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Biomedical subjects

G Meco

Publications and source records attributed to G Meco.

At least 55 records · Page 3Linked to original sources
PubMed1998

The alpha-synuclein Ala53Thr mutation is not a common cause of familial Parkinson's disease: a study of 230 European cases. European Consortium on Genetic Susceptibility in Parkinson's Disease.

We report the results of a screen of 230 European familial index cases of Parkinson's disease for the recently described Ala53Thr mutation in the alpha-synuclein gene in an autosomal dominant Parkinson's disease kindred. No mutations were found from this broad white population, and we therefore conclude that although of great interest, this mutation is a very rare cause of familial Parkinson's disease.

Adult↗
PubMed1998

Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in European and Algerian families, extension of the clinical spectrum, and evidence of a small homozygous deletion in one family. The French Parkinson's Disease Genetics Study Group, and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recently has been mapped to chromosome 6q25.2-27 in Japanese families. We have tested one Algerian and 10 European multiplex families with early-onset Parkinson disease for linkage to this locus, with marker D6S305. Homogeneity analysis provided a conditional probability in favor of linkage of >.9 in eight families, which were analyzed further with eight microsatellite markers spanning the 17-cM AR-JP region. Haplotype reconstruction for eight families and determination of the smallest region of homozygosity in two consanguineous families reduced the candidate interval to 11.3 cM. If the deletion of two microsatellite markers (D6S411 and D6S1550) that colocalize on the genetic map and that segregate with the disease in the Algerian family is taken into account, the candidate region would be reduced to <1 cM. These findings should facilitate identification of the corresponding gene. We have confirmed linkage of AR-JP, in European families and in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus for AR-JP in European patients. The clinical spectrum of the disease in our families, with age at onset <=58 years and the presence of painful dystonia in some patients, is broader than that reported previously.

Age of Onset↗
PubMed1998

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD).

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha-synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha-synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.

Adult↗
PubMed1998

Mortality in a population-based cohort of patients treated with antiparkinsonian drugs.

OBJECTIVES: A number of studies have been focused on the mortality of parkinsonian patients, as compared with the rest of the population. In these studies, a mortality greater than expected on the basis of mortality of the general population has been shown. Nevertheless, just a few of these studies have investigated in detail the specific causes of death, probably as a consequence of both small cohort sizes and a short time period of observation. The aim of this study was to estimate cause-specific mortality in a cohort of patients treated with antiparkinsonian drugs. METHODS: The study was performed on a wide population-based cohort of patients identified and followed-up through the computerized health databases of the Italian province of Rome (about 3,800,000 inhabitants). The follow-up lasted from January 1987 to December 1994. Standardized Mortality Ratios (SMR) were calculated for each specific cause of death, using the Rome province population as reference. RESULTS: A cohort of 10,322 subjects, receiving antiparkinsonian drugs, were identified. There were 4328 deaths on an average follow-up of 5.7 years. This figure was 17% higher than was expected. A gradual decrease in SMR was observed in the oldest age groups. Statistically significant (95%) excesses of death were related to the nervous system (SMR = 1037; 95% CI 964-1110), mental disorders (SMR = 182; 95% CI 129-246), and endocrine and metabolic diseases (SMR = 117; 95% CI 102-133). Lower than expected mortality was found to be caused by malignant neoplasms (SMR = 56; 95% CI 51-61). CONCLUSIONS: Apart from deaths specifically related to Parkinson's disease, the main differences between our cohort of patients and the general population were related to mortality due to malignant neoplasms and mental disorders. The gradual decrease in SMR for the oldest age groups, seems to indicate a greater reduction of life expectancy for patients with early onset of symptoms. This age-related trend could explain the relatively small excess of mortality, as in our cohort the median age of patients at entry was 74 years.

Adult↗
PubMed1998

Direct genetic evidence for involvement of tau in progressive supranuclear palsy. European Study Group on Atypical Parkinsonism Consortium.

OBJECTIVE: To confirm whether a dinucleotide repeat sequence in an intron of the microtubule-associated protein tau is associated with progressive supranuclear palsy (PSP) in an independent study population and to establish an improved methodology for allelotyping. BACKGROUND: It has recently been reported that a genetic variant of tau, known as the A0 allele, was represented excessively in PSP patients when compared with control subjects. METHODS: In a multicenter study, the authors examined the allelic distribution of this dinucleotide repeat marker in a set of clinically ascertained PSP patients (n = 30), multiple system atrophy (MSA) patients (n = 35), and matched control subjects (n = 70). Individuals were allelotyped using automated analysis of fluorescently labeled PCR products. RESULTS: The A0 allele was significantly overrepresented in the PSP patients (93.3% versus 76.4%; p = 0.0067; odds ratio [OR] = 4.33; 95% confidence interval [CI], 1.36 to 13.60), but not in the MSA patients. Likewise, A0 homozygotes were overrepresented in the PSP group (86.7% versus 61.1%; p = 0.02; OR = 4.14; 95% CI, 1.19 to 14.48) compared with control subjects. CONCLUSIONS: The findings of this study, which is the largest to date, support those of a previous investigation that used pathologically confirmed PSP patients. These data provide additional strong evidence that genetic variation at or near the tau gene plays an important role in the pathogenesis of PSP.

Aged↗
PubMed1997

Cognitive improvement during Tolcapone treatment in Parkinson's disease.

The aim of this study was to evaluate the effects of Tolcapone, a reversible, selective inhibitor of catechol-O-methyltransferase, on the cognitive function of eight patients with advanced Parkinson's disease. They underwent neuropsychological and motor assessment at baseline and were re-evaluated after 6 months. During this period, they received Tolcapone three times daily, while the L-dopa dosage was progressively reduced. Significant improvements were observed in the attentional task, auditory verbal short-term memory, visuo-spatial recall, constructional praxia and motor symptoms. These data suggest that treatment with Tolcapone, in combination with L-dopa therapy, may determine a significant improvement in cognitive resources of patients with advanced Parkinson's disease.

Aged↗
PubMed1997

Effects of cocaine treatment on the nervous system of planaria (Dugesia gonocephala s. l.). Histochemical and ultrastructural observations.

Acute high dose treatment with cocaine in planaria has been shown to produce hyperkinesia followed by immobilization, thus suggesting progressive neuronal dopamine (DA) depletion. On the contrary, treatment with low doses of cocaine inhibits motor activity in planaria, without producing hyperkinesias. Here we investigated the morpho-functional changes of the DA presynaptic terminals following cocaine treatment in planaria (acute high dose and chronic low dose). Neuronal DA content was determined by means of histochemical methods, and nerve cell ultrastructure was examined by electron microscopy. The effects of cocaine were compared to those of L-dopa, reserpine (used as positive and negative controls, respectively) and normal untreated specimens. Presynaptic vesicles and DA content were significantly reduced by chronic low-dose cocaine treatment. These effects were even more robust when the drug was acutely administered at high dose. Thus, depletion of DA vesicles is produced by cocaine in planaria, as well as in mammals. The behavioral effects of chronic low-dose treatment with cocaine, however, suggest that the drug acts not only as a DA reuptake blocker, but also as a direct agonist on presynaptic DA receptors. Acute high-dose administration of cocaine also produced signs of neuronal suffering, thus providing evidence for a direct neurotoxic effect of the drug.

Animals↗
PubMed1996

Attentional functions in multiple system atrophy and Parkinson's disease.

OBJECTIVE: To assess cognitive performances of patients with striatonigral degeneration type multiple system atrophy compared with those of patients with Parkinson's disease. METHODS: The cognitive performances of a group of patients with multiple system atrophy of the striatonigral type were compared with those of matched patients with Parkinson's disease and controls, using tests sensitive to frontal lobe dysfunction. RESULTS: The multiple system atrophy group, when compared with the Parkinson's disease group, showed significant deficits in attention tasks, particularly in the Stroop test. CONCLUSION: There was a consistently greater impairment in attention resources in patients with multiple system atrophy than in patients with Parkinson's disease.

Aged↗
PubMed1995

Familial Parkinson's disease: a clinical genetic analysis.

OBJECTIVE: To study the frequency, clinical features and clinical genetics of familial Parkinson's disease (PD). METHODS: Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were compared between personally verified familial and sporadic PD cases, from the same consecutive clinical series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families. RESULTS: Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse controls (p < 0.001). When family history for isolated tremor is also considered, the number of positive cases rises to 43% compared with 9% in controls (p < 0.001). Nine of the consecutive cases had at least one living affected relative, for a total of 20 familial PD cases. These familial cases showed an earlier onset age when compared with sporadic ones from the same consecutive series. Within 22 non-consecutive PD families with at least two living and personally examined PD cases (total 52 PD cases), the crude segregation ratios were similar for parents and siblings and the lifetime cumulative risks approached 0.4 in siblings and tended to be comparable, but at later ages, in parents. Ancestral relatives were all unilaterally distributed. In some families, anticipation of onset age in new generations was observed. CONCLUSIONS: The frequency of positive family history for PD and for PD and tremor is higher among PD cases than controls. Familial and sporadic PD only differ in onset age. The clinical genetic analyses support autosomal dominant inheritance with strongly age-related penetrance as most likely in familial PD.

Age of Onset↗
PubMed1995

Estimate of parkinsonism prevalence through drug prescription histories in the Province of Rome, Italy.

INTRODUCTION: The objective of the study was to estimate the prevalence of parkinsonism in the Province of Rome using antiparkinsonian prescription histories from 1986 to 1991. METHODS: A subject was defined as a case of parkinsonism if he/she had received "specific" and "consistent" antiparkinsonian therapy in the study period. RESULTS: In November 1990, 6,572 patients were defined as prevalent cases of parkinsonism. The crude prevalence ratio, for the total population of the Province of Rome, is 173.5 per 100,000 inhabitants (165.9 per 100,000 in men and 180.5 per 100,000 in women). The method was validated by record-linkage with clinical records of all patients visited during 1990 at the Department of Neurological Sciences of the University of Rome "La Sapienza". The sensitivity of the prevalence study was 83.6%. CONCLUSIONS: The use of a computerized data base of all prescription data, routinely collected for administrative purposes, enabled us to obtain a prevalence estimate based on a very large population, with low costs and in a relatively short time.

Adolescent↗
PubMed1994

Buspirone in levodopa-induced dyskinesias.

We made a double-blind, crossover comparison of buspirone (10 mg orally, twice a day) and placebo in 10 patients with Parkinson's disease and levodopa-induced dyskinesias. The duration of the study was 3 weeks, for both buspirone and for placebo treatment. Chronic therapies remained unchanged. The extrapyramidal symptoms, dyskinesias, and anxious/depressive symptoms were evaluated at the beginning of the study and after the buspirone and placebo treatments. Seven patients concluded the trial. The extrapyramidal symptoms, evaluated in both the "off" and "on" states during an oral L-Dopa test, did not show any worsening during the trial. Buspirone significantly lessened the severity of levodopa-induced dyskinesias in five of the seven patients, whereas it proved ineffective in the two patients with the mildest dyskinesias. There were no changes in the mild anxious and depressive symptoms at any time during the study. The activities of buspirone on the serotonin and dopamine systems might have led to the antidyskinetic effect we observed. At daily dosages of 20 mg, buspirone might prove effective in reducing levodopa-induced dyskinesias without worsening of parkinsonism.

Aged↗
PubMed1994

The mortality rates for multiple sclerosis in Italy (1969-1987).

The mortality for multiple sclerosis in Italy was analyzed for the period 1969-1987. The age-adjusted (to Italian 1981 population) death rates decreased slightly during these years for both sexes. The average national female/male ratio of the age-adjusted rates is 1.33 and shows a north-south gradient, with values < 1 in the South-Islands area where multiple sclerosis cases are probably heavily underreported on the death certificates. A positive, significant correlation between the age-adjusted death rates and latitude of the 20 Italian regions exists for the period 1969-1975; in recent years (1981-1987), these parameters show a weaker, but not statistically significant positive correlation. Moreover, the 95% confidence intervals of the death rates in the 20 regions overlapped extensively in both periods studied (1969-1975 and 1981-1987). Death rates for multiple sclerosis are a weak index of the frequency of the disease and their utility is restricted to national surveys. The descriptive epidemiological data (incidence, prevalence, mortality) available at present in Italy do not seem to support a link between multiple sclerosis and latitude.

Female↗
PubMed1994

Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate).

Permanent parkinsonism was observed in a man with chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Symptoms developed at 37 years of age, two years after exposure had ceased. To our knowledge, this is the second report on parkinsonism associated with exposure to maneb. Manganese is a well-known parkinsonigen toxin in humans. More recently, it has been shown that dithiocarbamates can also induce extrapyramidal syndromes. The biochemical effects of manganese and dithiocarbamates are reviewed and their possible neurotoxic mechanisms are discussed. Both of these components may have played a role in this case.

Humans↗