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Biomedical subjects

S Gauthier

Publications and source records attributed to S Gauthier.

At least 181 records · Page 10Linked to original sources

Oxytocin administered intrathecally preferentially increases heart rate rather than arterial pressure in the rat.

Oxytocin was administered intrathecally at a dose of 6.5 nmol to the 9th or 2nd thoracic level of the spinal cord in the rat. This increased heart rate but had no effect on arterial pressure. The increase in heart rate began within 1 and 5 min and reached a peak at 10-30 min; the maximum increase, at 10 min after administration, at the second thoracic level was 65.4 +/- 13.8 (S.E.M.) bpm (n = 9). When administration was at the 9th thoracic level the change at 10 min was 36.9 +/- 18.0 bpm (n = 14). Administration of hexamethonium systematically, to block nicotinic transmission in autonomic ganglia, prevented the cardioacceleration in response to intrathecal administration of oxytocin. When 6.5 nmol of oxytocin were administered i.v., there was an immediate decrease in heart rate by 42.5 +/- 16.5 bpm (n = 4) and an increase in systolic (6.3 +/- 6.4 mm Hg) and in diastolic (38.8 +/- 8.3 mm Hg) pressures (n = 4); this effect lasted 5-10 min. Administration of 1.625 nmol of oxytocin at the 9th thoracic level had an effect qualitatively similar to that seen with the higher dose, but the response was smaller in magnitude and more delayed in onset; 0.65 nmol of oxytocin were without effect. Transfer of label to the blood after intrathecal administration of [125I]oxytocin indicated that the level in the blood reached a maximum of 0.6% of the total injected by 30 min after administration. It is concluded that the intrathecal administration of reached a maximum of 0.6% of the total injected by 30 min after administration. It is concluded that the intrathecal administration of oxytocin increases heart rate via an action in the spinal cord, presumably on sympathetic preganglionic neurons. Our results are consistent with earlier suggestions that oxytocin may be a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons.

Animals↗

Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain.

Receptor binding parameters and autoradiographic distribution of various opioid receptor sites have been investigated in normal human brain, post-mortem. [3H]DAGO, a highly selective mu ligand, binds to a single class of high affinity (Kd = 1.1 nM), low capacity (Bmax = 160 fmol/mg protein) sites in membrane preparations of frontal cortex. These sites show a ligand selectivity profile that resembles that of the mu opioid receptor. On the other hand, [3H]bremazocine, in presence of saturating concentrations of mu and delta blockers, appears to selectively bind to a single population of kappa opioid sites (Kd = 0.13 nM; Bmax = 93.0 fmol/mg protein) in human frontal cortex. Whole hemisphere in vitro receptor autoradiography reveals that [3H]DAGO-mu, [3H]DSLET-delta and [3H]bremazocine (plus blockers)-kappa binding sites are discretely and differentially distributed in human forebrain. In the cortex, mu sites are concentrated in laminae I and IV, delta sites in laminae I and II while kappa sites are found in deeper layers (laminae V and VI). In subcortical nuclei, high densities of mu and delta sites are seen in the caudate and putamen while high amounts of kappa sites are present in the claustrum and amygdala. The nucleus basalis of Meynert is enriched in all three classes of sites while the globus pallidus only contains moderate densities of kappa sites. Thus, the possible alterations of these various classes of opioid receptors in neurological and psychiatric diseases certainly deserve further investigation.

Aged↗

Current status of levodopa therapy in idiopathic Parkinson's disease.

Levodopa is currently used at all stages of Parkinson's disease, particularly from Stage 3 onward. Most patients start levodopa within four years of the onset of disease, earlier in the akineto-rigid patients (average delay of 2.1 years) than in those where resting tremor predominates (average delay of 3.4 years). Advanced age (greater than 80) is no deterrent to the use of levodopa if required. Wearing off is most noticeable in Stage 3 or after 10 years of therapy with levodopa. An inverse correlation was found between age and wearing off, suggesting a marked sensitivity of younger patients to levodopa. Future studies on the use of dopamine agonists should thus be stratified according to age.

Adult↗

Relationship between in vitro digestion of proteins and in vivo assessment of their nutritional quality.

The relationship between the nature of in vitro digestion products and protein quality evaluation in rats was established. Eleven protein sources of animal and vegetable origin and of various purities were digested by pepsin then by pancreatin in a dialysis bag of 1,000 molecular weight cutoff. Animal proteins were generally better digested in vitro than vegetable proteins. Amino acid release partly reflected enzyme specificity and varied depending on the nature of the protein. Essential amino acids were generally released rapidly at the expense of non-essential amino acids. The composition of protein hydrolysis products was thus markedly different from that of the protein before digestion. Digestibility determination in rats showed much less variation between proteins than the in vitro method; the two digestibility measurements did not correlate. However, by using stepwise multiple regression analysis, the amino acid composition of in vitro digestion products was found to correlate with the protein efficiency ratio (PER) more accurately than protein composition (R2 = 0.981 and 0.934, respectively). A regression analysis with net protein ratio (NPR) gave lower R2 coefficients than with PER (0.941 and 0.921, respectively). When regression equations were employed to predict the PER and digestion products were used instead of protein composition, an improvement was seen for almost all the test proteins, especially beef, rapeseed and wheat gluten. Better evaluation of protein quality by the use of protein digestion products demonstrates the possible impact of amino acid availability on protein quality.

Amino Acids↗

Hemodynamic and metabolic effects of cerebral revascularization.

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.

Aged↗

The benefits of group occupational therapy for patients with Parkinson's disease.

The medical treatment of idiopathic Parkinson's disease has improved the quality of life and increased survival of patients with Parkinson's disease. However, as the illness progresses, impairments in daily living activities occur. A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients. The research protocol consisted of a pretreatment evaluation, random assignment to experimental or control groups, and posttreatment evaluations after therapy, at 6 months and at 1 year. The results showed that the subjects of the treated experimental group maintained their functional status after 1 year, demonstrated a significant decrease of bradykinesia, and perceived a significant improvement in their psychological well-being. This study confirms the value of an occupational therapy group approach and its benefits to the functional independence, to the improvement of physical and motor symptoms, and to the quality of life of persons with Parkinson's disease.

Activities of Daily Living↗

Treatment of blepharospasm with medication, surgery and type A botulinum toxin.

A total of 39 patients with essential blepharospasm and 2 patients with hemifacial spasm were treated with one or more forms of therapy. All patients underwent neurologic and ophthalmic assessment to rule out ocular causes of blepharospasm. Thirty-six patients were given a trial of various medications. Only one patient was successfully treated: her condition was markedly improved with pimozide after benztropine mesylate, clonazepam and amantadine hydrochloride had failed to help. Patients who did not respond to drug therapy were offered the option of undergoing eyebrow-eyelid muscle stripping surgery. The six patients who underwent surgery showed considerable improvement; however, side effects such as frontal anesthesia, exposure keratitis, lagophthalmus, scarring and eyelid malposition occurred, and three of the six had residual spasm. At this point type A botulinum toxin became available. A total of 27 patients (26 who did not respond to drug therapy, including the 3 with residual spasm after surgery, and 1 previously untreated patient) received type A botulinum toxin injections. Most experienced rapid relief from their spasms. The beneficial effects lasted weeks to months, and there were no major side effects. Treatment with type A botulinum toxin appears to be a safe and effective means of temporarily relieving blepharospasm. The long-term results with repeated injections are yet to be determined.

Baclofen↗

Quantitative assessment of the effect of cyproheptadine on spastic paretic gait: a preliminary study.

The effects of cyproheptadine were studied in two patients with spastic paresis. The study consisted of two phases: a control phase (no medication) and a cyproheptadine phase (8 mg t.i.d.). The effects were evaluated from electromyographic (EMG) and kinematic analysis of treadmill walking with a portion of body weight supported, and from clinical examination and subjective assessments. Episodes of spontaneous spasms and elicited clonus were reduced with cyproheptadine. Improvement in locomotor function was evidenced by a decreased cycle duration, more regular foot-floor contact, functional joint excursions, and increased walking speed. In addition, a tonic EMG activity pattern was replaced by phasic muscle activation in the proximal extensors especially. Selective proximal movements were unmasked (hip flexion) and certain functional activities (transfers, dressing) were facilitated. The results support the role of cyproheptadine as an antispastic medication. Study of the short-term and long-term benefits of cyproheptadine is continuing.

Adult↗

Antemortem laboratory diagnosis of Alzheimer's disease.

The accuracy of diagnosis for AD by conventional clinical and laboratory means is in the order of 80%. Neurophysiological techniques (EEG, evoked potentials) show abnormalities in AD that could prove to be useful for diagnosis after pharmacological challenges. CSF analysis show a reduction of the concentration of various neuropeptides, reduction shared by other types of dementias. Among the existing imaging techniques PET using 18F-fluorodeoxyglucose is the most diagnostic in AD because of the early and often asymmetrical decrease in parietotemporal metabolic activity. Cortical biopsy with histological and biochemical analysis can provide an accurate in vivo diagnosis of AD.

Alzheimer Disease↗

Nucleus basalis neuronal loss, neuritic plaques and choline acetyltransferase activity in advanced Alzheimer's disease.

All our advanced, severe cases of Alzheimer's disease have dramatic cholinergic cell losses in the nucleus basalis of Meynert even after correction for cell or nucleoli shrinkage. There is a good correlation between choline acetyltransferase activity and "healthy" cell number in the nucleus basalis of Meynert. Half of the Alzheimer disease cases have markedly reduced cortical choline acetyltransferase activity in spite of preserved nucleus basalis of Meynert choline acetyltransferase activity, suggesting a deficiency of cortical origin and/or of axonal transport in Alzheimer disease. The relationship between cell loss in the various sub-divisions of the nucleus basalis of Meynert and plaque counts in corresponding and non-corresponding projection areas of the cortex has also been examined. Globally, this relation appears more obvious when cell loss in a sub-division of the nucleus basalis of Meynert is compared to plaque counts in its cortical projection area. However, the relation is discontinuous with few or no data to document the intermediary stages of the process, probably reflecting the severity of our Alzheimer disease cases.

Aged↗

Transmitter-replacement therapy in Alzheimer's disease using intracerebroventricular infusions of receptor agonists.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

Alzheimer Disease↗

Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type.

Multiple neurotransmitter systems are affected in senile dementia of the Alzheimer's type (SDAT). Among them, acetylcholine has been most studied. It is now well accepted that the activity of the enzyme, choline acetyltransferase (ChAT) is much decreased in various brain regions including the frontal and temporal cortices, hippocampus and nucleus basalis of Meynert (nbm) in SDAT. Cortical M2-muscarinic and nicotinic cholinergic receptors are also decreased but only in a certain proportion (30-40%) of SDAT patients. For other systems, it appears that cortical serotonin (5-HT)-type 2 receptor binding sites are decreased in SDAT. This diminution in 5-HT2 receptors correlates well with the decreased levels of somatostatin-like immunoreactive materials found in the cortex of SDAT patients. Cortical somatostatin receptor binding sites are decreased in about one third of SDAT patients. Finally, neuropeptide Y and neuropeptide Y receptor binding sites are distributed in areas enriched in cholinergic cell bodies and nerve fiber terminals and it would be of interest to determine possible involvement of this peptide in SDAT. Thus, it appears that multi-drug clinical trials should be considered for the treatment of SDAT.

Alzheimer Disease↗

Nucleus basalis neuronal loss and neuritic plaques in advanced Alzheimer's disease.

All our advanced severe cases of Alzheimer's disease had dramatic cholinergic cell loss in the basal forebrain, even after correction for cell or nucleolus shrinkage. We examined the relation between cell loss in the various subdivisions of the nucleus basalis of Meynert and plaque counts in corresponding and noncorresponding projection areas. This relation was not interpretable because of the ambiguity in the data.

Aged↗

Anxiety attacks in a patient with a right temporal lobe meningioma.

The role of neurologic factors leading to the appearance of anxiety attacks is incompletely understood. The case of a 69-year-old woman with no previous psychiatric illness who began to experience frequent anxiety attacks is described. These attacks were later associated with depersonalization and visual perceptual disturbances. The symptoms disappeared following the discovery and removal of a right temporal lobe meningioma.

Aged↗

Platelet 3H-imipramine binding distinguishes depression from Alzheimer dementia.

Platelet 3H-imipramine binding and serotonin uptake were studied simultaneously in normal subjects and in depressed, parkinsonian and Alzheimer's disease patients to investigate the usefulness of these variables in the diagnosis of depression in the elderly. Whereas Vmax of platelet serotonin uptake was significantly reduced in all patient groups compared to age matched normal subjects, the density of 3H-imipramine binding was reduced in depressed patients only. The lower Bmax values in depressed patients was independent of patient age. These data suggest that platelet 3H-imipramine binding may be a useful laboratory index which discriminates depression from dementia in the elderly.

Age Factors↗