Biomedical subjects

A Barbeau

Publications and source records attributed to A Barbeau.

At least 55 records · Page 3Linked to original sources

PubMed1984

The Quebec Cooperative Study of Friedreich's Ataxia: 1974-1984--10 years of research.

In this paper the author reviews the progress accomplished in the understanding of Friedreich's disease since the start of the "Quebec Cooperative Study of Friedreich's Ataxia" in 1974. The last ten years have indeed seen important strides taken in the definition and nosography of the hereditary ataxias and the characterization of a number of new entities. Biochemically, the principal leads uncovered during the initial prospective survey, have been pursued to great detail. Unfortunately no clear-cut constant and severe enzyme block in the principal metabolic pathways has yet been identified, despite intensive studies. It is postulated that the defect may instead be a regulatory one and involve a decreased availability or utilization of one of the vitamin cofactors that are known experimentally, or clinically, to produce central nervous system damage with ataxia: Vitamin E, Biotin or Pantothenic Acid. Studies in that direction and in molecular genetics to localize the Friedreich's disease gene are being undertaken for the next phase of the Cooperative Study.

Amino Acids↗

PubMed1984

Etiology of Parkinson's disease: A research strategy.

In this essay I present a new "global approach hypothesis" to explain the pathophysiology of Parkinson's disease: "Susceptibility to Parkinsonism is genetically determined and is reflected in all cells. I propose that idiopathic Parkinson's disease is the combined result of a generalized cell aging process accelerated, in susceptible individuals, by a variety of often repetitive trigger factors. These factors have in common the fact that they cause a transient increase in turnover within catecholamine producing neurons, centrally as well as peripherally. This results in accumulation within these neurons of free radicals. When the level of the toxic substances, in quantity or in time of exposure, exceeds the scavenging capacity of the cell, damage to organelles and to membranes results, leading to the formation of Lewy bodies through an autoimmune reaction to damaged filaments and to cell death, particularly in the pigmented neurons of the brainstem. The progressive cell depletion leads to a compensatory increase in catecholamine turnover in the remaining pigmented cells, and an ever-accelerating degenerative process. The resulting neurotransmitter imbalance in the basal ganglia explains the symptoms of Parkinson's disease". In the light of this hypothesis, our research objectives should be (1) to delineate the limits of true Parkinson's disease from all phenocopies; (2) to identify individuals susceptible to parkinsonism and the most common trigger factors; (3) to reduce the metabolic effects of unavoidable trigger factors and (4) to protect susceptible individuals by increasing the functional availability of free radical trapping agents.

Aging↗

PubMed1984

Familial subsets in idiopathic Parkinson's disease.

In the present paper we explore in some detail the hypothesis that the presence of familial aggregations in 10-15% of Parkinson's disease cases is due in great part to the existence of well-defined familial subsets, rather than to chance occurrences. We describe the clinical and genetic characteristics of the two main subsets: "Essential tremor-related Parkinsonism" and the "Familial akineto-rigid Syndrome" previously identified. The former type of Parkinsonism is associated at random, but with increased frequency, to an autosomal dominant disorder, usually essential tremor but occasionally OPCA. Two possible susceptibility factors were uncovered in this entity: an increased incidence of familial hyperthyroidism (augmentor factor) and a decreased incidence of the generally frequent HLA Haplotypes A1B8 or A2B5 (Protective factors). The other presentation, the "familial akineto-rigid syndrome", appears to be a definite disease entity with an autosomal recessive mode of inheritance (normal parents, increased incidence of identical parkinsonism in sibs, increased consanguinity rate in parents). This newly defined disorder deserves much further genetic and biochemical analysis.

Consanguinity↗

PubMed1984

Manganese and extrapyramidal disorders (a critical review and tribute to Dr. George C. Cotzias).

In this essay we first review the important contributions of Dr. George Cotzias to the understanding of chronic manganese intoxication and of manganese metabolism in man and animals. We also indicate the original contribution of Dr. John Donaldson to the mechanism of the neurotoxicity of manganese. In a second phase, the author challenges the tenet that Parkinson's disease is a form of chronic manganese intoxication and that manganism is an experimental model for Parkinson's disease. Clinical, pathological, experimental and biochemical evidence are brought to bear on this argument. Thirdly the author proposes that the necessary event to the so-called "depigmentation" of the substantia nigra and subsequent bradykinetic "low dopamine" syndrome is an early enhanced turnover of dopamine. Manganese intoxication is only one of the factors which may serve as a trigger to this event. Many others are also listed. In opposition to current views, who look for causal factors in Parkinson's disease along the pathways for melanogenesis, the author thus proposes a novel hypothesis which envisions a variety of transient "trigger factors" acting at the dopamine synapse to increase dopamine turnover. In turn, this increased synthesis of dopamine favours the production of large quantities of free radicals within the cell bodies in the substantia nigra, eventually overflowing the scavenging capacity of neuromelanin and their protective barrier, and causing cell death. The resulting decreased pool of dopamine-producing cells leads to a self-perpetuating situation of ever increasing demand on the remaining cells, and "progression" of the disease. Finally the author stresses the fact that genetic factors may play a role in an individual's susceptibility to such triggers. Again defective manganese transport, metabolism or binding are only some of the mechanisms possibly underlying such genetic predisposition to induced basal ganglia disorders. Further studies relating to manganese in these disorders and particularly in Parkinson's disease should focus not on the "intoxication" part of the overload and its striatopallidal consequences, but on the intimate mechanism of destabilization of the homeostatic regulator in neuromelanin bearing cells, even after the exposure period.

Animals↗

PubMed1984

Genetic studies in Parkinson's disease.

In a previous paper (2), we had demonstrated the existence of familial cases of Parkinson's disease. We have now identified two main patterns to these familial cases within our own clinical material. The total familial subgroup of 50 kinships that we report represents 13% of our 342 kinships personally examined in detail. Only 2 of these familial cases turn out to be phenocopies of Parkinson's disease. A further 34 kinships (10% of all Parkinson's disease) are classified within the essential-tremor related Parkinsonism subgroup that we have previously described and 10 kinships (3% of all Parkinson's disease) form what we now call the recessive akineto-rigid syndrome. A further 4 kinships (called pseudodominant) are probably examples of this same entity. These subgroups have quite distinct inheritance patterns and deserve more thorough metabolic investigations and clinical characterization. On the basis of these studies, we propose that a genetic type of Parkinson's disease be included in any classification of the disorder.

Genes, Dominant↗

PubMed1983

Neurotensin affects hyperactivity but not stereotypy induced by pre and post synaptic dopaminergic stimulation.

The effects of intraventricular administration of neurotensin (0.9, 3.75 and 15.0 micrograms) on hyperactivity and stereotypy induced by either amphetamine (1 mg/kg), nomifensine (20 mg/kg), apomorphine (0.5 mg/kg) or N-n-propylnorapomorphine (0.5 mg/kg) were examined. Results indicate that for each drug treatment, the effects of neurotensin were identical: hyperactivity was significantly reduced while stereotypy remained unaffected. Results also revealed that neurotensin significantly increased the hypothermia induced by apomorphine and N-n-propylnorapomorphine. Possible mechanisms which could underly neurotensin's selective inhibitory action on hyperactivity produced by both pre and post synaptic dopaminergic stimulation are discussed.

Amphetamine↗

PubMed1983

Oropharyngeal dysphagia and oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy is an autosomal dominant transmitted condition seen mainly in French Canada. The largest number of publications on these patients concerns a Quebec family whose descendants have spread throughout the United States. Families of different ethnic origins have also been reported from around the world, although there is no evidence that the neuromuscular disease reported is the same, despite the similarity of the syndrome. When severe oropharyngeal dysphagia results, these patients can significantly benefit from a cricopharyngeal myotomy.

Blepharoptosis↗

PubMed1983

A prospective study of 50 cases of familial Parkinson's disease.

In a recent paper (Barbeau and Pourcher, 1982) we demonstrated that so-called "idiopathic" Parkinson's disease is not a homogeneous entity, and defined the existence of a sub-group of patients with genetic parkinsonism. To investigate this last possibility, and to uncover possible metabolic clues as to the etiology of such cases, we carried out a prospective study of 50 kindreds with "familial" parkinsonism. Two control groups were similarly studied: 50 kindreds with essential tremor (neurological control group) and 50 kindreds originating from spouses of the previous patients (non neurological control group). We uncovered two main patterns of genetic transmission within the parkinsonian patients: a parkinsonism related to dominant essential tremor (34 kindreds; 10% of all Parkinsonians) and a recessive "akineto-rigid syndrome" (10 kindreds; 3-4% of all Parkinsonians). A further 4 kindreds assumed a pseudo-dominant pattern but were probably recessive. Finally 2 kindreds were obviously other entities presenting as "phenocopies" of Parkinson's disease. Metabolically, hyperthyroidism appeared to be more frequent in essential tremor and "essential-tremor related parkinsonism" kindreds, while hypothyroidism and possibly hypoparathyroidism (post surgery) seemed more frequent in the recessive akineto-rigid syndrome kindreds.

Humans↗

PubMed1983

Taurine and tolerance to opioid peptides.

The finding that taurine may possess an ability to inhibit development of tolerance to opioid peptides was demonstrated in the present study. Tolerance was produced in rats by five IVT administrations of DAME during 3 consecutive days. Pretreatment with taurine that had been injected IVT 10 min prior to every administration of DAME suppressed the development of tolerance to both the akinetic and analgetic effects of the peptide. In addition, taurine pretreatment inhibited the induction of hyperlocomotor activity which was observed in tolerant animals as the number of the DAME injections was increased. Tolerance to WDS effects also resulted from the repeated administration of the peptide. However, it could not be concluded from the present experimental condition that taurine affects development of tolerance to WDS, since the amino acid suppressed the induction of WDS from the first injection of DAME.

Analgesia↗

PubMed1982

Effects of taurine on tolerance to [D-Ala2, Met5]enkephalinamide in rats.

Effects of taurine on tolerance to [D-Ala2, Met5]enkephalinamide (DAME) were investigated in rats. Tolerance was produced by five intraventricular administrations of DAME (50 microgram) during 3 consecutive days. The magnitude of developed tolerance to DAME was not uniform for each behavioral parameter; tolerance to analgesia effects developed more intensively and rapidly from the repeated injections of the peptide than that to akinesia effects. Pretreatment with taurine (9.5 X 10(-2) M) which was injected in a volume of 10 microliter intraventricularly 10 min prior to every administration of DAME suppressed the development of tolerance to both analgesia and akinesia effects of this peptide, whereas pretreatment with L-leucine at the same concentration did not. Spontaneous locomotor activity was measured for 1 h after the 90-min behavioral observation period was completed. That activity increased with the number of the peptide injections. Taurine pretreatment inhibited the induction of 'hyper'-locomotor activity. These results support the view that taurine may possess an ability to inhibit development of tolerance to morphine-like peptides in rats.

Analgesia↗

PubMed1982

New data on the genetics of Parkinson's disease.

We investigated the clinical and metabolic characteristics of Parkinsonian patients whose illness started before the age of 40. A pilot study of 32 of our own such cases revealed the existence of 3 subgroups: 1. Post-Encephalitic, 2. Onset and course with predominant tremor, 3. Onset and course with akinesia and rigidity. In this early onset group of patients, there was a 46% incidence of familial cases (as opposed to 10-15% in the general Parkinson populations). The cases with tremor onset had a high prevalence of essential tremor in their families, while those with an akineto-rigid onset had a high familial incidence of other cases of Parkinson's Disease. Familial grey hair, hypertension, diabetes and thyroidopathies appeared to be in higher than expected frequency.

Adult↗

PubMed1982

A tentative classification of recessively inherited ataxias.

We present a working classification of recessively inherited ataxic syndromes based on the use of simple tools available to every clinician: a good history (particularly pinpointing the age of onset) and a good neurological examination (simplified to the verification of the presence of ataxia, deep tendon reflexes in the knee, optic nerve, retinal and/or 8th nerve signs). In the three groups of disorders (non progressive, intermittent or progressive) patients can be hyper/normo reflexic, or they can be hypo/areflexic. Six principal types of progressive ataxic disorders are further delineated by the age of onset. Sub-types depend on the presence of absence of eye and ear signs, whereas eponymic or regional denominations are used only for simplicity while awaiting exact delineation of the biochemical defects.

Ataxia↗

PubMed1982

Pilot study of threonine supplementation in human spasticity.

Threonine supplementation (500 mg/day) was given to 6 patients with genetic spasticity syndromes for a period of 12 months, followed by a 4-month observation period without medication. All 6 patients showed partial improvement of spasticity, intensity of knee jerks and muscle spasms without changes in true pyramidal tract signs. The improvement in motor performance, objectively measured, averaged 29% (19% in upper limbs and 42% in lower limbs). The range of overall improvement was 19--35% (7--30% for upper limbs; 25--67% for lower limbs). No toxic clinical or biochemical side effects were encountered. Thus threonine, a precursor of glycine, produced the same effect on spasticity than that previously observed with glycine. It is concluded that threonine supplementation is feasible and safe and that it deserves a controlled trial in well defined (preferably genetic) cases of spasticity.

Adult↗

PubMed1982

Oral lecithin and linoleic acid in Friedreich's ataxia: I. Design of the study, material and methods.

A clinical and biochemical evaluation of twenty-two patients with Friedreich's Ataxia and ten normal controls was undertaken in 1980 to assess the effect of lecithin and linoleic acid supplements on the course of the disease. The trial consisted of two consecutive six months periods on either supplements in a double-blind crossover fashion. Clinical appraisal was performed with regards to the following parameters: joints mobility, muscle strength, equilibrium, coordination, motor accuracy, speech and numerous day to day activities. Blood samples were obtained at the beginning and in the course of the trial for enzymatic determinations. This paper describes the methodology of the study.

Administration, Oral↗

PubMed1982

Influence of nicotinamide on neurobehavioral effects of 3-acetylpyridine.

The purpose of the present study was to examine the ability of nicotinamide to prevent the appearance of neurobehavioral symptoms induced by 3-acetyl pyridine (3-AP) in rats. Nicotinamide in doses of 5,50 and 500 mg/kg was injected immediately after administration of 65 mg/kg 3-AP, and neurobehavioral measurements were made at 6, 12, 24, 48 and 72 hours after injections. The effects of 500 mg/kg nicotinamide injected at 3 and 6 hours after 3-AP treatment were also investigated. The results indicate that, starting at 50 mg/kg, nicotinamide can protect animals against most of the neurobehavioral effects of 3-AP. However, the muscular rigidity induced by 3-AP can only be reversed by 500 mg/kg nicotinamide, and the depressing influence of 3-AP on locomotor activity is not blocked by any of the doses of nicotinamide tested. In terms of time course, the protective action of 500 mg/kg is seen when injected 3, but not 6 hours after 3-AP.

Animals↗

PubMed1982

Glutamate and aspartate do not modify the ataxic gait of acrylamide treated animals.

The purpose of this experiment was to examine the effects of intraventricular injections of glutamate and aspartate on the gait of animals rendered ataxic by the administration of acrylamide. Contrary to their previously reported corrective influence on ataxia induced by 3-acetyl pyridine, these amino acids did not modify the ataxic gait of acrylamide treated animals. This suggests that glutamate and aspartate can act in cerebellar but not in peripheral types of ataxia in animals.

Acrylamides↗

PubMed1982

Tissue lipids in acute acrylamide intoxicated rats.

A preliminary survey of tissue lipid composition in acrylamide intoxicated rats is reported. The animals were injected intraperitoneally with acrylamide 50 mg/kg body weight per day for 10 days. Liver cholesterol, mainly in the ester fraction, was decreased in treated rats. When fatty acid composition of liver cholesterol esters was examined, the proportions of linoleate and stearate were found to be decreased and were compensated by the increase of palmitate. Atrophy of epididymal fat pad resulted in severe triglyceride depletion and a relative increase in the proportion of phospholipids and cholesterol. There was also a reduction of linoleate, palmitate and palmitoleate in triglycerides and phospholipids of this tissue. There were, however, only minor changes in the fatty acid profile of the sciatic nerve.

Acrylamides↗

PubMed1982

Pituitary responses to a neuroactive tripeptide (TRH) in Friedreich's ataxia families.

Oral glucose tolerance, thyroid function tests, as well as thyrotropin, prolactin and growth hormone release after administration of thyrotropin releasing hormone, were evaluated in patients with Friedreich's ataxia and unaffected family members. Impaired glucose tolerance was found in the majority of family members, affected or not. Thyroid hormone levels and PRL and TSH responses to TRH, were similar in all and normal. However, GH responses to TRH were abnormal in half of the patients, but in none of the unaffected family members. Paradoxical responses to neuropeptides may characterize some Friedreich's ataxia patients, and may predict the possibility of therapeutic maneuvers with such peptides in these patients.

Adolescent↗