Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have suggested a possible association between HIV-1 infection and primary pulmonary hypertension (PPH), but most of the patients described to date have either had acquired immunodeficiency syndrome (AIDS) with concurrent lung infections or have administered Factor VIII intravenously for hemophilia. We report three human immunodeficiency virus type 1 (HIV-1)-positive homosexual white males with clinical and hemodynamic diagnoses of PPH. None of the patients had any opportunistic lung infections or other pulmonary pathology, nor were they hemophiliacs. They had no histories of intravenous drug use. Lung tissue from two of the patients revealed hypertensive arteriopathy consistent with PPH and no other pulmonary pathology. Attempts at localizing HIV-1 infection to the vascular endothelium with electron microscopy, immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction techniques did not reveal direct pulmonary artery infection with the virus. These data and the finding of tubuloreticular structures on electron microscopy suggest that HIV-1 may play a role in the pathogenesis of these cases of PPH through mediator release associated with HIV-1 infection rather than by direct endothelial infection.
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PMID:Primary pulmonary hypertension in association with human immunodeficiency virus infection. A possible viral etiology for some forms of hypertensive pulmonary arteriopathy. 158 65

The polymerase chain reaction (PCR) detected specific hepatitis C viral (HCV) RNA sequences in plasma from 15 of 21 haemophiliacs (12 HCV-antibody positive) and 7 of 27 intravenous drug users (13 HCV-antibody positive). Quantification of RNA-positive samples showed high levels of HCV (10(5) to 10(6) copies of RNA/ml) in infected patients. HCV was more frequently found in haemophiliacs infected with human immunodeficiency virus (11/11 HIV-positive and 4/10 HIV-negative patients). HCV-RNA was detected in all batches of commercially available factor VIII tested and in low concentrations in some pools of plasma donations from volunteers. Factor VIII, manufactured from volunteer donations, was uniformly negative by PCR. Phylogenetic analysis of viral sequences showed two distinct groups: one was associated with intravenous drug users and the other with haemophiliacs infected with Scottish factor VIII preparations. Both were distinct from sequences found in commercially available factor VIII.
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PMID:Hepatitis C quantification and sequencing in blood products, haemophiliacs, and drug users. 197 93

Six hemophilia patients previously seronegative for human immunodeficiency virus (HIV) seroconverted between September 1986 and September 1987. None had risk factors for HIV infection other than hemophilia. We compared the factor concentrates received by these patients with the concentrates received by 10 seronegative hemophilia patients. A statistically significant association was observed between seropositivity and the receipt of two lots of Factor VIII produced from the same plasma pool (odds ratio 77, p = 0.0014); five of the six case subjects but none of the control subjects had received concentrate from one of the two lots. Available evidence suggests that the sixth case subject had also received concentrate from an implicated lot. Symptoms including rash and fever were reported in five cases within 6 weeks after the implicated concentrate had been given. The implicated lots were produced from plasma from paid donors that had been screened and then heated at 60 degrees C for 30 hours in the lyophilized state. Subsequent to our investigation all concentrate produced by this process was removed from distribution.
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PMID:HIV transmission to patients with hemophilia by heat-treated, donor-screened factor concentrate. 211 26

Thirteen semiconstrained total knee arthroplasties (TKA) were performed in nine men with classic hemophilia. The average age at surgery was 38 years, the average Factor VIII administration during hospitalization was 84.222 units, and the average hospitalization time was 33 days. Four patients (44%) died during the observation period, three from acquired immunodeficiency syndrome (AIDS) contracted through contaminated Factor VIII plasma concentrates and one from sudden cardiac arrest. One of the patients who died from AIDS had a positive test for human immunodeficiency virus (HIV) at surgery. He died three months after the arthroplasty. The remaining two patients contracted AIDS one year and four years after the arthroplasty. All but one patient were followed for at least one year, with an average follow-up period of 43 months. Using The Hospital for Special Surgery Knee Rating Scale, the overall result was excellent in nine knees and good in three knees. All patients were completely relieved of pain. TKA in hemophiliacs is an effective treatment for otherwise intractable chronic knee pain due to severe joint degeneration. However, caution should be taken in HIV-positive patients owing to the challenge of the patient's immune system and the risk of transmitting the virus to the hospital staff.
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PMID:Total knee arthroplasty in classic hemophilia. 211 46

Factor VIII concentrate inhibits T-cell function in vitro and in vivo. The mechanisms underlying the phenomenon were investigated. Factor VIII concentrate has a direct effect on lymphocytes, uninfluenced by haemophilic monocyte dysfunction, since it inhibited lymphocyte transformation with phorbol myristate acetate, a reaction unaffected by monocyte depletion. Inhibition of lymphocyte transformation by factor VIII concentrate is not corrected by the addition of exogenous IL2, suggesting that it does not inhibit lymphocyte function by suppression of IL2 secretion alone. Factor VIII concentrate causes profound inhibition of IL2-receptor expression (CD25); with an 89% reduction in CD25-positive CD4 cells and a 50% reduction in CD25-antigen molecules per cell. CD8 lymphocytes are similarly affected. Smaller reductions in CD71 and HLA-DR expression are also observed. Down modulation of CD25-antigen may explain the reduced IL2 secretion observed by others, and may be an important cause of immunodeficiency in HIV-seronegative haemophiliacs.
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PMID:Inhibition of lymphocyte IL2-receptor expression by factor VIII concentrate: a possible cause of immunosuppression in haemophiliacs. 211 76

In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV infection and natural killer cytotoxicity in hemophilic patients. 238 63

The development of factor VIII concentrates has greatly facilitated hemophilia care and has made the home care of hemophilia possible. However, factor VIII concentrate that has been produced using traditional methods contains large amounts of foreign proteins and viruses. This has resulted in the development of immunologic abnormalities in many hemophiliacs and has exposed many of these patients to blood-borne viruses such as the human immunodeficiency virus (HIV) and hepatitis viruses. Factor VIII circulates in plasma in complex with the von Willebrand factor (vWF). Both factor VIII and vWF have been purified and monoclonal antibodies (mAb) have been generated to both of these proteins. When bound to a solid support, these mAb's can be used to isolate selectively the proteins of interest. Recently, two separate procedures have been used in the immunoaffinity purification of factor VIII on a commercial scale. One product (Monoclate) has been prepared using a mAb to the vWF bound to a chromatography column. The other product (Hemophil M) uses immobilized mAb to the factor VIII molecule. Factor VIII concentrate purified using either of these approaches is far more pure than traditional factor VIII concentrates. In addition, the use of both viral purification and viral inactivation procedures has greatly reduced the risk of viral contamination. Early clinical studies have demonstrated that these products are effective in treating bleeding episodes and that the risk of viral infection with HIV or hepatitis viruses is low. Factor VIII concentrate produced using mAb technology appears to be the product of choice in previously untransfused hemophiliacs. Its role in the treatment of patients who have already been infected with HIV is less clear.
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PMID:Immunoaffinity purification of factor VIII. 250 62

French hemophiliacs have been infected with HIV between 1980 and 1985 initially by american Factor VIII concentrates and later by french Factor VIII and IX concentrates. Viral inactivation methods applied to these plasma derivatives appear to have interrupted infection the rate of which is currently about 50 p. 100. An increasing number of these individuals develop clinical complications related to immunodeficiency and AIDS. Biological tests are available to indicate the intensity of viral replication causing clinical symptoms, and these could be used to initiate an early anti-viral therapy. A major educational effort should be undertaken to limit the HIV infection spread among female sex partners of hemophiliacs.
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PMID:[Hemophilia and acquired immunodeficiency]. 251 81

At the change from unheated to heat-treated Factor VIII concentrates for the treatment of hemophilia A, 17 severe adult hemophiliacs (mean monthly dose, 4927 IU) were evaluated prospectively for signs of infection with human immunodeficiency virus (HIV). Viral serology and lymphocyte subpopulations (OKT3, OKT4, and OKT8-positive cells) were examined monthly for 1 year. One patient seroconverted for HIV in the enzyme-linked immunoabsorbent assay but was positive on the Western blot analysis from the outset. There was a slight but significant increase in OKT4+ cells and OKT4/OKT8 ratio. These data suggest that heat-treated Factor VIII concentrates even when used in large amounts have a low risk of transmitting HIV.
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PMID:Risk of transmission of human immunodeficiency virus (HIV) by heat-treated factor VIII concentrates in patients with severe hemophilia A. 312 Mar 76

The eradication of a high-response Factor VIII inhibitor in patients with severe hemophilia A is extremely rare even with prolonged immunosuppressive therapy. This report presents a patient with severe hemophilia A, in whom the disappearance of such an inhibitor coincided with the development of the acquired immunodeficiency syndrome (AIDS). Laboratory studies demonstrated a marked decrease in helper T-cells and marked depression of cell-mediated immunity by in vivo and in vitro testing. In addition, humoral immune responses were abnormal. Thus, anamnestic antibody formation to different antigens was absent and in vitro pokeweed mitogen-induced immunoglobulin synthesis by the patient's B-cells was markedly impaired even in the presence of normal T-cells. These findings indicate that the disappearance of the Factor VIII inhibitor and the lack of an anamnestic antibody response to infused Factor VIII observed in this patient may be secondary to a humoral immunodeficiency associated with AIDS.
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PMID:Disappearance of a high response factor VIII inhibitor in a hemophiliac with AIDS. 312 44


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