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Biomedical subjects

A Gringeri

Publications and source records attributed to A Gringeri.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inhibitor development and substitution therapy in a developing country: Turkey.

Prevalence of inhibitor in developing countries, such as Turkey, where fresh frozen plasma (FFP) is still in use due to high cost of concentrates, is unknown. To determine the frequency of inhibitors in Turkish haemophiliacs exposed to blood products, 53 haemophilia A patients (age range 1-20; median: 11 years) and 12 haemophilia B patients (age range 3-20; median: 10 years), were evaluated; 31 haemophilia A patients (23 severe) received plasma-derived concentrates and 22 patients (10 severe) only FFP. No haemophilia B patients developed inhibitor, compared with seven of 53 (13%) haemophilia A patients, all with a severe defect (7/33; 21%) and treated with concentrates (7/23; 30%), whereas severe patients treated with FFP showed a lower risk to develop inhibitors (0/10, P = 0.07). Inhibitors were detected after 8-125 exposure days (median: 52). Intermediate-purity concentrates and pasteurization seemed to be linked with a higher risk of inhibitor compared to high-purity concentrates and solvent-detergent inactivation for seven patients with inhibitor. In four of seven inhibitor patients low-dose concentrate was administered at 25 IU kg-1 twice weekly and inhibitor disappeared in 1-4 months. This regimen might be recommended for immune tolerance in developing countries for its lower cost.

Adolescent↗
PubMed1997

A multicenter controlled, randomized, open trial of interferon alpha2b treatment of anti-human immunodeficiency virus-negative hemophilic patients with chronic hepatitis C. Hepatitis Study Group of the Association of Italian Hemophilia Centers.

There is limited information about the long-term efficacy of prolonged therapy (more than 6 months) with interferon alpha in hemophilic patients with chronic hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1). One hundred and seven hemophiliacs were randomly assigned to 3 million U of interferon alpha2b three times weekly for 12 months or no therapy. The patients were followed up for at least 12 months posttreatment. Response was assessed by both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before treatment, serum levels of HCV-RNA were measured quantitatively by second-generation branched-DNA assay and the HCV genotype was determined by RT-PCR. Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was cleared in 6 of 45 treated patients, compared with none of the 50 untreated controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that was associated with an increased likelihood of sustained response (P < .01). This study shows that multitransfused hemophiliacs with chronic hepatitis C not coinfected with HIV-1 respond at low rates to prolonged interferon therapy.

Adolescent↗
PubMed1997

Hemophilia and nonprogressing human immunodeficiency virus type 1 infection.

Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.

Adolescent↗
PubMed1997

Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization.

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS: Twenty-six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period. RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.

Adolescent↗
PubMed1997

Augmented serum neutralizing activity against primary human immunodeficiency virus type 1 (HIV-1) isolates in two groups of HIV-1-infected long-term nonprogressors.

Neutralizing activity against primary human immunodeficiency virus type 1 (HIV-1) isolates from 17 persons who were long-term disease nonprogressors (LTNPs) and 13 persons who were fast progressors (FPs) was compared. Sera from LTNPs showed higher neutralizing activity both in titer and in host spectrum than did sera from FPs. However, LTNP sera had limited neutralizing activity against HIV-1 subtypes from different geographic areas. Sera collected 6 years earlier from both groups had limited neutralizing activity, indicating that early responses are not predictive for disease progression. LTNPs had very low virus loads, as reflected by only one positive isolation, which was an MT-2-negative phenotype. Virus was isolated from all FPs, and the isolates showed a phenotype switch from MT-2 negative to MT-2 positive. Development of high-titer, broadly cross-reactive neutralizing antibodies is associated with control of virus replication and low virus load in HIV-1-infected LTNPs.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Absence of clinical, virological, and immunological signs of progression in HIV-1-infected patients receiving active anti-interferon-alpha immunization: a 30-month follow-up report.

Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-alpha (IFN-alpha) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-alpha overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-alpha levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-alpha immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 micrograms formalin-inactivated recombinant IFN-alpha-2b (iIFN-alpha) followed by intramuscular injections of 250 micrograms iIFN-alpha adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-alpha-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-alpha titers, while nonprogression of IFN-alpha-immunized patients was associated with decreased levels of circulating IFN-alpha.

Adolescent↗
PubMed1995

Biological effect of active anti-IFN alpha immunization in HIV-infected patients.

Circulating interferon (IFN) was investigated in HIV-1 seropositive patients by measuring the IFN alpha antiviral effect in the serum. While serum of healthy seronegative individuals exhibits an antiviral effect, not due to IFNs, considered as background, serum of seropositive patients showed an additional antiviral effect due to the abnormal presence of IFN alpha. Increased titers of IFN alpha were found in the course of the HIV infection and seemed to correlate with the evolution of AIDS disease. Furthermore, patients immunized against IFN alpha had both stabilized CD4 cell count and decreased IFN alpha in their serum. HIV-1-infected patients also exhibited higher titers of natural anti-IFN antibodies than seronegative controls and the level of specific antibodies (Abs) markedly increased in immunized patients. Finally, serum from immunized patients, when compared to seronegative controls, exhibits an interferon neutralizing capacity.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Factors associated with progression to AIDS and mortality in a cohort of HIV-infected patients with hemophilia followed up since seroconversion.

Progression to AIDS and death were evaluated in 112 patients, 84 with hemophilia A and 28 with hemophilia B. Seroconversion period and age at seroconversion were similar in both groups. 36/112 patients died: 21/84 with hemophilia A (25%) and 15/28 (54%) with hemophilia B. Mean survival time was 11.7 years. The 10-year cumulative survival was 75.8%. It was lower in hemophilia B (56.2%) compared to hemophilia A patients (82.4%; p = 0.002). 37 patients (33%) developed full-blown AIDS: 26 with hemophilia A (31%) and 11 with hemophilia B (39%). Mean AIDS-free survival time was 11.4 years. The 10-year cumulative AIDS-free survival was 71.2%. It was 74.8% in hemophilia A and 60.3% in hemophilia B patients. CD4 counts lower than 200/cmm occurred in 62 patients (56%): 45 with hemophilia A (54%) and 17 with hemophilia B (63%). The mean time to CD4 counts lower than 200 was 9.4 years. Mean survival time in older seroconverters (35 year old or more) was shorter than in younger (9.5 vs. 11.7 years, p < 0.05). Mean CD4 cell counts at seroconversion were similar in hemophilia A and B patients and in different age classes at seroconversion. CD4 cell counts at seroconversion affected the survival: 90% seroconverters with CD4 cell counts of 800/cmm or more were alive at 10 years vs. 60% of seroconverters with CD4 cell counts lower than 800 (p < 0.05).

Acquired Immunodeficiency Syndrome↗
PubMed1995

Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Evidence for an antiviral effect and interferon neutralizing capacity in human sera; variability and implications for HIV infection.

The antiviral effect (AVE) and interferon neutralizing capacity (INC) of sera originating from either seronegative or HIV-infected individuals were determined. As a rule, sera from seropositive subjects exhibited higher AVE titers than sera from seronegative individuals. Similarly, the INC of sera from HIV-infected patients, was most often stronger than that of sera from seronegative individuals. Furthermore, sera from HIV-infected patients actively immunized with i-IFN alpha invariably expressed INC in response to treatment, which was not the case for sera from control unimmunized patients. All sera from HIV-infected patients were found by ELISA to contain antibodies specifically directed to IFN alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Inhibitors to factor VIII in a family with mild hemophilia: molecular characterization and response to factor VIII and desmopressin.

Inhibitor development in patients with mild hemophilia is a rare event. We report the occurrence of a persistent, high-responding inhibitor in two affected members of a mild hemophilia A family and discuss the therapeutic approaches employed in these patients in terms of their efficacy and effect on antibody titer. Desmopressin was an effective option for bleeding management, because endogenous factor VIII released by DDAVP was less immunogenic than exogenous factor VIII replacement, which invariably triggered anamnestic responses. Genetic analysis performed to investigate whether or not a peculiar molecular lesion accounted for this particular phenotype identified a G-A transversion at nucleotide 6507 in exon 23. This missense mutation has been already described in mild hemophilia A, but not in patients with inhibitors.

Adult↗
PubMed1994

Transmission of hepatitis A to patients with hemophilia by factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. The Italian Collaborative Group.

OBJECTIVE: To determine whether an outbreak of hepatitis A virus (HAV) infection that occurred in 52 patients with hemophilia in Italy was acquired through infusion of contaminated factor VIII or through environmental enteric transmission. DESIGN: A case-control study and a molecular analysis of HAV sequences from implicated lots of factor VIII and from infected patients. PATIENTS: The first 29 patients with hemophilia and jaundice in whom hepatitis A developed were compared with one to three matched controls with hemophilia but no jaundice. MEASUREMENTS: Type of concentrate and batches infused, number of doses, contacts with persons who had jaundice or hepatitis A, travel abroad to countries reported to have a high attack rate for hepatitis A, and consumption of raw shellfish. Hepatitis A viral sequences sought by polymerase chain reaction in lots of factor VIII and in serial serum samples from two patients with hemophilia in whom hepatitis A developed. Amplification by polymerase chain reaction of cDNA transcribed with reverse transcriptase from matched sets of factor VIII and recipient serum samples. Determination of nucleotide sequence of amplified hepatitis A virus genome. MAIN RESULTS: Case patients were neither more nor less likely than controls to have traveled to high-risk countries, consumed raw shellfish, or had contact with persons with jaundice. Case patients were more likely than controls to have received a factor VIII concentrate treated with a solvent-detergent mixture to inactivate viruses (odds ratio, infinity; 95% CI, 4.5 to infinity) and to have had larger infusions of the concentrate during the presumed HAV incubation period (odds ratio, 8.54; CI, 2.78 to 27.5). Hepatitis A viral sequences were found in 5 of 12 tested lots of factor VIII. Genomic sequences of HAV obtained for two matched sets of factor VIII and recipient serum samples were identical within each set but different for the two sets. CONCLUSION: Hepatitis A was transmitted by a factor VIII concentrate treated by a virucidal method (solvent-detergent) that ineffectively inactivates nonenveloped viruses.

Adolescent↗
PubMed1994

Beriate-P study.

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CD4-Positive T-Lymphocytes↗
PubMed1994

Prevalence of pancreatic disorders in HIV-infected hemophiliacs: diagnostic methods and their clinical significance.

Pancreatic damage has been well described in HIV+ patients and can occur both for therapy and opportunistic infections, but its prevalence is not clear. The aim of our study was to evaluate the prevalence of pancreatic damage in a cohort of HIV+ hemophiliacs together with the clinical and prognostic value of the diagnostic methods commonly used. We studied 75 HIV+ patients and 26 HIV- as a control group: they were evaluated by biochemical tests, indirect pancreatic functional tests, abdominal ultrasound (US) and computed tomography (CT). No differences were observed between HIV+ and HIV- in elevation of pancreatic enzymes. Eleven patients had slight CT alterations and none had abnormal US. In HIV+ there was no relationship between enzyme elevation and CDC group, CD4+ cell count or therapy. In conclusion, pancreatic disorders have a very low prevalence in HIV+ hemophiliacs and biochemical alterations we found had a doubtful clinical significance. Lipase and isoamylase are the more reliable tests and lipase, being the cheapest and easiest to perform, has to be considered as the first test of choice for monitoring pancreatic damage in HIV+ patients.

Adolescent↗
PubMed1994

Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. European-Australian Haemophilia Collaborative Study Group.

In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.

Acquired Immunodeficiency Syndrome↗