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)

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

Leukopenia or pancytopenia as a result of bone marrow dysfunction are manifestations of various diseases or complications of therapeutic regimens. The spectrum of diseases associated with leukopenia is wide and includes congenital as well as acquired neutropenias secondary to conditions such as myelodysplastic syndromes, AIDS, malignant tumors with or without chemotherapy-enhanced neutropenia, bone marrow transplantation or therapeutic or accidental radiation. The morbidity and mortality of infectious diseases is greatly enhanced during neutropenic phases. Over the last few years attempts have been made to shorten the duration and lessen the severity of neutropenia in patients with the above conditions by administration of Granulocyte Macrophage Colony Stimulating Factor (G-CSF). Both cytokines were successfully tested in phase I and II trials. Treatment with GM-CSF or G-CSF results in a dose-dependent increase of the neutrophil count. GM-CSF also increases the number of eosinophils and monocytes in peripheral blood. The effect of both cytokines on the neutrophil count is transient as long as the underlying disease persists. This prompted the institution of maintenance therapy, which has been successfully used with either cytokine. Long-term treatment is usually well tolerated and results in a reduction in the frequency of infections as well as in the duration of antibiotic treatments. Side effects of GM-CSF or G-CSF are usually mild and include fever, myalgia, bone pain, and erythema. A number of patients developed dyspnea, hypotension, sweating, flushing and erythema after the first dose of GM-CSF in each treatment cycle. This first-dose reaction occurs more frequently after intravenous than reactions were reported with G-CSF. Some patients with myelodysplastic syndrome progressed to acute myeloic leukemia during or after treatment with GM-CSF or G-CSF. Most of these patients presented with an increased fraction of blasts in the bone marrow, which preceded the treatment with the colony stimulating factors. Since GM-CSF and possibly G-CSF may increase the risk of developing acute leukemia in patients with myelodysplastic syndrome, it appears prudent to limit the use of these cytokines in patients with this disease. The subcutaneous route of administration appears to be preferable to intravenous administration, since the incidence and severity of side effects are reduced. While many questions concerning dosage, long-term therapy and combination therapy still remain unanswered, the information presented in this review concerning the clinical use of these cytokines warrants an optimistic outlook.
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PMID:[GM-CSF and G-CSF: cytokines in clinical application]. 170 94

Acute episodes of erythroblastopenia in children with chronic hemolytic anemias have been recognized for a considerable length of time. In 1981, a small virus with a single strand of DNA, parvovirus B 19, was identified as the causative agent in most such episodes. Other diseases have been ascribed to parvovirus B 19, including erythema infectiosum or fifth disease, polyarthralgia, fetal death. Schonlein-Henoch disease, and bone marrow aplasia. In acute attacks of erythroblastopenia, anemia is the most prominent manifestation, but coexistence of neutropenia and thrombopenia has been reported. Hematologic disorders last for approximately ten days. The diagnosis of recent parvovirus B 19 infection rests on detection of specific IgM antibodies, or direct visualisation of the virus by electron microscopy. More recently, detection of the viral genome using molecular hybridization techniques has been achieved. In vitro studies have confirmed the inhibiting effect of parvovirus B 19 on red cell line progenitors, particularly CFU-E, but the exact mechanism of the inhibition remains uncertain. Other diseases due to parvovirus B 19 or other parvoviruses probably remain to be discovered.
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PMID:[Parvovirus infections in children with hemolytic anemia]. 255 72

Healthy adult volunteers were inoculated intranasally with human parvovirus obtained from an asymptomatic blood donor. One week after inoculation, intense viremia was observed in seronegative volunteers, accompanied by a mild illness with pyrexia, malaise, myalgia, itching, and excretion of virus from the respiratory tract. In the following week hematologic studies revealed reticulocytopenia with an associated slight drop in hemoglobin concentration, lymphopenia, neutropenia, and a drop in platelet counts. At 17-18 days after inoculation a second-phase illness with rash and arthralgia lasting three to four days occurred in three of four infected volunteers. This study confirms the etiologic role of human parvovirus in erythematous rash illness, with the second-phase illness being consistent with adult cases of erythema infectiosum. Moreover, the hematologic changes associated with infection support the hypothesis that the same virus is responsible for the temporary arrest of erythropoiesis that leads to aplastic crisis in persons with chronic hemolytic anemia.
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PMID:Experimental parvoviral infection in humans. 299 31

Aspergillosis may complicate the course of the child in an immunocompromised state. When sinus or pulmonary infections present in immunocompromised children, one third of these patients are diagnosed accurately premortem as resulting from aspergillosis and two thirds remain undiagnosed. Mortality remains quite high, despite prompt treatment. Four children in our hospital during the last 4 years have had invasive aspergillosis presenting other than sinus or pulmonary infections. Each presented with extensive soft tissue infection. Three presented after traumatic devascularizing injuries to the leg in which massive soil and fecal contamination occurred. One child presented with absolute neutropenia secondary to treatment of acute lymphocytic leukemia. The child had a chest wall lesion develop at the site of an EKG electrode. All patients had a punctate black skin lesion with a halo of intense erythema surrounded by a zone of blanching. These lesions rapidly expanded. Initial extensive debridement of the lesions, combined with systemic chemotherapy with amphotericin B failed to halt the progression of the disease. Histology showed vascular invasion with hyphal forms. Each patient then responded well to radical debridement (three hemipelvectomies and one chest well resection). The child in an immunocompromised state who develops a red papule, then a black eschar with surrounding erythema, should have immediate biopsy that can easily demonstrate the characteristic hyphal forms. Early radical surgical debridement and antifungal therapy can be lifesaving. The initial debridement should include tissues well beyond any apparent involvement.
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PMID:Invasive aspergillosis in children. 361 39

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Human parvovirus B19 has been associated with several diseases. Aplastic crisis in patients with chronic hemolytic anemia, erythema infectiosum, hydrops fetalis and arthritis are among the common diseases caused by this virus infection. In the period between July, 1991, and March, 1992, 48 patients with aplastic crises were hospitalized at Saudi Aramco-Dhahran Health Center, Dhahran, Saudi Arabia. Forty-six patients had homozygous sickle cell disease, one had hemoglobin H disease and one had hereditary elliptocytosis. Evidence of recent human parvovirus infection was present in 91% of the cases. Leukopenia was present in 21%, neutropenia in 27% and thrombocytopenia in 42%. This differs from previous reports in which red blood cell aplasia causing anemia was the only hematologic finding reported in most patients. There were no cases of erythema infectiosum in either the patients or the community during the epidemic and the reason for this phenomenon is not obvious. The almost limited occurrence of aplastic crisis in patients with sickle cell disease in a population with a high incidence of other types of chronic hemolytic anemias is of interest.
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PMID:An epidemic of aplastic crisis caused by human parvovirus B19. 771 86

B 19 parvovirus is a widespread virus with primary infestation generally occurring in childhood through family and community outbreaks. Its most typical manifestation is transient erythroblastopenia with aplastic crisis, often profound, mostly affecting patients with chronic hemolytic anemia, and eventually patients with defective erythropoiesis (chronic hypoplastic anemia, iron deficiency anemia). In normal individuals the primary infestation is usually asymptomatic but may give transient hematological signs for few days: moderate reticulocytopenia, thrombopenia and neutropenia. Clinically two phases of the infection are described: 1.) a first phase of viremia of 2 to 3 days which may be accompanied by fever and myalgias; 2.) a second phase which may last for several weeks with dermatological signs, the most typical being erythema infectiosum, vasculitis, arthralgias or arthritis. In pregnant women, the primary infestation with B 19 parvovirus may lead to fetal anemia and hydrops fetalis with uneven outcomes: fetal death, chronic erythroblastopenia after birth, spontaneous resolution. Although the incidence of fetal infestation in non immunized pregnant women is still unknown, the question is raised of the recognition and protection of non immunized pregnant women at high risk of exposition to infested subjects. Long term persistence of the virus in the organism may be responsible for chronic manifestation, essentially but not exclusively in immunodeficient-patients: prolonged erythroblastopenia and chronic rheumatologic manifestations. It may be also responsible for cases of juvenile arthritis, thrombocytopenic purpura and chronic neutropenia of childhood. The diagnosis of the viral infestation is mainly based upon the detection of specific IgM, then IgG, antibodies by Elisa technique.
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PMID:[Parvovirus B19 and pediatric pathology]. 795 39

Human parvovirus B19 (B19) is a known cause of erythema infectiosum (fifth disease) and aplastic crisis in patients with hemolytic anemias. When patients with malignant diseases are infected by B19 during chemotherapy, erythroid suppression of bone marrow sometimes occurs. We performed a retrospective investigation of B19 infection among 95 children with malignant diseases in our hospital during the past 14 years. By the method of dot blot hybridization, 9 of 95 patients were found to be positive for B19 DNA during chemotherapy. All 9 patients had reticulocytopenia at the time B19 DNA was detected in their serum samples. Neutropenia and thrombocytopenia were not found. Seven of them had only transient reticulocytopenia. Serum samples from 2 other patients were positive for B19 DNA for a longer time. They suffered from persistent anemia for about 2 and 13 month, respectively. The years when B19 DNA was detected from the 9 patients corresponded to the prevalence of erythema infectiosum in Japan.
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PMID:Retrospective study on the influence of human parvovirus B19 infection among children with malignant diseases. 823 78

A nineteen-year-old woman whose Hodgkin's disease had relapsed experienced acral erythema in association with a asymptomatic pericardial friction rub following autologous bone marrow transplantation. An echocardiogram revealed a large pericardial and right pleural effusion. Since blood cultures gave negative results, renal function was normal, and the patient had neither neutropenia nor elevated temperature, an infectious cause was deemed unlikely and invasive procedures were not performed. These effusions resolved spontaneously. We propose that this patient's acral erythema and associated pericardial and pleural inflammation represent cutaneous and serosal toxic reactions to high-dosage chemotherapy that occur with the onset of leukocyte recovery. If so, acral erythema may signal the beginning of a toxic drug reaction. The appearance of erythema associated with lymphocyte recovery is due to immune hypersensitivity secondary to immaturity of the reconstituting immune system. Thus, we recommend that patients with acral erythema be examined for pleuropericarditis, especially if they experience chest pain.
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PMID:Pericarditis associated with acral erythema of chemotherapy: a syndrome of cutaneous and serosal toxicities? 840 22


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