Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased susceptibility to infections in patients with myelodysplastic syndromes (MDS) is thought to be due to neutropenia as well as functional abnormalities of neutrophils. In the present study we examined the effect of two different stimulants (fMLP, PMA) and three cytokines (alphaTNF, G-CSF and GM-CSF), both singly and in combination on granulocyte (RB) in 25 MDS patients compared to seven healthy controls. Single fMLP and PMA-stimulation showed similar results for both groups. Preincubation with cytokines enhanced fMLP-stimulated RB in most MDS patients and controls, but in patients to a significantly lesser extent when compared to the control group (p < or = 0,05). Combinations of alphaTNF + GM-CSF and alphaTNF + G-CSF were highly synergistic in priming fMLP-stimulated burst in both groups. But again, as with the single cytokine priming this effect was markedly reduced in MDS patients compared to controls (p < or = 0,05). A specific priming defect for one of the cytokines or a cytokine combination could not be demonstrated. Serum alphaTNF levels were measured in 18 and neutrophil alkaline phosphatase (NAP) index in 23 patients. Results did not correlate with variations of the RB in MDS patients. We conclude that reduced alphaTNF, GM-CSF and G-CSF priming of granulocyte RB is a frequent finding in MDS and may contribute to the enhanced susceptibility to bacterial infections.
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PMID:Cytokine priming of the granulocyte respiratory burst in myelodysplastic syndromes. 937 5

Multilineage hematopoietic defects occur in patients with human immunodeficiency virus (HIV) infection and affect therapy of the disease and of associated opportunistic infections and neoplasms. Anemia and neutropenia are common in HIV patients, and can occur as a result of HIV-related myelosuppression or complications or may be secondary effects of antiretroviral or other agents used in management of the disease. With the advent of combination drug therapy for the treatment of HIV infection and prophylaxis and treatment of infectious complications, myelosuppression is frequently encountered and may be treated with synthetic hematopoietic growth factors. Erythropoietin has been shown to increase mean hematocrit levels and to reduce transfusion requirements in anemic HIV-infected patients receiving zidovudine. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor have been shown to increase neutrophil counts in patients with AIDS-related bone marrow failure and those receiving zidovudine, interferon-alpha, or ganciclovir. Although recent research using interleukin-2 (IL-2) has shown that use of this cytokine in AIDS patients can lead to increases in CD4 cell counts that appear to be functional, further study is needed to determine whether cytokines can play a role other than palliation in HIV-infected patients.
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PMID:Cytokine use in the management of HIV disease. 938 9

Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. There is increased mortality with vesnarinone at the 120 mg daily dose, however, suggesting a narrow therapeutic window for the drug. Its predominant toxic side effect is a 2% incidence of reversible neutropenia.
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PMID:Vesnarinone: a new inotropic agent for treating congestive heart failure. 942 Jun 57

Ten pediatric patients with solid tumors and chemotherapy-induced neutropenia were given recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM CSF). The duration of the neutropenic phase was then compared with the results obtained from eight patients also with solid tumors, but not treated with rHuGM-CSF. It was found that rHuGM-CSF treatment significantly decreased the duration of the neutropenic phase. Endogenous plasma GM-CSF, IL-3, and IL-4 levels were also measured in the study group and in healthy children. No significant correlation has been found between plasma GM-CSF concentrations and absolute neutrophil counts. However, IL-3 levels of the neutropenic patients positively correlated with platelet counts. Furthermore, IL-4 concentrations were positively correlated with the GM-CSF level in the same individual. Plasma GM-CSF, IL-3, and IL-4 levels in the neutropenic solid tumor group were found to be significantly higher than those in healthy children. Plasma IL-4 levels were significantly elevated in patients with osteosarcoma as compared to patients with other solid tumors. Although rHuGM-CSF has a half-life of only two to three hours, one day after rHuGM-CSF therapy, plasma GM-CSF levels were found to be higher than initial values. In contrast, plasma IL-4 values decreased significantly after administration of rHuGM-CSF. The probable mechanisms for the changes in cytokine levels are discussed.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor therapy and endogenous plasma GM-CSF, IL-3, IL-4 concentrations in pediatric patients with solid tumors. 943 49

We describe the medical management of isolated renal zygomycosis in an adult patient with AIDS during chemotherapy for AIDS-related lymphoma. After initial presentation during the first cycle of chemotherapy, the infection was contained within the kidney following recovery of the neutrophil count without medical or surgical intervention. Since he was not considered to be a candidate for nephrectomy, his infection was treated with amphotericin B lipid complex during subsequent chemotherapy. Neutropenia was minimized by the addition of cytokine support therapy with granulocyte colony-stimulating factor and reduced doses of chemotherapy. Following this strategy, his lymphoma completely resolved, and renal zygomycosis was controlled. At the time of this writing, he had been in complete remission for 18 months without evidence of progressive fungal infection. This report and our literature review indicate that isolated renal zygomycosis can be associated with a favorable prognosis, occurs with greatest frequency in patients with AIDS, is associated with parenteral access, and may be managed by medical therapy alone.
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PMID:Successful medical management of isolated renal zygomycosis: case report and review. 952 30

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G-CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in-vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.
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PMID:Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor. 955 64

Granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) are cytokines which have been extensively administered as monotherapy to patients with a variety of hematopoietic disorders at dosages of 5 mcg/kg/day. Because their spectrum of activity is both singular and simultaneously overlapping, we postulated that combined therapy would be more advantageous than monotherapy. Since 1992 we have carried out a study of G-CSF and GM-CSF as monotherapy or in combination in pediatric patients with solid tumors following chemotherapy induced nadirs of 0-800 WBC/mm3. When combined, the cytokines were given twice per day at 2.5 or 5.0 mcg/kg. For the monotherapy groups, either cytokine at 5 mcg/kg or 10 mcg/kg was given once daily. The mean time to recovery from neutropenia nadir ranged from 6.6-8.2 days in patients receiving a total of 10 mcg/kg/day compared to 10.4-10.6 days in patients treated with 5 mcg/kg/day. Side effects were ephemeral eosinophilia. The dosage of 10 mcg/kg/day appears to be a better dosage for pediatric patients with a slight advantage in the combined twice a day schedule (6.6 days).
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PMID:Shortened time to recovery from chemotherapy induced neutropenia in pediatric patients with high dose combined cytokines. 956 67

Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and CD56+, but not CD57+, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages of perforin-expressing and granzyme B-expressing CD16+ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified.
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PMID:Defective natural killer cell activity of peripheral blood lymphocytes correlates with the degree of neutropenia in patients with chronic idiopathic neutropenia of adults. 961 29

Management of fungal infections is a major medical problem. The risk of developing a fungal infection is higher for patients who are undergoing dose-intensive therapy, are immunocompromised, have neutropenia, are receiving prophylactic antibiotics, have other infections, have invasive catheters, or have a history of severe trauma or burns. Survival is decreased among patients who develop fungal infection in these situations. In view of the high morbidity and mortality associated with fungal infections in transplant recipients, cytokines that enhance cell function, such as macrophage colony-stimulating factor (M-CSF), have been investigated. M-CSF enhances cytotoxicity, superoxide production, phagocytosis, chemotaxis, and secondary cytokine production in monocytes and macrophages. Animal models and clinical data suggest efficacy of M-CSF in controlling fungal infection.
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PMID:Use of macrophage colony-stimulating factor in the treatment of fungal infections. 963 46

Thrombopoietin, also termed the c-Mpl ligand, is a lineage-dominant hematopoietic factor that primarily regulates megakaryopoiesis and thrombopoiesis. Treatment of normal animals with recombinant human megakaryocyte growth and development factor, a truncated molecule of the c-Mpl ligand, which is modified with polyethylene glycol (PEG-rHuMGDF), and glycosylated recombinant thrombopoietin stimulates the expansion of bone marrow megakaryocytes and their progenitors, and greatly enhances the production of morphologically and functionally normal platelets. In contrast, this cytokine has only minimal effects on peripheral leukocyte and erythrocyte counts. In myelosuppressed animals, PEG-rHuMGDF or glycosylated thrombopoietin accelerates multilineage hematopoietic recovery effectively improving thrombocytopenia and, in most models, leukopenia (or neutropenia) and anemia. In addition to daily multiple injections, even a single injection of PEG-rHuMGDF after myelosuppressive treatment is fully effective for hematopoietic recovery. In clinical trials, PEG-rHuMGDF or glycosylated recombinant human thrombopoietin potently stimulates thrombopoiesis in cancer patients before chemotherapy. The administration of PEG-rHuMGDF alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces the duration of severe thrombocytopenia and in some cases platelet nadirs in patients with advanced cancers after dose-intensive chemotherapy. The recombinant hormone is well-tolerated with little drug-related toxicity.
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PMID:Update on thrombopoietin in preclinical and clinical trials. 966 60


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