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Biomedical subjects

S Gauthier

Publications and source records attributed to S Gauthier.

At least 145 records · Page 8Linked to original sources
PubMed1991

Environment, genetics and idiopathic Parkinson's disease.

Since Idiopathic Parkinson's disease (IPD) was first described more than 170 years ago, there have been major advances in the understanding of the etiology of the disease as well as in its treatment. This article will review current knowledge concerning the role of the environment, genetic hypotheses and the aging factor in the etiology of IPD and proposes a complex interaction involving all these factors. Hypotheses regarding mitochondrial inhibition and free radical generation in IPD are discussed in relation to the mechanism of action of neurotoxins known to produce parkinsonian syndromes.

Aging↗
PubMed1991

Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients.

This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antagonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.

Adult↗
PubMed1991

Treatment of Alzheimer's disease: hopes and reality.

The relative failure of symptomatic therapeutic trials for Alzheimer's disease using non-selective cholinergic agonists brings about the need for longitudinal studies with parallel designs aimed at disease stabilization, using trophic substances or amyloid suppressors.

Alzheimer Disease↗
PubMed1991

Spatial disorientation in persons with early senile dementia of the Alzheimer type.

Although spatial disorientation is frequently observed in persons with Alzheimer disease, it is not well understood. A descriptive study was conducted to examine spatial skills associated with spatial orientation. Spatial tasks were selected and grouped into three types of spatial skills: perceptual, cognitive, and functional. These spatial tasks were administered to a group of 15 persons with senile dementia of the Alzheimer type (SDAT) (early Alzheimer disease) and a group of 15 control subjects. The results indicated that the subjects with SDAT were impaired on half of the perceptual spatial tasks and all of the cognitive spatial tasks. On the functional spatial tasks, however, the subjects with SDAT showed impaired skills in the new environment but intact skills in familiar environments. Spatial disorientation poses a danger and limits a person's ability to independently perform daily activities that require navigation outside of the home. Occupational therapy should therefore include the assessment of spatial orientation skills in persons who are in the early stages of dementia.

Activities of Daily Living↗
PubMed1990

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Administration, Oral↗
PubMed1990

Delayed visual feedback and movement control in Parkinson's disease.

The dependence of movement on visual information was compared for healthy individuals and Stage II-III patients with Parkinson's disease (PD). A time delay (0-1400 ms) was introduced into a visually guided motor tracking task which required the subject to maintain constant index finger position relative to a stationary baseline on an oscilloscope. For healthy individuals, delayed visual feedback induced complex oscillations in finger displacement. Similar results were obtained for four of eight patients with PD. However, oscillations were not induced in four of eight patients with PD because of reduced gain and/or a higher tremor amplitude at zero delay which obscured the tracking error. These results suggest that some patients with PD are able to utilize visual information for controlling tracking in this motor task in the same manner as healthy individuals.

Adult↗
PubMed1990

Red cell choline in spasmodic torticollis and in a monozygotic twin pair with Tourette's syndrome.

1. Alterations in cholinergic function may play a role in the pathophysiology of idiopathic spasmodic torticollis (ST) and Gilles de la Tourette's syndrome (GTS). We measured red blood cell (RBC) choline in (i) ST (n = 24) and paired controls matched for age and gender (ii) a 20-year old pair of monozygotic twins with GTS, one of whom was moderately affected (CV) and the other virtually recovered (DV) (iii) both parents of the GTS twins, using gas chromatography-mass spectrometry. 2. RBC choline decreased with age in control men (r = -0.76; p less than 0.01) but not in control women. 3. RBC choline (nmol/ml) was higher in control men (18.3 +/- 4.8, X +/- SD) vs control women (13.1 +/- 4.3) (p = 0.025). 4. There was no significant difference in RBC choline (nmol/ml) between ST patients (16.6 +/- 5.0) and controls (15.5 +/- 5.2). 5. The RBC choline values (nmol/ml) in the twins and parents were: 56.6 (CV), 58.3 (DV), 89.8 (father), 38.3 (mother) and in the controls (age 20-24) (n = 5) 18.2 +/- 3.6. 6. These data suggest (i) RBC choline is affected by age and gender (ii) RBC choline is unchanged in ST (iii) the regulation of RBC choline is under genetic control (iv) elevated RBC choline is not a state marker for GTS.

Adult↗
PubMed1990

Lack of association between two restriction fragment length polymorphisms in the genes for the light and heavy neurofilament proteins and Alzheimer's disease.

The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a TaqI-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Adult↗
PubMed1990

Neurochemical deficits in pathological brain aging: specificity and possible relevance for treatment strategies.

Normal brain aging is accompanied by the losses of certain neuronal populations and the appearance of structures such as neuronal plaques and neurofibrillary tangles. Additionally, various neurotransmitter systems are altered in the elderly, although marked variations are observed between individuals, suggesting important differences between successful and unsuccessful aging. In certain pathological conditions, only certain features of normal aging are exacerbated. For example, the densities of forebrain cholinergic neurons are markedly decreased in cortical and hippocampal (but not striatal) areas in Alzheimer's disease. We discuss here the comparative alterations of cholinergic markers in certain neurological disorders such as Alzheimer's disease, Parkinson's disease, and the combined pathology. Differential alterations of brain cholinergic profile are observed in each disorder, this most likely having functional significance. We also found that muscarinic receptors of the M2 subtype act as negative autoreceptors to decrease brain acetylcholine release, whereas nicotinic agonists induced the opposite effect. This suggests that blockade of negative M2 or stimulation of positive nicotinic autoreceptors could have beneficial effects in Alzheimer's disease. Additionally, modulation of heteroreceptor activation such as the serotonergic or interleukin-2 sites located on or in proximity to cholinergic nerve terminals could offer alternate strategies for the treatment of cholinergic deficits in pathological brain aging.

Aging↗
PubMed1990

Validity and reliability of the dementia behavior disturbance scale.

Behavioral disturbance is a common and distinctive feature of Alzheimer's disease and other dementias. Existing instruments designed to quantify behavior disturbance among patients with dementia tend to be quite heterogeneous, including many items that do not refer to behavioral disturbance as such, but rather to cognitive, psychological, or somatic symptoms, or functional impairments. A 28-item Dementia Behavior Disturbance (DBD) scale was developed to avoid some of the problems encountered with the older instruments. In two samples of patients with dementia (n = 50 and n = 46), the most common symptoms were repetitive questions, losing or hiding things, lack of interest in daily activities, nocturnal wakefulness, unwarranted accusations, excessive daytime sleeping, and pacing. The coefficient of internal consistency was greater than .80 in both samples, and the correlation between scores obtained from the same subjects at a two-week interval was moderately high (Pearson's correlation coefficient = .71). There was a relatively high correlation between DBD scores and scores on Greene's Behavior and Mood Disturbance scale, and higher DBD scores were associated with increased duration and severity of disease. These preliminary results indicate that the DBD may be a useful and valid measure of one dimension of the dementia syndrome.

Aged↗
PubMed1990

The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries.

The effects of cyproheptadine, a serotonergic antagonist, were studied in seven patients with spastic paresis of spinal origin. Six patients were included in a double blind crossover trial (maximal dose 24 mg/day). The patients were evaluated on both their spasticity and locomotor function. Four of the patients also participated in an open trial in which cyproheptadine was administered for a minimum of six months at optimal dose. Patients walked on a treadmill at full weight bearing when possible, or with 40% of their body weight externally supported, as required, by an overhead harness system. Cyproheptadine considerably decreased the sustained ankle clonus and episodes of spontaneous spasms observed in all the patients who previously presented these manifestations of spasticity. Two patients who required body weight support (BWS) during locomotion could walk at full weight bearing during cyproheptadine therapy. A more normal timing of EMG patterns in these patients during cyproheptadine therapy was associated with temporal distance changes and marked improvement of joint angular displacement. In contrast, the other patients showed marginal changes in the EMG and the kinematic pattern but eventually managed to walk at a higher speed. These preliminary results suggest that cyproheptadine can reduce spasticity and enhance locomotor function in spinal cord injured patients.

Adult↗
PubMed1990

Assessment of functional changes in Alzheimer's disease.

Functional difficulties occur in all patients with Alzheimer's disease. Instrumental skills (shopping, handling money) are involved first, then self-care activities (toileting, dressing). Drug trials in intermediate stage Alzheimer's disease should monitor self-care activities with structured diaries and rating scales.

Alzheimer Disease↗
PubMed1990

Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.

Adult↗
PubMed1990

Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats.

There is a tendency for increased hypothalamic-pituitary-adrenal (HPA) activity with age in the rat, and the resulting elevations in circulating glucocorticoid levels have been implicated in the occurrence of hippocampal pathology and memory deficits. In the experiments reported here, we examined whether HPA dysfunction is selectively associated with cognitive impairments in a population of aged rats. Fifty-eight 23-27-month-old male Long-Evans rats were screened for spatial memory impairments using the Morris swim maze, and 2 groups of aged animals were selected; aged, cognitively impaired (AI) animals whose performance was significantly different (greater than 2 SD) from that of 6-month-old controls and aged, cognitively unimpaired (AU) animals whose performance was comparable to that of the young controls (a difference of less than 0.5 SD). Twenty-eight percent of the animals tested were designated as AI and 20% as AU. Histological analysis of a subset of these animals showed that, while both AU and AI animals showed neuron loss in the pyramidal cell fields of the hippocampus, the loss was significantly greater in the AI animals. The AI animals showed clear evidence of increased HPA activity. Thus, basal ACTH and corticosterone levels were significantly higher in the AI animals compared with both AU animals and young controls, especially during the dark phase of the cycle. The AI, AU, and young animals exhibited comparable corticosterone levels during a 20-min immobilization stress; however, following the termination of the stressor, corticosterone levels in AI animals were significantly elevated compared with both AU animals and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1990

Canadian Study of Health and Aging (CaSHA).

A Canada-wide study of the epidemiology of dementias was initiated in the summer of 1990 with the support of Health and Welfare Canada. The four objectives are to estimate the prevalence of dementias among elderly Canadian citizens, to determine the risk factors for dementia of the Alzheimer type, to describe the current pattern of caring for demented patients and assess the burden on informal caregivers, and to establish a uniform database for future incidence and longitudinal studies of dementias. Trained interviewers will screen a representative sample of senior citizens in the community. The screening is followed by a standardized clinical assessment for putative cases of dementia, for institutionalized patients and for a number of controls. Diagnosis will follow DSM-III-R criteria for dementia, the NINCDS-ADRDA criteria for dementia of the Alzheimer type and the ICD-10 criteria for other dementias. A sample of cases and controls will then enter the caregiver and risk factor sub-studies.

Aged↗
PubMed1989

Angiotensin II stimulates sympathetic output by a direct spinal action.

When administered intrathecally in a dose of 10 mu to the ninth thoracic segment of the spinal cord in the anesthetized rat, angiotensin II produced a transient increase in systolic and diastolic arterial pressures lasting 1-4 min. Heart rate was also increased, but in this case for more than 30 min. Similar administration of 5 micrograms or of CSF had no effect on either arterial pressure or heart rate. Neither the arterial pressure nor the heart rate response to 10 micrograms of angiotensin II was observed in rats given hexamethonium (10 mg/kg, i.v.), suggesting that the effects were mediated by spinal activation of sympathetic output. When the rats were pretreated with 10 micrograms of [Sar1, IIe8]-angiotensin II three min prior to angiotensin II, there was a block of the increase in arterial pressure but not of the increase in heart rate. When the antagonist was given 15 min prior to angiotensin II, the full pressor response appeared, suggesting that the antagonist was effective for less than 15 min; in addition, after the antagonist alone, while arterial pressure remained unaltered, there was a gradual increase in heart rate suggesting that the analogue had agonistic effects on mechanisms regulating heart rate. These results suggest that angiotensin II activates sympathetic mechanisms by a spinal action and that arterial pressure and heart rate are regulated differentially, arterial pressure via a mechanism which is antagonized by [Sar1, IIe8]-angiotensin II, and heart rate via a mechanism in which the analog can act as an agonist.

Angiotensin II↗