Casa Sollievo della Sofferenza

About: Casa Sollievo della Sofferenza is a healthcare organization based out in San Giovanni Rotondo, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 2234 authors who have published 6183 publications receiving 239811 citations. The organization is also known as: Home for Relief of the Suffering.

Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option?

Abstract: Introduction: Compounds that inhibit or modulate γ-secretase, the pivotal enzyme which generates β-amyloid (Aβ), are potential therapeutics for Alzheimer's disease (AD). Areas covered: This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic and discusses the clinical issues surrounding this new class of anti-AD compounds. Expert opinion: γ-Secretase inhibitors may cause significant toxicity in humans. Two large Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of detrimental cognitive and functional effects of the drug. These detrimental effects were mainly ascribed to the inhibition of Notch processing and the accumulation of the neurotoxic precursor of Aβ resulting from the block of the γ-secretase cleavage activity on amyloid precursor protein. New Notch-sparing γ-secretase inhibitors are being developed with the hope of overcoming the previous setbacks. It has also been argued that γ-secretase inhibito...

Abnormal functional lateralization of the sensorimotor cortex in patients with schizophrenia.

Abstract: PREVIOUS neuroimaging studies have suggested that patients with schizophrenia fail to recruit appropriate focal patterns of cortical responses to cognitive tasks. We investigated whether patients with schizophrenia show a normal focal response to a simple motor task. Seven strongly right-handed pati

NSAID and Aspirin Use by the Elderly in General Practice Effect on Gastrointestinal Symptoms and Therapies

Abstract: The relationship between NSAID use and gastrointestinal (GI) symptoms and their treatment in elderly patients is not well defined. To identify the prevalence of specific drug use in elderly outpatients and to identify the relationship between NSAID use and GI disturbances and treatments in elderly subjects treated by their general practitioner (GP). The study was carried out by 63 GPs in north-eastern Italy; 3154 elderly subjects were included in the study over a 2-week period. By using a structured interview, subjects’ medical histories and current medication were identified. In particular, the presence and use pattern (i.e. occasional, ‘acute’ or ‘chronic’) of NSAIDs and/or aspirin (acetylsalicylic acid) were recorded. In all subjects, the presence of upper GI symptoms, i.e. abdominal pain, reflux symptoms and indigestion syndrome, were noted. The prevalence of drug use was 96.4% (males 96%, females 96.7%). The most prescribed drugs were ACE inhibitors (38%), diuretics (26.7%), NSAIDs and regular-dose aspirin (24.7%), GI drugs (20.6%), and anxiolytics/hypnotics (20.3%). Of 779 subjects who had taken NSAIDs or regular-dose aspirin, 32.9% were ‘chronic’ users, 24.9% were ‘acute’ users and 42.1% occasional users. A significantly higher prevalence of upper GI symptoms was observed in elderly NSAID and low-dose aspirin users compared with non-users (24.9% vs 28% vs 16.6% respectively, p < 0.0001). GI symptoms were reported by 27.6% of ‘chronic’ NSAID users, 22.9% of ‘acute’ users and 24.7% of occasional users. A significantly higher prescription rate for any GI drug was found in NSAID users than in low-dose aspirin users and non-users (24.0% vs 19.6% vs 19.4% respectively, p = 0.007). This difference was mainly because of a higher number of upper GI drugs taken by NSAID users than by low-dose aspirin users and non-users (18.1% vs 16% vs 13.7% respectively, p = 0.004). Multivariate analysis demonstrated that female gender (odds ratio [OR] = 1.32, 95% CI = 1.16–1.44), low-dose aspirin (OR = 1.88, 95% CI = 1.33–2.65), NSAIDs and/or regular-dose aspirin (OR = 1.48, 95% CI = 1.19–1.83) and multiple therapies, i.e. taking more than four drugs per day (OR = 1.42, 95% CI = 1.14–1.77) were risk factors for GI symptoms in elderly outpatients. NSAIDs and/or aspirin use was very high in this elderly outpatient population. The use of these drugs was significantly associated with a greater number of upper GI symptoms and prescriptions for GI drugs. Educational and clinical strategies need to be implemented in order to reduce the GI impact of NSAID and aspirin use in elderly people.

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

Abstract: Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.