Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

435 hemophiliacs are usually being attended in the La Paz hemophilia Center (Madrid, Spain). 257 (59%) of these patients have been infected by the human immunodeficiency virus (HIV-1) because of human plasma derivate substitution therapy. The infection has been more frequent among the severely affected patients and among the most treated patients. 82% of the infected patients are between 14 and 40 years old. By December 1991, 95 (37%) of 257 seropositive patients have developed full-blown AIDS. The most frequent opportunistic infection they had suffered was esophageal candidiasis. Looking for an evolution marker, we can point that the patients older than 35 years with CD4 levels below 200/mm3 had the worst prognosis. There was no difference in the evolution among the patients aged below 17 and those aged between 17 and 35 years. The amount of concentrate used between 1980 and 1984 did not hold any relation to the evolution. 49 patients (51%) of the 95 suffering from AIDS had died by December 1991. The evolution to the death was unrelated to the patient age, CD4 lymphocyte levels, and amount of substitution therapy. In our opinion, the most valuable marker could be the kind of opportunistic infection or tumor the patient suffers from. Finally, Retrovir has demonstrated to be useful in increasing the survival rate of the patients, but after 36 months of treatment, only 33% of those AIDS patients who began taking it remained alive. Retrovir was also used in asymptomatic patients, and during an average period of time of 15 months, a lesser bone marrow toxicity and a stabilization in CD4 lymphocyte levels could be observed, but this was unable to modify the disease progression in those patients who presented circulating p24 antigen.
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PMID:AIDS and hemophilia: experience in the La Paz Hemophilia Center. 136 77

Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody-mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection.
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PMID:Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children. 190 19

Heat-treated factor VIII has been implicated in the transmission of HIV to hemophiliacs. Previously, evidence has been limited to documenting cases of seroconversion following administration of heat-treated factor VIII. Here, we present evidence of active HIV infection, i.e., infected and not merely sensitized following factor VIII injections. Six Canadians with hemophilia had seroconverted during a longitudinal study of their HIV immune status. Two of the three patients tested by this method demonstrated HIV gag-specific sequences upon amplification by polymerase chain reaction. In addition, HIV-1 virus was isolated from peripheral blood lymphocytes of one of these two persons as shown by reverse transcriptase activity of culture supernatants as well as neutralizable p24 antigen. This, we believe, is the first evidence of active HIV infection following administration of 60 degrees C, 30 h heat-treated factor VIII.
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PMID:Laboratory evidence of active HIV-1 infection in Canadians with hemophilia associated with administration of heat-treated factor VIII. 210 24

We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.
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PMID:A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. 232 15

We have demonstrated that a sensitive, nonisotopic in situ hybridization (ISH) assay can be used to detect HIV-infected cells from seropositive, asymptomatic individuals. Our assay is based on the detection of a biotinated HIV DNA probe hybridized to human immunodeficiency virus (HIV)-infected peripheral blood lymphocytes (PBL) using streptavidin and alkaline phosphatase to identify positive cells. This assay is rapid in that it can be performed within a day and is sensitive enough to unambiguously identify a rare, single, positive cell. Patient samples derived from HIV-seropositive hemophiliacs and HIV-seropositive infants were analyzed before and after coculture with normal PBL. The same samples were investigated using a Dupont P24 antigen-capture kit. It was found that ISH always detected the same positive samples as antigen capture, often in shorter times of coculture. In situ hybridization detected over half of our HIV-infected hemophilia patient population as virus positive, whereas the antigen capture assay detected less than one fourth as virus positive. In situ hybridization detected positive cells directly, without coculture, in 12 out of 35 (34%) hemophiliacs and in three out of eight (37%) infants. The speed, sensitivity, and confidence of ISH and nonisotopic detection indicates that it will be useful as a tool for clinical research and diagnosis.
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PMID:Detection of HIV-1-infected cells from patients using nonisotopic in situ hybridization. 280 64

As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophilia, peripheral blood mononuclear cells (PBMs) from 72 individuals without acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were cultured for virus. HIV was isolated from PBMs from 16 (24%) of 66 patients with hemophilia who were seropositive for HIV and from none of six seronegative patients. Cells from five of six patients from which HIV was isolated were again successfully cultured for virus 3 to 12 months later. HIV core P24 antigen was detected in serum from seven of 15 patients with HIV-positive cells and from eight of 50 with HIV-negative cells. Patients with hemophilia with isolation-positive cells had significantly fewer T helper cells and significantly lower T helper/T suppressor ratios, pokeweed mitogen responsiveness, and total platelet counts than did those whose cells did not yield HIV on cultivation. HIV neutralizing antibody titers did not differ between hemophiliacs with or without HIV-positive PBMs. Three of the 16 patients with virus-positive cells developed AIDS, and two ARC, within 18 months of the study, compared with three of 50 seropositive hemophiliacs whose cells did not yield virus, who developed ARC during the same period. The significant decrease in the number of T helper cells, decreased platelet counts, and higher rate of progression to AIDS in the group with HIV isolation may reflect a heavier virus load, indicating that the ability to culture HIV may be an early marker of more significant disease.
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PMID:Isolation of human immunodeficiency virus from hemophiliacs: correlation with clinical symptoms and immunologic abnormalities. 295 63

Human T-cell leukemia virus (HTLV-I) is known to be associated with certain hematologic malignancies, and a related virus, HTLV-III/LAV, might be the cause of AIDS. Some persons with AIDS have had evidence of HTLV-I infection. Unrelated to these findings, it has been suggested that HTLV-I is transmitted via blood products. We therefore evaluated the serologic status to the HTLV-I core antigen p24 of 48 persons with hemophilia (Hem A) receiving factor concentrate therapy (a group at risk for AIDS), 49 persons with beta-thalassemia major (Thal) receiving frozen packed red blood cells therapy (FPRC), 26 patients with sickle cell anemia (SCA) receiving FPRC, and 18 persons not receiving any blood products. All participants were clinically well; only one had a risk factor other than hemophilia for AIDS, and all were from New York City, an area with a high incidence of AIDS. No Hem A or nontransfused persons had serum antibody to HTLV core p24 antigen; three with Thal and one with SCA were antibody-positive. These results were confirmed by both radioimmunoprecipitation and Western blot techniques. Positive serology did not correlate with any immune findings or quantity of blood products used. These data support that HTLV-I is preferentially transmitted through cellular blood products and that it is an infection for which cellular blood product recipients in at least some areas of the United States are at risk. Concentrate products appear free of transmission risk relative to cellular blood products, but we cannot be certain that this safety is absolute. The public health implications of blood product transmission of HTLV-I merit active, long-term investigation.
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PMID:Human T-cell leukemia virus (HTLV-I) p24 antibody in New York City blood product recipients. 299 70

Clinical courses and several hematological and serological markers were evaluated in 34 patients with HIV infection (32 with hemophilia and 2 with homosexuality) who had been followed up at Shizuoka Prefecture Children's Hospital for 3 to 13 years, with the reference to the results observed in 1,082 patients with HIV infection registered with the Ministry of Health and Welfare Study Group, Natural History Committee. The results indicated as significant follow-up markers as (1) CD4- and CD8-positive lymphocyte count, (2) IgA, IgG and beta-2 microglobulin, (3) HIV p24 antigen and HIV culture isolation, and (4) serum HIV-RNA. Of these markers, the quantification of serum HIV-RNA seemed particularly useful for prognosis estimation, determination of therapy onset, and efficacy assessment of a given anti-HIV agent. In addition, we encountered 2 HIV-infected patients who seemed to meet the definition of long-term survivors. Factor analysis in these patients will be an important subject of investigation from a clinical point of view as well.
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PMID:[HIV infection: pathophysiology and its clinical features--clinical course and surrogate marker]. 778 46

Patients with haemophilia, particularly that due to factor VIII deficiency, have been exposed to a wide range of infective agents transmitted through blood products that have in other ways revolutionized their care. The most devastating of these transfusion transmitted infections has been the human immunodeficiency virus (HIV). AIDS in haemophilic patients was first described in 1982 and it has significantly reduced the life expectancy of these patients. In this article, the impact of the HIV epidemic within haemophilic patients treated with coagulation factor concentrate is discussed. The effect of age at time of exposure to HIV and the value of disease markers such as P24 antigenaemia and CD4 counts are considered in detail. The relationship between HIV disease and coexisting hepatitis C infection is described and the incidence of secondary malignancies such as lymphoma is reviewed. In this patient population the recent elucidation of the life cycle and dynamics of HIV as well as the technological advances in the development of the HIV RNA PCR assay for HIV viral load have revolutionalized the diagnosis, prognosis, management and treatment of HIV infection.
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PMID:The natural history of HIV disease in haemophilia. 974 83

This longitudinal study examines differences in hepatitis B immune titres in children and adolescents with haemophilia to determine if they are dependent on how immunity was acquired (vaccination or natural infection), and whether they are related to the child's HIV status and/or are influenced by HIV disease progression. Serologic titres (HBcAb, HBsAb) and HBsAg were measured prospectively at baseline, and at years 1, 2 and 3 of follow-up in 126 HIV- and 207 HIV+ children and adolescents with haemophilia. Analyses were performed to assess the impact of HIV status on the measured titres, and for HIV+ subjects to examine the association with CD4+ lymphocyte counts and p24 antigen status. The results show that HIV+ children were more likely than HIV- children to lose vaccine-induced immunity as indicated by the loss of HBsAb. There was an increased risk of losing HBsAb with higher CD4+ counts and younger age. Re-immunization was not successful in seven of eight HIV+ children. Two subjects (one HIV+, one HIV-) entered the study HBsAg- but became HBsAg+ over the course of follow-up. Seven HIV+ subjects lost natural immunity as indicated by the loss of HBcAb. The loss of either HBsAb or HBcAb in HIV--subjects was negligible to absent. In conclusion, because of the loss of immunity in HIV+ children the viral safety of factor replacement concentrates for these children is an important consideration. HIV- children rarely lose immunity, therefore frequent measures of HBsAb are not necessary.
Haemophilia 1999 Sep
PMID:Changes in hepatitis B serologic titers in HIV+ and HIV- children with haemophilia. 1058 18


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