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)

We have analysed 139 consecutive cases (71 males and 68 females) of nutritional megaloblastic anaemia over a period of four and a half years. The majority of these patients belonged to the low socio-economic class and many of them were strict vegetarians. Sixty one percent were in the second and third decades of life. At the time of presentation, 46% had mild hepatomegaly, 42% fever, 34% mild splenomegaly and 20% bleeding manifestations. Of 102 cases in whom the biochemical parameters were available, vitamin B12 deficiency was detected in 76%, folate deficiency in 6.8%, combined B12 and folate deficiency in 8.8%; the remaining 7.8% had normal vitamin levels at presentation. All 139 patients had severe anaemia, 80.5% had thrombocytopenia and 43.8% had neutropenia as well as thrombocytopenia. It appears that during progression (in terms of duration) of megaloblastosis, anaemia is followed by thrombocytopenia and then neutropenia. Infection and bleeding in these patients may be aggravated by impaired functions of neutrophils and platelets, respectively.
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PMID:Pancytopenia in nutritional megaloblastic anaemia. A study from north-west India. 263 48

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.
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PMID:The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. 329 90

Congenital dysgranulopietic neutropenia (CDN) is a recently proposed entity that describes a small subgroup of children with clinically severe neutropenia. We followed and studied a 3-year-old girl with neutropenia (less than 500/mm3) and recurrent severe infections in whom repeated marrow evaluations revealed large (30-50 microns) multinucleated promyelocytes to polymorphonuclear cells with as many as 4 to 16 nuclei or nuclear lobes, respectively. In addition to the nuclear endoreduplication, ultrastructural and cytochemical evaluation of these cells demonstrated abnormalities in granule genesis and centriole structure. Concomitantly, immunoperoxidase staining indicated that many of the granules were devoid of lactoferrin but not lysozyme. In vitro proliferation studies revealed normal to increased thymidine labeling, normal numbers of colony-forming cells, and normal colony-stimulating activity from blood and marrow mononuclear cells, findings consistent with ineffective myelopoiesis. However, serum folate, B12, and lysozyme levels were normal. The nuclear and cytoplasmic abnormalities in this patient result in an extreme example of CDN, distinct from previously described cases.
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PMID:Severe congenital neutropenia with unique features of dysgranulopoiesis. 396 63

Clearance of urea, creatinine, phosphate and B12 in dialyzers reused up to 30 times were unchanged from the initial values. Residual formalin values were within acceptable levels and in several thousand dialyses no untoward reactions of any sort attributable to reuse were encountered. Neutropenia was constantly present with dialyzers prepared by automated reuse.
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PMID:Prolonged dialyzer reuse. 653 28

Three patients with idiopathic pancytopenia and hypercellular bone marrow who developed carcinoma of the lung within two years of diagnosis are reported. All three patients had macrocytic anemia associated with a megaloblastic marrow in the presence of normal serum vitamin B12 and folic acid levels. Neutropenia with monocytosis, elevated serum muramidase and LAP scores, and increased fetal hemoglobin levels were also found. In all cases Ham's tests were negative with a normal bone marrow karyotype. In all three patients, pancytopenia due to myelodysplasia, a probable preleukemic state, was diagnosed initially prior to the appearance of carcinoma of the lung. One of the patients showed improved leukocyte and platelet counts during chemotherapy, while the other two died before chemotherapy could be administered. In the light of the above findings we suggest that carcinoma of the lung may be the cause of a paraneoplastic syndrome with pancytopenia, particularly in patients with a hypercellular marrow with a normal karyotype.
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PMID:Pancytopenia with hypercellular bone marrow--a possible paraneoplastic syndrome in carcinoma of the lung: a report of three cases. 672 Jun 84

A study of 196 healthy geriatric females and 26 males confirmed the high prevalence of anemia in this population. Forty-two females (21.4%) had a hematocrit of less than 36% and nine (34%) of the males had a value of less than 40%. A careful evaluation, including a therapeutic trial of oral iron in some subjects, made a diagnosis of iron deficiency anemia in only three and the anemia of chronic disease could be diagnosed in two. No subject had folate or B12 deficiency and hemolytic anemia was not present. Thus, in most of these subjects, the lower hematocrit was not due to commonly recognized causes. Further evaluation revealed a high prevalence of leukopenia in this population; 30% having counts less than 5 X 10(3)/microliter and 10% having values less than 4 X 10(-3)/microliter. Of most importance, leukocyte counts were significantly lower in anemic subjects in whom a high incidence of neutropenia was also demonstrated. This suggests that the mechanisms of the unexplained anemia and neutropenia is an overall reduction in hematopoietic cell numbers. This conclusion is consistent with the observation that many aged subjects have a decreased ability to mount an adequate leukocyte response to infection. These findings suggest that the presence of anemia marks an overall reduction in hematopoietic reserve and provides a clue to those aged subjects of greatest risk of an inadequate response to stress.
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PMID:The anemia of senescence. 727 May 45

The mechanism of neutropenia was studied in 6 patients with pernicious anemia. While the peripheral blood of these patients disclosed neutropenia, the number of myeloid committed stem cells in the bone marrow was increased when compared with values obtained from 15 patients with undisturbed granulopoiesis. In 2 of 3 patients investigated, the number of circulating stem cells was also elevated. In 2 patients the number of stem cells was monitored during treatment with vitamin B12: A rapid decline of stem cells was observed, which was followed by an increase in mature granulocytes. These studies demonstrate an expanded stem cell pool, which is associated with ineffective granulopoiesis.
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PMID:[Ineffective granulopoiesis in pernicious anemia (author's transl)]. 728 79

Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is based on the examination of both blood films and bone marrow aspirate. Diseases such as vitamin B12 and/or folate deficiency, or cytotoxic therapy leading to a marrow dysplasia should be ruled out. Five subtypes are described in the FAB classification : refractory anaemia or refractory cytopenia, refractory sideroblastic anaemia, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation, chronic myelomonocytic leukaemia. This FAB classification is based on a small number of parameters: percentage of blood and marrow blasts, percentage of ringed sideroblasts and blood monocytes. The anaemia is typically normo- or macrocytic, non regenerative, and in half cases is associated with neutropenia and/or thrombocytopenia. During blood film examination, cell abnormalities have to be notified, i.e. anisocytosis, poikilocytosis of red cells, morphological abnormalities of neutrophils including hypogranulation, hypolobulation, abnormal large platelets. The prognostic and the treatment of MDS depend on the subtype of the FAB classification, the patient's age, the percentage of marrow blasts, the importance of cytopenia, the presence or not of cytogenetic abnormalities and the existence or not of HLA-identical donor.
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PMID:[Myelodysplastic syndromes]. 1093 40

Pemetrexed, a thymidylate synthase (TS) and transferase inhibitor, is in phase III trials with Eli Lilly as a potential treatment for several common solid tumors, including non-small cell lung cancer (NSCLC) and mesothelioma [321789], [410731]. Studies on pemetrexed have concluded that not only is the compound a TS inhibitor but also a potent inhibitor of human dihydrofolate reductase (DHFR). The results suggest that pemetrexed acts upon multiple intracellular targets and that the antitumor effect may be derived from its simultaneous inhibition of multiple folate-requiring enzymes [203662]: this compound has been designated as a multitargeted antifolate (MTA) [386680]. The drug also causes concentration- and time-dependent apoptosis [284380]. Other studies in which the 4-oxo group of the pyrimidine ring portion of pemetrexed was replaced with a hydrogen atom, demonstrated that the resulting analogs were potent DHFR inhibitors with very little activity against the enzymes glycinamide ribonucleotide formyltransferase (GARFT) and TS [310674]. In phase II European studies in 64 patients with advanced breast cancer, encouraging responses were seen in anthracycline-failure (23%) and anthracycline-refractory (19%) patients. Responses were observed in 28% of patients who had been previously treated with a taxane [326097]. Data from a phase II trial of pemetrexed (500 mg/m2 once every 21 days as a 10 min i.v. infusion) as a salvage therapy in advanced breast cancer showed that supplementation of the treatment regime with folic acid (FA) and vitamin B12 reduced its already manageable and tolerable toxicities [408821], [409650]. At doses of 500 mg/m2, the drug was also safely administered to 35 patients with impaired renal function [409953]. Phase I and II trials have shown that the main side effects include neutropenia, thrombocytopenia, mucositis, nausea and vomiting [203666], [272241]. Princeton University holds the patent rights to this drug under EP-00432677. In June 2001, Lilly expected to launch the product in 2003 [412318]. In February 1999, Lehman Brothers predicted launch of the drug in 2001 [319225]. In February 1999, Deutsche Bank predicted sales of $100 million in 2001 rising to $400 million in 2003 [316821]. In November 1999, Lehman Brothers estimated peak revenues in excess of $1 billion [348368]. By September 2001, Bear Stearns & Co predicted sales of $35 million in 2002, rising to $125 million in 2005 [422325].
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PMID:Pemetrexed disodium (Eli Lilly). 1176 66

Pemetrexed (Alimta) is a novel multitargeted antifolate that has activity against non-small-cell lung cancer (NSCLC). As a single agent, the response rate is 16%-23%. As second-line therapy, it has a 5% and 14% response rate with pemetrexed in NSCLC patients who have had prior cisplatin or nonplatinum chemotherapy, respectively. Pemetrexed combined with cisplatin has a response rate of 38.9%-44.8%, with a median survival of 8.9-10.9 months. Pemetrexed plus gemcitabine in NSCLC has a response rate of less than 25%. The major toxicity associated with pemetrexed is neutropenia, which may be reduced with vitamin B12 and folate nutritional supplement. Additional studies with pemetrexed in combination with other agents are needed for the treatment of NSCLC patients.
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PMID:Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. 1472 Mar 51


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