Biomedical subjects

S Olivieri

Publications and source records attributed to S Olivieri.

13 recordsLinked to original sources

PubMed2004

The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease.

OBJECTIVE: To determine the efficacy of donepezil in the treatment of neuropsychiatric symptoms in patients with Alzheimer disease (AD) in a randomized withdrawal study. METHOD: Patients with mild to moderate AD with marked neuropsychiatric symptoms at baseline (Neuropsychiatric Inventory [NPI] > 11 points) were treated openly with donepezil 5 mg daily for 6 weeks followed by 10 mg daily for a further 6 weeks. Patients were then randomized (60:40) to either placebo or 10 mg donepezil daily. All patients were assessed at 6 weeks and provided there was no marked cognitive deterioration their blinded treatment was continued for a further 6 weeks. NPI and carer distress were assessed at 6 weekly intervals throughout the study. RESULTS: A total of 134 patients participated. Following randomization patients who continued on donepezil 10 mg for 12 weeks had improvements in NPI compared with the placebo group (mean change -2.9 vs 3.3 points; ITT-LOCF p = 0.02) and in NPI-Distress scores (median change -2.0 vs 1.0 points; ITT-LOCF p = 0.01). During the open-label phase the total NPI and NPI-Distress scores were lower after 12 weeks treatment with open label donepezil compared with baseline (total NPI 22 points vs13 points; ITT-LOCF p < 0.0001; NPI-Distress 13.5 vs 7.9 points; ITT-LOCF p < 0.0001). In the open-label phase all domains of the NPI (with the exception of elation) were improved (all p < 0.05 after Bonferroni correction). CONCLUSIONS: Donepezil has significant efficacy in the treatment of neuropsychiatric symptoms in patients with mild to moderate AD.

Aged↗

PubMed2004

Evaluation of three quinoline-carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration.

The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain parenchyma, where they are primarily localized in glial cells. Their basal expression rises in different neurodegenerative disorders, due to the presence of infiltrating inflammatory cells and activated microglia. [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET monitoring of neurodegeneration in clinical observations. We recently developed and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M, [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for the in vivo measuring of PBRs expression in neurodegenerations and compare their kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands were evaluated in a preclinical model of Huntington's disease consisting in the monolateral striatal injection of quinolinic acid (QA). Activated microglia and astrocytic gliosis was present only within the affected striatum. A concomitant increase in radioactivity accumulation was observed for all the tracers examined (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the results of the study indicate that [11C]VC195 is a promising candidate for in vivo PET monitoring of neurodegenerative processes but its in vivo behavior overlap that of [11C]PK11195.

Amides↗

PubMed2004

Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours.

OBJECTIVE: To determine the interest of Chromogranin A (CgA) determination for diagnosis and follow-up in patients with gastroenteropancreatic endocrine tumours (GEP-ET) and multiple endocrine neoplasia type 1 (MEN-1). PATIENTS AND METHODS: CgA levels were measured with an immunoradiometric assay in 124 sporadic GEP-ET, 34 MEN-1 and 127 controls. Serial determinations were performed in 56 patients (212 visits). Changes in CgA levels over 25% were considered as significant. RESULTS: Using a cut-off value of 130 micro g/l, established from a receiver-operating characteristic curve, the specificity of CgA was 98.4%, with a sensitivity of 62.9%, higher in secreting than in nonsecreting tumours (73%vs. 45%; P < 0.003) and related to the extent of metastatic spreading (P < 0.001). In nonsecreting tumours, the positive predictive value (PPV) of CgA for the presence of metastases was 100% but the negative predictive value (NPV) was only 50%. In MEN-1, high CgA levels indicated a pancreatic tumour with a 100% specificity but the sensitivity was 59%. During the follow-up, the concordance between CgA and tumour evolution was 80%, whatever the secretory status. In patients with carcinoid tumours, the concordance was higher for CgA than for serotonin (81%vs. 54%; P < 0.001). CONCLUSION: Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN-1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow-up of GEP-ET tumours.

Adolescent↗

PubMed2001

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.

3T3 Cells↗

PubMed1997

Chronic intraaneurysmal pressure measurement: an experimental method for evaluating the effectiveness of endovascular aortic aneurysm exclusion.

PURPOSE: To evaluate and compare the intraaneurysmal pressure (IAP) after exclusion using two different endovascular grafts. METHODS: Eight mongrel dogs had a 3 x 3 cm polytetrafluoroethylene (PTFE) aneurysm sewn as an interposition graft of the infrarenal aorta. A pressure transducer implanted into the aneurysm wall permitted continuous electronic IAP monitoring. Four aneurysms were excluded with a transluminally placed endovascular graft made of a PTFE graft and two Palmaz stents (PTFE-EG), three were excluded with a tantalum-Dacron endovascular graft (TD-EG), and one was surgically treated with a standard PTFE graft (PTFE-Surg). The dogs were observed for 18 to 50 days (mean, 37.5 days) and were evaluated after surgery with duplex and spiral computed tomographic scans. RESULTS: All grafts successfully excluded the aneurysms without perigraft channels or leaks as documented by arteriogram and duplex and computed tomographic scans. The mean IAPs after repair with all PTFE-EGs were significantly lower (p < 0.001) than the mean systemic pressures. In addition, the mean IAP reduction was significantly greater (p < 0.005) in the PTFE-EG group than in the TD-EG group. CONCLUSIONS: Aneurysm exclusion with PTFE-EG significantly lowered IAP, did so significantly better than the TD-EG, and approached the IAP reduction obtained by standard repair. Such pressure reduction is necessary for effective protection against aneurysm rupture.

Animals↗

PubMed1990

Chronic benzodiazepine dependence. A comparative study of abrupt withdrawal under propranolol cover versus gradual withdrawal.

Thirty-one patients dependent on benzodiazepines were randomly assigned to either slow withdrawal (SW) or abrupt withdrawal under propranolol cover (PW). Of 16 patients in the SW group, 11 successfully withdrew from their drugs, while only 4 out of 15 in the PW group did so. Patients in the SW group had only mild withdrawal symptoms, while those in the PW group suffered more severe symptoms, which lasted around four weeks. In all, 81% of the whole group suffered withdrawal symptoms of some kind. Patients in both groups were significantly less anxious at the end of the study than at baseline. Younger subjects and those who were more severely anxious at the start of the trial had more difficulty in withdrawing than older and less anxious patients.

Adolescent↗

PubMed1990