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Background: Alzheimer's disease (AD) and cancer increase their frequency with age and can be considered main negative consequences of senescence. Few previous studies reported a lower incidence of cancers in persons with Alzheimer's disease (AD) and lower incidence of AD in persons with cancers. This result needs to be confirmed in different sets and with different study designs since it might be due to confounding due to underreporting and/or shortening of life expectancy of persons with cancer or AD. Methods: This was a prospective/retrospective cohort study. Persons living in the geographical area of the local health authority (ASL) of Milano 1 (Mi1) of 60 or more year from 2004 to 2009 with a first diagnosis of AD or cancer were recruited in their specific diagnostic cohort. Diagnoses were retrieved from the ASL Mi1 informative health system. Based on the person-years of observation during the time period from 2004 to 2009 we calculated the incidences of AD in the cohort of cancers and the incidence of cancers in the AD cohort in the period preceding and following the index diagnosis. The incidence of AD and cancers were calculated also for the general population of ASL Mi1 and observed cases in the two cohorts with respect to those expected from the general population were compared. Separate comparisons were made for the period preceding and following the diagnosis of AD or Cancer, for AD occurrence in smoking and non smoking related cancers and for persons surviving or dying during the period 2004-2009. Results: In the whole population of ASL Mi1 we registered 21451 (12225 men) newly diagnosed cancers and 2832 AD (947 men) giving respectively a crude incidence rate per 10000 p-y of 175.1 and of 22.1. The cohort of persons with AD contributed a total of 15063.0 p-y of observation and the corresponding figure for the cancer cohort was 101317.9 p-y. In 161 cases cancer and AD were diagnosed to the same person with AD preceding cancer in 68 cases. In persons with cancer 246 cases of AD were expected from the incidence observed in the whole population of 60 years or older; the risk of AD occurrence, relative to that of the general population of the same age and gender was therefore significantly reduced (observed/expected = 0.65 95% Confidence Interval [CI] 0.56-0.76). The corresponding figure for the cohort of AD were 241.2 cancer expected with a relative risk (RR) of 0, 57 (95% CI 0.49-0.67). No significant differences in the estimates were observed for the follow-up periods preceding and following the diagnosis, for smoking related cancers or for members of the cohort not surviving for the entire period of follow-up. Conclusion(s): Cancer and AD are negative manifestation of senescence and have an inverse relationship of occurrence. This result might be interpreted as a confirmation for the theory of pleiotropic genes for aging and senescence.

Purpose: To compare the safety of conventional and nonconventional antipsychotics in older persons. Specific aims included to i) compare the risk of all-cause mortality among users of conventional versus atypical antipsychotic drugs, ii) investigate whether any increased mortality risk was limited to specific causes of death, and was still present after adjusting for comorbidities and, iii) examine mortality risks among users of conventional versus atypical antipsychotic in people with Alzheimer's Disease (AD). Method: The study included a retrospective cohort study of residents in Milan, Italy, aged 60+ who were prescribed an antipsychotic drug for the first time during April 1, 2002 to June 15, 2005. Data were obtained from the health authorities' information systems. 7739 persons using antipsychotic drugs (n = 2908 conventional, n = 4831 atypical) were included. Overall and cause-specific mortality over six months following first prescription of an antipsychotic drug was investigated. Covariates included, age, sex, and comorbities (cancer, cardio/cerebrovascular and other diseases). Mortality was assessed both in the whole cohort, and a subset of people with AD who were prescribed cholinesterase inhibitors. Results: People prescribed atypical antipsychotics had 65% lower all-cause mortality (HR 0.35, 95% CI 0.31-0.39) than those prescribed conventional antipsychotics. This mortality risk was explained by cancer deaths, with no differences within deaths for other conditions. Among people using cholinesterase inhibitors, no statistically significant difference in mortality was observed for users of conventional versus atypical antipsychotics. Conclusion: The characteristics of the observed differences in mortality suggest that there might be a preferential prescription of conventional drugs in terminally ill cancer patients. There is no evidence of a differential survival in AD patients using conventional or atypical antipsychotics.

Objectives: The objective was to assess the incidence of sepsis, severe sepsis and septic shock and their mortality in Italian Pediatric Intensive Care Units (PICUs). Design: This is a prospective, observational, multi-center, 1-year study. Setting: Fifteen medical-surgical PICUs participated in this study. Patients: Two-thousand and seven hundred and forty-one children (2,741), aged 0-16 years, who were consecutively admitted in the participating PICUs, from 1 March 2004 to 28 February 2005, were enrolled in the study. Interventions: There were no interventions in this study. Measurements and main results: Data on infection, systemic inflammatory response syndrome (SIRS), severe sepsis and septic shock were collected using criteria defined by Proulx in 1996. Sepsis-related diagnosis was stratified for five age groups (neonates, infant, preschool, school, adolescent) and type of admission (medical, surgical, trauma). The presence of existing comorbidities has been considered for children with and without sepsis diagnosis. The results showed a lower overall incidence of sepsis, severe sepsis and septic shock (7.9, 1.6 and 2.1%, respectively) if compared with other studies. Children with sepsis diagnosis had a higher morbidity and higher mortality than those without sepsis. Severe sepsis and septic shock had a mortality rate of 17.7 and 50.8%, respectively. Mortality is significantly higher for children with existing comorbidities than those without existing comorbidities. Conclusions: Septic shock mortality is still high in Italian PICUs and attempts to improve medical treatment are necessary. We suggest that application of the new definitions for sepsis diagnosis and diffusion of guidelines for early recognition and aggressive treatment of severe sepsis and septic shock in Italy represent a high priority to reduce mortality. Descriptor: The descriptor is pediatrics.

The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid P-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important sub-units of the gamma-secretase complex. We previously Studied Sequence variations in both genes and their association with AD in a small Italian population. the rare polymorphism c + 651T>G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon 4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P = 0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR = 28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein. these data suggest that a cooperative mechanism involving APOE and APH-1b play, a role in the susceptibility to develop AD. (C) 2007 Elsevier Inc. All rights reserved.

Scopo dello studio è identificare nei soggetti con infezione da HIV non affetti da AIDS la presenza o meno di disturbi neuropsicologici, i parametri indicativi di gravità di malattia (conta dei linfociti CD4 o presenza di sintomatologia) associati a deficit cognitivi, i fattori maggiormente implicati in una deflessione della performance nei test psicometrici. Lo studio è stato condotto in 20 centri italiani di Malattie infettive da medici precedentemente addestrati sulle metodiche di somministrazione e di valutazione di una breve batteria neuropsicologica. i 503 soggetti arruolati sono stati suddivisi in base ai livelli ematici di CD4 (500/ul) e alla presenza di sintomatologia (suddivisi in : gruppo1=soggetti asintomatici senza linfoadenopatia, gruppo2=soggetti con linfoadenopatia e gruppo3= soggetti con sintomi senza AIDS). é stata evidenziata una deflessione, che non ha mai raggiunto i valori patologici , di 4 test psicometrici nel gruppo a più basso livello di CD4, e di un solo test nel gruppo di soggetti sintomatici. nell'analisi multivariata, il livello ematico dei linfociti CD4 inoltre risulta l'unico fattore tra quelli considerati (presenza di sintomi, fattore di rischio per infezione da HIV, livello di linfociti CD4) correlabile con l'esito dei test psicometrici. lo studio sembra evidenziare nelle fasi pre-AIDS l'assenza di compromissioni cognitive di rilievo; tuttavia , con livelli di CD4

The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid beta-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the gamma-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651TG in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P=0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR=28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.

Sepsis study group

Frontotemporal dementia regards a group of presenile progressive neurodegenerative form of dementias which includes Pick's disease, corticobasal degeneration, frontotemporal dementia with motor neuron disease, frontal lobe degeneration, dementia-parkinsonism-amyotrophy complex, familial non-specific dementia mapping to chromosome 3, non-Alzheimer degenerative dementia lacking distinctive histological features as well as a number other infrequent syndromes with dementia and focal neurological signs. The aim of this study was to investigate the regional distribution of metallothionein-I-II, an ubiquitary group of buffering proteins, in cases of frontotemporal dementia. The aim of the present study was to study the metallothionein-I-II expression in relationship to the expression in astrocytes of glial fibrillary acidic protein (GFAP) as we have already done in previous studies of Alzheimer's and Binswanger's diseases [31, 32]. Our findings indicate that metallothionein-I-II expression in the most affected areas is likely to be regionally distinct and layer-dependent, in that it is highest in the deep layers of the frontotemporal cortex and the allocortex (hippocampus) while insignificantly immunopositive in the occipital cortex. In addition, the potential use of metallothionein-I-II as a new pharmacological approach to contrast some deleterious aspects of this disease has been also discussed. © 2005 - IOS Press and the authors. All rights reserved.

OBJECTIVE: To determine whether and how patient characteristics and the time of initiation and duration of rehabilitation influence early and long-term patient outcome after cerebrovascular accident. DESIGN: A cohort study. SETTING: Twenty rehabilitation hospitals and wards located throughout Italy. PARTICIPANTS: A total of 1716 stroke patients (874 men, 842 women) consecutively admitted to Italian hospital rehabilitation centers in 1997 and 1998. Patients had moderate to severe disability (FIM instrument score, < or =90). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Three negative patient outcomes were considered: death, early failure (premature, unwanted interruption of rehabilitation program; absence of any improvement at hospital discharge), and late failure in terms of severe disability (Barthel Index score

To investigate the risk factors for man-to-woman sexual transmission of the human immunodeficiency virus (HIV), we carried out a cross-sectional study of 368 women who were steady partners of HIV-infected men attending 16 Italian clinical centers. Information was collected from the medical records of the infected men and by direct interviews with the women. In a logistic regression analysis, the woman's awareness of her partner's seropositivity (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.0 to 1.1), use of condoms (OR, 0.3; 95% CI, 0.1 to 1), and oral contraceptive use (OR, 0.5; 95% CI, 0.3 to 1.0) were negatively associated with transmission of the HIV infection. An increased risk was found in women having sexual intercourse more than twice a week (OR, 2.4; 95% CI, 1.2 to 4.9) and in women who had been sexually exposed to HIV for between 2 and 5 years (OR, 3.5; 95% CI, 1.8 to 6.7). The transmission rate was higher in couples who engaged in anal sex (OR, 2.8; 95% CI, 1.3 to 6.3); in women reporting vaginitis (OR, 4.9; 95% CI, 2.4 to 10.2) or genital warts (OR, 33.3; 95% CI, 4.5 to 244.1); and in those using intrauterine devices (OR, 3.1; 95% CI, 1.4 to 7.1). The risk for women was also associated with a CD4+ cell count lower than 400/mm3 in their partners. Knowledge of the HIV status of the partner led to increased condom use but did not induce a lower frequency of sexual intercourse or an avoidance of anal sex.

We employed the [C-14]2-deoxyglucose method in order to map local brain metabolic activity of rats administered 1, 5, or 20 mg/kg of clozapine, or 0.5 mg/kg of haloperidol, as compared to saline. Clozapine produced a dose-dependent reduction of glucose utilization. At the dose of I mg/kg, the effects were limited to limbic areas. An additional number of structures were significantly affected following administration of 5 mg/kg (the whole hippocampal formation and septal area, and cortical limbic areas). The dose of 20 mg/kg markedly reduced glucose utilization in most of the areas examined. Haloperidol (0.5 mg/kg) reduced glucose utilization of the orbital cortex, hippocampal formation and septal area, globus pallidus, amygdala, ventral thalamus, and substantia nigra reticulata. The results show that acute administration of clozapine or haloperidol are associated with different distribution patterns of altered cerebral energy metabolism. Clozapine differently from haloperidol, reduces energy metabolism of the nucleus accumbens and other Limbic areas. Haloperidol, but not clozapine (1 or 5 mg/kg), affects the substantia nigra reticulata. (C) 1997 Elsevier Science B.V.

Following the report of an increased mortality among patients with amyotrophic lateral sclerosis given high daily doses of branched-chain aminoacids, we assessed the plasma concentrations of large neutral aminoacids and glutamic acid and the large neutral aminoacid brain influx in 24 amyotrophic lateral sclerosis patients receiving placebo or branched-chain aminoacids (L-leucine 12 g, L-isoleucine 6 g, L-valine 6 g daily), in 15 untreated amyotrophic lateral sclerosis patients and in 15 healthy volunteers. The branched-chain aminoacid plasma concentrations increased three- to six-fold in the treated group compared to the patients receiving placebo or no treatment and to the healthy controls. Plasma glutamic acid concentrations in healthy volunteers were 51.59 +/- 7.53 nmol/ml while in the amyotrophic lateral sclerosis patients receiving no treatment, placebo or branched-chain aminoacids were 92.33 +/- 12.15 nmol/ml, 91.21 +/- 15.86 nmol/ml and 95.08 +/- 17.96 nmol/ml respectively. The glutamic acid concentration was significantly higher (P0.01) in amyotrophic lateral sclerosis patients than in healthy individuals. Plasma phenylalanine and tyrosine were lower in the amyotrophic lateral sclerosis patients than in healthy controls, regardless of treatment, whereas tryptophan levels were not significantly different. The branched-chain aminoacid brain influx of the treated group was 110-140% of that measured in the patients receiving placebo and in the healthy controls. The aromatic aminoacid brain influx was lower in the treated group than in the placebo group or healthy controls. An impairment of brain large neutral aminoacid availability might possible contribute to enhancing the progression of symptoms in patients with amyotrophic lateral sclerosis.

Objective: To determine the incidence of heterosexual human immunodeficiency virus type 1 disease transmission and the effect of zidovudine therapy on this risk of transmission. Design: A cohort of 436 monogamous seronegative female sexual partners of human immunodeficiency virus type 1-infected males was followed up for 740 person-years with regular structured interviews and laboratory tests.

A cross-sectional study of stable monogamous couples, recruited from 16 clinical and surveillance centers in Italy between 1987 and 1992, was carried out to investigate the risk factors of woman-to-man sexual transmission of human immunodeficiency virus (HIV). The male partners of all HIV-infected women attending the centers were invited to participate in the study. Of the 275 male partners who were tested for HIV and interviewed with use of a structured questionnaire, 51 were excluded because they had other possible risk factor for HIV infection, no established risk factor was found in the index case, or they had stopped engaging in sexual intercourse. Fourteen of the 224 men (6.3%) were seropositive for HIV. At logistic regression, the highest risks of transmission were for men practicing peno-anal intercourse [odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-22.2] and for men whose partner had acquired immune deficiency syndrome (AIDS) or a CD4+ lymphocyte count of less than or equal to 400/mm(3). No seropositive men were observed among those who were aware of the woman's HIV seropositivity since the beginning of the relationship or were partners of a zidovudine-treated woman. The results suggest that the risk factors described in man-to-woman and man-to-man HIV sexual transmission also operate in woman-to-man transmission.