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)

Enzymaticaly homogeneous fractions of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from peripheral blood of a patient with hairy cell leukemia, or leukemic reticuloendotheliosis, LRE,(with leukopenia, neutropenia, lymphocytosis, and massive splenomegaly). To detect enzymatic deficiencies, the cells were analyzed quantitatively for six leukocytic enzymes on three occasions: 1) before splenectomy, 2) 5 days after splenectomy, and 3) 6 weeks after splenectomy. Before splenectomy, the patient's cells showed moderate deficiency of beta-glucuronidase in lymphocytes and monocytes; server to modorate deficiency of lysozyme and myeloperoxidase in monocytes and granulocytes; and complete absence of neutral protease and alkaline phosphates in neutrophils. Full restoration of neutral protease and a three-fold rise in alkaline phosphatase activities occurred in the patient's neutrophils 5 days after splenectomy. Lysozyme and myeloperoxidase returned to normal in both monocytes and neutrophils of the patient. Six weeks following splenectomy, the alkaline phosphatase activity again disappeared from patient's neutrophils, although neutral protease remained normal. The patient's lymphocytes were unresponsive to PHA and PW mitogen before splenectomy but became responsive 6 weeks postoperatively. Monocytic transfomation into macrophges was supressed before and after splenectomy. The findings indicate that developmenally, in lymphocytic leukemia, a biochemical defect involves the patient's monocytes and neutrophils much more severely than it affects the leukemic lymphocytes. Functionally, the results partly explain the susceptibility of LRE patients to microbial infections.
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PMID:Absence of neutral protease and alkaline phosphatase in neutrophils of a case of hairy cell leukemia. 43 13

Since circulating and marginated human granulocytes are in rapid kinetic equilibrium, cells of these two compartments have been considered to be a homogeneous population. Our studies on the relationship between neutrophil maturity and the granulocyte alkaline phosphatase (GAP) activity cast doubt on this assumption. After iv administration of hydrocortisone, 12 male volunteers showed an augmentation in circulating granulocytes of 5730 cells/mm3, accompanied by an increase of band neutrophils from 18% to 33% (p less than 0.001). During this influx phase, the GAP activity decreased by 73% when measured cytochemically and by 28% when assayed biochemically (p less than 0.001 and less than 0.01, respectively). When granulocytes were demarginated by epinephrine, the mean count increased by 38%, accompanied by a rise in the portion of segmented forms from 74% to 79% (p less than 0.005) and by an increase of the cytochemical GAP activity by 24% (p less than 0.01). Exact complementary results were obtained during an excessive transient margination, the hemodialysis neutropenia: bands increased from 24% to 54% (p less than 0.02), while the cytochemical GAP dropped by 40% (p less than 0.005). Thus, our analysis of three situations with an acute transient shift of granulocytes indicates that functionally or chronologially "older" cells have a higher GAP activity, and that the transfer of granulocyte from the circulating to the marginal pool is selective.
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PMID:Disparity between circulating and marginated neutrophils: evidence from studies on the granulocyte alkaline phosphatase, a marker of cell maturity. 54 24

In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.
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PMID:Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria. 127 74

The study embraces 122 workers from two productions, where the leading chemical noxious in the working environment is benzol. The workers are distributed in groups according to the calculated index of exposure in view of looking for dependence dose-effect. Routine indices of peripheral blood are examined as well as the activity of myeloperoxidase and alkaline phosphatase in leucocytes. An organ-orientated screening, most frequently used for assessing the state of the liver was used. In a large group of workers (mainly from those with high index of exposure) are established early changes in leucocytes: neutropenia, toxic granules, strongly inhibited alkaline phosphatase in the granulocytes and tendency to leukopenia. It was confirmed, that the strongly inhibited alkaline phosphatase, find, which is established also in other workers with benzol exposure, is an early sign for myelotoxic effect of benzol. The biochemical study of workers gives no data for deviations in the functional status of the liver. Single changes in the indices are found characterizing lipid metabolism in workers from Ist risk group of both productions.
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PMID:[The hematological and biochemical changes in workers exposed to benzol]. 136 33

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance may be mediated by repair of chloroethylated guanine before stable cross-linking occurs. Guanine adducts may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (O6-AGAT). Such repair irreversibly inactivates O6-AGAT. Streptozotocin (STZ) forms adducts at the O6 position of guanine; repair of these adducts consumes O6-AGAT. In vivo STZ potentiates BCNU cytotoxicity. The purpose of this trial was to determine the maximum tolerated dose of BCNU that can be administered together with STZ. The STZ dose was 500 mg/m2/day for 4 days and was not escalated. BCNU was given 4 h after the third dose of STZ at a starting dose of 75 mg/m2. A total of 43 patients were entered in the study. There were 4 dose escalations, reaching a maximum tolerated BCNU dose of 175 mg/m2. At this dose, thrombocytopenia was the dose-limiting toxicity (one patient, 25-49 x 10(9)/liter; 2 patients, less than 25 x 10(9)/liter); neutropenia was less severe (2 patients, 2.0-3.9 x 10(9)/liter, 1 patient, 1.0-1.9 x 10(9)/liter). Two other commonly seen toxicities were elevations in the serum alkaline phosphatase and mild elevations in the serum creatinine. Peripheral blood lymphocyte O6-AGAT levels decreased from a mean of 212 fmol/mg protein pretherapy to 8.2 fmol/mg protein on day 3 prior to BCNU (P = 0.03). Three partial responses were seen. There were no therapy-related fatalities, and toxicity was easily managed. This study established that 150 mg of BCNU can be administered safely together with STZ, 500 mg/m2/day for 4 days. Additional studies are required to determine whether O6-AGAT-mediated BCNU resistance is suppressed.
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PMID:Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial. 153 74

Hepatosplenic candidiasis has increased in frequency among immunocompromised hosts. Risk factors include hematologic malignancy, intensive chemotherapy, prolonged neutropenia, and treatment with broad-spectrum antibiotics. Patients most commonly present with abdominal pain, persistent fevers despite antibiotic therapy, and an elevated alkaline phosphatase level that is out of proportion to other hepatic enzyme levels. Gastrointestinal mucosal damage secondary to intensive chemotherapy may allow colonization with Candida species and subsequent seeding of the portal vein. Treatment has consisted of prolonged courses of amphotericin B, with mortality rates approaching 50%. We report a case of hepatosplenic candidiasis in a patient with acute myelogenous leukemia who had clinical and radiographic improvement during fluconazole therapy. Fluconazole may be an efficacious and less toxic alternative to amphotericin B.
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PMID:Fluconazole in the treatment of hepatosplenic candidiasis. 173 74

We describe 5 preterm infants (25th to 30th week of gestation) suffering from alimentary copper deficiency. The diagnosis was confirmed by low serum copper and caeruloplasmin concentrations. Characteristic clinical findings were repeated apnoeic attacks, hypopigmentation of skin and hair, anaemia, neutropenia and leucopenia refractory to other therapy, as well as increasing serum alkaline phosphatase activity in the first month of life. Starting in the 3rd to 12th week of life the radiographic findings were general skeletal osteoporosis and retardation, metaphyseal radiodense lines, irregular metaphyses, cupping and spurring of the metaphyses, followed by multiple fractures and subperiosteal new bone formation and enlarged costochondral junctions. Copper was substituted orally resulting in complete healing of fractures and improvement in both clinical symptoms and laboratory parameters.
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PMID:[The skeletal changes in premature infants with a copper deficiency]. 185 33

Eleven patients with acute non-lymphocytic leukemia developed hepatosplenic candidiasis following the termination of chemotherapy. Five who did not receive amphoteicin B (AMPH) died of liver failure, whereas the other six who received AMPH and/or miconazole or fluconazole were cured. The features of hepatosplenic candidiasis included prolonged high fever not responsive to antibiotics and hepatomegaly with right-sided hypochondrial pain developing after severe neutropenia. Even if the neutropenia recovered, these symptoms did not subside. In addition, elevation of the serum alkaline phosphatase and total bilirubin levels were observed at onset. CT scan revealed multiple low-density areas of varying size that showed no contrast enhancement. Ultrasonography also demonstrated hypoechoic or hyperechoic lesions, and a so-called "target sign appearance" in the liver and spleen. The clinical diagnosis for hepatosplenic candidiasis is not so difficult because of the uniform symptoms, signs and laboratory abnormalities. The importance of the early administration of antifungal agents to obtain a cure is discussed in this article.
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PMID:[Hepatosplenic candidiasis in acute non-lymphocytic leukemia]. 191 11

Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocytosine was successful in two children. At autopsy, one child had signs of active infection. We reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up.
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PMID:Hepatosplenic candidiasis in children with cancer. Three cases in leukemic children and a literature review. 220 7

A 46-year-old male was admitted to our hospital because of relapse of acute myeloblastic leukemia (M2). Remission was successfully reinduced after reinduction chemotherapy consisting of daunorubicin, cytosine arabinoside, etoposide and vincristine, but was complicated by neutropenia. After the therapy, the patient had persistent fever of about 38 degrees C despite broad-spectrum antibiotics therapy and the patient developed pain in the right quadrant of the abdomen. The white blood cell count rose to 23000/mm3. Liver function tests showed abnormal findings mainly consisting of an elevated serum alkaline phosphatase level. Ultrasonography showed multiple hypoechoic lesions in the liver and CT scans also revealed multiple low density areas. Therefore he was suspected of having a complication of liver abscesses. Amphotericin B was administered 75 mg/day intravenously every other day. A percutaneous liver biopsy was performed, but was not diagnostic. Blood cultures were negative for pathogens. Amphotericin B was administered up to a cumulative dosage of 2.3 g, but the patient remained febrile. Then he had an exploratory laparotomy and an open liver biopsy. The liver biopsy samples showed fungal elements proved by PAS staining. A catheter was inserted into the portal vein. Administration of Amphotericin B was started 20 mg daily through the catheter. The temperature fell to normal after institution of this therapy. The abnormal findings in CT scans almost disappeared and the inflammatory findings became negative after he had received intraportal administration of Amphotericin B over three months. Through the analysis of this case study, we confirmed that the intraportal administration of Amphotericin B was effective to the intractable liver abscesses due to fungi.
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PMID:[Liver abscesses successfully treated by intraportal administration of amphotericin B in a case of acute myeloblastic leukemia (M2)]. 221 57


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