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)

Human recombinant erythropoietin has been approved by the Food and Drug Administration for treatment of anemia due to chronic renal failure or malignancy and in zidovudine-treated patients with the human immunodeficiency virus. It is highly effective in reducing the anemia commonly seen in these patients, with minimal adverse effects. Approximately 20% of patients undergoing elective orthopedic procedures are not able to donate adequate amounts of autologous blood prior to surgery. Additionally, patients who cannot donate 3 or more units of blood prior to large procedures are at increased risk for receiving a homologous transfusion despite the use of intraoperative and postoperative blood conservation techniques. Investigational use of this drug as an adjuvant to autologous blood donation has been shown to increase the amount of blood donated by patients prior to surgery and, therefore, will decrease homologous blood transfusions after surgery. Perioperative use of this drug, dosage, route of administration, and clinical indications are currently being evaluated in multicenter clinical trials.
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PMID:The potential use of human recombinant erythropoietin in orthopedic surgery. 878 23

We have previously demonstrated that continuous administration of dose-escalation zidovudine (AZT) in either normal or LP-BM5 MuLV immunodeficient virus-infected mice (MAIDS) was associated with the development of anemia, neutropenia, and thrombocytopenia. Hematopoietic growth factors/cytokines are being evaluated to determine their efficacy in ameliorating the hematopoietic toxicity associated with AZT. In normal mice receiving AZT, an increase in only plasma erythropoietin and not GM-CSF, Meg-CSF or TNF-alpha has been reported. This article describes studies that investigated the effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) administered in normal non-viral, viral-infected, and viral-infected C57BL6 mice receiving dose-escalation AZT, i.e. 0.1 mg/ml, 1.0 mg/ml, and 2.5 mg/ml placed in the drinking water. Non-viral control mice responded to IL-3/GM-CSF by increasing erythropoiesis, myelopoiesis and platelet production measured by increased bone marrow and spleen derived erythroid, myeloid and platelet precursor stem cells cultured in semi-solid media. Virus-infected control mice not receiving IL-3/GM-CSF developed pancytopenia. Administration of IL-3/GM-CSF to virus-infected mice receiving dose-escalation AZT did not ameliorate the peripheral pancytopenia associated with immunodeficiency disease and AZT treatment, even though erythroid, myeloid and platelet precursor progenitor cells were increased at certain times when compared to either normal or viral-infected mice receiving IL-3/GM-CSF. These results indicate that the combination use of IL-3 and GM-CSF in vivo is only a partially effective growth factor/cytokine treatment to ameliorate the hematopoietic toxicity associated with the use of the anti-viral drug zidovudine.
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PMID:Effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on hematopoiesis administered to retrovirus-infected immunodeficient mice receiving dose-escalation zidovudine (AZT). 878 16

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.
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PMID:Macrophage colony stimulating factor involvement in uremic patients. 887 77

We conducted a cross-sectional survey to determine the relative course of patients with end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection sustained on maintenance hemodialysis. All 34 patients with ESRD and HIV infection receiving hemodialysis in one hospital-based and three community-based outpatient hemodialysis facilities in Brooklyn, NY, were studied. We documented their known duration of HIV infection, duration of ESRD, and hemodialysis prescription, and noted the presence of clinical acquired immunodeficiency syndrome (AIDS). Total CD4 count, serum albumin concentration, and percent reduction of urea (predialysis blood urea nitrogen minus postdialysis blood urea nitrogen, divided by predialysis blood urea nitrogen x 100) were measured. The 34 study subjects (26 men and eight women) included 31 blacks (91%) and three Hispanics (9%) with a mean age of 42 +/- 7.5 years, 29 (85%) of whom had AIDS. Twenty subjects (59%) had a history of intravenous drug abuse. Only six subjects (18%) were receiving an antiretroviral drug (zidovudine = five, dideoxyinosine = one). In 23 subjects (68%), AIDS was diagnosed prior to ESRD and was presumed to be the cause of renal failure (HIV-associated nephropathy). The mean known duration of HIV infection was 50.5 +/- 34 months (median, 48 months); the mean duration of ESRD was 57 +/- 50 months, the mean total CD4 count was 140 +/- 150 cells/microL (median, 70 cells/microL), the mean hematocrit was 28% +/- 5%, and the mean serum albumin concentration was 3.5 +/- 0.37 g/dL. All subjects were receiving erythropoietin for anemia correction. The mean length of the prescribed thrice-weekly hemodialysis sessions was 3.5 +/- 0.4 hours. Our results suggest that the survival of many ESRD patients with HIV infection receiving hemodialysis has improved compared with the uniformly dismal survival rate reported in the 1980s. Decisions on whether to initiate renal replacement therapy in patients with AIDS and advanced renal failure should be individualized because the combination of ESRD and HIV infection does not necessarily signal near-term death.
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PMID:Uremia therapy in patients with end-stage renal disease and human immunodeficiency virus infection: has the outcome changed in the 1990s? 910 43

To determine the factors that govern their response to erythropoietin (EPO), we conducted a cross-sectional study of all patients in four outpatient hemodialysis facilities in Brooklyn, NY, who had end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection and were receiving recombinant EPO. We also compared the hematocrit and EPO requirements of these patients to those of a control group of hemodialysis patients without HIV infection. We documented known duration of HIV infection, and total CD4 count was measured once. In both groups, hematocrit was measured weekly for 5 weeks and a mean value calculated for each subject. Transferrin saturation was measured twice and a mean value calculated for each subject. Intensity of hemodialysis was assessed by measuring both percent reduction of urea and serum albumin concentration twice; mean values were calculated for each subject. Twenty-nine (88%) of 33 study subjects had acquired immunodeficiency syndrome. Mean known duration of HIV infection was 49 +/- 32.5 months (median, 48 months), and mean total CD4 count was 143 +/- 152.4 cells/mm3 (median, 72 cells/mm3). Mean hematocrit in the study subjects was 27.4% +/- 4.7% compared with 27.6% +/- 3.7% in the controls (P = 0.69). Mean thrice-weekly EPO dose was higher in the study subjects (90 +/- 52 U/kg body weight) than in the controls (62 +/- 36 U/Kg body weight) (P = 0.001). Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55). There was an inverse correlation between hematocrit and dose of EPO (r = -0.5; P = 0.003). Multiple regression analysis showed that transferrin saturation (P = 0.01) and percent reduction of urea (P = 0.003) had direct correlations with hematocrit after adjustment for other factors. There was an inverse relationship between hematocrit and dose of EPO (P = 0.0006). We conclude that in patients with ESRD and HIV infection receiving hemodialysis, the response to EPO (hematocrit) is modulated by the dose of EPO, quantity of hemodialysis, and transferrin saturation, but not by the severity of HIV disease. Hemodialysis patients infected with HIV receive a higher dose of EPO than those without HIV infection.
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PMID:Severity of AIDS and the response to EPO in uremia. 921 98

The anaemia that is a common complication of human immunodeficiency virus (HIV) infection bears many similarities to the anaemia of chronic disease. These similarities include an impaired erythropoietin (EPO) response to anaemia, reduced concentrations of marrow progenitors giving rise to erythroid colonies, abnormalities of reticuloendothelial iron metabolism, and correction of anaemia with recombinant human EPO. A model has been developed in which the pathophysiologic processes producing the anaemia of chronic disease may be attributed to actions of the cytokines that mediate the immune response, such as interleukin-1, tumor necrosis factor and the interferons. These cytokines are also implicated in HIV-related anaemia. In this review, the applicability of this cytokine-mediated anaemia model to the anaemia of HIV infection is explored.
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PMID:Cytokines and anaemia in human immunodeficiency virus infection. 942 76

Anemia occurs frequently among patients seropositive for human immunodeficiency virus (HIV), but its multifactorial origin complicates its differential diagnosis and adequate treatment. In addition, the etiology of anemia in HIV infection often remains unclear. In recent years several attempts have been undertaken to elucidate the mechanisms leading to HIV-associated anemia. Direct infection of erythroid progenitors has been discussed, but could not be proven. Furthermore, soluble factors like HIV proteins and cytokines have been suggested to inhibit growth of hematopietic cells in the bone marrow of HIV-infected patients. However, so far no statements can be made whether these factors are directly involved in myelosuppression or mediate their effect by inhibiting growth-factor synthesis. Opportunistic complications represent the underlying cause for anemia in a large number of HIV-infected patients. Next to this rather obvious reason for anemia, iatrogenic anemia induced by myelosuppressive drugs is also very common. It is of note, however, that modern dosages of < 600 mg zidovudine (ZDV) daily rarely cause anemia. Instead, other drugs that can induce anemia itself or by enhancing ZDV plasma concentrations must be considered important contributing factors. Deficiency of vitamin B12, folate and iron are frequently reported in HIV patients. However, specific investigations revealed appropriate storage amounts of these micronutrients. Supplementation may be beneficial in some patients, but often fails to reverse anemia in this population. In anemic HIV patients reticulocytopenia is a consistent finding. Additionally, inadequately low endogenous erythropoietin concentrations have been repeatedly reported. Thus, it is speculated that a blunted erythropoietin feedback mechanism contributes substantially to the pathogenesis of anemia in HIV patients.
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PMID:Pathogenesis and pathophysiology of anemia in HIV infection. 943 73

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.
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PMID:Experience with epoetin alfa and acquired immunodeficiency syndrome anemia. 967 34

Bcl-3 is a proto-oncogene involved in the chromosomal translocation t(14;19) found in some patients with chronic lymphocytic leukemia. It shares structural similarities with and is a member of the IkappaB family of proteins. In this report, involvement of Bcl-3 in hematopoietic growth factor-stimulated erythroid proliferation and differentiation was examined. In TF-1 cells, an erythroleukemia cell line, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) greatly enhanced Bcl-3 expression at both the protein and mRNA levels in association with stimulation of proliferation. Bcl-3 protein was also highly expressed in early burst-forming unit-erythroid (BFU-E)-derived erythroid precursors (day 7) and decreased during maturation (days 10 and 14), suggesting that Bcl-3 is involved in normal erythroid proliferation. In these hematopoietic cells, Bcl-3 was hyperphosphorylated. GM-CSF and Epo modulated the subcellular localization of Bcl-3. Upon stimulation of TF-1 cells with GM-CSF or Epo, the nuclear translocation of Bcl-3 was dramatically enhanced. Overexpression of Bcl-3 in TF-1 cells by transient transfection along with the NF-kappaB factors p50 or p52 resulted in significant induction of an human immunodeficiency virus-type 1 (HIV-1) kappaB-TATA-luceriferase reporter plasmid, demonstrating that Bcl-3 has a positive role in transactivation of kappaB-containing genes in erythroid cells. Stimulation with GM-CSF enhanced c-myb mRNA expression in these cells. Bcl-3 in nuclear extracts of TF-1 cells bound to a kappaB enhancer in the c-myb promoter together with NF-kappaB2/p52 and this binding activity was enhanced by GM-CSF stimulation. Furthermore, cotransfection of Bcl-3 with p52 or p50 in TF-1 cells resulted in significant activation of a c-myb kappaB-TATA-luceriferase reporter plasmid. These findings suggest that Bcl-3 may participate in the transcriptional regulation of certain kappaB-containing genes involved in hematopoiesis, including c-myb.
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PMID:Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors. 969 11

Concerns about the transmission of the human immunodeficiency virus (HIV) have driven the evolution of surgical transfusion practices including the use of preoperative erythropoietin (rhEPO). Although there is significant experience documenting the efficacy of preoperative rhEPO in reducing transfusion requirements for adult patients, there is little experience in the pediatric population. With 178 pediatric patients who underwent surgery for spinal deformity, a retrospective cohort study was performed using patient charts, administrative records, and blood bank computer data. Of these patients, 44% received erythropoietin and 55% did not. From the entire population, 17.5% were in the rhEPO treatment group that received homologous blood transfusion compared with 30.6% in the untreated group (p < 0.05). Among the children with idiopathic scoliosis, this effect was more pronounced, with 3.9% of rhEPO patients receiving blood transfusion compared with 23.5% of nontreated patients (p = 0.006). Additionally, rhEPO treatment was associated with a significantly decreased length of stay only for patients in the idiopathic group (9.3 vs. 6.7, p = 0.02). Use of preoperative erythropoietin in pediatric patients undergoing scoliosis surgery resulted in higher preoperative hematocrit levels. Significantly lower rates of transfusion were noted only in the idiopathic group, however. Although there is a possibility of erythropoietin "resistance" in the neuromuscular and congenital patients, alternative explanations for the lack of effect on transfusion rates may include underdosing and biases existent in this nonrandomized retrospective study.
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PMID:The effectiveness of preoperative erythropoietin in averting allogenic blood transfusion among children undergoing scoliosis surgery. 970 70


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