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A Preti

Publications and source records attributed to A Preti.

At least 37 records · Page 2Linked to original sources
PubMed2000

Season and suicide: recent findings from Italy.

Seasonal asymmetry in yearly suicide occurrence is a long-observed phenomenon in psychiatric, suicidological, and sociological research, and the effects of seasonal factors on suicidal behavior have been the focus of a number of earlier studies. Taking into account limitations of data and methods, these studies have generally favored interpretations based on psychosocial factors. Recent studies have challenged the widely held notion that seasonal effects on suicide are a unitary phenomenon, not influenced by age, gender, or circumstances of the act. In particular, the seasonal occurrence of suicides has been found to differ significantly between the young and the elderly, and differences have also been found between male and female cycles of occurrence. Suicides using violent methods have been shown to follow clearer seasonal patterns than suicides by less violent methods (such as drug or gas poisoning), possibly reflecting the greater impulsive component involved in the choice of a violent lethal means. In this paper, findings from Italy are used to illustrate the clinical implications of studies into the topic of season and suicide, with the aim of developing more effective preventative strategies.

Female↗
PubMed2000

Influence of method on seasonal distribution of attempted suicides in italy.

To verify if attempted suicides follow different seasonal distributions according to the method chosen, we studied the Italian monthly distribution of admissions for attempted suicide in the period 1984-1995 according to gender and age, distinguishing between non-violent (ICD 950-952) and violent (ICD 953-958) attempted suicides. The effect of temperature was also taken into account. A clear asymmetry in seasonal distribution of events can be observed in the oldest age groups in both genders, with a peak in warmer months. Only male attempted suicides by violent methods show a clear asymmetry in seasonal distribution, with a peak in spring months and a trough in autumn months. Spectral analysis, more accurate in detecting seasonal rhythms than analyses that only compare monthly seasonal means, identifies a circannual rhythm for violent suicides in both genders. The seasonal components of total variance in attempted suicides account for 16.5 and 12.4%, respectively, of violent male and female attempted suicides. Among males, a significant (p < 0.05) 4 cycles/year pattern is seen alongside the more relevant (89.4%, p < 0.01) 1 cycle/year distribution. Among females, aside from the 1 cycle/year distribution (63.3%, p < 0.01) noted, a 6 cycles/year pattern is found to contribute significantly (16.9%, p < 0.05) to the seasonal component of variance. A clear relationship with temperature indicators is noted among males: higher temperatures positively correlate with attempted suicides, whereas cooler temperatures seem to exert a protective action. Female attempts show a less evident correlation with indicators of temperature. Sample composition by age and gender and the lack of distinction between methods of attempted suicide may have obscured the seasonal component of some classes of attempted suicide in previous studies. The circannual rhythm found in this study of violent attempted suicide in relation to climate seasonal change confirms the importance of taking chronobiological variables into account in the evaluation of patients at risk of suicide.

Adolescent↗
PubMed2000

Death by homicide in Italy, 1980-94: age and gender differences among victims.

To investigate the role of sociodemographic factors in the risk of death by homicide in Italy, official statistics from 1980 to 1994 concerning death by homicide have been studied. Homicide rates increase from 1980 to 1994 for males and, to a much lesser extent, for females. Clear differences exist by age and gender, with rates peaking in both genders at young adult age (25-34) and men having five times higher rates than women. Mean rate in the general population is 1.98 per 100,000, one of the highest rates in the civilized world. These findings are mostly influenced by higher homicide rates for both males and females in southern regions, where cultural attitudes towards violence, linked to the greater diffusion of criminal organizations, greatly influence the risk of death by homicide. About 75% of homicides involve firearms: clearly in Italy availability of lethal weapons is a key factor in homicide. Intervention aimed at increasing community awareness of the causes and methods of prevention of violence (including the roles of substance abuse and social inequality) are needed if adequate policies are to be developed to reduce the risk of death by homicide. Differences in homicide rates across countries clearly indicate that homicide is a preventable cause of death.

Adolescent↗
PubMed2000

Vanoxerine National Institute on Drug Abuse.

Vanoxerine (GBR-12909) is a high-affinity dopamine reuptake inhibitor that was synthesized in the late 1970s and was initially tested in Europe as a potential antidepressant. In 1989, it was suggested that GBR-12909 might be useful in the treatment of cocaine addiction [346980]. The drug has completed phase I clinical trials conducted by the US National Institute on Drug Abuse for the potential treatment of cocaine abuse [346245,376621]. A multidose, safety and pharmacokinetics, open-label, fixed-order dose-escalating study has been completed. Four doses of vanoxerine in healthy normal volunteers were administered, to assess the safety and tolerability of the drug at 25, 50, 75 and 100 mg. Further development is likely to continue, pending review of the data [376621]. Dopamine transporter occupancy has also been measured. After 2 weeks of dosing at either 50, 75 or 100 mg oral vanoxerine in 8 human subjects, preliminary results of subsequent PET scans show that occupancy increased with dose, reaching 25 to 35% at 100 mg [346245]. At these doses, the drug did not cause the behavioral symptoms such as those of cocaine, suggesting that the drug does not have abuse potential. If no safety issues arise, the compound will be evaluated in trials with cocaine-dependent subjects, along with its derivative, compound 5 [346980]. It is thought that prolonged treatment with vanoxerine could reverse the addiction process, following studies in rats showing that dopamine transporter levels returned to normal when animals were switched to vanoxerine therapy immediately after cocaine administration [346980]. Vanoxerine has an affinity constant (Ki), at the human dopamine transporter, of 9 nM [347021]. Gist-Brocades originally initiated studies of vanoxerine, along with another piperazine, GBR-12935, for the treatment of cocaine dependence. The company was also investigating vanoxerine as a potential antipsychotic therapeutic agent; development for this indication has been discontinued [190331]. In 1995, the NIDA began to fund studies into the potential of vanoxerine to reduce cocaine self-administration by rhesus monkeys. Early data showed that vanoxerine could decrease cocaine-maintained responding (CMR) in rhesus monkeys, without affecting similar levels of food-maintained responding (FMR). Furthermore, a decanoate ester of a hydroxylated analog of vanoxerine, DBL-583, could decrease CMR by 80% while leaving FMR unaffected; this effect lasted almost 30 days with a single injection [227488,346980]. Similar studies have shown that, by inhibiting the dopamine transporter, for which vanoxerine has a 500-fold increased affinity in comparison to cocaine, vanoxerine could selectively reduce(1 mg/kg i.v.) or eliminate (3 mg/kg i.v.) cocaine self-administration in primates. The drug was well tolerated with no changes in blood pressure or oxygen saturation. Oral administration of the drug in clinical trials was planned following this study [346990].

Animals↗
PubMed2000

BP-897 Bioprojet.

BP-897 is a dopamine D3 receptor agonist which is under development by Bioprojet for the potential treatment of drug craving and vulnerability to relapse that are elicited by drug-associated environmental stimuli; it is undergoing phase I trials [318397,334036,340721]. Preclinical investigations were carried out by Cambridge University and INSERM [295680]. BP-897 functions as a partial agonist in vitro and as either an agonist or an antagonist in vivo. It inhibits cocaine-seeking behavior that depends upon the presentation of drug-associated cues, without having any intrinsic, primary rewarding effects [334036]. In preclinical studies, BP-897 administration before testing reduced cocaine-seeking behavior in rats in a dose-dependent manner [304557,307758,334036]. In D3 receptor knockout mice, BP-897 has no effect [345710]. It does not reduce self-administration of cocaine in monkeys [318397].

Animals↗
PubMed1999

Cloning and characterization of NEU2, a human gene homologous to rodent soluble sialidases.

Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely distributed in nature, that cleave sialic acid residues from the oligosaccharide components of glycoconjugates. All of the sialidase enzymes thus far characterized share an Asp block, repeated three to five times in the primary structure, and an F/YRIP sequence motif that is part of the active site. Using a sequence homology-based approach, we have identified a novel human gene, named NEU2, mapping to chromosome 2q37. The nucleotide sequence analysis of the gene has shown that it contains only one intron of about 1.25 kb, and the longest open reading frame encodes a protein of 380 amino acids, with a two-Asp block consensus, and the YRIP sequence. In the putative promoter sequence there are a classical TATAA box and four E boxes, which are consensus binding sites for muscle-specific transcription factors. Northern blot analysis revealed expression of the NEU2 transcript only in skeletal muscle.

Amino Acid Sequence↗
PubMed1999

Phase II study of paclitaxel in combination with mitoxantrone and ifosfamide/mesna for patients with relapsed or refractory non-Hodgkin's lymphoma after failure to cytarabine/cisplatin combination.

PURPOSE: Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL). METHODS: Thirty-eight patients with relapsed/refractory NHL who had been exposed to doxorubicin as well as the cytarabine-cisplatin combinations received Mesna 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour; ifosfamide 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour (same bag); Novantrone 8 mg/M2/D i.v. day 1; and Taxol 27.5 mg/M2/D daily days 1, 2, 3, 4 by continuous 24-hour intravenous infusion. Premedication for Taxol included dexamethasone, diphenhydramine, and cimetidine on day 1. RESULTS: Of 35 evaluable patients, 9 (26%) achieved a complete response and 7 (20%) a partial response for a total response rate of 46%. The median failure-free and overall survival times were 2 and 10 months, respectively. Major toxicity was hematologic with a median absolute neutrophil nadir of 196/mm3. Only 10% of the cycles were associated with a grade 3-4 infection. CONCLUSION: MINT is an active and safe regimen for relapsed/refractory NHL that have failed both an Adriamycin-containing regimen and a cytarabine/cisplatin-containing regimen.

Adult↗
PubMed1999

Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival.

BACKGROUND: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD). PATIENTS AND METHODS: Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10. RESULTS: Among healthy adult volunteers serum IL-10 levels ranged from 4.8-9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels > or = 10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, serum beta 2-microglobulin > or = 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population. CONCLUSIONS: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.

Adolescent↗
PubMed1999

Expression of a novel human sialidase encoded by the NEU2 gene.

Sialidases (E.C.3.2.1.18) belong to a group of glycohydrolytic enzymes, widely distributed in nature, which remove sialic acid residues from glycoproteins and glycolipids. All of the sialidase so far characterized at the molecular level share an Asp block, repeated three to five times in the primary structure, and an F/YRIP sequence motif which is part of the active site. Using a sequence homology-based approach, we previously identified a human gene, named NEU2, mapping to chromosome 2q37. NEU2 encoded protein is a polypeptide of 380 amino acids with two Asp block consensuses and the YRIP sequence in the amino terminal part of the primary structure. Here we demonstrate that NEU2 encodes a functional sialidase. NEU2 was expressed in COS7 cells, giving rise to a dramatic increase in the sialidase activity measured in cell extracts with the artificial substrate 4-MU-NANA. Using a rabbit polyclonal antiserum, on Western blots a protein band with a molecular weight of about 42 kDa was detectable, and its cytosolic localization was demonstrated with cell fractionation experiments. These results were confirmed using immunohistochemical techniques. NEU2 expression in E.coli cells allowed purification of the recombinant protein. As already observed in the enzyme expressed in COS7 cells, NEU2 pH optimum corresponds to 5.6 and the polypeptide showed a K(m)for 4-MU-NANA of 0.07 mM. In addition, based on the detectable similarities between the NEU2 amino acid sequence and bacterial sialidases, a prediction of the three-dimensional structure of the enzyme was carried out using a protein homology modeling approach.

Amino Acid Sequence↗
PubMed1999

Suicide and unemployment in Italy, 1982-1994.

OBJECTIVE: To investigate whether either the condition of being unemployed, or changes in unemployment rates are associated with suicide risk. DESIGN: Administrative data for suicide according to occupational status have been analysed considering three employment categories: employed, seeking new job (unemployed), seeking first job (never employed). Comparison of suicide rates by economic position and correlation between suicide and unemployment rates have been made. SUBJECTS AND SETTINGS: 20,457 deaths by suicide registered in Italy among economically active people from 1982 to 1994. MAIN OUTCOME MEASURES: Change over time in suicide rates by economic position; coefficient of aggravation according to occupational status. RESULTS: Suicide rates among the unemployed are clearly and constantly higher than those among the employed: up to three times higher among men, and twice as high among women. Among the unemployed a clear and significant rise in suicide rates in both sexes took place over the study period; suicide rates among the employed showed a less marked increase. The rise in suicide rates was accompanied by a concurrent rise in unemployment rate percentage. Men seem to be affected most by this change in unemployment rate percentage; women are subject to less evident influences and variations. CONCLUSION: Different suicidal behaviour trends among unemployed compared with employed people indicate that unemployment (and above all the prospect of not having access to a working role) acts as a contributing factor for suicide. Unemployment, even if symptomatic of a mental disorder, should therefore always be taken into consideration as a risk factor for suicide: the potentially lethal consequences of its negative influence on both self esteem and the ability to use supportive networks in a efficient way is an element to which great attention should be paid.

Adolescent↗
PubMed1999

Suicide among eminent artists.

To evaluate suicide risk by profession among eminent artists data from Garzanti's Encyclopedia, a broad biographical repertory, were used. Six categories in the visual and literary arts were compared: architects, painters, sculptors, writers, poets, and playwrights. Only people whose deaths occurred in the 1800s or 1900s were included since it is likely that underestimation of suicide has been lower in the more recent centuries. A total of 59 suicides were observed in a sample of 3,093 people: this corresponds to a ratio of 1.90%. Suicides were 51 among men (ratio 1.75%) and 8 among women (ratio 4.30%). The comparison by profession indicates that poets and writers exceed the mean suicide ratio of the sample. Painters and architects, conversely, have a clearly lower risk than the mean. Mean age of suicides was 44 yr. (SD = 12), with writers being slightly older (48 yr., SD = 12) than other artists. Artists who died of causes other than suicide reach a mean of 65 yr. (SD = 10). Suicide among artists seems to have a peculiar pattern, clearly different from the pattern of the general population, wherein suicide risk is higher among men and older people. Adverse financial circumstances and the stress attributed to rejection of personal products may contribute to the specific risk of suicide among artists. The link between mental disorders, such as manic-depression, which imply a higher risk of suicide, and creativeness is discussed as a contributing factor.

Art↗
PubMed1999

Some social correlates of homicide rates in Italy.

In Italy, as elsewhere, homicide rates are higher in poorer regions. Unemployment rates associated strongly and positively with homicide rates, explaining up to 54% of variance in regional distribution of homicide rates across the 20 Italian administrative regions.

Homicide↗
PubMed1998

Seasonality in suicides: the influence of suicide method, gender and age on suicide distribution in Italy.

In order to ascertain if and how age, gender and choice of lethal means influence the seasonal distribution of suicide in Italy, data concerning all suicides registered in Italy from 1984 to 1995 have been analyzed, taking these variables into account. In the age group 14-65 years and over a total of 31771 male suicides (mean yearly rate, 12.6 per 100000) and 11984 female suicides (mean yearly rate, 4.4 per 100000) have been identified in Italy during the study period. Suicides in the younger age ranges, both among males and females, show a less marked asymmetrical seasonal distribution than those in the older age groups. Only suicides committed by violent methods (ICD 953-958) show clear evidence of seasonality, with a peak in spring and a low in late autumn. Suicides committed by non-violent methods (950-952) follow no seasonal trend in either sex. Spectral analysis reveals a circannual rhythm for violent suicides (ICD 953-958) in both genders. For male non-violent suicides (ICD 950-952), a period with a frequency of 0.0833 (12 months) has been identified, but with a polarity opposite to that of male violent suicides. For female non-violent suicides, no period of frequency of 0.0833 could be identified, but, as for female violent suicides, a period with frequency close to 0.2500 (4 months) has been found. Changes in climate, then, correlate with the monthly distribution of violent and non-violent suicides in opposite ways: male violent suicides show a significant positive relationship with indicators of temperature and exposure to the sun, and a significant negative relationship with indicators of humidity and rainfall. Female suicides show less significant relationships with climate indicators. Work aimed at suicide prevention should therefore take into account the complex influence of seasonal climate both on human biological rhythms (particularly on 5-HT related functions and their actions on mood and impulsivity) and on sociorelational habits.

Adolescent↗
PubMed1998

Ganglioside GM2 is substrate for a sialidase in MDCK cells.

GM1 ganglioside carrying a fluorescent fatty acid in substitution of the natural one, has been administered to cultured Madin-Darby canine kidney (MDCK) cells for different pulse times (0.5-24 h), and its metabolic fate was followed. The fluorescent GM2, asialo-GM2, asialo-GM1 and ceramide were the only detectable metabolites. The complete absence of fluorescent GM3 is consistent with the presence in these cells of a sialidase working on GM1 and GM2 gangliosides. After treatment of the cells with chloroquine the fluorescent GM1 remained essentially undegraded, indicating a catabolic processing at lysosomal level.

Animals↗
PubMed1998

The influence of climate on suicidal behaviour in Italy.

A growing number of studies report an asymmetry in the seasonal distribution of suicides, with a peak in the late spring months for both sexes. The aim of this study is to verify if the climate, apart from its seasonal change, exerts a direct influence on suicidal behaviour. To this end, deaths by suicide in 17 Italian towns which all have a meteorologic station have been analyzed, taking into account some climatic indicators. Results of analyses show an unequal distribution of suicides with respect to latitude, with a peak in the North. The distribution of deaths by suicide shows a negative relationship with mean yearly temperature values, max and min, and with sun exposure indicators, and a positive, but less significant relationship with rainfall values. As far as climatic variables considered as a whole are concerned, stepwise regression identifies three relevant factors with significant relationships to suicide rates: humidity grade, rainfall mean, and sunlight exposure. These three climatic indicators explain up to 63% (Adj R2) of the variance in the distribution of suicide rates for both genders, with sunlight exposure offering the most significant contribution, when regressed on suicide rates via a multiple regression model. Higher suicide rates, therefore, correspond to dry places which are less exposed to the sun. However, the variable which shows the most significant correlation with suicide rates for both sexes is not a climatic one, but the percentage of the population aged 65 and over. The distribution of people at greater biological risk for possible disruption of brain neurochemistry (i.e. older people), therefore, predicts the distribution of suicide rates. Climate contributes to this biological risk by modifying both the responsiveness of the circuits that control mood and behaviour, and also the frequency and intensity of social interaction.

Climate↗
PubMed1998

High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome.

PURPOSE: This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy. PATIENTS AND METHODS: A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995. RESULTS: Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression. CONCLUSION: Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.

Adolescent↗
PubMed1998

Use of the international prognostic index and the tumor score to detect poor-risk patients with primary mediastinal large B-cell lymphoma: a study of 37 previously untreated patients.

We tested two prognostic models devised for intermediate-grade lymphomas, the age-adjusted international prognostic index and the tumor score, in 37 consecutive untreated patients treated for a diagnosis of primary mediastinal large B-cell lymphoma (PMLCL). Neither model selected for a group of patients with statistically significant differences in rates of complete response, failure-free survival (FFS) and overall survival (OS). Because the level of beta microglobulin (beta2m) is consistently low in the serum of patients with PMLCL despite bulky disease, we tested the median value of this continuous variable in the 37 patients and found it to be statistically significant for predicting FFS. A hypothetical tumor score model using the adjusted value for beta2m improved the prognostic accuracy for achievement of complete response (93% vs. 60%; P = 0.02), FFS (73% vs. 35%; P = 0.02), and OS (80% vs. 55%; P = 0.05). This hypothetical model merits further testing in a larger population of patients with PMLCL.

Adult↗