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)

Drug induced agranulocytosis (DIA) is a potentially lethal disorder characterized by selective neutropenia. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been utilized for its treatment. We report four cases of DIA treated with GM-CSF at the dose of 5 micrograms/kg/day. The patients presented infectious diseases at diagnosis. Median days to obtain 1 x 10(9)/L neutrophils and a normal neutrophil count (NNC), were 7(5-9) and 7.5 (6-10) days, respectively. The infectious disease at diagnosis improved and all patients are alive at the moment of this report. No other adverse effects than thrombocytosis (two cases) and thrombocytopenia (one case) were observed. We consider that GM-CSF could be a safe and effective alternative in the treatment of DIA.
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PMID:Drug-induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor. 807 66

All cases of transient erythroblastopenia in children less than 10 years of age, diagnosed in Sweden during the years 1987-89, were identified. Almost all (51/53) were less than 3 years of age. In this group, the incidence was 4.3/100 000, which is the same as that of acute lymphatic leukaemia. No geographical, but a possible temporal, cluster was seen in 1989. The anaemia was severe in some cases; haemoglobin concentration was less than 40 g/l in 8 of 53 children. Thrombocytosis and neutropenia were common and were attributed to high endogenous erythropoietin activity. Thirty-seven of 53 children were given a blood transfusion. All children recovered and no complications or relapses were seen. Transient erythroblastopenia of childhood is a benign disease, and it is important to make a correct diagnosis to prevent unnecessary anxiety for leukaemia or aplastic anaemia.
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PMID:Transient erythroblastopenia of childhood in Sweden: incidence and findings at the time of diagnosis. 833 93

Interleukin-1 (IL-1) produces many direct and indirect effects in hematopoiesis. Il-1 stimulates hematopoietic progenitors, and enhances production of other cytokines. Experimental data suggest a role in ameliorating the myelosuppression that occurs following cytotoxic chemotherapy. Recombinant human interleukin-1 has now entered clinical trial. We conducted a phase I trial of IL-1 beta alone, and following a myelosuppressive dose of 5-fluorouracil in patients with cancer. A prominent neutrophilia was noted within several hours, with a later, more sustained thrombocytosis. Hypotension was dose-limiting. We observed fewer days of neutropenia following 5-FU plus IL-1 compared to IL-1 alone, but the difference did not reach statistical significance. Early results from other investigators suggest a possible protective effect from chemotherapy-induced myelosuppression. Preclinical data suggest that combinations of IL-1 and lineage specific growth factors may produce synergistic hematologic effects.
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PMID:Interleukin-1: biological effects in human hematopoiesis. 833 49

Recently, four groups reported the cloning of thrombopoietin (TPO), also called c-Mpl ligand, from various species. In this study, we examined the in vitro and in vivo biological activity of TPO and its therapeutic efficacy in experimental animal models. Recombinant human TPO (rhTPO) supported the formation of only megakaryocyte (MK) colonies from rat marrow MK progenitor cells [colony-forming units-megakaryocyte (CFU-MK)] and predominantly acted on GpIIb/IIIa+ CFU-MK at the late stage of differentiation. MKs generated from rat GpIIb/IIIa+ CFU-MK after 3 days of liquid culture in the presence of rhTPO had mature characteristics. rhTPO stimulated an increase in the size of TPO-induced cultured rat MKs and in the number of elongated cytoplasmic processes, also called proplatelets, from these MKs in a dose-dependent manner. Administration of rhTPO to normal BALB/c mice daily for 5 days caused dose-dependent thrombocytosis. Treatment with rhTPO induced an increase in the size and number of marrow MKs and an expansion of the marrow CFU-MK pool. We further examined the effects of rhTPO on chemotherapy-induced thrombocytopenia in animal models. Following treatment with mitomycin C, mice received daily injections of various doses of rhTPO. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the recovery of platelets in a dose-dependent fashion: there was a significant reduction in the decrease in numbers of marrow MKs and CFU-MK with rhTPO treatment. Treatment with rhTPO also significantly improved neutropenia in mitomycin C-treated mice. Similar therapeutic efficacy was observed in cynomolgus monkeys with thrombocytopenia induced by nimustine. In addition, there was no significant change in several serum-chemistry parameters, in C-reactive protein, an acute phase protein, or in some variables involved in the blood-coagulation system. Furthermore, platelets from mice made thrombocytotic by repeated administration of rhTPO showed normal aggregation function. These results strongly suggest the clinical usefulness of rhTPO for the treatment of thrombocytopenia.
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PMID:Cloning of thrombopoietin and its therapeutic potential. 876 22

Diamond-Blackfan anemia (DBA) is a rare, congenital, hypoplastic anemia that usually presents in early infancy. Congenital anomalies, particularly of the head and upper limbs, are present in about a quarter of reported patients. The disease is characterized by a moderate-to-severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Nonresponders usually are transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.
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PMID:Diamond-Blackfan anemia. 944 46

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.
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PMID:Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study. 981 5

Meropenem is a parenteral carbapenem that has been used clinically since 1994. Since the first review of its safety profile in 1995, the patient database has increased substantially. This new safety analysis includes data from 46 clinical trials in hospitalized patients with serious bacterial infections. The additional data comprise patients with lower respiratory tract and intra-abdominal infections, septicaemia and meningitis, and cancer patients with febrile neutropenia, and represents a group of more severely ill patients compared with the earlier review. In total, 4872 patients with 5026 meropenem treatment exposures were compared with 4642 patients treated with comparator agents (4752 exposures). Meropenem was administered most often by intravenous injection at 1g or 500 mg every 8 h. Meropenem-related adverse events most frequently reported were diarrhoea (2.3%), rash (1.4%), nausea/vomiting (1.4%) and injection site inflammation (1.1%). The most commonly reported meropenem-related laboratory adverse events were thrombocytosis (1.6%) and increased hepatic enzymes (1.5-4.3%). In meropenem-treated patients with meningitis, the incidence of seizures was low and none were drug related. In patients with infections other than meningitis, the incidence of seizures considered by the investigators to be related to meropenem was 0.08%. In general, the safety profile of meropenem was similar to that of the comparator agents. Withdrawals and deaths were similarly infrequent in the meropenem, cephalosporin and imipenem-cilastatin groups. Increased doses of meropenem were not associated with an increased incidence of adverse events. Meropenem was well tolerated in all patients, including children and patients with neutropenia. This new analysis supports the previous findings that meropenem has a favourable and acceptable safety profile.
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PMID:Safety profile of meropenem: a review of nearly 5,000 patients treated with meropenem. 1038 Dec 10

A six-year-old cat presented with clinical signs consistent with distal aortic thromboembolism while clinical signs of cardiovascular disease were absent. Diagnostics, including thoracic radiographs, electrocardiography, and echocardiography revealed no cardiovascular anomalies. Thoracic radiographs revealed multifocal pulmonary lesions consistent with neoplasia. Complete blood cell count demonstrated a marked thrombocytosis, leukopenia, and neutropenia. Histopathology of the pulmonary lesions confirmed multiple bronchoalveolar carcinomas. Myelodysplasia with megakaryocytic hyperplasia and ineffective myelopoiesis was noted on bone-marrow histopathology from multiple sites. The absence of other causes suggested a paraneoplastic thrombocytosis. The diagnosis of paraneoplastic thrombocytosis-induced thromboembolism was made due to the lack of underlying cardiac disease and the presence of a marked thrombocytosis. The presence of thrombocytosis and thromboembolism associated with neoplasia is discussed.
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PMID:Paraneoplastic thrombocytosis-induced systemic thromboembolism in a cat. 1058 Sep 7

Over a 16 month period 307 children with suspected tuberculosis (TB) and an available full blood count (FBC) seen at Tygerberg Hospital in South Africa were evaluated and categorized as confirmed (A), probable (B), and no TB (C) according to WHO criteria. There was no difference in the mean age of the 168 group A (33.6 months), 83 group B (34.4 months), and the 56 group C (31.6 months) children. A lower mean haemoglobin (Hb 10.2 vs. 10.8 g/dl) was the only significantly different haematological parameter in children with TB compared with the comparison group (Group C). There were no differences in median total white cell count, neutrophils, lymphocytes, monocytes, platelets, or the proportion of children in each group with anaemia, microcytosis, neutrophilia, neutropenia, lymphocytosis, lymphopenia, monocytosis, thrombocytosis or thrombocytopenia. The most common haematological abnormalities in children with TB were the presence of anaemia, neutrophilia, and monocytosis but these changes were found with equal frequency in control patients. Although haematological abnormalities are fairly common in children with TB, in a developing country these abnormalities also occur frequently in children with other non-tuberculosis respiratory infections. An FBC has no diagnostic predictive value when investigating a child for TB.
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PMID:Haematological abnormalities in children with tuberculosis. 1058 77

Diamond Blackfan anemia is a rare congenital hypoplastic anemia that usually presents early in infancy. Congenital anomalies, in particular of the head and upper limbs, are present in about 25% of reported patients. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. Recent genetic studies have led to the identification of mutations in the ribosomal protein RPS19 in approximately 25% of sporadic and familial cases, a second gene on chromosome 8p, and evidence for an additional locus (or loci). The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Patients who do not respond to treatment are usually transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.
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PMID:Diamond-Blackfan anemia. 1069 94


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