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)

Hemodynamic and hematologic effects of protamine reversal of low molecular weight heparin (LMWH) anticoagulation with and without protamine pretreatment, as well as reversal of anticoagulation with unfractionated standard heparin (SH), were studied in canine subjects. Protamine reversal caused less severe thrombocytopenia in the two LMWH groups compared to SH animals, while neutropenia occurred equally in all groups. Cl-esterase inhibitor levels were minimally increased, whereas C3 levels and leucotriene levels were unaltered. TxB2 and 6-keto-PGF1 alpha increased during protamine reversal of LMWH anticoagulation. TCT and APTT were affected less with LMWH than SH anticoagulation. Anti-Xa levels increased with anticoagulation in all animals, but protamine did not reverse the elevated anti-Xa levels in LMWH anticoagulated dogs to the same degree as occurred with SH anticoagulation. TCT, APTT and bleeding times were normalized by protamine in all animals. Protamine reversal of LMWH anticoagulation with or without protamine pretreatment did not reveal any clear differences in eicosanoids or complement factors compared to SH anticoagulation, although differences in anti-Xa activity clearly separated these two heparins.
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PMID:Protamine reversal of anticoagulation achieved with a low molecular weight heparin. The effects on eicosanoids, clotting and complement factors. 282 39

Cutaneous biopsy specimens from 22 patients showed the distinctive histopathologic pattern of necrobiotic xanthogranuloma within the dermis or subcutaneous tissue (or both). Twenty of the 22 patients had 1 or more serum protein abnormalities, consisting of an IgG monoclonal protein in 16, multiple myeloma in 3, cryoglobulinemia in 3, and an abnormal serum protein electrophoresis in 1. Cutaneous lesions were seen as discrete, slowly developing red nodules and plaques with a xanthomatized hue and a predilection for the face (periorbital region in particular), trunk, and extremities. Ulceration was a notable finding in 10 patients. Histologically, the dermis and lobules of subcutaneous tissue were involved with a granulomatous infiltrate containing bands of hyaline necrobiosis and bizarre foreign body, as well as Touton giant cells. Cholesterol clefts, lymphoid nodules with or without germinal centers, and foci of plasma cells were variable but significant features. Leukocyte monoclonal antibody studies in 6 patients demonstrated helper T cells within the granulomas. Electron microscopy in 3 cases showed lipid vacuoles in macrophages in the dermis and dendritic cells in the epidermis, and study confirmed this entity as a non-X histiocytosis. Pertinent laboratory findings, in addition to the serum protein abnormalities, included elevation of the erythrocyte sedimentation rate, leukopenia with absolute neutropenia, and decreased serum complement levels, as well as decreased levels of C1-esterase inhibitor in some patients. Thirteen of the 22 patients have survived, the mean duration being 9.5 years after the onset of cutaneous disease. While given to only a few patients in the current series, low-dose chemotherapy seems to induce a favorable response in both the cutaneous and the hematologic disease.
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PMID:Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. 309 54

Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia.
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PMID:Disturbances of blood coagulation associated with Salmonella typhi infections. 335 16

1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.
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PMID:Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. 367 93

A patient with low-grade lymphocytosis, splenomegaly, and neutropenia, but adequate myeloid leukogenesis, was found to have chronic lymphocytic leukemia, which represented a clonal proliferation of a distinct T-lymphocyte subset. The lymphocytes did not form E rosettes but had an OKT3+, OKT4+, OKT6+, OKT8+, OKT11+, HNK-1+, HNK-36+, OKIa1+, OKM1+ phenotype and functionally had suppressor and natural killer activity. Morphologically, they were large granular lymphocytes, which were strongly acid phosphatase positive and nonspecific esterase negative. They did not respond to mitogens, or to allogeneic cells. Initially, the spleen appeared to be the most involved organ and, judging from the high proportion of leukemic splenic lymphocytes in the S and G2/M phases of the cell cycle, was also the organ of origin of the leukemic cells. Only a few leukemic cells in the blood and bone marrow were in S and G2/M phases. After splenectomy, the lymphocyte count rose considerably and the bone marrow became progressively more infiltrated by tumor nodules. One year after diagnosis, the patient was started on chemotherapy because of progressive anemia. He responded to the chemotherapy by normalization of the hemoglobin and neutrophil count and had a moderate decrease in the bone marrow involvement and peripheral lymphocytosis.
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PMID:Natural killer and suppressor T-cell chronic lymphocytic leukemia. 622 21

Twenty-one patients are described with a proliferation of morphologically mature T lymphocytes. The clinical course was chronic in most, and splenic enlargement the main clinical finding; skin involvement and lymphadenopathy were rare. The mean lymphocyte count at presentation was 8 X 10(9)/1 (range 0.75-24 X 10(9)/1). Nineteen of these patients showed some form of cytopenia (18 neutropenia, two red cell aplasia, eight thrombocytopenia) and one had hypogammaglobulinaemia. Seven patients had long-standing arthropathy serologically proven to be rheumatoid arthritis and these had previously been considered to have Felty's syndrome. Five of the group have died (three with an aggressive course), but most have remained stable for prolonged periods with a slow increase in peripheral lymphocyte count and marrow infiltration. Spontaneous regression was never observed but in two patients a prolonged remission was achieved by chemotherapy. The lymphocytes were morphologically and phenotypically homogeneous at presentation and remained so post-splenectomy; they contained azurophilic granules, stained with acid phosphatase but weakly or not at all with alpha napthyl acetate esterase. Membrane phenotyping shows the majority of the cells to be E+, Fc gamma+, OKT3+, OKT8+. Most cells do not stain with OKT1-like reagents and a significant number express HLA-Dr. From these and other reported cases it is clear that this condition represents a distinct entity resulting from the expansion of a subset of cytotoxic/suppressor T cells--the question of the benign or neoplastic nature of the disease remains open. Using T cell-specific antisera and E-rosetting techniques, a small percentage of CLL cases have been shown to be of T-cell origin (TCLL) (Dickler et al, 1973; Lille et al, 1973). Estimates of the percentage vary but in most series T-CLL has been diagnosed in less than 5% (Brouet & Seligmann, 1981), and this is supported by date from the M.R.C. Leukaemia Unit which found T-CLL in only 1.5% of 600 cases of CLL examined by marker studies (D. Catovsky, unpublished). Amongst the published reports of T-CLL a variety of clinical and morphological entities have been described including T prolymphocytic leukaemia (TPLL) (Brouet et al. 1975) and adult T cell disease in Japanese (Uchiyama et al, 1977) and West Indian Caribbean groups (ATLL) (Catovsky et al, 1982). In the original series of Brouet & Seligmann (1981) the group was defined as presenting in middle age with marked hepatosplenomegaly, some lymphadenopathy, skin involvement and with an aggressive disease course; peripheral blood and marrow lymphocytosis were variable.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic T cell lymphocytosis: a review of 21 cases. 633 88

This communication reports the clinical and cellular features of five elderly female patients with persistent moderate to severe neutropenia and concomitant relative expansions of CD3+TCR gamma delta+ (n = 4) or CD3+TCR alpha beta+CD4-CD8- (n = 1) lymphocyte populations. In clinical terms, severe neutropenia was the main contributing factor to patient symptoms although two additionally had long-standing histories of rheumatoid arthritis. The absolute lymphocyte counts did not exceed the normal upper limit in these patients, and morphologically the lymphocytes were not typically of large granular lymphocyte (LGL) type although LGL-associated BLT-esterase staining was consistently increased. Expression of NK-associated (NKa) membrane determinants (CD16, CD56 and CD57) were variable but there was an apparent correlation between weak membrane CD8 and CD16 expression. DNA genotypic studies confirmed that the four CD3+TCR gamma delta+ cases were clonal in nature and add further support to an emerging impression that expansions of these lymphocyte subpopulations may frequently be clinically associated with autoimmune phenomena in general and neutropenia in particular.
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PMID:Persistent clonal expansions of CD3+TCR gamma delta+ and CD3+TCR alpha beta+CD4-CD8- lymphocytes associated with neutropenia. 781 2

A 46-year-old female presented with acute myeloid leukemia during complete remission of multiple myeloma after extensive treatment with alkylating agents. Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT-PCR analyses of peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels of MDR1. The patient expired during neutropenia shortly after induction chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190-type BCR-ABL rearrangement has not previously been reported. The possibility that the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have contributed to the treatment-refractory course is discussed.
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PMID:Drug resistance of secondary acute myeloid leukemia with megakaryoblastic features and p190 BCR-ABL rearrangement. 978 5

Exatecan mesylate (DX-8951f) is a new hexacyclic camptothecin analogue with favorable attributes compared to topotecan and CPT-11, including watersolubility, greater potency against topoisomerase I, lack of esterase-dependent activation, broad antitumor activity, and low cross-resistance against MDR-1 overexpressing tumors. In preclinical studies, the compound demonstrated a favorable toxicology profile with hematologic dose-limiting toxicity and moderate gastrointestinal toxicity, linear pharmacokinetics, P450 hepatic metabolism (CYP3A4 and CYP1A2), and predominately fecal excretion. The results of six U.S. and European phase I clinical trials as well as two Japanese studies are presented including total DX-8951 and lactone DX-8951 pharmacokinetics. The toxicity profile was similar for all schedules of administration. Hematologic toxicity was dose-dependent and reversible. Neutropenia was dose-limiting in minimally pretreated patients, whereas neutropenia and thrombocytopenia were dose-limiting in heavily pretreated patients. Non-hematologic toxicity included moderate gastrointestinal toxicity (nausea, vomiting > diarrhea), transient elevation of hepatic transaminases, asthenia, and alopecia. Two cases of acute pancreatitis not predicted by preclinical toxicology were also observed. Antineoplastic activity was detected in several solid tumor types: non-small cell lung cancer, extrapulmonary small cell cancer, colorectal cancer, hepatocellular cancer, and sarcoma. Antitumor activity was seen in CPT-11 and topotecan-resistant tumors. Pharmacokinetics were linear within the dose range tested. A pharmacokinetic/pharmacodynamic model predictive of DX-8951f-induced neutropenia in individual patients was developed. The daily x5, every 3-week schedule with the drug administered as a 30-minute intravenous infusion was selected for future phase II clinical trials based on its superior antitumor activity.
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PMID:DX-8951f: summary of phase I clinical trials. 1119 1

An 18-year-old female alpaca was presented to the Colorado State University Veterinary Teaching Hospital for chronic ill thrift over a 1-year period. Six weeks previously, an infected left mandibular cheek tooth was removed by oral extraction. On physical examination the patient was cachectic, lethargic, and weak. Abnormalities on the CBC included neutropenia, thrombocytosis, and severe nonregenerative, macrocytic, hypochromic anemia. Dysplastic nucleated erythrocytes and micromegakaryocytes were observed on the peripheral blood smear. Neutrophils, bands, and metamyelocytes appeared markedly toxic. Numerous blasts containing variable numbers of fine azurophilic granules were also observed. Based on their morphology, the cells were interpreted to be progranulocytes and myeloblasts, and a presumptive diagnosis of acute myeloid leukemia (AML) was made. The blast cells accounted for 60% of the nucleated cell population on bone marrow aspirates, further supporting a diagnosis of AML with multilineage dysplasia. Post mortem examination showed infiltration of the neoplastic cells into spleen, liver, kidney, and lymph nodes. Based on histologic findings, the morphologic diagnoses were disseminated myeloid neoplasia, chronic regionally extensive tooth root abscess, and membranous glomerulonephritis. The neoplastic cells were CD172a-positive on flow cytometry, chloroacetate esterase-positive by cytochemistry, and myeloperoxidase-positive by immunohistochemistry, confirming myeloid origin. To our knowledge, this is the first case of AML with multilineage dysplasia in an alpaca, with only one other case of myelodysplasia described previously in this species.
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PMID:Acute myeloid leukemia with multilineage dysplasia in an alpaca. 1876 21


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