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Biomedical subjects

Giuseppe Nicoletti

Publications and source records attributed to Giuseppe Nicoletti.

At least 19 recordsLinked to original sources

Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy.

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from Parkinson's disease is difficult in the early stage of the disease. In order to identify objective markers for differential diagnosis, we studied these three groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16 with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, thalamus, white matter, pons and middle cerebellar peduncles (MCPs). rADC calculated in the MCP completely differentiated MSA-P patients (median: 0.93 x 10(-3) mm2/s) from PSP patients (median: 0.82 x 10(-3) mm2/s, P < 0.001), Parkinson's disease patients (median: 0.79 x 10(-3) mm2/s, P < 0.001) and healthy volunteers (median: 0.81 x 10(-3) mm2/s, P < 0.001). Other regions considered showed an overlapping among groups. DWI discriminates MSA-P from PSP and Parkinson's disease and healthy volunteers on the basis of MCP rADC values. These in vivo results confirm the pathological findings that the majority of MSA-P patients have moderate or severe degenerative changes not only in the nigrostriatal but also in the olivopontocerebellar systems. Our findings indicate that, in order to substantially contribute to the in vivo differential diagnosis of MSA-P, PSP and Parkinson's disease, rADC measurements should not be limited to the basal ganglia but should also include the MCP.

Aged↗

Antibiotic prescribing for acute and recurrent cystitis in primary care: a 4 year descriptive study.

OBJECTIVES: To explore the antibiotic prescribing pattern for cystitis and the patient-related variables associated with prescription during a 4 year period among Italian general practitioners (GPs). METHODS: We obtained information from the 'Health Search Database' (HSD), an Italian general practice research database. From a total sample of 457 672 eligible patients aged >16 years registered up to December 2002, we included those whose diagnoses could be classified as acute (uncomplicated and complicated) and recurrent cystitis. Patients' features and prevalence of antibiotic users were assessed. RESULTS: Of 35 129 cases diagnosed during the period 1999-2002, 96.0% of them were acute cystitis (39.2% recorded as uncomplicated). The prevalence of cases with acute complicated and uncomplicated cystitis slightly increased during the 4 year period, whereas it remained stable for recurrent cystitis. Most of the cystitis cases reported no diagnostic tests. More than 70% of patients were prescribed with at least one antibiotic, with a 4-fold increased risk of antibiotic use for acute cystitis throughout the study period. The prevalence of antibiotic users reached 86.2% for both acute uncomplicated and complicated cystitis in 2002, and 81.5% for recurrent cystitis. Fluoroquinolones represented the most common antibiotics being prescribed although they markedly decreased during these years. Fosfomycin trometamol use increased dramatically, becoming the first choice for any type of cystitis. CONCLUSIONS: Data indicate an evident rise in antibiotic use mostly related to fosfomycin trometamol. They also indicate that such a prescriptive trend finds confirmation from the available evidence for acute uncomplicated cystitis, although the management of recurrent cystitis could be further improved.

Acute Disease↗

Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial Surveillance Program (2001-2004).

Fluoroquinolones are key antimicrobials in the treatment of more serious pneumococcal infections, especially for treating infections caused by penicillin-resistant strains. Increased use of newer fluoroquinolones should be accompanied by greater surveillance efforts to monitor resistance development as well as clonal dissemination. Streptococcus pneumoniae (n=551) collected from 3 medical centers in Italy (Catania, Genoa, and Rome) over a period of 4 years (2001-2004) as part of the SENTRY Antimicrobial Surveillance Program were susceptibility tested against >30 antimicrobials using reference broth microdilution methods. Mutations in the quinolone resistance-determining region (QRDR) were characterized by PCR and sequencing of parC, parE, and gyrA. Epidemiological relationships among levofloxacin-resistant isolates were determined using ribotyping, PFGE, serotyping combined with antimicrobial resistance profiles augmented by QRDR mutation patterns. Eighty-three (15.1%) isolates showed reduced susceptibility to ciprofloxacin (MIC>or=4 microg/mL) and 31 (5.6%) were resistant to levofloxacin. In 2001, all pneumococcal isolates were susceptible to levofloxacin and resistance rapidly emerged in all 3 medical centers in 2002. The overall rates of levofloxacin resistance in 2002-2004 were the following: Catania 10.9%, Genoa 3.3%, and Rome 6.5%. All resistant strains showed at least one mutation in parC and gyrA. Each isolate from Genoa with a unique resistance phenotype also showed distinct ribotype/PFGE, serotype, and QRDR mutation patterns. All isolates from Catania (n=19) showed an identical ribotype/PFGE pattern (333.3/A1); however, 3 distinct clusters could be identified based on further resistance phenotype, serotypes, and QRDR mutation pattern analysis. Two clusters were documented among isolates from Rome based on ribotype/PFGE. One isolate from Genoa shared ribotype/PFGE (333.3/A1) and serotype (9 not V) results with clusters from the other 2 institutions monitored, indicating clonal dissemination between the geographically diverse cities. In conclusion, fluoroquinolone resistance rates have increased among S. pneumoniae recovered in Italian medical centers evaluated by the SENTRY Program. Although resistance has emerged in many epidemiologically distinct strains, clonal dissemination seems to be a key contributing factor for increasing resistance to fluoroquinolones among pneumococci in this nation.

Anti-Bacterial Agents↗

MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease.

PURPOSE: To prospectively assess if middle cerebellar peduncle (MCP) atrophy, evaluated at magnetic resonance (MR) imaging, can help differentiate multiple system atrophy (MSA) from Parkinson disease (PD). MATERIALS AND METHODS: All participants provided informed consent for participation in the study, which was approved by the institutional review board. Sixteen consecutive patients with MSA, 26 consecutive patients with PD, and 14 healthy control subjects were examined with MR imaging. Images were interpreted independently by two experienced neuroradiologists blinded to clinical information, who visually inspected the images for the presence or absence of putaminal atrophy, putaminal hypointensity, slitlike hyperintensity in the posterolateral margin of the putamen, brainstem atrophy, hyperintensity of the MCP, and cruciform hyperintensity of the pons. Measurements of MCP width on T1-weighted volumetric spoiled gradient-echo images were performed in all subjects. Differences in MCP width among the groups were evaluated by using the Kruskall-Wallis test, followed by the Mann-Whitney U test for multiple comparisons and Bonferroni correction. RESULTS: All patients (mean age, 63.88 years; range, 55-72 years) with MSA had at least one of the features commonly observed in this disease on MR images, whereas control subjects (mean age, 66.93 years; range, 61-77 years) and all but one patient with PD (mean age, 65.31 years; range, 51-79 years) had normal MR images. The average MCP width was significantly smaller in patients with MSA (6.10 mm+/-1.18 [standard deviation]) than in those with PD (9.32 mm+/-0.77, P<.001) or control subjects (9.80 mm+/-0.66, P<.001). CONCLUSION: Measurement of MCP width on MR images may be useful for distinguishing patients with MSA from those with PD.

Aged↗

Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis.

Cortical reorganization has been demonstrated during performance of a motor task in patients with multiple sclerosis. Converging evidence suggests that changes in gray matter volume represent an early hallmark of the disease. We used functional MRI to investigate the role of cortical adaptive mechanisms in maintaining visuo-motor function in the face of structural damage. Two cohorts of patients with clinically definite relapsing-remitting multiple sclerosis were compared with healthy controls matched for demographic, motor and cognitive characteristics during the performance of a visuo-motor integration task. Direct comparison between the two groups demonstrated a greater response of the contralateral dorsal premotor cortex and of the ipsilateral superior parietal cortex in relapsing-remitting multiple sclerosis patients. The functional MRI changes in these areas were strongly correlated with decreased gray matter volumes and increased lesion burden, respectively. Our study demonstrated a selective involvement of the parieto-premotor circuitry in a relatively early stage of the disease, which was not influenced by clinical, motor or cognitive variables. Moreover these results confirm the potential for functional recovery and the adaptive role of these areas in the motor reorganization of multiple sclerosis patients.

Adolescent↗

Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity.

BACKGROUND: Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers. METHODS: We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging in 24 healthy men. RESULTS: Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmann's area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers. CONCLUSIONS: These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.

Adolescent↗

Comparison of different MR venography techniques for detecting transverse sinus stenosis in idiopathic intracranial hypertension.

Cerebral venous outflow abnormalities, as transverse sinuses (TSs) stenosis,may underlie a picture of idiopathic intracranial hypertension (IIH). To identify the best non-invasive MR venography (MRV) technique for exploring the disturbance of flow of TSs in IIH patients, we compared three dimensional phase contrast (3-DPC) MRV images, acquired with different velocity encodings (15 and 40 cm/s) with two-dimensional time-of-flight (2D-TOF) MR images in 6 subjects with IIH and 12 age-matched normal controls. In both groups, we also measured flow velocity in TSs by using single slice 2D-CINE PC acquisitions. In all subjects with IIH, 3D-PC showed marked flow disturbance in the mid-lateral portion of both TSs when velocity encoding (VENC) was set to 15 cm/s while only a slightly irregular flow in TSs was detected when VENC was set to 40 cm/s or when 2D-TOF was used. By contrast, 3D-PC (VENC 15 and 40) and 2D-TOF techniques were comparable in detecting TS signal flow in normal controls. Measures of flow velocity, by using 2D-CINE PC, revealed a three-fold increase of velocity at the level of the flow disturbance in IIH patients compared to normal controls (p<0.0001), suggesting a marked stenosis of mid-lateral portion of TSs in these patients. Setting the VENC to 15 cm/s on 3D-PC MRV may represent the best technical approach for visualizing disturbances of flow in TSs in subjects with symptoms suggestive of IIH.

Adult↗

Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.

BACKGROUND: Several factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD. OBJECTIVE: To examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease. DESIGN: Cohort study. SETTING: Referral center for Parkinson disease in Calabria, southern Italy. Patients Two hundred fifty patients with Parkinson disease were screened for the presence or absence of PDD following a short-term levodopa administration, and 215 subjects were available for further evaluations, including genotypic analysis of the CA dinucleotide short tandem repeat (CAn-STR) polymorphism located in the dopamine receptor D2 gene (DRD2). RESULTS: One hundred five patients (48.8%) exhibited PDD following short-term levodopa administration, and 110 patients (51.2%) did not. Multivariate logistic regression analysis showed that independent predictors for the occurrence of PDD were female sex, earlier age at onset of Parkinson disease, longer duration of treatment, and higher dose of levodopa. Genetic factors related to the DRD2 CAn-STR polymorphism were not independent predictors for PDD in the total population, but they had a strong protective effect on the appearance of PDD when the multivariate analysis was performed in men (odds ratio, 0.34 [95% confidence interval, 0.14-0.84]). In women, a genetic protective effect on PDD was not evident. CONCLUSIONS: Risk factors for PDD, both clinical and genetic, act in different ways for men and women. Genetic factors related to the DRD2 polymorphic status have a protective effect on PDD development in men but not in women. A female sex-related effect for the risk of PDD may be so strong that it overcomes any protective effect due to genetic factors.

Age of Onset↗

Movement time and aging: a normative study in healthy subjects with the "Movement Time Analyzer".

BACKGROUND AND AIMS: Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders characterized by bradykinesia, tremor at rest, and rigidity. Movement Time (MT) has been investigated in PD to evaluate bradykinesia and its levodopa-induced modifications. The Movement Time Analyzer (MTA) is a simple, objective and reliable instrument to study MT, but no normative study has been reported to date. METHODS: In a sample of normal subjects (n = 68), we studied MT detected by MTA in order to assess normative values, so that the MTA could be used to evaluate patients with PD in daily clinical practice. RESULTS: In normal subjects, MT progressively increased with aging, and was slower on the non-dominant side than on the dominant side. No differences were found between men or women. CONCLUSION: Our data provide further information about normative values on MT detected by MTA, and indicate that age and handedness are the main variables influencing motor task performance.

Adolescent↗

FRAXE intermediate alleles are associated with Parkinson's disease.

There is evidence that male subjects with a clinical picture of action tremor, Parkinsonism, and cerebellar ataxia may have Fragile X premutations (FRAXA). We analyzed FRAXA and FRAXE triplet repeats in 203 male subjects with Parkinson's disease (PD) and 370 healthy controls. No full mutations or premutations at the FRAXA and FRAXE loci were found in the subjects with PD or in the controls. FRAXA allele distribution was similar in patients and controls. FRAXE intermediate alleles (31-60 repeats CCG) were found in 13 of 203 (6.4%) subjects with PD and in only one of the 370 (0.27%) healthy controls (P < 0.001), thus indicating that these relatively large alleles may be associated with PD.

Adult↗

Increased risk for Alzheimer disease with the interaction of MPO and A2M polymorphisms.

BACKGROUND: The genes encoding myeloperoxidase (MPO) and alpha(2)-macroglobulin (A2M) are involved in molecular pathways leading to beta-amyloid deposition. Two polymorphic sites in these genes (MPO-G/A and A2M-Ile/Val) have been associated with Alzheimer disease (AD), but conflicting findings have been reported in populations with different ethnic backgrounds. OBJECTIVES: To study the association of MPO-G/A and A2M-Ile/Val polymorphisms with sporadic AD and to investigate the interactions among the MPO, A2M, and apolipoprotein E (APOE) gene polymorphisms in determining the risk of the development of AD. DESIGN: Case-control study. SETTING: Referral center for AD in Calabria, southern Italy. PARTICIPANTS: One hundred forty-eight patients with sporadic AD and 158 healthy control subjects. RESULTS: The MPO-G and A2M-Val alleles were found more frequently in cases than in controls, as were the MPO-G/G and A2M-Val/Val genotypes. The odds ratio (OR) for the MPO-G/G genotype was 1.78 (95% confidence interval [CI], 1.13-2.80); for the A2M-Val/Val genotype, 3.81 (95% CI, 1.66-8.75). The presence of MPO-G/G and A2M-Val/Val genotypes synergistically increased the risk of AD (OR, 25.5; 95% CI, 4.65-139.75). Stratification of cases by sex, age at onset of AD, and APOE-epsilon 4 status did not show significant differences in the distribution of MPO or A2M polymorphisms. CONCLUSIONS: The MPO and A2M polymorphisms are associated with sporadic AD in southern Italy. Moreover, a genomic interaction between these polymorphisms increases the risk of the development of AD.

Age of Onset↗

Molecular alterations of VanA element in vancomycin-resistant enterococci isolated during a survey of colonized patients in an Italian intensive care unit.

To screen for vancomycin-resistant enterococci (VRE) colonization in hospitalized patients and to study molecular evolution and alterations of Tn1546-like elements in VRE among potentially at-risk patients, a 3-year surveillance protocol in an Intensive Care Unit was performed. A total of 397 patients were screened in the period June, 1997-June, 2000, and VRE were isolated from rectal swabs taken at admission, weekly, and when clinically indicated. The susceptibility of the enterococci was determined by the disk diffusion and broth dilution methods. The presence of vancomycin-resistance genes (vanA, vanB, and vanC) was assessed by polymerase chain reaction (PCR); genetic clonality of isolates was assessed by pulsed-field gel electrophoresis (PFGE); Tn1546 types were obtained by restriction fragment length polymorphism (RFLP) analysis of Tn1546 PCR fragments. Thirty-four strains, 31 identified as Enterococcus faecium and 3 strains as E. faecalis, were isolated from 12 of the 397 patients (3.0%); all strains were VanA as assessed by PCR and were resistant to the other antibiotics tested and showed high-level resistance to aminoglycosides. Enterococci isolated during the study period showed that different genetic backgrounds of strains, determined by PFGE combined with RFLP of Tn1546, are present in all the strains isolated in the study. PFGE type B was predominant in 1998 and 1999, and insertion sequence movements were found to have a role in the evolution of VanA resistance elements found in all strains. This study demonstrates that single patients may be colonized by closely related VRE with several PFGE types containing a wide variety of VanA elements. Moreover, isolates with identical PFGE types may contain different VanA elements reflecting rearrangements mediated by insertion sequences in VRE strains during their stay in the gastrointestinal tract.

Adolescent↗

Characterization of clinical isolates of Enterobacteriaceae from Italy by the BD Phoenix extended-spectrum beta-lactamase detection method.

Production of extended-spectrum beta-lactamases (ESBLs) is an important mechanism of beta-lactam resistance in Enterobacteriaceae: Identification of ESBLs based on phenotypic tests is the strategy most commonly used in clinical microbiology laboratories. The Phoenix ESBL test (BD Diagnostic Systems, Sparks, Md.) is a recently developed automated system for detection of ESBL-producing gram-negative bacteria. An algorithm based on phenotypic responses to a panel of cephalosporins (ceftazidime plus clavulanic acid, ceftazidime, cefotaxime plus clavulanic acid, cefpodoxime, and ceftriaxone plus clavulanic acid) was used to test 510 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Providencia stuartii, Morganella morganii, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii, and Citrobacter koseri. Of these isolates, 319 were identified as ESBL producers, and the remaining 191 were identified as non-ESBL producers based on the results of current phenotypic tests. Combined use of isoelectric focusing, PCR, and/or DNA sequencing demonstrated that 288 isolates possessed bla(TEM-1)- and/or bla(SHV-1)-derived genes, and 28 had a bla(CTX-M) gene. Among the 191 non-ESBL-producing isolates, 77 isolates produced an AmpC-type enzyme, 110 isolates possessed TEM-1, TEM-2, or SHV-1 beta-lactamases, and the remaining four isolates (all K. oxytoca strains) hyperproduced K1 chromosomal beta-lactamase. The Phoenix ESBL test system gave positive results for all the 319 ESBL-producing isolates and also for two of the four K1-hyperproducing isolates of K. oxytoca. Compared with the phenotypic tests and molecular analyses, the Phoenix system displayed 100% sensitivity and 98.9% specificity. These findings suggest that the Phoenix ESBL test can be a rapid and reliable method for laboratory detection of ESBL resistance in gram-negative bacteria.

Algorithms↗

No evidence of association between the alpha-2 macroglobulin gene and Parkinson's disease in a case-control sample.

Alpha-2 macroglobulin (A2M) is a component of Lewy bodies, a hallmark of Parkinson's disease (PD). In 159 PD patients and 190 normal controls, we studied two A2M polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method: a five-nucleotide deletion at the 5' splice site of exon 18; and a valine to isoleucine exchange in amino acid position 1000 near the thiolester active site. No significant differences in allelic and genotypic distribution were found between cases and controls or between early and late-onset PD patients. The present data suggest that these polymorphisms do not represent a risk factor for PD and do not modulate the age at onset of PD.

Age Factors↗

Exploring the variability in antibiotic prescribing profiles among paediatricians from two different areas of Italy.

We carried out a multicentre community-based study in order to describe the antibiotic therapeutic approach of paediatricians from two different areas of Italy in the treatment of respiratory tract infection (RTIs), and to assess which factors are involved in a possible variability of prescribing habits. Forty paediatricians participated in the study between October 1998 and April 1999. They had to complete a questionnaire for each therapeutic intervention resulting in an antibiotic prescription. A logistic regression model was used to identify possible predictors in choosing parenteral antibiotics for the treatment of RTIs. In 2 975 questionnaires of antibiotic treatment, RTIs represented 90.2% of the total antibiotics used. Upper respiratory tract infections were the most commonly treated diagnostic group (59.6%), followed by lower respiratory tract infections (20.4%), and middle ear infections (19.8%). Statistically significant differences between northern and southern Italy were reported in the antibiotic prescription profile and the duration of the therapy. Another marked difference was reported in the frequency of laboratory analysis requests. The logistic regression model indicated that the use of parenteral antibiotics appears significantly related to the type of infections [lower RTIs: (OR: 3.99; 95% CI: 2.49-6.37)], the geographic location [northern Italy: (OR: 0.20; 95% CI: 0.20-0.39)], and the presence of concurrent diseases (OR: 3.21; 95% CI: 1.46-7.02). The lack of adherence to clinical guidelines and the marked variability of antibiotic prescription rates between different areas of the country appear to be related to factors other than bacterial resistance, and highlight the importance of carrying out educational programmes targeted at the national level for improving the antibiotic prescription habits for the treatment of RTIs.

Anti-Bacterial Agents↗