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Biomedical subjects

G Meco

Publications and source records attributed to G Meco.

At least 37 records · Page 2Linked to original sources
PubMed2001

Epidemiology of progressive supranuclear palsy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Progressive supranuclear palsy (PSP) is a rare form of parkinsonism. The incidence rates are about 0.3-1.1 cases per 100,000 persons. The only two case-control studies performed up to now show conflictual results as regards education and residence in rural areas. Recently, a cluster of PSP and atypical parkinsonism has been observed in French Antilles. The hypothesis is that a consumption of both tropical fruit and herbal tea may be associated with PSP onset. Some PSP families with a probably autosomal dominant transmission have been described. A high frequency of a tau haplotype (H1/H1) associated with PSP is reported by some authors. The significance of this association is still not clear. We have performed a case-control study on 58 PSP cases, 116 hospital controls and 58 population controls.

Age of Onset↗
PubMed2001

Donepezil in the treatment of progressive supranuclear palsy.

OBJECTIVES: To evaluate the effect of 3 month therapy with donepezil, a centrally acting cholinesterase inhibitor, on cognitive performances, motor function and daily living activities in progressive supranuclear palsy (PSP). MATERIALS AND METHODS: Six patients with a diagnosis of PSP were evaluated at baseline and after 3 months of treatment with donepezil, 10 mg given at bedtime. Cognitive functions, motor symptoms and daily activities were evaluated by means of appropriate rating scales. RESULTS: Donepezil was not effective on cognitive dysfunction and did not change ratings of daily living. Parkinsonian symptoms were unaffected by donepezil treatment. CONCLUSIONS: Cholinergic replacement therapy alone is not likely to improve symptoms in a disorder characterized by a more widespread impairment of monoaminergic systems. Larger studies may be necessary to confirm the lack of effect of donepezil in this disorder.

Aged↗
PubMed2001

Three parkin gene mutations in a sibship with autosomal recessive early onset parkinsonism.

The objective was to describe a family with autosomal recessive, early onset parkinsonism, with affected siblings carrying three different exon rearrangements in the parkin gene. The living affected siblings were personally examined. Molecular genetic analyses included exon dosage of the parkin gene using a semiquantitative multiplex polymerase chain reaction (PCR) protocol and haplotype analysis. The index case was a compound heterozygote with a deletion of exon 5 and a duplication of exon 3. His affected sister was a compound heterozygote for a deletion of exon 5 and a deletion of exons 3-9. Haplotype analysis confirmed the presence of three mutant alleles at the parkin locus. The phenotype was early onset parkinsonism with marked response to levodopa, and a very slow, prolonged course. In conclusion, the frequency of mutations in the parkin gene in certain populations might be high enough to cause allelic heterogeneity in the same sibship.

Aged↗
PubMed2000

Heart rate variability in Parkinson's disease patients treated with tolcapone.

Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson's disease (PD) patients in chronic Levodopa (L-dopa) therapy. The interaction between tolcapone and the endogenous metabolism of catecholamines points to a possible influence on autonomic cardiovascular function.Cardiovascular reflexes have been analysed in a group of seven PD patients (four males, three females; mean age 69.7years, mean disease duration 14.1years) by means of the heart rate variability (HRV) method using a continuous 24-h ECG (ECGD), before and after six months of treatment with tolcapone (in addition to L-dopa).We have observed no statistically significant differences in HRV parameters, nor any changes in the incidence of hyperkinetic and hypokinetic arrhythmias, which suggest that autonomic cardiovascular function in PD patients is not influenced by six months of treatment with tolcapone.

Journal Article↗
PubMed2000

Association between early-onset Parkinson's disease and mutations in the parkin gene.

BACKGROUND: Mutations in the parkin gene have recently been identified in patients with early-onset Parkinson's disease, but the frequency of the mutations and the associated phenotype have not been assessed in a large series of patients. METHODS: We studied 73 families in which at least one of the affected family members was affected at or before the age of 45 years and had parents who were not affected, as well as 100 patients with isolated Parkinson's disease that began at or before the age of 45 years. All subjects were screened for mutations in the parkin gene with use of a semiquantitative polymerase-chain-reaction assay that simultaneously amplified several exons. We sequenced the coding exons in a subgroup of patients. We also compared the clinical features of patients with parkin mutations and those without mutations. RESULTS: Among the families with early-onset Parkinson's disease, 36 (49 percent) had parkin mutations. The age at onset ranged from 7 to 58 years. Among the patients with isolated Parkinson's disease, mutations were detected in 10 of 13 patients (77 percent) with an age at onset of 20 years or younger, but in only 2 of 64 patients (3 percent) with an age at onset of more than 30 years. The mean (+/-SD) age at onset in the patients with parkin mutations was younger than that in those without mutations (32+/-11 vs. 42+/-11 years, P<0.001), and they were more likely to have symmetric involvement and dystonia at onset, to have hyperreflexia at onset or later, to have a good response to levodopa therapy, and to have levodopa-induced dyskinesias during treatment. Nineteen different rearrangements of exons (deletions and multiplications) and 16 different point mutations were detected. CONCLUSIONS: Mutations in the parkin gene are a major cause of early-onset autosomal recessive familial Parkinson's disease and isolated juvenile-onset Parkinson's disease (at or before the age of 20 years). Accurate diagnosis of these cases cannot be based only on the clinical manifestations of the disease.

Adolescent↗
PubMed2000

Smoking habits in multiple system atrophy and progressive supranuclear palsy. European Study Group on Atypical Parkinsonisms.

OBJECTIVE: To evaluate smoking habits in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in a multicenter case-control study to determine whether these two forms of atypical parkinsonism share the inverse association with smoking previously found in PD. BACKGROUND: No epidemiologic studies have been performed on smoking habits in MSA. A previous investigation in PSP revealed no differences in smoking habits between patients and hospital control subjects. METHODS: Seventy-six MSA patients, 55 PSP patients, 140 PD patients, and 134 healthy control subjects were enrolled consecutively at seven neurologic clinics from January 1, 1994, to July 31, 1998. Detailed information on smoking habits was obtained using a structured questionnaire. RESULTS: The comparison between frequencies of never-smokers versus ever-smokers (ex-smokers/current smokers; adjusted odds ratio [ORadj], 0.56; 95% CI, 0.29 to 1.06) and a dose-response analysis for never-smokers, moderate smokers (ORadj, 0.64; 95% CI, 0.31 to 1.32), and heavy smokers (ORadj, 0.47; 95% CI, 0.21 to 1.05) suggest that MSA patients smoke less than population control subjects. By contrast, the comparison of frequencies of never-smokers versus ever-smokers (ORadj, 0.91; 95% CI, 0.42 to 1.98) and a dose-response analysis for never-smokers, moderate smokers (ORadj, 0.68; 95% CI, 0.27 to 1.69), and heavy smokers (ORadj, 1.24; CI 95%, 0.51 to 3.06) revealed no differences in smoking habits between PSP patients and population control subjects. CONCLUSIONS: The fact that the inverse association with smoking found previously in PD is shared by multiple system atrophy but not by progressive supranuclear palsy lends epidemiologic support to the notion that different smoking habits are associated with different groups of neurodegenerative disease.

Aged↗
PubMed2000

A possible association between exposure to n-hexane and parkinsonism.

Recently, some case-control studies and case reports have shown an association between solvent exposure and parkinsonisms. We present a 55-year-old male parkinsonian patient with chronic exposure to n-hexane for 17 years. The results of neurophysiological (electromyography, evoked potentials), neuroradiological (MRI) and neuropsychological tests performed on the patient suggest a role of this solvent at the level of the central nervous system. Biological susceptibility to neurotoxic compounds is discussed briefly.

Antiparkinson Agents↗
PubMed2000

Dopamine and migraine: does Parkinson's disease modify migraine course?

As brainstem mechanisms and dopaminergic neurotransmission are involved in migraine pathophysiology, we decided to investigate the course of migraine in Parkinson's disease (PD), the paradigm of brainstem dopaminergic disease. We screened 237 consecutive PD out-patients by direct interview to assess the prevalence of lifetime and current migraine. Moreover, we compared the course of migraine in PD patients with that of otherwise healthy age- (+/- 3 years) and sex-paired migraine controls in a cross-sectional study. PD patients showed a lifetime migraine prevalence of 27.8% and a current migraine prevalence of 13.1%. A positive family history of migraine was less frequent in PD patients than in controls. The frequency of current migraine was significantly lower in PD patients than in controls (47.0% vs. 68.2%; odds ratio = 0.41, 95% confidence interval = 0.19-0.89). Approximately two-thirds of PD patients reported an improvement in or remission of migraine after PD onset. Effects of menopause on migraine course were similar in patients and controls. These findings suggest that PD might somehow shorten the clinical course of migraine. Possible explanations include a prolonged prophylactic effect by chronic dopaminergic therapy or a positive effect of PD pathophysiology, namely nigral degeneration, on migraine mechanisms.

Aged↗
PubMed1999

A study of five candidate genes in Parkinson's disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism.

OBJECTIVE: To determine whether reported genetic association of polymorphisms in the CYP2D6, CYP1A1, N-acetyltransferase 2 (NAT2), DAT1, and glutathione s-transferase M1 (GSTM1) genes with PD were evident in a population of 176 unrelated patients with sporadic PD and to extend these findings to other disease groups (familial PD [n = 30], ALS [n = 50], multiple system atrophy [n = 38], progressive supranuclear palsy [n = 35], and AD [n = 23]). METHODS: A combination of allele-specific PCR and analysis of restriction fragment length polymorphisms were performed. RESULTS: We genotyped 1,131 individuals. After matching each patient with a control subject by age, sex, ethnicity, and geographic origin, there was no association of any allele/genotype with any of the six disease groups. There was an increased frequency of NAT2 slow acetylators in the ALS group compared with controls (70% versus 50%; OR 2.33 [95% CI, 1.03 to 5.30]), but this was not significant after adjusting for multiple testing. CONCLUSIONS: This is one of the most extensive candidate gene studies performed in PD and the first time that some of these loci have been studied in multiple system atrophy and progressive supranuclear palsy. In contrast with previous studies, we found no role for these polymorphisms in the etiology of PD, ALS, multiple system atrophy, progressive supranuclear palsy, or AD.

Aged↗
PubMed1999

The tau gene in progressive supranuclear palsy: exclusion of mutations in coding exons and exon 10 splice sites, and identification of a new intronic variant of the disease-associated H1 haplotype in Italian cases.

Mutations in coding exons or exon 10 5'-splice-site of the gene for microtubule-associated protein tau can cause chromosome 17-linked frontotemporal dementia and parkinsonism (FTDP-17). We sequenced the 11 coding exons plus exon-intron boundaries of the tau gene in 15 cases of progressive supranuclear palsy (PSP), and found no mutations in coding exons or exon ten 5'-splice sites. These data indicate that typical PSP is not associated with tau gene mutations similar to those causing FTDP-17. We also observed a +39deltaG base change in the intron following exon 4 in three out of 69 PSP cases (all three Italians), whereas it was not found in 150 Dutch controls and once in 112 Italian controls. The +39deltaG variant arose in the context of the PSP-associated tau H1 haplotype. Although a pathogenic role cannot be entirely excluded, +39deltaG is likely to be a rare polymorphism that may be in linkage disequilibrium with a biologically relevant locus inside or near to the tau gene.

Aged↗
PubMed1999

The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease.

Recently an Ile93Met mutation in the ubiquitin-carboxy-terminal-hydrolase-L1 gene (UCH-L1) has been described in a German family with Parkinson's disease (PD). The authors showed that this mutation is responsible for an impaired proteolytic activity of the UCH-L1 protein and may lead to an abnormal aggregation of proteins in the brain. In order to determine the importance of this or any other mutation in the coding region of the UCH-L1 gene in PD, we performed mutation analysis on Caucasian families with at least two affected sibs. We did not detect any mutations in the UCH-L1 gene, however, we cannot exclude mutations in the regulatory or intronic regions of the UCH-L1 gene since these regions were not sequenced. We conclude that the UCH-L1 gene is not a major gene responsible for familial PD.

Aged↗
PubMed1999

Mortality cancer risk in parkinsonian patients: a population-based study.

Cancer mortality in a population-based cohort of 10,322 parkinsonian patients (448 deaths observed during 1987 to 1994) was compared with that of the Italian province of Rome using the standardized mortality ratio (SMR). The overall cancer mortality risk was lower in this cohort than in the reference population (SMR, 56; 95% CI, 51 to 61). This reduction included most cancer sites as well as both smoking-related (SMR, 51; 95% CI, 42 to 60) and nonsmoking-related cancers (SMR, 58; 95% CI, 52 to 65). The observed reduction in cancer mortality risk in this cohort cannot be explained entirely by the hypothesis that smokers are less likely to develop PD.

Adult↗
PubMed1999

Increased expression of dopamine receptors on lymphocytes in Parkinson's disease.

Dopamine D1-like and D2-like receptors on peripheral blood lymphocytes (PBL) were assayed in 50 de novo patients with idiopathic Parkinson's disease (PD), in 36 neurologic control subjects (multiple-system atrophy, n = 16; essential tremor, n = 10; other neurodegenerative diseases, n = 10), and in 26 healthy control subjects by radioligand binding assay techniques using [3H]SCH 23390 and [3H]7OH-DPAT as ligands. Patients with PD revealed a higher density (Bmax) of dopamine D1-like (p <0.001) and D2-like (p <0.00001) receptors on PBL than either neurologic or healthy control subjects, whereas no differences in Bmax were observed among patients affected by other neurologic diseases and healthy control subjects. The affinity (Kd) of both radioligands was similar in the groups investigated. The pharmacologic profile of [3H]SCH 23390 and [3H]7OH-DPAT binding was consistent with the labeling of dopamine D5 and D3 receptor subtypes, respectively. Twenty-five of the 50 patients with PD were retested after 3 months of therapy with levodopa or bromocriptine. Both treatments reduced the density of D1-like (p <0.001) and D2-like (p <0.001) receptors on PBL to values comparable to those of control subjects. The increased density of D1-like and D2-like receptors on PBL in de novo PD patients may represent an upregulation mechanism resulting from the diffuse impairment of the dopaminergic system in PD.

Aged↗
PubMed1999

New, selective catechol-O-methyltransferase inhibitors as therapeutic agents in Parkinson's disease.

Levodopa remains the most effective drug for Parkinson's disease (PD). However, its benefits are limited owing to extensive metabolism by catechol-O-methyltransferase (COMT), especially if levodopa is used in combination with peripheral dopa-decarboxylase inhibitors. A new generation of potent, orally active, selective, and reversible COMT inhibitors has become available recently. Among these, tolcapone and entacapone have been best characterised. Preclinical and clinical studies have shown that COMT inhibitors markedly enhance levodopa availability and prolong its plasma half-life. In recent large clinical trials they proved to be able to ameliorate motor fluctuations, reduce disability, and decrease levodopa requirements in PD patients. The tolerability profiles of entacapone and tolcapone are good. COMT inhibition promises to become an important means of extending the benefits of levodopa therapy in PD.

Animals↗
PubMed1999

A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.

Binding Sites↗
PubMed1999

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease.

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.

Aged↗