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Biomedical subjects

A Mele

Publications and source records attributed to A Mele.

At least 73 records · Page 4Linked to original sources
PubMed1999

Lack of evidence for increased risk of hepatitis A infection in homosexual men.

In 1997, prevalence of and risk factors for hepatitis A virus (HAV) infection were evaluated in 146 homosexual and 286 heterosexual men attending a Sexually Transmitted Disease (STD) Clinic in Rome, Italy. Total HAV antibody (anti-HAV) was detected in 60.3% of homosexuals and 62.2% of heterosexuals. After adjustment for the confounding effects of age, years of schooling, number of sexual partners, use of condoms, and history of STD, homosexuals were not found to be at increased risk of previous HAV exposure than heterosexuals (OR 1.1; 95% CI 0.7-1.9). Independent predictors of the likelihood of anti-HAV seropositivity among homosexuals and heterosexuals were: age older than 35 years and positive syphilis serology which is likely a proxy of lifestyles that increase the risk of faecal-oral infections. These findings do not support a higher risk in homosexual men but could suggest a role for the vaccination of susceptible patients attending STD clinics.

Adult↗
PubMed1999

Human herpes virus-6 seroprevalence and leukaemias: a case-control study. GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto).

The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07-1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB.

Adolescent↗
PubMed1999

Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF.

Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36. 2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P = 0. 0001; odds ratio 3.4) and >5 days on ANC <100/microl (P = 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC <100/microl affected infection outcome (P = 0.0024) whereas the antibiotic regimen did not. After day +30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0. 8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Gram-positive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.

Adolescent↗
PubMed1999

Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukaemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.

Adolescent↗
PubMed1999

Inactivation of hepatitis A virus in heat-treated mussels.

Hepatitis A is a widespread infectious disease world-wide. In Italy, shellfish consumption was shown to be a major risk factor for hepatitis A infection, especially when these products are eaten raw or slightly cooked. The aim of the present study was to evaluate Hepatitis A virus (HAV) resistance in experimentally contaminated mussels treated at different temperatures (60, 80 and 100 degrees C) for various times. The presence of HAV was evaluated by cell culture infection and reverse transcriptase-polymerase chain reaction confirmation. The experiments, carried out on HAV suspension and contaminated mussel homogenate both containing about 10(5) 50% tissue culture infectious dose ml-1, showed that, under our experimental conditions, the treatments at 60 degrees C for 30 min, 80 degrees C for 10 min and an immersion at 100 degrees C for 1 min were not sufficient to inactivate all the viruses; it was necessary to prolong the treatment at 100 degrees C for 2 min to completely inactivate the virus. Thus it is advisable to eat only cooked shellfish, paying particular attention to the times and temperatures used in the cooking process, since evidence suggests that the shellfish body may protect the virus from the heat effect.

Animals↗
PubMed1999

[Idiopathic thrombocytopenic purpura: diagnostic-therapeutic approach in adults, children and pregnant women].

Idiopathic thrombocytopenic purpura (ITP) is an acquired haematologic disorder, common among children and adults, with unknown etiology and autoimmune pathogenesis. Nowadays, appropriate diagnostic and treatment strategies are still uncertain; therefore, the attending physicians behaviour in front of thrombocytopenic patients remains heterogeneous. Through a Medline research, we selected eighteen scientific works with practical application. Some of these studies tried to settle the diagnostic-therapeutic approach to thrombocytopenic patient by adopting specific guidelines developed by skilled medical panels. In this review we describe the main features of ITP in adults, in children and pregnant women and we also synthetize the diagnostic-therapeutic behaviours for which there is a sufficient agreement in order to standardize ITP patients management reducing unsuitable diagnostic tests and therapies and the costs too.

Adult↗
PubMed1999

Heterosexual transmission of hepatitis C in Italy.

Data from a surveillance system for type-specific acute viral hepatitis in Italy has been used to evaluate the risk of heterosexual transmission of hepatitis C virus (HCV) associated with sexual activity with multiple partners in subjects > or = 15 years of age. Hepatitis A cases were used as controls. During the period 1991-1996, 1,359 acute hepatitis C and 4,365 hepatitis A cases were recorded among subjects > or = 15 years of age. Intravenous drug use was the most frequent source of infection (35.9%) reported by HCV cases; two or more sexual partners during the 6 months before disease onset accounted for 34.9% of hepatitis C cases. Adjusting by multiple logistic regression analysis for the confounding effect of all risk factors considered (blood transfusion, intravenous drug use, surgical intervention, dental therapy, other parenteral exposure), and for age, sex, area of residence, and educational level of subjects, showed that having two or more sexual partners is an independent predictor of the likelihood of hepatitis C (OR=2.2; 95% CI=1.7-2.7). After excluding intravenous drug users and patients transfused with blood from analysis, the increase in the adjusted OR for the association between HCV and the number of sexual partners correlated with the increase in the number of sexual partners. The risk of hepatitis C was 2.0 times higher (95% CI=1.4-2.9) for subjects with two sexual partners and 2.8 times higher (95% CI=2.1-3.8) for subjects with three or more sexual partners, as compared to subjects with less than two sexual partners. These findings suggest that heterosexual transmission may play an important role in the spread of hepatitis C in Italy.

Adolescent↗
PubMed1998

Drug use and acute leukemia.

OBJECTIVE: To study the occurrence of acute leukemia in relation to preceding use of drugs a case-control study has been carried out in Rome, Italy. PATIENTS AND METHODS: Two hundred and two patients (age >15 years) with a diagnosis of acute leukemia during the period July 1992-June 1994 were enrolled. For each patient, 10 controls matched by age and gender were randomly drawn from the source population. Through the individual beneficiary code the information relevant to the drugs received within the National Health Service during the period January 1989-December 1992 was retrieved. The use of drugs was considered etiologically related to leukemia if the prescription occurred before the 12 months preceding the diagnosis. Exposure was categorized as 'any use' (at least one prescription during the etiologic period), 'high use' (duration of use greater than the median in the control group) and, for NSAIDs, 'very high use' (duration of use greater than 180 days). RESULTS: Among drugs suspected to cause leukemia, users of high doses of chloramphenicol presented an OR of 1.8 (95% CI: 0.6-5.3). Among other categories of drugs with an increase in the ORs, though not statistically significant, we found tricyclic antidepressants (OR=1.7; 0.8-3.4) and oral contraceptives (OR=1.8; 0.8-4.0). No excess risk was observed for users of calcium-channel blockers (OR=0.9; 0.5-1.7). Use of very high doses of NSAIDs appeared to decrease the occurrence of acute leukemia (OR=0.4; 0.1-1.5). CONCLUSION: Even with several limitations, this study provides an initial frame of reference for the potential causal role of drugs in acute leukemia.

Journal Article↗
PubMed1998

The rhGM-CSF-EPO hybrid protein MEN 11300 induces anti-EPO antibodies and severe anaemia in rhesus monkeys.

A recombinant human GM-CSF-EPO hybrid protein named MEN 11300 was administered biweekly for a total of 6 weeks to rhesus monkeys in order to evaluate its pharmacokinetic behaviour, tolerability and immunogenicity. In this primate species a strong antibody response was induced which neutralized the in vitro biological activity of human EPO while no antibody response could be detected against human GM-CSF. A severe drop in reticulocyte counts at approximately 2 weeks after initiation of treatment was followed by a dramatic decrease in the number of erythrocytes. No effects were observed on GM-CSF-dependent hematopoietic lineages and the clinical chemistry analyses did not reveal signs of general toxicity. Reticulocyte and erythrocyte counts started to recover 3-4 weeks after discontinuation of treatment in concert with a decline in anti-EPO antibody titres. Nevertheless, cell numbers remained below basal levels up to 50 days after the last MEN 11300 administration. Haematological impairment indicates that the administration to non-human primate of human EPO fused to human GM-CSF, induces neutralizing autoantibodies to the self EPO. Present data do not allow prediction of the immunogenic potential of the fusion protein in humans and a dose-escalating phase I study should be addressed to investigate the safety of the product.

Anemia↗
PubMed1998

Overproduction of soluble, extracellular cytotoxin alpha-sarcin in Escherichia coli.

The goal of the present study was to establish the condition to obtain preparative amounts of the recombinant cytotoxin alpha-sarcin to be used for immunoconjugate production. alpha-Sarcin cDNA was isolated from Aspergillus giganteus strain MDH 18,894 and its expression in Escherichia coli was attempted by the use of both two-cistron and fusion protein-expression systems. Whereas the former resulted in low intracellular expression level of recombinant alpha-sarcin (r-Sar), the latter allowed high-level expression of the fusion protein in the culture supernatant. A variant form of alpha-sarcin with an additional threonine residue in position 1 (Thr-Sar) was obtained by proteolytic processing of the fusion protein with a final yield after purification of 40 mg/L of culture. Both recombinant proteins r-Sar and Thr-Sar were identical to native a-sarcin with respect to the biochemical properties and to the in vitro biological activity.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetic and immunogenic behavior of three recombinant human GM-CSF-EPO hybrid proteins in cynomolgus monkeys.

MEN 11,300, MEN 11,301, and MEN 11,303 are three recombinant human hybrid proteins that, as has recently been described, induce in vitro erythroid differentiation. This article provides data on their pharmacokinetic and immunogenic behavior after repeated i.v. administration to cynomolgus monkeys at 0.8 or 1.6 micrograms/kg doses. Pharmacokinetic data, obtained after the first administration, showed that the half-life (t1/2) and clearance (CL) values are dose dependent, with no significant differences among the three hybrid proteins. After the tenth administration, MEN 11,300 and MEN 11,301, both a high and low dose, and MEN 11,303 at high dose were undetectable in plasma, whereas MEN 11,303 at the lower dose showed no alteration in its pharmacokinetic profile. Immunologic analyses of plasma provided an explanation for this different pharmacokinetic behavior. In fact, plasma samples from animals treated repeatedly with MEN 11,300 and MEN 11,301 showed specific antibody formation in response to both the high- and the low-dose regimens. These antibodies exerted in vitro a strong neutralizing activity of the hybrid proteins, with a predominant specificity for the erythropoietin (EPO) portion. By contrast, MEN 11,303 at the lower dose did not induce a detectable antibody response whereas the antibodies observed on the high-dose regimen did not exert neutralizing activity against the hybrid proteins nor against granulocyte-macrophage colony-stimulating factor (GM-CSF) or EPO. Hematologic parameters were not affected by the treatments, thus indicating that the anti-EPO neutralizing antibody response does not cross react with the endogenous monkey cytokine. The overall immunogenicity data suggest that among the three fusion proteins, MEN 11,303 could have a lower immunogenic potential.

Animals↗
PubMed1998

The role of striatal dopaminergic mechanisms in rotational behavior induced by phencyclidine and phencyclidine-like drugs.

Phencyclidine (PCP) and phencyclidine-like drugs (TCP, dexoxadrol, MK-801, and SKF 10,047) were evaluated for their ability to induce rotational behavior in rats with unilateral 6-OHDA lesions of the medial forebrain bundle and for their ability to alter striatal dopamine (DA) overflow with microdialysis procedures. All of the compounds tested produced rotational behavior ipsilateral to the lesion, suggesting that they were enhancing extracellular dopamine in the intact striatum. The microdialysis studies, however, did not support this contention. There appeared to be a complete dissociation between the ability of the five compounds to produce ipsilateral rotations and their ability to enhance extracellular dopamine levels in the striatum. PCP was the only compound able to elicit significant increases in striatal dopamine overflow following i.p. injections and also produce dramatic rotational behavior. MK-801 was the most potent compound in enhancing rotational output while it had no effect at all on striatal dopamine overflow. Dexoxadrol also produced significant rotational output without having any effect on extracellular levels of dopamine following i.p. injections. TCP and SKF 10,047, at doses which produced significant rotational behavior, only elevated dopamine 16% and 12%, respectively, at peak effect. It is most parsimonious to conclude that the effects of PCP-like drugs on nigro-striatal function are mediated through their ability to act as indirect NMDA receptor antagonists and not through their ability to alter striatal dopamine activity.

Animals↗
PubMed1998

N-methyl-D-aspartate receptors in the nucleus accumbens are involved in detection of spatial novelty in mice.

The aim of this study was to investigate the role played by intra-accumbens N-methyl-D-aspartate (NMDA) receptors in spatial information encoding. For this purpose, the effect of local administration of both competitive (AP-5) and non-competitive (MK-801) NMDA antagonists was assessed in a task designed to estimate the ability of rodents to encode spatial relationships between discrete stimuli. The task consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). The results show that both doses of MK-801 (0.15 and 0.3 microg/side) induced a selective impairment in the capability of mice to detect spatial novelty. A similar effect was obtained by injecting the low dose of the competitive antagonist AP-5 (0.1 microg/side), whereas the high dose (0.15 microg/side) abolished detection of both spatial and object novelty. Taken together, these results show that intra-accumbens injections of low doses of competitive and non-competitive NMDA antagonists can produce selective deficits in processing spatial information resembling those observed after hippocampal damage. Moreover, the fact that pharmacological treatments spare memory processes involved in habituation suggests that NMDA antagonists may interfere with the formation of spatial representations rather than producing memory deficits per se.

Animals↗
PubMed1998

N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes.

In this study we report on the effects of N-methyl-D-aspartate (NMDA)- and dopamine (DA)-receptor manipulation on the modulation of one-trial inhibitory avoidance response and the encoding of spatial information, as assessed with a non-associative task. Further, a comparison with the well-known effects of the manipulation of these two receptor systems on locomotor activity is outlined. It is well assessed that NMDA-receptor blockage induces a stimulatory action on locomotor activity similar to that exerted by DA agonists. There is evidence showing that the nucleus accumbens is involved in the response induced by both NMDA antagonists and DA agonists. We show results indicating a functional interaction between these two neural systems in modulating locomotor activity, with D2 DA-receptor antagonists (sulpiride and haloperidol) being more effective than the D1 antagonist (SCH 23390) in blocking MK-801-induced locomotion. A different profile is shown in the effects of NMDA antagonists and DA agonists in the modulation of memory processes. In one-trial inhibitory avoidance response, NMDA antagonists (MK-801 and CPP) impair the response on test day, while DA agonists exert a facilitatory effect; furthermore, sub-effective doses of both D1 (SKF 23390) and D2 (quinpirole) are able to attenuate the impairing effect in a way similar to that induced by NMDA antagonists. The effects of NMDA- and DA-acting drugs on the response to spatial novelty, as assessed with a task designed to study the ability of animals to react to discrete spatial changes, are in good accord with the effects observed on passive avoidance. The results show that NMDA as well as DA antagonists, at low doses, selectively impair the reactivity of mice to spatial changes. In a last series of experiments, the possible role of NMDA receptors located in the nucleus accumbens was investigated regarding reactivity to spatial novelty. The experiments gave apparently contrasting results: while showing an impairing effect of focal administrations of NMDA antagonists in the nucleus accumbens on reactivity to spatial novelty, no effect of ibotenic acid lesions of the same structure was observed.

Animals↗
PubMed1998

Correlation between virus genotype and chronicity rate in acute hepatitis C.

BACKGROUND/AIMS: Forty-two patients with the diagnosis of acute hepatitis C virus hepatitis were studied to investigate the relationship between hepatitis C virus genotype and progression to chronic infection. METHODS: The patients were followed for more than 1 year (mean age 29 years, male/female ratio 2.5). Intravenous drug use was documented in 15 cases, blood transfusion in four, surgical intervention, dental therapy or other parenteral exposure in 15, and unknown factors in the remaining eight. The evolution to chronicity was diagnosed on the basis of a persistent increase in transaminase levels, the presence of HCV-RNA and the histological pattern of chronic hepatitis. RESULTS: The majority of cases presented hepatitis C virus infection of subtype 1a (38.1%) or 1b (33.9%). Six cases showed the presence of genotype 3a (14.3%). Subtype 2c was observed in three out of four cases infected with genotype 2. No significant association was demonstrated with documented risk factors. The overall chronicity rate was 59.5%. This value increased to 92% in individuals infected with genotype 1b. By multivariate analysis the age-adjusted odds ratio for infection with genotype 1b as compared with all other genotypes was 14.4 (95% confidence interval; 1.52-137). Moreover, significant differences (p= 0.0002) were present in this group for histological activity index (8.7 as compared with 5-7). CONCLUSIONS: The results of this prospective study are consistent with an independent association between hepatitis C virus genotype 1b and a poor prognosis.

Acute Disease↗
PubMed1998

Ad hoc survey of hepatitis B vaccination campaign in newborns of HBsAg positive mothers and in 12-year-old subjects in southern Italy.

The ongoing vaccination campaign against hepatitis B (HB) for newborns of hepatitis B surface antigen (HBsAg) positive mothers and for 12-year-old subjects was evaluated in Naples, Italy, an area of relatively high HB endemicity. Subjects were recruited by a random sampling procedure. Among 2060 pregnant women studied, 1887 (91.6%) were screened for HBsAg. HBsAg prevalence was 2.5% (47/1887). Immunoprophylaxis according to the protocol (immunoglobulins within 24 h plus vaccine within 7 days after birth) was administered in 26 (55.3%) out of the 47 newborns of HBsAg positive mothers; vaccination was delayed (later than 7 days after birth) for 14 (29.8%) infants; in the remaining seven newborns (14.9%) were not given immunoglobulins at birth. All infants were vaccinated. Out of the 1000 adolescents sampled 130 (13%) were not found due to an inaccurate census list; 727 (83.3%) of the 870 investigated had received a three-dose HB vaccine series. Overall, the HB vaccination program in Italy is working well. However, further efforts should be made to improve the efficacy and effectiveness of the campaign.

Adolescent↗
PubMed1998

Different neural mechanisms underlie dizocilpine maleate- and dopamine agonist-induced locomotor activity.

This study evaluated and compared the role of mesoaccumbens dopamine and the ventral pallidal region in the locomotor stimulatory action of the non-competitive N-methyl-D-aspartate antagonist dizocilpine maleate and dopamine agonists. Intra-accumbens injections of both amphetamine (1, 5 and 25 nmol) and dizocilpine maleate (1, 5, 25 and 50 nmol) induced a dose-dependent increase in locomotor activity. The N-methyl-D-aspartate antagonist was somewhat less effective than amphetamine. 6-Hydroxydopamine dopamine-depleting lesions of the nucleus accumbens completely blocked locomotor stimulation induced by focal administrations of amphetamine (5 nmol), but were ineffective in altering the actions of dizocilpine maleate (50 nmol). Ibotenic acid lesions of the ventral pallidal region and muscimol injections into this area also prevented the stimulatory effects of systemic amphetamine (1 mg/kg), while having no effect on the locomotor-activating actions of systemic dizocilpine maleate (0.3 mg/kg). Microdialysis studies revealed that systemically administered apomorphine (2 mg/kg) significantly decreased extracellular GABA in the pallidum, which was accompanied by substantial increases in locomotor output. Systemically administered dizocilpine maleate (0.3 mg/kg), on the other hand, also increased locomotor activity without having any effect on pallidal GABA. These data, taken together, indicate that while the locomotor effects of dopamine agonists are dependent upon intact mesoaccumbens dopamine and involve GABAergic efferents from the nucleus accumbens to the ventral pallidum, dizocilpine maleate's stimulatory actions are independent of such mechanisms.

Amphetamine↗