Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).
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PMID:Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients. 1200 Oct 34

The vast majority of infants and children undergoing craniosynostosis correction receive a blood transfusion. The risks of blood transfusion include, but are not limited to, acute hemolytic reactions (approximately 1 of 250,000), human immunodeficiency virus (approximately 1 of 200,000), hepatitis B and C (approximately 1 of 30,000 each), and transfusion-related lung injuries (approximately 1 of 5000). This prospective, single-blinded, randomized study was undertaken to examine the safety and efficacy of preoperative single weekly dosing with erythropoietin (epoetin alfa) in reducing the rate of transfusion in infants and small children undergoing craniosynostosis repair. A total of 29 patients (<8 years) undergoing craniosynostosis repair were randomized into two groups: one received preoperative erythropoietin (600 U/kg) weekly for 3 weeks, and the other served as a control. All caregivers responsible for blood transfusions were blinded, and strict criteria for transfusion were established. A pediatric hematologist monitored both groups, and all patients received supplemental iron (4 mg/kg). Fourteen patients were randomized to receive erythropoietin, and eight of these 14 patients (57 percent) required transfusion (mean age, 17 months; mean weight, 10.1 kg). Of the six patients not requiring transfusion, three were younger than 12 months old (mean, 6 months). Fourteen of 15 patients (93 percent) in the control group (mean age, 13 months; mean weight, 9.3 kg) required a blood transfusion during the study. The only control patient not requiring transfusion was the eldest (5 years old). The difference between the two groups was statistically significant (Fisher's exact test = 0.03). The control group showed no change in hemoglobin levels from baseline to preoperative levels, but the erythropoietin group increased their average hemoglobin levels from 12.1 to 13.1 g/dl. There were no adverse effects noted among children receiving erythropoietin, nor were there any surgical complications. The authors conclude that the preoperative administration of erythropoietin significantly raised hemoglobin levels and reduced the need for a blood transfusion with craniosynostosis correction. More suggestions are made that may further reduce the need for blood transfusions, and a cost-benefit analysis is discussed.
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PMID:The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children. 1457 11

Lentivectors, derived from human immunodeficiency virus-1 (HIV-1), represent a novel investigational and therapeutic tool for targeting hematopoietic progenitor cells. We describe a new protocol whereby we achieved a highly efficient lentiviral transduction of erythroid precursor cells originating from the bone marrow of healthy adults and patients with myelodysplastic syndromes (MDS). CD34(+) stem cells from healthy subjects were cultured with erythropoietin, IL-3 and stem cell factor, and thereby expanded approximately 300-fold. When these cultures were transduced with a lentiviral vector expressing GFP as a reporter gene, 70% glycophorin(+) cells were GFP(+). Although proliferation and levels of transduction were reduced in cultures of CD34(+) stem cells from patients with myelodysplastic syndromes, 50% of glycophorin(+) cells became GFP(+), amongst which 30% were sideroblastic erythroid precursors. This study demonstrates that lentiviral vectors are capable of efficiently transducing MDS precursors and offers new perspectives to investigate the influence of specific genes on normal erythroid differentiation. This may eventually help to correct defects in patients suffering from myelodysplastic syndromes.
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PMID:Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes. 1209 56

Anemia of chronic disease (ACD) is frequent in patients with human immunodeficiency virus (HIV) and its etiology is multifactorial. In a group of 111 patients with HIV, 19 were diagnosed with ACD. Parameters related to iron metabolism, such as serum iron (SI), serum ferritin (SF), and soluble transferrin receptor (sTfR) were correlated to levels of interferon-gamma (IFN-gamma) and results compared to a group of 42 nonanemic patients with HIV. Measurements of erythropoietin (EPO), CD4/CD8 T-cell ratio, and reticulocyte count (RTC) were determined to verify aspects related to severity of disease and bone marrow response. The results showed higher SF concentrations in ACD patients and normal or slightly increased sTfR measurements in both groups. There was no correlation between IFN-gamma and SF and between IFN-gamma and sTfR determinations. Lower CD4/CD8 values were obtained in ACD, and an inverse correlation was observed between IFN-gamma and CD4/CD8 in groups with and without anemia. RTC counts and EPO concentrations were similar in both groups: immature RTC were increased in patients with anemia, indicating an apparent attempt of marrow response to compensate the increased demand. Our data showed no correlation between IFN-gamma levels and iron disturbances in ACD, but results reinforced the observation of enhanced immunologic system deterioration in patients with HIV and ACD.
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PMID:Human immunodeficiency virus-related anemia of chronic disease: relationship to hematologic, immune, and iron metabolism parameters, and lack of association with serum interferon-gamma levels. 1222 86

The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that are predominantly T cell subtype CD8 driven predominate. There is evidence for B cell stimulation and many autoantibodies are reported in HIV patients. We propose a staging of autoimmune manifestations related to HIV/AIDS manifestations and the total CD4 count and viral load that may be beneficial in identifying the type of autoimmune disease and establishing the proper therapy. In stage I there is the acute HIV infection, and the immune system is intact. In this stage, autoimmune diseases may develop. Stage II describes the quiescent period without overt manifestations of AIDS. However, there is a declining CD4 count indicative of some immunosuppression. Autoimmune diseases are not found. During stage III there is immunosuppression with a low CD4 count and the development of AIDS. CD8 T cells predominant and diseases such as psoriasis and diffuse immune lymphocytic syndrome (similar to Sjogren's syndrome) may present or even be the initial manifestation of AIDS. Also during this stage no autoimmune diseases are found. In stage IV there is restoration of immune competence following highly active anti-retroviral therapy (HAART). In this setting, there is a resurgence of autoimmune diseases. The frequency of reported rheumatological syndromes in HIV-infected patients ranges from 1 to 60%. The list of reported autoimmune diseases in HIV/AIDS include systemic lupus erythematosus, anti-phospholipid syndrome, vasculitis, primary biliary cirrhosis, polymyosits, Graves' disease, and idiopathic thrombocytopenic purpura. Also, there is an array of autoantibodies reported in HIV/AIDS patients which include anti-cardiolipin, anti-beta2 GPI, anti-DNA, anti-small nuclear ribonucleoproteins (snRNP), anti-thyroglobulin, anti-thyroid peroxidase, anti-myosin, and anti-erythropoietin antibodies. The association of autoantibodies in HIV-infected patients to clinical autoimmune disease is yet to be established. With the upsurge of HAART, the incidence of autoimmune diseases in HIV-infected patients is increasing. In this review, we describe the various autoimmune diseases that develop in HIV/AIDS patients through possible mechanisms related to immune activation.
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PMID:HIV and autoimmunity. 1284 88

Infection with human immunodeficiency virus (HIV)-1 can lead to neurological complications that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). The mechanism of brain injury and dementia remains poorly understood. Interestingly, post mortem brain specimen from HAD patients and transgenic mice expressing the viral envelope protein gp120 present with similar neuropathological signs. The cytokine erythropoietin (EPO) is clinically used to treat anemia but has also been found to prevent neuronal death due to inflammation or excitotoxicity. Here we show that EPO protects cerebrocortical neurons against apoptosis induced by HIV-1/gp120.
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PMID:Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage. 1507 10

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.
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PMID:A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. 1547 Jul 51

Hepatitis C (HCV) contributes significantly to the morbidity and mortality of patients coinfected with human immunodeficiency virus (HIV) and those with recurrent hepatitis C after successful liver transplantation. Treatment of hepatitis C in these patient populations, while crucial, can be quite challenging. Baseline cytopenias, in particular, may limit dosing of interferon and/or ribavirin or preclude therapy entirely when standard guidelines are followed. Concomitant medications, opportunistic infections, and other bone marrow insults account for the anemia, neutropenia, and thrombocytopenia frequently encountered in these patients. Sustained virologic response rates in published series for HIV/HCV and post-transplantation HCV have not reached those seen in treatment of HCV alone, despite the highly selected patient populations chosen for these studies. Hematopoietic growth factors such as erythropoietin and granulocyte-colony stimulating factors may be used to improve the anemia and neutropenia seen during treatment of HCV. Reported experience with these growth factors is limited in HIV/HCV coinfected patients, but studies are underway to determine if growth factors improve adherence to therapy and perhaps virologic response rates. Post-transplantation studies of HCV therapy have reported more liberal use of growth factors; however, discontinuation rates have been high and virologic response rates have been disappointing. Further study of growth factors as a means to increase sustained virologic response rates and maintain adequate dosing and duration of interferon and ribavirin therapy in these patient populations is needed.
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PMID:Role of growth factors in the treatment of patients with HIV/HCV coinfection and patients with recurrent hepatitis C following liver transplantation. 1559 23

Anemia, the most common hematological disorder in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), is associated with decreased quality of life and survival. Hypogonadism is prevalent in advanced HIV disease, however, low testosterone levels have not been customarily implicated in HIV-associated anemia. This study was undertaken to determine whether there is a relationship between testosterone levels and androgen use with anemia in HIV, and to characterize other clinical correlates of HIV-associated anemia. This was a cross-sectional, observational study of 200 HIV-positive patients at a public hospital HIV clinic from July 2000 to August 2001. A written questionnaire detailed previous and current medication use, opportunistic infections, and malignancies. Hematological and virological parameters, testosterone, and erythropoietin levels were measured; CD4(+) T lymphocyte count and viral load nadir and peak levels were obtained from the computerized medical record. Anemia was defined as hemoglobin <13.5 g/dl in men and <11.6 g/dl in women. Twenty-four percent of women and 28% of men were anemic. Anemia was associated with lymphopenia (adjusted OR 4.0, 95% CI 1.36-11.80), high erythropoietin levels (adjusted OR 7.73, 95% CI 2.92-20.48), and low testosterone levels (adjusted OR 3.27, 95% CI 1.01-10.60). Anemia was negatively associated with female sex (adjusted OR 0.30, 95% CI 0.11-0.85), current antiretroviral therapy (adjusted OR 0.43, 95% CI 0.20-0.95), current androgen use (adjusted OR 0.20, 95% CI 0.05-0.84), and macrocytosis (adjusted OR 0.23, 95% CI 0.09-0.61). Low testosterone levels may have a positive association and supplemental androgens a negative association with anemia in HIV disease.
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PMID:Anemia and HIV in the antiretroviral era: potential significance of testosterone. 1579 25

There is a close association between the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, infection and immunity. Infection with the human immunodeficiency virus (HIV) is often associated with a decrease of the concentrations of IGF-I, IGF-II, IGF-binding protein 3 (IGFBP-3) and an increase of IGFBP-1 and -2. Many investigators have studied the relationship between the GH-IGF-I system and some of the most common characteristics of disease progression, such as decreased CD4 cell counts, weight loss and fat redistribution. Although conditions for restoration of thymic function and lymphopoiesis with GH or IGF-I are still not well defined, many studies led to the development of clinical trials on the therapeutic use of GH, IGF-I and GHRH for the treatment of weight loss or fat redistribution, two problems which persist despite the introduction of highly active antiretroviral therapy. Monitoring IGF-I concentrations during treatment with GH and GHRH is likely to become an essential component of their therapeutic use. IGF-I levels are the first indicator of treatment efficacy and can be used to monitor compliance. High levels of IGF-I are a warning sign for the increased risk of potential adverse effects, such as acromegalic-like symptoms or malignancy. This could lead to a reduction of the therapeutic dose or the temporary interruption of treatment until IGF levels reach a safe range. IGF-I levels are also likely to increase with other hormones used in HIV patients, such as erythropoietin for the treatment of anemia or anabolic androgens in HIV-infected women.
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PMID:Monitoring insulin-like growth factors in HIV infection and AIDS. 1597 Feb 80


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