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)

Virucidal methods to inactivate infectious agents are based on various methods of heating or chemically treating plasma concentrates of coagulation factors VIII and IX used in the treatment of hemophilia A and B. This clinical evaluation of the viral safety of such 'treated' concentrates is mainly based on the prospective study of previously untreated hemophiliacs by means of clinical and serological markers of viral infection. Although there have been a few focal episodes of human immunodeficiency virus (HIV) transmission by clotting factors, these have been traced to ineffective virucidal methods that are no longer used or to clerical errors during the manufacturing process. Viral inactivation by pasteurization, vapor heating, heating in the lyophilized state at 80 degrees C and addition of solvent/detergent definitely decreases the risk of infection with hepatitis B and C. The current screening of plasma units for antibody to hepatitis C virus prior to inclusion in pools for concentrate production should further decrease the risk of hepatitis C infection. Other viruses, such as parvovirus and the hepatitis A virus, may still cause infections because they are quite resistant to virucidal methods. On the whole, virucidal methods have greatly reduced the risk of new HIV infections and, to a lesser degree, hepatitis.
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PMID:Clinical evaluation of viral safety of coagulation factor VIII and IX concentrates. 803 99

Twenty-six knee arthroplasties were performed in 15 patients with hemophilia A and human immunodeficiency virus infection from 1984 to 1991. Patient age range was 27 to 48 years. After an average follow-up period of 6.4 years (range, 1-9 years) all patients were alive and none of the implants had become infected. T4 lymphocyte counts showed some deterioration, which was not clinically significant. All of the patients were improved following surgery. Nineteen implants were rated excellent, four good, and three fair. Infection with human immunodeficiency virus did not adversely affect the clinical outcome of knee arthroplasty at follow-up periods up to 9 years.
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PMID:Total knee arthroplasty in human immunodeficiency virus-infected hemophiliacs. 852 2

Prophylaxis has been practiced for many years in Europe and is gaining acceptance worldwide with current viral inactivation procedures. Unfortunately, the high cost of prophylaxis is currently the major obstacle to its implementation in developing countries such as Turkey. The aim of this controlled preliminary study is to evaluate the efficacy, safety, and feasibility of prophylaxis. Seven boys aged 1.5-7 years (5.0 +/- 1.8), who had severe hemophilia (six A, one B) received 20-50 IU/kg factor twice weekly and were followed up for 6-24 months (14.5 +/- 6.6). Intermediate concentrates have been used in hemophilia A and ultrapure product for hemophilia B. The data obtained for the same group of patients before prophylaxis were used as a control group. Another control group was selected in another group of 10 hemophiliacs, mean age 12.5, and received treatment on demand. During prophylactic treatment, the episodes of bleeding were decreased (from 10.5 +/- 3.2 to 4.5 +/- 3.6). Orthopedic and radiologic joint scores were stable (from 0 to 1 and from 1.1 +/- 1.2 to 1.0 +/- 1.5). The patients spent significantly fewer days in the hospital (from 18 +/- 12 to 0.7 +/- 0.6). None of the patients was infected with hepatitis A, hepatitis B, or human immunodeficiency virus. One patient was seroconverted with anti-hepatitis C virus in the third month of prophylaxis. Mean consumption of concentrates for prophylaxis was 3489 +/- 960 IU/kg per year compared with 2073 +/- 1302 in conventional therapy. Prophylaxis was superior to treatment on demand even when given in a twice-weekly period with intermediate concentrates. In Third World countries, prophylaxis should be tried at least in selected severely hemophilic children in order to prevent disabilities.
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PMID:Prophylactic therapy for hemophilia in a developing country, Turkey. 908 43

This analysis evaluated the extent to which infections with selected blood-borne viruses, specifically infection with hepatitis B virus, hepatitis C virus, and/or the human immunodeficiency virus (HIV), continue to contribute to the morbidity of persons with hemophilia. The Georgia Hemophilia Surveillance System collected information on 336 state residents with hemophilia A or B who were followed by a physician in 1994. Data abstracted from medical records included information on demographics, sources of hemophilia care, clinical characteristics, joint range of motion measurements, hospitalization, and results of laboratory testing for hepatitis B, hepatitis C, and the human immunodeficiency virus. Prevalence of infection with one or more of these viruses was determined, and relationships with disease severity, bleeding frequency, and amount of clotting factor prescribed were explored. No child under the age of ten was positive for the human immunodeficiency virus; hepatitis infection was also uncommon in this age group, in contrast to the very high frequency of such infections among older subjects. There was a strong association between HIV positive status and infection with one of the hepatitis viruses. The likelihood of all types of viral infection increased with frequency of bleeding and with amount of clotting factor received. Efforts to prevent transmission of lipid-enveloped viruses via clotting factor have been extremely effective. However, currently infected hemophilia patients will likely experience significant morbidity and mortality due to chronic liver disease and AIDS-related complications.
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PMID:Viral infections among patients with hemophilia in the state of Georgia. 972 74

The aim of this study was to investigate whether the immune system of patients with hemophilia A is skewed toward an aspecific activation and to identify the causative factors. It is well known that an immune derangement does exist in patients with hemophilia A. At least three factors potentially play a role: hepatitis C virus (HCV) infection, alpha-interferon therapy and the administration of factor VIII (FVIII). Sixty human immunodeficiency virus (HIV)-negative patients with severe or moderate hemophilia A were studied retrospectively. The serological markers of autoimmunity were evaluated and the results correlated with anti-HCV antibodies, FVIII treatment and alpha-interferon therapy. The role of these factors in the development of the anti-FVIII antibody was estimated concomitantly. The prevalence of autoantibodies and anti-FVIII antibodies was higher in HCV-positive than in HCV-negative patients before any treatment, although the difference was not statistically significant. The administration of FVIII further influenced the development of autoantibodies both in HCV-negative and HCV-positive patients, with no difference being observed between the two groups. As expected, fewer HCV-negative than HCV-positive patients developed anti-FVIII antibodies after administration of FVIII (31.8% versus 38%, respectively). Therapy with alpha-interferon did not seem to enhance significantly the risk of developing autoantibodies nor anti-FVIII antibodies. We observed a high prevalence of humoral signs of autoimmunity among patients with hemophilia A. Treatment with FVIII concentrate is probably the most important triggering factor. Monitoring these patients for autoimmune manifestations is recommended.
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PMID:Serological markers of autoimmunity in patients with hemophilia A: the role of hepatitis C virus infection, alpha-interferon and factor VIII treatment in skewing the immune system toward autoreactivity. 1049 22

A case is reported of septic arthritis in a child with human immunodeficiency virus-negative hemophilia A associated with a Staphylococcus aureus catheter-associated septicemia. The infection occurred in relation to the use of a totally implantable central venous catheter. The organism was eventually eradicated with antibiotics injected via the catheter. With increasing use of such catheters in the hemophilic population, clinicians should be alerted to the possibility of septic arthritis for prompt diagnosis and treatment.
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PMID:Septic arthritis in hemophilia with central venous catheter: a case report. 1073 63

Chronic renal failure is an unusual complication of hereditary clotting disorders (HCDs), but this situation could change in the near future. The modality of dialysis for end-stage renal disease (ESRD) in patients with an HCD is a difficult choice. Hemodialysis (HD) may be considered, but intensive treatment with coagulation factors is required for vascular access execution and for each HD procedure. Peritoneal dialysis (PD) has been infrequently proposed. However, PD requires coagulation replacement therapy only during peritoneal catheter placement. The aim of this paper is to describe our experience of three patients with ESRD and HCD, successfully treated with chronic PD in the medium term. Case 1 was a 58-year-old man with moderate hemophilia A, type 2 diabetes mellitus, and hepatitis C virus (HCV) infection. His ESRD was secondary to glomerulonephritis. A double-cuff peritoneal catheter was surgically placed with pre-emptive factor VIII administration. He began treatment with continuous ambulatory peritoneal dialysis (CAPD). An inguinal hernia was repaired without complications. After eleven months of follow-up, no hemorrhage episodes have been observed and clinical outcome is optimal. Case 2 was a 46-year-old man with severe hemophilia A, type 2 diabetes mellitus, and HCV and human immunodeficiency virus (HIV) infections. He developed a diabetic nephropathy that required renal replacement therapy. A permanent silicone catheter was inserted in the left internal jugular vein, and the patient started HD treatment. Later on, PD therapy was proposed. A peritoneal catheter was implanted with simultaneous factor VIII infusion. Minimal bleeding was observed at the subcutaneous tunnel over the following 48 hours. The patient started PD treatment without complications, and two months later, remaining asymptomatic, transferred to another center. Case 3 was a 41-year-old woman diagnosed with von Willebrand disease type 2A, HCV infection, and polycystic kidney disease, who presented with ESRD. An internal arteriovenous fistula was performed under coagulation factor cover. During a fistulography, and despite coagulation factor substitutive treatment, the patient showed an important hematoma. Afterwards, PD was considered. A peritoneal catheter was implanted under coagulation factor cover. The postoperative course was uncomplicated, and the patient started CAPD treatment. During follow up, she suffered two hemoperitoneum episodes that were resolved with cold dialysate. After nine months, she uneventfully continued on PD. In conclusion, PD is the therapy of choice for patients with hereditary clotting disorders and ESRD requiring dialysis. Peritoneal dialysis therapy avoids many of the complications related to HD therapy.
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PMID:Peritoneal dialysis is the therapy of choice for end-stage renal disease patients with hereditary clotting disorders. 1104 86

Hematologic diseases potentially benefiting from gene-based therapies involving hematopoietic stem cells (HSCs) include hereditary hemoglobinopathies, immunodeficiency syndromes, and congenital bleeding disorders such as hemophilia A, as well as acquired diseases like AIDS. Successful treatment of these blood diseases with gene-modified HSCs requires high efficiency gene delivery to the target cell population and persistence of transgene expression following differentiation. We review flow cytometric procedures that permit simultaneous, noninvasive measurements of transgene expression and phenotypic discrimination of hematopoietic cell subsets. Central to this approach has been the recent development of a spectrum of blue, cyan, and yellowish-green fluorescent reporters based on the jellyfish Aequorea victoria green fluorescent protein and the discovery of a red fluorescent protein in DISCOSOMA: coral. This methodology should facilitate the optimization of oncoretroviral and lentiviral vectorology and HSC transduction protocols for the ultimate purpose of HSC-directed gene therapy.
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PMID:"Rainbow" reporters for multispectral marking and lineage analysis of hematopoietic stem cells. 1123 66

Because of changes in factor replacement therapy and in treatment of human immunodeficiency virus (HIV) infection, we examined death record data for persons with hemophilia A in the United States to evaluate effects of HIV infection on age and causes of death. Multiple cause-of-death data from 1968 through 1998 were examined to assess death rates for persons with hemophilia A. ICD-9 coded causes of death from 1979 through 1998 were examined to assess long-term trends. From 1979 through 1998, 4,781 deaths among persons with hemophilia A were reported, of which 2,254 (47%) had HIV-related disease listed as a cause of death. In the late 1980s, mortality among persons with hemophilia A increased markedly, and the age-adjusted death rate peaked at 1.5 per 1,000,000 population in 1992. Median age at death decreased from 55 years in 1979-1982 to 40.5 years in 1987-1990, and increased to 46 years in 1995-1998. In the period 1995-1998, the median age of hemophilia A decedents with HIV-related disease was 33 years, compared to 72 years for those without HIV-related disease; the most frequently listed causes of death for those without HIV-related disease were hemorrhagic and circulatory phenomena; the most frequently listed for those with HIV-related disease were diseases of liver and the respiratory system. From 1995 to 1998, hemophilia A-associated deaths decreased by 41%, with a 78% decrease among those who had HIV-related disease. Although HIV infection has adversely effected mortality for persons with hemophilia A, the marked recent decrease in the death rate among persons with hemophilia A appears to reflect advances in care for those with HIV-related disease and is consistent with a decline in HIV mortality observed in the general population.
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PMID:Effects of HIV infection on age and cause of death for persons with hemophilia A in the United States. 1127 32

Gene therapy holds great promise for the treatment of a variety of inherited diseases, including hemophilia A and mucopolysaccharidosis type VII (MPS VII). In both these disorders, subnormal levels of replacement protein have therapeutic effects. Thus we hypothesized that transduction of a small proportion of cells by feline immunodeficiency virus (FIV)-based lentiviral vectors might provide sufficient levels of transgene expression for phenotypic correction. We intravenously injected replication-deficient FIV-based vectors encoding either human factor VIII or human beta-glucuronidase into factor VIII-deficient or beta-glucuronidase-deficient mice, respectively. This route of delivery targeted multiple organs, with the liver as the primary transduction site. In the hemophilia A mice, factor VIII expression persisted for the duration of the experiments (approximately 5 months), and recipient mice survived an otherwise lethal bleeding episode (tail-clipping). In mucopolysaccharidosis type VII mice, substantial beta-glucuronidase activity was detected in several tissues and corresponded with marked reduction of lysosomal storage in liver and spleen. These findings indicate that gene transfer with FIV-based lentiviral vectors can permanently introduce transgenes into a sufficient number of hepatocytes for long-term therapeutic effect and suggest potential clinical value of FIV-based lentiviral vectors for treatment of hemophilia A and MPS VII.
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PMID:In vivo treatment of hemophilia A and mucopolysaccharidosis type VII using nonprimate lentiviral vectors. 1140 98


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