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Biomedical subjects

G Pastore

Publications and source records attributed to G Pastore.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hematopoietic stem cell transplantation in childhood: report from the bone marrow transplantation group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND AND OBJECTIVE: Transplantation of hematopoietic stem cells from different sources is being increasingly used to treat a variety of diseases in children. Transplant procedures and indications have changed considerably during recent years. Monitoring of information about these changes is useful for interpretation of nationwide collected data. DESIGN AND METHODS: Since 1985, Centers belonging to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica), performing hematopoietic stem cell transplants (HSCT) in children, and members of the AIEOP-Bone Marrow Transplant (BMT) Group annually report data on their transplant activity to the AIEOP-BMT Registry employing specially prepared patient-oriented forms. RESULTS: From January 1985 to December 1998, a total of 2,474 bone marrow (BM), peripheral blood (PB) or umbilical cord blood (CB) transplants were reported: 1,296 (52%) were allogeneic (Allo) and 1,178 (48%) autologous (Auto) transplants. These transplants were performed in 19 Italian Centers on 2,249 patients aged less than 17 years. Among Allo-transplants, 1,198 (92%) were performed using BM progenitor cells, whereas 49 (4%) CB, 42 (3%) were PB, 4 BM plus PB, and 3 BM plus CB allografts; they were performed using HLA-identical sibling donors in 867 cases (67%) and alternative donors (i.e. partially-matched relatives or unrelated donors) in the remaining 429 (33%) cases. Allogeneic transplants were performed on 786 (67%) patients with malignancy and on 395 (33%) patients with non-malignant disorders. In the last 6 years, the number of Allo-transplants per year exceeded that of Auto-transplants. Of the Auto-transplants, 775 (66%) were performed using BM, and 403 (34%) using PB alone or combined with BM hematopoietic stem cells. Indications for Auto-BMT were myelo-lymphoproliferative disorders in 524 (49%) cases, solid tumor in 533 (50%) cases and non-malignant disease in 11 (1%) cases. In the last 5 years, the use of PB for autografts has increased from 7% to 70%. INTERPRETATION AND CONCLUSIONS: These data reflect the development and present status of HSCT in Italy and provide a basis for patient counseling and health care planning.

Adolescent↗
PubMed2000

Frequent detection of HIV-1 RNA but low rates of HIV-1 isolation in cervicovaginal secretions from infected women.

Information regarding the presence of HIV-1 in the female genital tract is necessary to gain insight into the mechanism of HIV-1 heterosexual transmission. Herein, we present the results of a study on virus isolation and HIV-1 RNA detection from cervicovaginal lavage (CVL) samples from 25 HIV-1 seropositive women. Despite detectable levels of HIV-1 RNA in 88% of CVL samples, HIV-1 was isolated in only four (19%) samples. Although HIV-1 shedding in cervicovaginal secretions is a common event at all disease stages, the recovery of infectious virus in cell cultures appears to be rare; this renders viral isolation in studies aimed to evaluate the infectivity of cervicovaginal secretions relatively useless.

Cervix Uteri↗
PubMed2000

Limited secretory-IgA response in cervicovaginal secretions from HIV-1 infected, but not high risk seronegative women: lack of correlation to genital viral shedding.

The presence and antigen specificity of IgG and secretory-IgA (s-IgA) to HIV-1 were evaluated in cervicovaginal lavages (CVL) from 26 infected and 10 high-risk seronegative women. All the seropositive women had detectable IgG recognizing several viral antigens, while a smaller percentage of women demonstrated s-IgA to the virus. In addition, s-IgA were of limited specificity and provided weak reactivities on Immunoblot bands; an almost constant absence of s-IgA to gp120 was also observed. Neither the presence nor the specificity of either IgG or s-IgA to the virus in CVL prevented the shedding of HIV-1 in this body fluid; in fact, viral RNA was detected in all the women studied and the amounts of viral shedding was unrelated to the genital antibody response. On the other hand, none of the high-risk seronegative women had detectable antibodies to HIV-1 in CVL of either the IgG or s-IgA isotype. Our results a) confirm an impairment of mucosal antibody response during HIV-1 infection and suggest that mucosal immunity is not able to prevent viral shedding in the female genital tract and thus cannot modulate the infectivity of genital secretions; aa) do not provide evidence for a mucosal "memory/protective" antibody response in the genital tract of high-risk seronegative women.

Cervix Uteri↗
PubMed1999

Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group.

This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P <.001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (>/=2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B.

Adolescent↗
PubMed1999

Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis.

BACKGROUND & AIMS: The aim of this study was to compare interferon (IFN)-ribavirin combination therapy with IFN monotherapy in chronic hepatitis C with particular focus on its efficacy in cirrhosis. METHODS: A multivariate analysis of individual patient data of all randomized controlled trials using an IFN-ribavirin arm, reported between 1991 and March 1998, was performed. Centers included 1 Asian and 5 European university-based referral centers for liver disease. A total of 197 patients with chronic hepatitis C received IFN-alpha (3 MU three times weekly) and ribavirin (1-1.2 g daily) for 6 months, and 147 patients received IFN-alpha (3 MU three times weekly) for 6 months. Patients were characterized according to previous IFN therapy, presence of cirrhosis, and genotype 1. Efficacy of therapy was evaluated by assessing the sustained response rate by logistic regression analysis. RESULTS: Patients without cirrhosis treated with IFN-ribavirin had a significantly higher sustained response rate than those treated with IFN, approximately 3-fold for previously untreated patients (IFN-ribavirin: genotype 1, 33%; genotype 2/3, 65%; IFN: genotype 1, 8%; genotype 2/3, 24%). In cirrhosis, sustained response rates with IFN-ribavirin (previously untreated: genotype 1, 7%; genotype 2/3, 24%) were also significantly higher than those with IFN (previously untreated: genotype 1, 1%; genotype 2/3, 5%). Clinical relevant superiority of combination therapy over IFN monotherapy was also observed for relapse; the same trend was observed for nonresponders. Tolerance for IFN-ribavirin was similar for patients with or without cirrhosis. CONCLUSIONS: Combination with ribavirin significantly enhances the sustained response rate of IFN therapy in major patient types (cirrhosis, genotype 1) with chronic hepatitis C. Thus, IFN-ribavirin combination is likely to become the antiviral therapy of choice for cirrhosis caused by hepatitis C.

Adult↗
PubMed1999

Long term response to therapy of chronic anti-HBe-positive hepatitis B is poor independent of type and schedule of interferon.

OBJECTIVE: The response rate to alpha interferon (IFN) of chronic anti-HBe-positive hepatitis B is variable. We studied whether type, dose, and schedule of IFN, and type and frequency of posttreatment monitoring, influence the response rate. METHODS: Seventy-two consecutive anti-HBe-positive chronic hepatitis B patients (59 male and 13 female, median age 41 yr) stratified by sex and histology were randomly allocated to three treatment arms. Twenty-seven patients (A) received 10 million units alpha-N1 IFN i.m. t.w. for 24 wk (total dose: 720 million units); 21 (B) received 9 million units alpha-2a IFN i.m. t.w. for 4 wk, followed by 18 million units for 12 wk and 9 million units for 8 wk (972 million units); 24 (C) received 2 alpha-2a IFN courses (9 million units i.m. t.w. for 16 and 12 wk separated by a 6-month interval [756 million units]). Primary response was defined by normal ALT and serum HBV-DNA levels below 10 pg/ml at the end of therapy and sustained response by normal ALT (tested monthly), undetectable HBV-DNA and IgM anti-HBc (<7 I.U. Paul Ehrlich Institute) (tested every 3 months) during the posttreatment follow-up. RESULTS: At the end of treatment, 12, 8, and 13 patients from groups A, B, and C, respectively, were responders. At the 18-month follow-up, two patients in group A and only one in groups B and C maintained the response. Overall, after 34 months (median posttreatment follow-up), three patients were long term responders, whereas three showed a sustained remission after relapse. CONCLUSIONS: The rate of long term response to interferon of anti-HBe-positive chronic hepatitis B is poor, independent of IFN type, dose, or schedule; the more stringent the monitoring, the higher the relapse rate.

Adult↗
PubMed1999

Reproductive choice in individuals HIV-1 infected in south eastern Italy.

OBJECTIVE: To evaluate the impact of counseling on reproductive choices in seropositive women in South-Eastern Italy. SETTING: University Hospital, Apulia region, South-Eastern Italy, tertiary referral center for high risk obstetrics and infectious diseases. METHODS: Between March 1985 and December 1996, two hundred and twenty-five HIV-infected women, receiving treatment at our clinic for infectious diseases were enrolled. They were all regularly given treatment and counseling and their sexual partners, if negative, tested for HIV-1 antibodies. Their reproductive choices and their attitude toward pregnancy were recorded and analyzed. RESULTS: Seventy-six pregnancies were observed during this period in 76 women. Twenty-one of these women (27.7%) decided to terminate the pregnancy. Women that were intravenous drug users or with a longer history of known seropositivity were more likely to have a termination. A decreasing trend in the request of abortion was observed with time. CONCLUSIONS: The data show that the scenario of HIV-infected women is changing in our setting. As a consequence, many seropositive women deliberately choose to have a pregnancy and factors different from those we expect to be modified by the counseling influence their reproductive choice. They should be taken into account in the management of these women before and during pregnancy.

Abortion, Induced↗
PubMed1999

Retreatment of non-responder or relapser chronic hepatitis C patients with interferon plus ribavirin vs interferon alone.

BACKGROUND AND AIM: Interferon-alpha treatment of chronic hepatitis C is beneficial in only 20-30% of patients. This study evaluates if combination therapy with Interferon-alfa plus ribavirin is effective in inducing a response in patients who did not respond to, or relapsed after, a standard Interferon-alfa treatment. PATIENTS AND METHODS: A total of 88 patients, 49 non-responders and 39 relapsers to previous Interferon-alfa therapy, were randomized to receive either natural Interferon-alfa (6 MU t.i.w.) plus ribavirin (1000 mg/daily) or natural Interferon-alfa alone (6 MU t.i.w.) for 6 months. All were followed for 12 months after stopping therapy. Serum aminotransferase levels were assessed monthly and HCV RNA was evaluated by RT-PCR (Amplicor, Roche) at end of therapy and the end of follow-up. RESULTS: After treatment, a higher response rate defined as return to normal of aminotransferases and absence of serum HCV RNA was observed among patients treated with Interferon-alfa-ribavirin: 4/28 (14%) vs 1/21 (5%) non-responder patients and 9/19 (47%) vs 5/20 (25%) in the relapsers group. At the end of follow-up, a sustained response was found only in the combination treatment group: 4% and 32% in non-responder and relapser patients, respectively. CONCLUSIONS: Our results suggest that retreatment with natural Interferon-alfa plus ribavirin is more effective than Interferon-alfa alone in increasing the response rate in patients with chronic hepatitis C who relapse after a previous standard IFN treatment whereas it is less effective in non-responder patients.

Adult↗
PubMed1999

[Critical review of 215 cases of non-palpable mammary lesions].

PURPOSE: The natural history of human breast cancer shows that lesion size correlates directly with nodal metastases and distant spread. Nodal metastases are found in only 6% of cases in the preclinical stage of the tumor and therefore imaging must detect a breast cancer before it becomes palpable. We reviewed 215 nonpalpable breast lesions studied in the last 10 years to assess observers performance and ultimately improve the interpretation of suspicious mammograms, evaluating "cost" in terms of the ratio between benign and malignant lesions (B/M). MATERIAL AND METHODS: From 1988 to October 1998, two hundred and fifteen women with nonpalpable breast lesions suspected at mammography were examined. The lesions were removed after stereotaxic or US location and a radiograph of the surgical specimen was always performed. Mammographic patterns were interpreted retrospectively by two blinded radiologist experienced in breast imaging and specialized in locating nonpalpable breast lesions. Mammographic patterns were classified as poorly/highly suspicious calcifications, regular/irregular masses, spiculated masses, masses with calcifications and parenchymal distortions. Radiographic findings were compared with surgical results and the data used to calculate the B/M, positive predictive value (PPV) for malignancy and the trend of operator's performance. RESULTS: Modern techniques permit to detect a very high number of in situ breast carcinomas. Nineteen of 22 lesions (86%) were detected by mammography as highly suspicious calcifications, 2/22 as spiculated masses and 1/22 as a mass with calcifications. No in situ carcinoma was detected as an irregular mass. All regular masses were proven to be benign at histology. B/M analysis showed a decreasing trend (from 1.94 in the first 3 years to .57 in 1994-96, to .83 in 1997-98) and an overall value of .90. The PPV for malignancy was 83.33% for spiculated masses, 65.5% for highly suspicious calcifications, 63.63% for irregular masses, 47.05% for masses with more or less dysmorphic calcifications, 32.65% for poorly suspicious calcifications, 8.33% for parenchymal distortions and 0% for regular masses. DISCUSSION AND CONCLUSIONS: All spiculated masses and highly suspicious calcifications and microcalcifications should be removed. Biopsy is recommended in parenchymal distortions, despite its low predictive value for malignancy, because these lesions are uncommon and the cost of biopsy is therefore acceptable. Needle aspiration or long-term monitoring can be reconsidered for irregular masses and poorly suspicious microcalcifications. Finally, relative to possible different interpretations of mammographic patterns by center and operator's experience, we suggest that the PPV for every single pattern be continually reassessed based on personal case records rather than on literature data. This holds true especially for microcalcifications.

Adult↗
PubMed1999

Phenotypic patterns of HIV-1 clonal populations during highly active antiretroviral therapy (HAART).

Several studies have demonstrated that during HIV-1 infection many different viral clones may co-exist in the same individual. These clones may differ regarding their biological phenotype and may influence both the natural history of infection and the clinical response to antiretroviral therapy. The aim of the present study was to investigate the influences of combination therapies including protease inhibitors (HAART) on the phenotypical pattern of HIV-1 biological clones in peripheral blood mononuclear cells. Viral isolation and biological characterisation of bulk isolates and clonal viral isolates were performed on two AIDS patients, before and after three months of antiretroviral therapy. A decrease of viral load in plasma specimens in association with a change of clonal composition during antiretroviral therapy was observed in both patients during treatment. Before therapy both of the patients had a syncytium inducing (SI) bulk isolate and the majority of the biological clones were characterised as SI. After treatment, the bulk isolates were still SI in both cases, but the majority of biological clones were characterised as non-syncytium inducing (NSI). These results suggest that HIV clonal composition and relative phenotypic pattern undergo different changes not only during the natural course of HIV infection but also while patients are on antiretroviral combination therapy.

Anti-HIV Agents↗
PubMed1998

Neurological disorders during HIV-1 infection correlate with viral load in cerebrospinal fluid but not with virus phenotype.

OBJECTIVES: To verify the compartmentalization of HIV-1 within the central nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence and type of neurological disorders. METHODS: A total of 33 HIV-1-infected patients with and without neurological disorders were included in the study. HIV-1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples was attempted by a standard cocultivation technique; the biological phenotype of HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels were measured by a quantitative reverse transcripase-polymerase chain reaction. RESULTS: The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and 85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related disorders and was often associated with high levels of HIV-1 RNA in the CSF. DISCUSSION: Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.

CD4 Lymphocyte Count↗