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)

Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.
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PMID:HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases. 1 83

Effective inhibition of cell division by anesthetics occurs only when cells are exposed to concentrations more than twice those required for anesthesia. Neutropenia following prolonged inhalation of nitrous oxide seems to be caused by a different mechanism, in which the cobalt in B12 is oxidised to the trivalent form by chemical reaction with nitrous oxide. B12 is thereby inactivated and this interferes with folate metabolism and thymidine synthesis: the effect may be detected after only a few hours in vivo exposure of mammals to 50% nitrous oxide. Unlike lymphocytes, the random motility of human neutrophils is not decreased by in vitro exposure to concentrations of halothane required for anesthesia. Similarly there is no effect on chemotaxis to casein and phagocytosis with exposure up to 2% halothane.
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PMID:Anesthesia and the leucocyte. 39 28

A case of agranulocytosis in a man with nonspecific seronegative polyarthritis treated with levamisole in the form of a proprietary veterinary anthelmintic is described. At the time of presentation he had a relative monocytosis. Recovery was uneventful and was heralded and paralleled by an increase in monocytes, serum vitamin B12 and total vitamin B12 binding capacity. Levamisole induced agranulocytosis and the significance of monocytosis and serum vitamin B12 binding proteins in neutropenia are briefly reviewed.
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PMID:Agranulocytosis in an arthritic patient treated with levamisole. A case report. 42 68

We studied the rate of disappearance of neutrophil hypersegmentation in 23 patients with megaloblastic anemia during therapy with vitamin B12 and folic acid. In 14 patients with uncomplicated megaloblastic anemia, the neutrophil lobe average began to fall towards normal 11.4 +/- 0.3 (SEM) days after treatment was begun and became normal by 13.9 +/- 0.6 days. In nine patients with associated inflammatory disorders, the lobe average returned to normal more rapidly. In six initially neutropenic patients, a five-fold increase in total granulocyte count occurred by the eighth day and a seven-fold increment in the total number of circulating hypersegmented neutrophils. Granulocyte folate concentrations in five folate-deficient patients rose to normal levels within 4 to 7 days of starting therapy. Hypersegmentation thus persists for many days after correction of neutropenia and restoration of normal granulocyte folate levels have occurred. We conclude that cobalamin and folate are needed at two different steps in granulopoiesis.
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PMID:Persistence of neutrophil hypersegmentation during recovery from megaloblastic granulopoiesis. 43 75

Serum unsaturated vitamin B12-binding capacity (UBBC) has been shown to fluctuate with neutrophil levels and has been reported to correlate with TBGP in normal and hyperleukocytic states. However, the present report demonstrates that the above relationship is not present in neutropenia, suggesting that some of our concepts regarding UBBC may have to be reexamined, since factors other than TBGP appear to be operative. There was a wide scatter of UBBC values among the 39 neutropenic subjects studied, the mean being significantly above normal. There were few low values. High UBBC was primarily confined to subjects with transient neutropenia. Normal values were generally seen in steady neutropenia. The difference in UBBC was primarily due to Transcobalamin I, the other serum binders being similar in both groups. No other significant diagnostic pattern of UBBC was found. Recovery from neutropenia was accompanied by a rise in UBBC in all cases except in four patients whose UBBC was initially very high and fell with recovery. No discernible pattern of serum B12 levels existed, although subnormal levels without evidence of B12 deficiency were found in three of the seven patients with aplastic anemia. Serum B12 levels did not change with recovery in approximately half of the neutropenic subjects, change being variable in the others. Neither serum B12, UBBC, total B12-binding capacity, or any of the three serum B12 binders correlated with neutrophil count, bone marrow findings, TBGP, or granulocyte turnover rate.
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PMID:Serum vitamin B12- binding proteins in neutropenia. 112 35

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurologic aspects of cobalamin deficiency. 164 56

The possible mechanisms of neutropenia associated with both human immunodeficiency virus (HIV) infection and drug treatment in adults are examined, and the current and investigational strategies for managing neutropenia are reviewed. Neutropenia associated with HIV arises from diverse mechanisms, including cellular immune dysfunction, direct effects on progenitor cells, humoral immune dysfunction, and vitamin deficiencies. Drug-induced neutropenia may be related to direct cytotoxic effects, immunologic mediators, and the effects of vitamin depletion on the bone marrow. Bone marrow toxicity in patients receiving zidovudine appears to be more frequent in those patients with advanced disease, low CD4 cell counts, a pretreatment anemia, low serum vitamin B12 levels, and low or low normal serum folic acid levels. Patients with AIDS also are at increased risk for adverse events associated with folate antagonists and sulfonamides compared with other patient populations. Lithium therapy has improved neutrophil counts in patients receiving zidovudine; however, the toxicities associated with use of lithium, combined with the lower dosages of zidovudine now recommended, may obviate its use. The use of colony-stimulating factors appears promising for increasing the number and function of circulating neutrophils. Although concomitant use of interferon alfa and zidovudine may result in a strong synergistic anti-HIV effect, dose-limiting neutropenia has been reported in patients receiving the combination. There are currently no controlled data assessing the effectiveness of intravenous immune globulin in the treatment of HIV-related or drug-related neutropenia. In evaluating neutropenia, the clinician must attempt to discern whether the neutropenia is more likely related to disease state(s) or drug therapies. Potential management strategies include modulation of the disease state, discontinuation or dose reduction of the offending agent, or administration of exogenous immune enhancer.
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PMID:Neutropenia in patients infected with human immunodeficiency virus. 203 44

A Phase I study of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was undertaken in 21 patients with advanced malignancy or neutropenia. rhGM-CSF was administered once daily by i.v. bolus injection (0.3 to 3 micrograms/kg/day) or 2-h i.v. infusion (3 to 20 micrograms/kg day) for 10 days. rhGM-CSF at all i.v. doses caused an immediate transient decrease in circulating neutrophils, eosinophils, and monocytes. By 6 h after rhGM-CSF, circulating leukocyte levels were restored. Daily i.v. bolus dosing (0.3 to 3 micrograms/kg/day) did not elevate leukocyte levels except in one neutropenic patient. Daily 2-h i.v. infusions (10 to 20 micrograms/kg/day) caused a dose-dependent leukocytosis with increased levels of neutrophils (up to 4.3-fold), eosinophils (up to 18-fold), and monocytes (up to 3.5-fold). Marrow aspirates showed increased proportions of promyelocytes and myelocytes during rhGM-CSF administration. Retreatment after 10 days without rhGM-CSF resulted in a more marked leukocytosis at doses greater than or equal to 10 micrograms/kg/day. Platelet levels decreased for the first 3 days and then increased during the first course of rhGM-CSF administration. Two patients with chronic lymphocytic leukemia had a transient reduction in lymphocytosis. Serum cholesterol and albumin levels decreased, and vitamin B12 levels increased during rhGM-CSF treatment. At doses of up to 15 micrograms/kg/day, rhGM-CSF was relatively well tolerated by the patients, but adverse effects included bone pain, lethargy, fever, rash, and weight gain. A first dose reaction characterized by hypoxia and hypotension was identified at dose levels greater than or equal to 1 microgram/kg. Dosing i.v. was less potent at inducing a leukocytosis than previously observed for equivalent s.c. doses and was associated with a higher incidence of generalized rash and first dose reactions. The maximal tolerated dose of i.v. rhGM-CSF was 15 micrograms/kg/day. Phase II studies in which the derived effect is to raise leukocyte levels should be undertaken at rhGM-CSF doses of 3 to 15 micrograms/kg/day.
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PMID:Phase I study of intravenously administered bacterially synthesized granulocyte-macrophage colony-stimulating factor and comparison with subcutaneous administration. 240 73

AZT is now the standard of care for all persons with AIDS, ARC or T4 helper cell levels less than 200/mm3. Some authorities are cautiously recommending it with full informed consent for patients who have fewer than 400 mm3 T4 cells or who have sustained a rapid fall in helper cells coupled with new symptoms. The optimum dosage remains to be determined. Although the package insert recommends 200mg p.o. q. 4 hours, b.i.d. and Q6 hour dosage regimes have been reported as being as effective with less toxicity. Folate and B12 levels should be measured and replaced when appropriate to avoid undue hematologic toxicity and therapy should be interrupted for hemoglobin less than 7.5 or neutropenia consisting of fewer than 750 leukocytes/cc. For progressive, less severe marrow toxicity the dose may be decreased to avoid a prolonged nadir. A CBC should be obtained every two weeks for at least the first eight weeks and monthly thereafter if counts are stable. Other toxicities to be monitored include elevated transaminases and co-administration with medications that affect hepatic glucuronidation such as probenecid, NSAID's and acetaminophen. In the eight years since this epidemic appeared on the medical horizon much has been learned about the disease and its treatment. More and more physicians are willing and eager to assume primary care responsibilities for their patients with AIDS and it is hoped AZT and other effective therapies will assist them in this process.
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PMID:AIDS in Arkansas. Zidovudine: an overview and rationale for use. 252 34

A poodle-type dog with bone marrow dyscrasia and macrocytosis was investigated by clinicopathological, cytological and ultrastructural means. Peripheral blood analysis revealed macrocytosis and the presence of nucleated erythroid cells, some with nuclear/cytoplasmic asynchrony. Tendencies towards neutropenia and granulocytic hypersegmentation were observed. Bone marrow examination revealed low normal myeloid to erythroid ratio, the presence of megaloblasts and some giant metamyelocytes. In addition, there were abnormal mitoses, binuclearity and multinuclearity, incomplete nuclear membranes and nuclear clefts, intracytoplasmic parallel-sided membranes and apparent degenerate erythroid cells. Blood biochemical tests indicated normal to high concentrations of serum vitamin B12, serum folate and red cell folate. Transcobalamin I/IIIB12-binding capacity was similar to values for normal dogs, but transcobalamin II-binding capacity appeared high. It was concluded that the condition had similarities to both congenital dyserythropoietic disorders and true megaloblastic conditions, but until further investigations are reported it might be wise to refer to it as "bone marrow dyscrasia" in poodles.
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PMID:Investigations of bone marrow dyscrasia in a poodle with macrocytosis. 258 46


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