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U Bonuccelli

Publications and source records attributed to U Bonuccelli.

At least 55 records · Page 3Linked to original sources
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

Acute and chronic effects of clozapine in essential tremor.

Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double-blind, crossover study in 15 drug-resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39+/-9 mg up to 50 mg) unblinded for a period of 15.8+/-7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6-7 weeks of therapy. No clozapine-induced hematologic side effects were observed in our cohort of patients during long-term treatment. Our results suggest that in selected drug-resistant ET cases, clozapine should be considered before resorting to neurosurgical options.

Antipsychotic Agents↗
PubMed1999

Spinocerebellar ataxia type 2 in southern Italy: a clinical and molecular study of 30 families.

Autosomal dominant cerebellar ataxia type I is the most common form of dominant ataxia. A genetic heterogeneity has been identified with five different loci (SCA1, 2, 3, 4, and 6). A pathological expansion of a CAG sequence has been identified in SCA1, 2, 3, and 6. We performed molecular analysis in 51 families with autosomal dominant cerebellar ataxia type I, mainly originating from southern Italy and Sicily. Thirty families carry an expanded CAG sequence within SCA2 gene. The mean number of repeats was 39.9 +/- 3.3 in 85 expanded alleles, with a range of 34-52. The number of triplets was inversely correlated with age at onset and explained 76% of the variance. The best fit was obtained with an exponential relationship between variables. Expanded alleles were unstable when transmitted from parents to offspring. Expansions were more common than contractions, accounting for 59% of the total meioses and for 80% of the father-child transmissions. The mean intergenerational variation was 1.9 repeats (range -3 to +15) with higher values for male transmissions. Bulbar and autonomic signs were related to disease duration, pyramidal signs to CAG size, cerebellar features and peripheral neuropathy to both. Among the remaining 21 families, three carried the SCA1 and one the SCA6 mutation. This study suggests that SCA2 is the prevalent mutation in southern Italy.

Adolescent↗
PubMed1999

Clinical outcome and magnetic resonance imaging of carbon monoxide intoxication. A long-term follow-up study.

The clinical and neuroradiological outcome of carbon monoxide (CO) intoxication was evaluated prospectively in 30 patients over a follow-up period of 3 years. Among the patients studied, 22 had been acutely exposed to CO while 8 were chronically exposed. One month after CO poisoning, 12 of the 22 patients with acute intoxication showed magnetic resonance imaging (MRI) abnormalities: 6 also had neurological sequelae and 6 were asymptomatic. The remaining 10 patients showed neither MRI abnormalities nor neurological sequelae. During the 3-year follow-up, 4 of the patients with both MRI abnormalities and neurological sequelae improved in both clinical features and MRI findings. One of the 6 asymptomatic patients with MRI abnormalities developed a progressive cognitive impairment 2 months after acute intoxication, with a concomitant severe worsening of the MRI lesions. Among the 10 patients with neither MRI abnormalities nor neurological sequelae, only 1 developed neurological sequelae after a clear period of 4 months. In the group of patients who experienced chronic CO intoxication, only 1 presented with a neuropsychiatric syndrome which improved at follow-up. Brain MRI showed white matter lesions which remained unchanged at control scan after 1 year. In conclusion, we observed that some patients with severe CO poisoning and neurological sequelae may fully regain normal functions after approximately 1 year. The presence of MRI lesions 1 month after CO poisoning did not accurately predict the subsequent outcome. The observation of a clear period longer than the usual 2-40 day interval in 2 patients should be considered for careful planning of follow-up and for prognosis in CO-poisoned patients.

Acute Disease↗
PubMed1999

Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

Adult↗
PubMed1999

Prevalence of headache syndromes in panic disorder.

We investigated the prevalence of headache in a group of patients attending a psychiatric clinic because suffering from panic disorder, according to DSM-IV criteria. The psychopathological assessment was performed with the 'Panic Disorder/Agoraphobia Questionnaire' and the presence of headache was evaluated according to the criteria of the International Headache Society. The results showed that two-thirds of patients met the criteria for a diagnosis of headache, with migraine without aura being the most frequent form, followed by tension headache, while two patients only were affected by migraine with aura. When we compared panic patients with and without headache, those with headache had a longer duration of panic disorder, a higher number of attacks and a heavier family loading for panic disorder and headache. This suggests that the comorbidity of headache with panic disorder renders this condition more severe and possibly responsive to different treatments compared to panic disorder alone.

Adult↗
PubMed1999

Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients.

To further investigate our finding of high levels of spontaneous aneuploidy in somatic cells of Alzheimer's disease (AD) patients (Migliore et al. 1997), we studied the molecular cytogenetics of eight patients with sporadic AD and six healthy controls of similar age. Cytochalasin B-blocked binucleated peripheral blood lymphocytes from the AD patients and unaffected controls were used to measure micronucleus induction or other aneuploidy events, such as the presence of malsegregation in interphase nuclei (representing chromosome loss and gain). Dual-color fluorescence in situ hybridization (FISH) with differential labeled DNA probes was applied. We used a probe specific for the centromeres of chromosomes 13 and 21 combined with a single cosmid for the Down's syndrome region (21q22.2) to obtain information on spontaneous chromosome loss and gain frequencies for both chromosomes (13 and 21). FISH data showed that AD lymphocytes had higher frequencies of chromosome loss (evaluated as fluorescently labeled micronuclei) for both chromosomes, as well as higher frequencies of aneuploid interphase nuclei, again involving both chromosomes, compared to control lymphocytes. However, aneuploidy for chromosome 21 was more frequent than for chromosome 13 in AD patients. This preferential occurrence of chromosome 21 in malsegregation in somatic cells of AD patients raises the hypothesis that mosaicism for trisomy of chromosome 21 could underlie the dementia phenotype in AD patients, as well as in elderly Down's syndrome patients.

Aged↗
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

Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease.

This study was aimed at assessing whether peripheral blood lymphocytes of patients with Alzheimer's disease (AD) show significant levels of aneuploidy and high percentages of cytogenetic events in vitro, indicating a predisposition to aneuploidy spontaneously, or after chemical treatment in vitro. A group of affected individuals and a group of unaffected, age-, sex- and smoking-habit-matched controls were identified. Lymphocytes were cultured for analysis of the following cytogenetic parameters: premature centromere division (PCD), satellite associations of acrocentric chromosomes (SA) and micronuclei (MN). In a subset of subjects, the fluorescence in situ hybridization (FISH) technique was combined with the MN assay, by means of a pancentromeric DNA probe for the detection of the presence of centric material. To evaluate the sensitivity to aneuploidogenic agents, in vitro treatment of lymphocytes of affected individuals was performed by adding griseofulvin, a chemical whose supposed target is microtubule-associated protein(s). Both the spontaneous frequency of MN and the frequency of PCD was significantly higher in patient cells than in controls. Furthermore, after application of the FISH technique, we found that the majority of MN were composed of whole chromosomes (because of the phenomenon of chromosome loss). Metaphase analysis for the detection of associative events between satellite regions of acrocentric chromosomes showed no differences between the two groups under study. Analysis of sensitivity to the aneuploidogen griseofulvin showed that the patient group was characterized by lower levels of MN induction compared with controls. Our data confirm that peripheral blood lymphocytes of AD patients are prone to undergo aneuploidy spontaneously in vitro and support the hypothesis that microtubule impairment might be associated with the disease.

Aged↗
PubMed1997

Species differences in the role of excitatory amino acids in experimental parkinsonism.

The present review discusses species differences in relation to the effects produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); in particular, it focuses on recent evidence regarding the role of excitatory amino acids in experimental parkinsonism. The main aim of the review is to provide a phylogenetic perspective which may serve as a useful tool to study Parkinson's disease in rodents. Excitotoxicity might represent the final common pathway on which the actions of different neurotoxins, selectively directed towards nigrostriatal dompaminergic neurons, converge. This is clearly demonstrated in methamphetamine- and 6-dihydroxy-dopamine-induced parkinsonism. The role of excitotoxicity in the mechanism of action of MPTP is less clear. Although there are several species differences for MPTP it is possible to obtain in mice the same effects induced in MPTP-treated primates by combining acetaldehyde or diethyldithiocarbamate with MPTP administration. When mice are administered these combined treatments, the onset of experimental parkinsonism can be prevented using the same pharmacological agents (i.e. glutamate N-methyl-D-aspartate antagonists) that are effective in primates.

Animals↗
PubMed1997

Clinical and pharmacokinetic evaluation of L-dopa and cabergoline cotreatment in Parkinson's disease.

Previous investigations on the mutual pharmacokinetic influence of L-dopa and dopamine agonists in Parkinson's disease (PD) have shown controversial results. Two studies of the possible clinical and pharmacokinetic interaction between L-dopa and cabergoline were performed in 10 patients with de novo PD and 12 patients with fluctuating PD. In the first study (de novo patients), cabergoline was administered at increasing dosages until the maximum dosage of 2 mg/day once a day for 8 weeks; subsequently L-dopa (250 mg/day) was added. Blood levels of cabergoline were assayed in two different days, before starting L-dopa, and 1 week thereafter. In the second 8-week study (fluctuating patients), cabergoline was added to the current L-dopa therapy (maximum dosage 4 mg/day once a day). Blood levels of L-dopa were measured in two different days, before cabergoline was added, and at the end of the study. In both studies motor performance was evaluated by means of the Unified Parkinson's Disease Rating Scale (motor examination) and the Clinical Global Impression Scale; on-off diaries of daily motor condition also were filled by fluctuating patients. In patients with de novo PD, cabergoline pharmacokinetic parameters were unmodified by the adjunct of L-dopa, except that the time to reach the peak concentration (Tmax) significantly increased after L-dopa. In patients with fluctuating PD, no modification of L-dopa pharmacokinetics was observed before and after cabergoline coadministration. Clinical evaluations confirmed that cabergoline is effective in the treatment of advanced PD as well as in the management of de novo patients.

Aged↗
PubMed1997

Different effects of levodopa and apomorphine on blink reflex recovery cycle in essential blepharospasm.

With the aim of assessing dopaminergic responsiveness in essential blepharospasm, we investigated the effects of oral levodopa and subcutaneous apomorphine on blink reflex recovery cycle in 7 blepharospasm patients. We found that in blepharospasm the excitability of the blink reflex recovery cycle was increased compared with control subjects. The oral administration of levodopa/carbidopa (500/50 mg) did not significantly modify the blink reflex recovery cycle. The 50 micrograms/kg dose of apomorphine decreased the amplitude of conditioned responses at 300 and 500 ms, whereas the 10 micrograms/kg dose was ineffective. We conclude that the excitability of the blink reflex recovery cycle in blepharospasm is partly under dopaminergic control. The partial normalization of the blink reflex recovery cycle excitability observed with 50 micrograms/kg apomorphine is consistent with the reported clinical efficacy of the drug in this condition.

Administration, Oral↗
PubMed1997

Clozapine in Parkinson's disease tremor. Effects of acute and chronic administration.

The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.

Aged↗
PubMed1997

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials.

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.

Activities of Daily Living↗
PubMed1996

Amitriptyline and dexamethasone combined treatment in drug-induced headache.

Frequent or regular intake of antimigraine drugs, including analgesics, constitutes a common cause of chronic daily headache. Discontinuation of symptomatic medication can produce an increase in head pain accompanied by withdrawal symptoms. We report the favourable outcome of treating a group of outpatients with the combination of amitriptyline, dexamethasone and sumatriptan. Dexamethasone (4 mg/day) was given intramuscularly for 2 weeks, amitriptyline orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously to treat acute headache attacks. Eighteen out of 20 patients abstained from drug abuse. Eleven of these 18 patients showed a marked reduction in headache frequency (at least 75% in relation to the basal value), and were considered "very good responders". The other seven patients experienced at least 50% reduction in headache frequency compared to baseline. This preliminary report suggests that drug-induced headache can be treated effectively in outpatients using dexamethasone, amitriptyline and sumatriptan in combination with significant benefit in everyday life conditions.

Adult↗
PubMed1996

Long-term follow-up after flunarizine or nimodipine discontinuation in migraine patients.

Various open and controlled studies have confirmed the antimigraine action of flunarizine, while the antimigraine properties of nimodipine are still open to controversy. Moreover, only a few studies include an additional follow-up after discontinuation of migraine prophylaxis with either drug. We carried out a single blind evaluation of the efficacy and tolerance of flunarizine (25 patients) in comparison with nimodipine (25 patients) and the long-term effect after discontinuation of a 6-month treatment. Both medications significantly reduced migraine frequently and severity. Flunarizine was more efficacious than nimodipine in reducing migraine frequency (p < 0.001), pain severity (p < 0.05), migraine index (p < 0.05) and corrected migraine index (p < 0.05). The positive effect lasted 8.4 +/- 4.0 months after discontinuation of flunarizine and 4.9 +/- 3.5 months after nimodipine (p < 0.05). Our results suggest that flunarizine is more effective than nimodipine in the prophylactic treatment of migraine. The positive effect after drug discontinuation lasts longer with flunarizine, compared to nimodipine.

Adult↗