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Biomedical subjects

G Pastore

Publications and source records attributed to G Pastore.

At least 91 records · Page 5Linked to original sources
PubMed1998

Measurement of viral sequences in cerebrospinal fluid of AIDS patients with cerebral white-matter lesions using polymerase chain reaction.

OBJECTIVES: To optimize the use of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS) white-matter lesions that along with clinical findings and magnetic resonance imaging (MRI) can allow a definite diagnosis to be made; also to evaluate treatment with zidovudine plus foscarnet. DESIGN AND METHODS: Fifteen AIDS patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA, cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF samples. The results were correlated with clinical and MRI findings and treatment with zidovudine plus foscarnet was evaluated. RESULTS: Four and five out of 15 patients with CMV DNA > or = 1 : 625 and JCV DNA > or = 10(3) copies/microl detected in the CSF were diagnosed with CMV and progressive multifocal leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative with the highest levels of HIV RNA (median, 6.87 log10 copies/ml) in CSF were considered as having HIV-1 encephalitis. Neurological symptoms were non-supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and two out of three patients with CMV leukoencephalopathy improved. In these two latter patients, relief of clinical symptoms coincided with decreased CMV DNA. JCV DNA remained unchanged and all three PML patients deteriorated. CONCLUSIONS: Measurement of CSF viral sequences supports the diagnosis of CNS white-matter lesions in AIDS patients. While effective therapy for PML remains elusive, treatment including zidovudine plus foscarnet may be a promising option for HIV-1 and CMV-related manifestations.

AIDS Dementia Complex↗
PubMed1998

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B.

Pilot studies have demonstrated that recombinant interleukin 2 (rIL-2) has an indirect antiviral activity against hepatitis B virus, but the minimal dose of rIL-2 for induction of this effect was not defined. The aim of the study was to ascertain the most efficient dose of rIL-2 for induction of the loss of detectable serum HBV-DNA or a 50% or greater decrease in its level. Thirty-one patients with chronic hepatitis B, hepatitis B e antigen and serum HBV-DNA positive were enrolled in this double-blind randomized controlled trial. Patients were divided: Group I (n = 8) placebo; Group II (n = 7) treated with 0.9 MU of rIL-2 subcutaneously administered daily for 8 weeks; Group III (n = 8) treated with 1.8 MU of rIL-2 under the same schedule; Group IV (n = 8) which received 3.6 MU of rIL-2 under the same conditions. At the end of treatment 25% of the patients in the placebo group, and 13% and 25% in rIL-2 groups III and IV, respectively, had a decrease in HBV-DNA higher than 50% of the basal value. None of the patients lost serum HBV-DNA. Only three patients (one from group II and two from group IV) normalized the ALT levels. Overall, during treatment, ALT levels decreased in the treated groups. This decrease occurred simultaneously with an increase in serum HBV-DNA concentration. Since the response rate in the treated groups was similar to that of the placebo group, rIL-2 is not useful as monotherapy for the treatment of chronic hepatitis B at the doses and schedules used in this study.

Adolescent↗
PubMed1998

The basal metabolic rate and energy cost of standardised walking of short and tall men.

OBJECTIVES: To assess the influence of stature on the basal metabolic rate (BMR) and on the energy cost of standardised walking. A second objective was assess the accuracy of the FAO/UNU/WHO (1985) equations to predict BMR. DESIGN/SUBJECTS: Forty-six young men were selected on the basis of their stature and assigned to the group of short, S (n = 25, mean stature = 1.65 +/- 0.03 m) or of tall, T (n = 21, mean stature = 1.87 +/- 0.04 m). SETTING: Rome, Italy. INTERVENTIONS: Body composition was assessed by underwater weighing. BMR and energy cost walking at 5 km/h was measured by the Douglas bag. RESULTS: Body fat % was similar in the two groups (15.2 +/- 4.3 for S; 17.4 +/- 5.3 for T; ns). The BMR of T was 20% higher than that of S, but 12% and 10% lower when standardised respectively for body weight (BW) and fat free mass (FFM). However these differences were removed when BMR was covaried for BW or FFM, or normalised by BW0.62 or FFM0.64. Measured BMR was 7% for T and 6% for S lower than that predicted by the FAO/WHO/UNU (1985) equation; the inclusion of stature did not reduce the overestimation. The energy cost of walking was 27% higher in T than in S, but 9% and 5% lower when standardised respectively for BW and FFM. The differences disappeared when expressing the energy cost of walking as net cost per kg FFM. CONCLUSIONS: Tall people have lower BMR per unit of BW or FFM than short people, and it is necessary to control for the diverse body mass by the appropriate method. However, qualitative differences in the composition of FFM are plausible, due to the diverse proportion of metabolically active internal organs in people of different height, which might be reflected in the higher BMR/kg FFM of the shorter subjects. The sex- and age-specific FAO/WHO/UNU (1985) equation significantly overestimates the BMR of both short and tall people, but there is no simple explanation of this observation. The energy cost of walking is not affected by stature when expressed as net cost per kg FFM.

Adipose Tissue↗
PubMed1997

Biological correlates of HIV-1 heterosexual transmission.

OBJECTIVES: To study the role of HIV-1 biological phenotype, viral load and neutralizing antibodies in male-to-female heterosexual transmission of HIV-1. METHODS: Seven transmitting and seven non-transmitting HIV-1-seropositive heterosexual male index cases were included in the present study. All couples had engaged in unprotected sex for a period of over 1 year. Transmission was defined by the seroconversion of the female sexual partner. Virus isolates were tested in MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was measured by the branched DNA technique. Serum neutralizing activity to primary HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as target cells. RESULTS: Non-transmitting index cases had a lower HIV-1 RNA concentration in plasma than transmitting index cases. Non-transmitting index cases also tended to have serum neutralizing activity with broad specificity and to have viruses with low replicative capacity, as characterized by 50% infectious dose titres in PBMC and by the lack of MT-2 tropism. CONCLUSIONS: The results indicate that plasma viral-RNA load is a marker for transmission. Moreover, an interplay between the host immune response and viral replication may modulate the level of viral load and thereby influence HIV-1 transmission.

Cell Line↗
PubMed1997

Familial clustering of HBV pre-C and pre-S mutants.

BACKGROUND/AIMS: Little is known about the persistence and risk of infection with hepatitis B viruses (HBV) containing mutations in the pre-C and pre-S region. The aim of this study was to study the long-term persistence and the risk of intrafamilial spreading of these variants. METHODS: Serological markers were analyzed immunologically and pre-C and pre-S sequences of HBV DNA in sera from several members of five families by DNA amplification and direct sequencing. RESULTS: In most HBV-DNA positive individuals of each family, either the dominant HBV population or a subpopulation had a stop codon in the pre-C region which prevented expression of e-antigen. The pre-S region of the dominant virus populations of 8/15 HBV-DNA positive sera showed different deletions or a pre-S2 translation initiation codon mutation in addition to various point mutations. Selection for pre-C and pre-S mutant viruses from a predominant "wildtype" virus population was observed in three individuals during the natural course of infection. Persistence of a pre-C/pre-S double mutant virus as a stable strain for 6 years was found in one patient. CONCLUSIONS: These data indicate extensive intrafamilial clustering of HBV variants with mutations in the pre-C and pre-S regions due to patient-specific selection mechanisms and long-term persistence of some mutants as stable strains. The type of viruses found suggests that occasionally virus subpopulations are selectively transmitted or become a dominant virus population after selection.

Cluster Analysis↗
PubMed1997

Epidemiological, clinical and therapeutic evaluation of the Italian cholera epidemic in 1994.

In the period between 18 October and 4 December 1994, 12 indigenous cases of cholera were registered in the southern Italian region of Puglia, 10 of them were diagnosed in our Departments of Infectious Diseases. All patients were infected by consumption of raw fish or mussels. The patients had an elevated mean age and most were affected with systemic pathologies. The clinical course was mild and rarely complicated, although frequently the characteristic riziform diarrhoea was absent. In all patients V. cholerae serotype Ogawa biotype El Tor, was isolated; one patient was co-infected by Salmonella typhi. All strains showed resistance to cotrimoxazole and tetracycline. Nine of ten patients were treated with oral ciprofloxacin at 1 g/day for 10 days resulting in disappearance of the symptoms within a median of 36 hours and negative fecal cultures within a median of 24 hours. Our data suggest that Italy is at high risk of infection imported from nearby nations. The resistance to commonly used antibiotics for treatment of cholera and the good response to ciprofloxacin suggest including fluoroquinolones among the drugs of first choice geographical areas involved in the circulation of resistant strains of V. cholerae O1.

Adult↗
PubMed1997

Lymphogranuloma venereum: a case report in an Italian traveller.

A 38-year-old man with a recent history of travel in India and unprotected sexual intercourse with Indian women, was admitted with painful enlarged lymphnodes predominantly in the right inguinal area. Diagnosis of lymphogranuloma venereum was made by means of a positive immunofluorescence test (Total Ig titer of 1:512) and a positive detection of chlamydial antigens by ELISA in a semen sample. He was successfully treated with ciprofloxacin. This observation emphasizes the relevance of infection due to C. trachomatis serotypes L1-L3 that may be acquired during travel in developing countries.

Adult↗
PubMed1997

The use of serum-free medium delays, but does not prevent, the cytotoxic effects of seminal plasma in lymphocyte cultures: implications for studies on HIV infection.

Evidence indicates that seminal plasma is cytotoxic when used in lymphocyte cultures. In fact, an amine oxidase which is normally present in Fetal Calf Serum (FCS) causes spermine oxidation and, finally, cytotoxic substances are released. This seminal quality might obviously hamper studies aiming to evaluate the role of semen in HIV sexual transmission, since lymphocytes are generally used as target or effector cells in virological or immunological studies on HIV. We evaluated the efficacy of FCS free-medium, heat inactivated seminal plasma and/or the washing-out of cultures after a three hour incubation period in preventing the cytotoxicity to lymphocytes. Results show that when cultures are carried out in the absence of FCS and/or after seminal plasma removal, cytotoxicity is not prevented, although delayed. This finding indicates that, along with still unrecognized additional factors, spermine oxidation is still an important factor for semen cytotoxicity, and this considerably hampers any immunological and virological study, requiring the use of lymphocytes, concerning seminal fluid.

Animals↗
PubMed1996

A randomized trial (ISS 901) of switching to didanosine versus continued zidovudine after the diagnosis of AIDS.

Although the efficacy of switching from zidovudine (AZT) to didanosine (ddI) has already been evaluated in controlled studies, prior investigations were not specifically designed to evaluate this issue in patients with acquired immune deficiency syndrome (AIDS). This open, randomized, multicenter study (ISS 901) was designed to evaluate the clinical benefit in patients with AIDS of switching to ddI after 6-18 months of AZT and no major intolerance. Patients were randomized to continue AZT, maintaining the current dosage at randomization (n = 79), or to receive ddI (n = 80) at the dosage of 375 mg and 250 mg b.i.d. for body weight > 60 and < or = 60 kg, respectively. Primary efficacy measures were survival and time to new AIDS-defining events, analyzed by the intent-to-treat approach. The two groups were comparable for baseline characteristics, follow-up (15 months), and time spent on allocated treatment. At the end of the study, 104 patients (48 AZT, 56 ddI) had died and 90 had at least one new AIDS-defining event (44 AZT, 46 ddI). Kaplan-Meier estimates of survival and of time to first new AIDS-defining event showed no differences between the treatment groups. No differences were detected in other efficacy measurements (p24 antigenemia, CD4+ count, Karnofsky score, and body weight), occurrence of severe toxicities, and treatment modifications. Pancreatitis occurred only in ddI-treated patients (6%). In our population of patients with advanced disease, switching from AZT to ddI did not produce apparent benefits, suggesting that application of this strategy earlier in the course of human immunodeficiency virus disease should be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Incidence of second primary malignancies after a malignant tumor in childhood: a population-based survey in Piedmont (Italy).

We have studied the frequency of second primary malignancies (SPM) among the 2,328 children registered in 1967-1969 at the Childhood Cancer Registry of Piedmont, the largest population-based childhood cancer registry in Southern Europe. Since the population of Piedmont is not served by a conventional cancer registry covering all ages, SPMs were identified through a number of ad hoc surveys within a variety of sources. Eighteen SPM (all histologically diagnosed) were observed after a thorough survey conducted in the ontological departments in Piedmont and after a postal questionnaire addressed to general practitioners. Death certificates were also examined. The crude incidence rate was 116.5 per 100,000 person-years. Risk was higher among children whose first malignancy was diagnosed more recently (SIR = 9.8 for diagnoses in 1983-1989 vs. 4.5 for diagnoses in 1967-1974). The same tendency was confirmed in analyses restricted to children in whom leukemia was diagnosed as the first cancer. Clinical data regarding the treatment of the first malignancy were available for 16 children out of 18: 15 had received chemotherapy and 12 radiotherapy (9 SPM originated in the irradiation field). The interest of measuring the risk of SPM on a population basis (and not only in clinical series) and the advantage of close cooperation between epidemiologists and clinical oncologists are underlined.

Adolescent↗
PubMed1996

Polymerase chain reaction for non-invasive diagnosis of brain mass lesions caused by Mycobacterium tuberculosis: report of five cases in human immunodeficiency virus-positive subjects.

To investigate whether the polymerase chain reaction (PCR) on the IS6110 sequence of Mycobacterium tuberculosis could permit the early and non-invasive diagnosis of tuberculous brain lesions without meningeal involvement in acquired immunodeficiency virus patients, we examined retrospective cerebrospinal fluid (CSF) samples from five patients diagnosed as having cerebral lesions caused by M. tuberculosis. M. tuberculosis deoxyribonucleic acid was detected in CSF samples obtained from each of the patients studied, but in none of the controls. The PCR results coincided with M. tuberculosis isolation from CSF in two patients. In an additional two subjects, culture for M. tuberculosis on CSF was negative, and the diagnosis of central nervous system tuberculosis was achieved by response to specific therapy. In the last patient the PCR result on CSF was confirmed by isolation of M. tuberculosis from brain biopsy. Interestingly, in this patient the CSF did not yield M. tuberculosis isolation when cultured. The data show the value of PCR as a potentially useful approach for the early and rapid diagnosis of cerebral tuberculosis even without meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-alpha2 therapy.

A number of trials have demonstrated that IFN-alpha is effective in chronic hepatitis C virus infection. It is known, however, that a number of chronic hepatitis C patients experience, after an initial response to IFN, disease reactivation or relapse (also called 'breakthrough') while IFN therapy is still ongoing. Since in a number of clinical conditions a significant correlation between development of antibodies to IFN and failure of therapy has been established, we addressed the possibility that the development of antibodies to IFN may take part in the relapse occurring in hepatitis C patients during recombinant IFN-alpha (rIFN-alpha) therapy. The prevalence of neutralizing (NA) and binding antibodies (BA) to rIFN-alpha2 has been evaluated in 45 patients with chronic hepatitis C treated with rIFN-alpha2a who first normalized aminotransferase (ALT) levels, and subsequently showed disease reactivation while on treatment. The presence of NA and BA was tested before therapy, during the response to IFN treatment, and at the time when ALT started to rise again to abnormal levels. The results showed that no patients had detectable antibodies to IFN before therapy and during the period of response to the therapy, while most of them (88.9%) developed NA and/or BA to IFN-alpha2 concomitantly with disease reactivation. In particular, in 29 of the 45 patients (64.4%) ALT normalized on treatment and rose to abnormal levels when NA appeared in their serum, while in 11 of the 16 (68.8%) remaining patients the relapse was associated with BA development. The frequency of seroconversion in these patients is significantly higher than that observed in the control group. These data indicate that antibodies to IFN may be responsible for breakthrough in the majority of patients showing disease reactivation while rIFN-alpha therapy is still ongoing.

Adolescent↗
PubMed1996

[Implementation of the pediatric services in the region of Piedmont. A Piedmont pediatric team].

A survey was carried out within the framework of the Association of Hospital Pediatricians (APO) on the implementation of the pediatric structure in Pediatric hospitals wards in Piedmont during 1990. There was a 100% adhesion rate. It was found that only in 7 out of 36 hospitals were children always admitted to the Pediatric Division irrespective of symptoms. In all remaining cases, hospitalisation was based on the pathology and therefore children were spread between pediatric and adult wards with a percentage of over 30% (it was only possible to verify this figure in a small number of hospitals). Children with surgical symptoms were admitted to adult wards for the entire duration of their hospital stay in 17 hospitals. Only in 7 hospitals were children with surgical problems given pre- and postoperative treatment in pediatric wards. In 18 out of 36 hospitals children undergoing surgery were not even examined before the operation by a pediatrician. The implementation of the pediatric structure mainly depended on the behaviour of the PS DEA and therefore the fact that when a child entered hospital he immediately came into contact with the pediatrician. It was also found that average hospital stay in pediatric wards was 4.4 days (range 2.1-7.4); the mean index of bed occupation was 50% (range 27.5-83.4). A pediatric doctor was on duty round the clock only in 10 out of 36 centres. In the majority of hospitals the number of beds destined for day-hospital activities was not specified. It is also worth pointing out that the number of neonatal cradles is never specified by the Regional Health Plan and there is no legal recognition of neonates admitted to the Nursery and, as a result, the number of neonatal medical staff is not quantified. A greater incisiveness of the current statutory requirements for the implementation of the pediatric structure might improve the level of assistance for children admitted to hospital.

Health Services↗
PubMed1995

Detection of HCV RNA in serum and seminal fluid from HIV-1 co-infected intravenous drug addicts.

The presence of hepatitis C virus (HCV) RNA in serum and seminal fluid was investigated in eleven drug addicts coinfected with HIV-1 and HCV. Serum and seminal fluid were taken from each patient at the same time point. HCV RNA was found in ten of the eleven serum samples tested, but only in one of the semen samples. No relationship was observed between CD4 cell counts, the stage of HIV infection, extent of liver damage and the presence of HCV RNA in serum and semen. The results indicate that HCV is not usually present in the semen and provide further evidence against sexual transmission as an important mode of transmission of HCV infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology-Oncology (AIEOP).

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy.

Adolescent↗
PubMed1995

Efficacy of itraconazole in treating AIDS-associated infections due to Candida krusei.

Candida krusei is an emerging pathogen, both in HIV negative immunocompromised patients and in HIV seropositive patients. Its onset appears to be due, at least in part, to the use of fluconazole. In HIV positive patients, a long term prophylactic use of fluconazole may select some less pathogenic Candida species, as C. krusei, that may determine persistent oral candidiasis and emerge as systemic pathogen. Itraconazole appears efficacious in treating AIDS-associated C. krusei infections.

AIDS-Related Opportunistic Infections↗