densities of sites found in the cingulate cortex, amygdala, hippocampus, ventral tegmental area, substantia nigra, and periaqueductal gray matter. A similar pattern is observed in the human brain. However, the laminar distribution of [125]NT binding sites in cortex varies between monkey and human brain. In monkey brain, [125I]NT binding sites are mostly concentrated in deep cortical layers while the laminar distribution of NT sites changes with cortical areas in human brain. The densities of [125I]NT binding sites are markedly decreased in the caudate, putamen, and substantia nigra in MPTP-treated monkeys. These results suggest strong interactions between NT and dopaminergic systems in both monkey and human brain tissues.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Long-term effects of MPTP on central and peripheral catecholamine and indoleamine concentrations in monkeys.

5 Macaca fascicularis monkeys developed a severe parkinsonian syndrome in the days following intravenous administration of the toxin MPTP. One monkey remained untreated while two groups of two animals were treated daily for 5 months with supramaximal oral doses of either Sinemet or bromocriptine. Both drugs relieved the parkinsonian symptoms. Plasma prolactin concentrations were elevated in MPTP-treated monkeys compared to intact monkeys. MPTP caused a rapid decrease of homovanillic acid (HVA) concentrations in the CSF of these monkeys within days of the toxin injection and these values remained low until sacrifice of the animals 5 months later. By contrast, CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were elevated a few days after the start of MPTP treatment and these values returned to control levels by 5 months. Five months after the start of MPTP treatment, epinephrine (E) and dopamine (DA) levels were decreased in the adrenal medulla while the norepinephrine (NE) concentration remained unchanged. Catecholamines were assayed in the caudate putamen, nucleus accumbens, amygdala and frontal cortex of these monkeys. NE concentrations were decreased in the frontal cortex of MPTP-treated monkeys while a decrease of E concentrations after MPTP was only observed in the n. accumbens. Dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and HVA were reduced in the caudate, putamen, n. accumbens and frontal cortex. Our results show that MPTP treatment in the long-term (5 months) not only affects the dopaminergic system of the caudate-putamen but also has effects on dopaminergic systems in other regions as well as on noradrenergic and adrenergic systems in the brain and the periphery.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Submammary skin incision as a cosmetic approach to median sternotomy.

Median sternotomy is the incision of choice to allow access to the anterior mediastinum, heart, or both lungs. The vertical skin incision leaves an unsightly scar for many female patients. A bilateral submammary horizontal skin incision with dissection of a flap including the subcutaneous tissue and breasts allows exposure of the sternum so that a median sternotomy can be performed. Since November 1981, we have used this incision 40 times in female patients undergoing open heart surgery. The exposure of the mediastinum was excellent, and there were no difficulties in cannulating the ascending aorta for cardiopulmonary bypass. Complications associated with this incision are insignificant if close attention is paid to details.

Adolescent↗

17 beta-Estradiol at a physiological dose acutely increases dopamine turnover in rat brain.

Ovariectomized rats injected with 17 beta-estradiol (30 ng, s.c.) showed an increase of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with no change of dopamine concentrations in the striatum and nucleus accumbens. This increase was observed 30 min after the steroid injection and coincided with peak plasma 17 beta-estradiol concentrations. Plasma prolactin concentrations were not significantly elevated after 30 ng of 17 beta-estradiol. In ovariectomized rats with a unilateral lesion of the entopeduncular nucleus, the same dose of 17 beta-estradiol induced a postural deviation to the lesioned side with a maximum at 30 min. Thus, very small doses of estradiol were able to increase dopamine turnover. This effect was seen within minutes and was relatively short. It is probably non-genomic, presynaptic and similar to the effect of a small dose of a dopamine releasing agent.

3,4-Dihydroxyphenylacetic Acid↗

Behavioral and biochemical evidence of apomorphine-induced supersensitivity of the striatal dopamine receptors.

The effect of repeated administration of apomorphine was studied behaviorally and biochemically in rats bearing either a unilateral lesion of the substantia nigra with 6-OHDA or an electrolytic lesion of the entopeduncular nucleus. Rats with the nigral lesion displayed a progressive increase in contralateral circling rate. In animals with the entopeduncular lesion, the ipsiversive circling response was unchanged after the eight injection of apomorphine. [3H] Spiroperidol binding to striatal membranes did not appear modified by the apomorphine treatment on the intact side. It was however increased on the side of the 6-OHDA lesion. We propose that a denervated striatum responds to repeated stimulation by dopamine agonists with a paradoxical increase in sensitivity. This may explain in part the appearance of dyskinesia in treated parkinsonian patients.

Animals↗

Influences of both thyroid and bovine growth hormones on substance P, thyrotropin-releasing hormone, serotonin and 5-hydroxyindoleacetic acid contents in the lumbar spinal cord of developing rats.

Neonatal hypothyroidism was induced by injection of 131I on the first living day whilst neonatal hyperthyroidism was induced by daily administration of high doses of thyroxine (T4). Following decapitation, segments of the lumbar spinal cord were microdissected by a punch technique. We measured serotonin and 5-hydroxyindoleacetic acid (5-HIAA) contents by high performance liquid chromatography and both substance P and thyrotropin-releasing hormone (TRH) levels by radioimmunoassay. We demonstrated that: (1) neonatal hyperthyroidism decreased substance P and TRH levels in the dorsal and ventral horns respectively, without modifying serotonin and 5-HIAA contents; (2) neonatal hypothyroidism increased the concentration of substance P in dorsal horn, of TRH in ventral horn (confirming our previous work), of serotonin in ventral horn, and of 5-HIAA in both ventral and dorsal horns; (3) T4-replacement therapy abolishes hypothyroid effects on substance P, TRH, and 5-HIAA, but not on 5-HT accumulation; and (4) bovine growth hormone-replacement therapy has no therapeutic action on the hypothyroid-induced accumulation of substance P, TRH, serotonin and 5-HIAA.

Animals↗

Comparative effects of neonatal hypothyroidism and euthyroidism on TRH and substance P content of lumbar spinal cord in saline and PCPA-treated rats.

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the content of substance P and TRH in the lumbar segment of the rat spinal cord were studied. The peptide content of discrete spinal cord regions removed by punches of frozen serial slices was measured by RIA. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. In hypothyroid animals without PCPA-treatment, levels of TRH and substance P were significantly increased by 100% in the ventral and the dorsal lumbar spinal cord, respectively. Inhibition of serotonin biosynthesis by PCPA increased by 90% the substance P content in the dorsal horn of euthyroid rats and abolished completely the stimulatory effect of hypothyroidism on the TRH content of the ventral horn. These findings suggest the existence of a physiological relationship between substance P and TRH with the serotoninergic system in the rat spinal cord and that thyroid hormone is implicated in the normal development of the peptide-containing neurons in the rat spinal cord.

Animals↗

Biphasic effect of estradiol and domperidone on lingual dyskinesia in monkeys.

In previous work, we demonstrated in animals and humans an antidopaminergic effect of estradiol at the level of the striatum. In the present study, we tested the effect of a large dose of estradiol (0.5 mg s.c.) administered either acutely or during several days in four female ovariectomized monkeys, displaying a persistent buccolingual dyskinesia due primarily to a midbrain lesion, but which is markedly enhanced by dopaminergic agonists. One of the monkeys also displayed a lesion-induced parkinsonian-like tremor of the opposite limbs. Chronic administration of estradiol markedly reduced the apomorphine-induced potentiation of the dyskinesia but did not affect the tremor. A single dose of estradiol was followed after 24 h by a 75% reduction of the effect of apomorphine on the dyskinesia but a 50% increase in the response to apomorphine was seen after 2 weeks. The response was at the control level after 30 days. Domperidone, a peripheral dopamine agonist that does not cross the blood-brain barrier and which causes an elevation of prolactin similar to that seen after estradiol, is followed by a similar biphasic modification of the response to apomorphine. Our results suggest that estradiol may have opposite effects on the sensitivity of the striatal dopamine receptors and therefore on dyskinesia, depending on the time of observation. An elevation of prolactin appears to have similar effects. Moreover, some effects of these hormones may be delayed by several days to weeks in primates.

Animals↗

The role of D-1 and D-2 receptors.

Dopamine receptors in intracerebral motor and endocrine systems have been divided into two main types, D-1 and D-2, dependent on the presence or absence of adenylate cyclase linkage. Here we have investigated a number of dopamine agonist and antagonist drugs in man that have different actions on D-1 and D-2 receptors in animals. Motor and endocrine effects in parkinsonian subjects seem to depend on drug interaction with D-2, but not D-1, receptors. These results may have important implications for the design of anti-parkinsonian and antipsychotic agents.

Adenylyl Cyclases↗

Direct revascularization of the septal artery.

Between July 1, 1976 and May 1, 1979, 21 patients underwent coronary artery grafting of the first septal artery. Blood flow in the septal bypass averaged 60.2 ml/min and the diameter of the distal anastomoses averaged 2.1 mm. Among the 20 survivors, 13 were subjected to angiography at an average of 7 months after the operation (from 2 weeks to 2 years). The bypass graft to the first septal artery was patent in 84% of the patients (11 of 13) and 90% of the grafts were open (57 of 63). The authors believe that if a patient has an important stenosis in the first septal artery, direct revascularization may be carried out. However, because of technical difficulties during dissection and anastomosis it is wise to select an artery at least 2 mm in diameter which supplies a large area.

Adult↗