Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental thrombocytopenia results in endothelial alterations associated with bleeding. In this study prednisone was shown to prevent or reverse these changes, which supports the clinical inference that adrenocorticosteroids decrease capillary fragility in thrombocytopenia. Rabbits (3-4 kg), intraperitoneally injected with busulfan, developed 98-99% reductions in platelet count and hemorrhaged profusely. Orally administered prednisone (0.2 mg/kg or 1.0 mg/kg daily) reduced bleeding despite persistent thrombocytopenia. Tongue biopsies obtained after 3 days of prednisone treatment were examined by electron microscopy. Normal rabbits served as controls. 25 consecutive capillaries or venules from each of four animals in the control group and each of five experimental groups were examined for fenestrations, "thin spots" (<800 A thick), and mean wall thickness as determined by planimetry. Vessels from control animals had no thin spots or fenestrations, and the mean vessel wall thickness was 4,254+/-105 A SEM. The 100 vessels from the thrombocytopenic animals had a mean vessel wall thickness of 2,081+/-218 A (P < 0.001), and 42 had thin spots of fenestrations. After administration of the smaller dosage of prednisone, the mean vessel wall thickness increased to 3,556+/-40 A (P < 0.001), and only nine vessels had thin spots or fenestrations. With the larger dosage, only six vessels had thin spots or fenestrations and the mean vessel wall thickness of this group increased to 3,704+/-206 A (P < 0.005). All preparations demonstrated normal endothelial junctions. The data are consistent with the hypothesis that the bleeding of thrombocytopenia is caused by altered capillary and venule endothelium and that diminished bleeding observed with prednisone administration results from amelioration of these endothelial changes.
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PMID:Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit. 90 55

Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital or acquired platelet function defect, or uremic bleeding to assess its effects and side effects. DDAVP significantly shortened the bleeding time as compared with basal values. The mean peak post-DDAVP level of factor VIII coagulant activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von Willebrand factor revealed that type I vWD had complete correction after DDAVP infusion transiently. Except for a mild drop in both systolic and diastolic blood pressures, few side effects were noted. By concomitant intravenous infusion of DDAVP and oral administration of tranexamic acid, we successfully treated two cases of type I vWD undergoing tooth extraction, and one case of acquired bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient complicated by intractable traumatic hematuria. Our experiences confirmed that most patients with vWD and some patients with congenital or acquired bleeding disorders can be treated effectively by DDAVP infusion without the need for plasma product replacement. In this study we found that a patient with a variant form of type I vWD had prolongation of the bleeding time, thrombocytopenia and platelet aggregation after DDAVP infusion.
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PMID:Experience of desmopressin (DDAVP) administration in patients with congenital and acquired bleeding disorders. 136 75

Ganciclovir (DHPG) was used in 32 renal transplant recipients with proven cytomegalovirus (CMV) disease. Mean time of CMV occurrence from grafting was 49 days. CMV disease was recognized on the combination of both clinical signs and histological or virological findings. DHPG treatment, adapted to renal function was given for 14 days and a pharmacokinetic study was performed at days 1, 7 and 14. Twenty nine patients, 10 of whom has severe to moderate disease, were improved by treatment. Three patients died, 2 of them with severe pulmonary and hepatic diseases. Few adverse effects were observed (leucopenia: n = 7, thrombopenia: n = 2, abdominal pain: n = 1). CMV was no longer found in virological samples in 80 percent of the patients. Maximal plasma concentration of DHPG (9.3 +/- 0.3 micrograms/ml, m +/- SEM) was reached at the end of the one hour infusion and decreased according to a biexponential model. The half life of elimination was 3.35 +/- 0.32 hours, the metabolic clearance 128 +/- 7 ml/min and the distribution volume about 50 percent body weight (0.48 +/- 0.02 l/kg). The clearance of DHPG was greater than creatinine clearance, and was linearly correlated with it, suggesting that renal elimination was important, both by glomerular filtration and tubular secretion. These results indicate that DHPG is effective and well tolerated for the treatment of CMV disease in renal transplant recipients. Renal elimination of the drug requires dosage adjustment to renal function.
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PMID:[Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients. Clinical and pharmacokinetic study]. 166 77

Hemodialysis induces thrombocytopenia and activation of coagulation. The severity of this reaction depends on the kind of membrane. In this study, we present the results of determination of platelet count, and of different factors of coagulation in 10 stable dialysis patients. Measurements were performed at the start and after 15 and 45 min of dialysis. Samples were taken before and after the dialyzer. All 10 patients were treated consecutively and in a random order during 14 days with the following membranes: polyacrylonitrile (Filtral 12, Hospal), hemophan (GFS 120 Plus, Gambro, and Bio-Nephros HF Andante, Organon), polysulfone (F6, Fresenius), cuprammonium (AM50-BIO, Asahi) and cellulose acetate (Duo-Flux, Cordis-Dow). The cellulose acetate membrane induced a small but significant drop of mean platelet count [results are mean (SEM)]: from 245,000 (17,000) to 224,000 (16,000)/microliters after 15 min. With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 (9) to 146.7 (35.7) pg/ml. The other membranes did not influence significantly prostanoid levels and platelet count. During dialysis no significant changes of fibrinopeptide A (FPA) and von Willebrand factor (VWF) were observed. Nevertheless, predialysis FPA and beta-thromboglobulin (beta TG) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes. It is concluded that the activation of coagulation depends on the membrane used. The activation may be dominated by one single system (e.g. prostanoids). The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period.
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PMID:Evaluation of platelets and hemostasis during hemodialysis with six different membranes. 176 95

To assess the incidence and mechanisms of thrombocytopenia and neutropenia in neonates with Rh hemolytic disease, we studied 20 consecutive patients with this condition who were born at our hospital. All five patients with severe disease (hydrops) had neutropenia and thrombocytopenia before and after exchange transfusions. Two of six patients with moderately severe disease (not hydropic but requiring exchange transfusion) had neutropenia; all six had thrombocytopenia. Of nine patients with mild disease (not treated with exchange transfusions), two had neutropenia but none had thrombocytopenia. The mean platelet volume was low or normal (7.5 +/- 0.2 ft) in the patients with thrombocytopenia, and the neutropenia was not accompanied by a "left shift" (ratio of immature to total neutrophils 0.26 +/- 0.03, mean +/- SEM). In two severely affected patients, erythroid progenitor levels were elevated and their proliferative rates (tritiated thymidine suicide) were increased, whereas their granulocyte-macrophage progenitor levels and the proliferative rates of those progenitors were diminished. In a severely affected patient, the in vitro maturation of multipotent progenitors was altered, with production of a greater than normal proportion of normoblasts (p less than 0.01) but fewer neutrophils (p less than 0.02) and megakaryocytes (p less than 0.03). It appears that the marked increase in erythropoiesis in fetuses with Rh hemolytic disease can be accompanied by a down-modulation of neutrophil and platelet production.
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PMID:Neutropenia and thrombocytopenia in infants with Rh hemolytic disease. 249 15

Therapy of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) with azidothymidine (AZT) and 2'-3'-dideoxycytidine (ddC) is complicated by severe anemia, neutropenia, and thrombocytopenia, the cause of which is unknown. We therefore tested the effect of AZT, ddC, and an additional 2'-3'-dideoxynucleoside analogue, 2'-3'-dideoxyadenosine (ddA), on the hematopoietic progenitor cells derived from the bone marrow of normal persons and patients with AIDS/ARC. All three substances dose-dependently inhibited the in vitro colony formation of the pluripotent (CFU-GEMM), as well as the erythroid (BFU-E) and granulocyte-macrophage progenitor cells (CFU-GM). The 50% inhibition of normal progenitors by AZT occurred at 0.13 microM for CFU-GEMM, 0.32 microM for BFU-E, and 1.9 microM for CFU-GM, by ddA at 15 microM for CFU-GEMM, 40 microM for BFU-E, and 140 microM for CFU-GM. ddC was the most toxic agent and already inhibited 71% +/- 16% (mean +/- standard error of the mean [SEM]) of CFU-GEMM and 52% +/- 22% of BFU-E at 0.1 microM, whereas the 50% inhibition of CFU-GM was reached at 0.3 microM. Hematotoxicity occurred at concentrations lower than necessary to inhibit the human immunodeficiency virus (HIV), except for ddA, which is 100 times less toxic than AZT whereas its antiviral effect is only 10 times less. The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT.
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PMID:Inhibitory effect of azidothymidine, 2'-3'-dideoxyadenosine, and 2'-3'-dideoxycytidine on in vitro growth of hematopoietic progenitor cells from normal persons and from patients with AIDS. 254 17

The in vitro effect of recombinant human GM-CSF (rHuGM-CSF) was tested on bone marrow-derived multilineage (CFU-GEMM) as well as megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitors in a group (n = 16) of patients with myelodysplastic syndromes (MDS). Hematopoietic progenitor cell growth was markedly impaired in MDS patients as compared to normal controls (p less than 0.05, at least). Recombinant HuGM-CSF supported the growth of CFU-GEMM, CFU-Mk, and BFU-E at lower, equivalent, or slightly higher frequencies that those found in cultures plated with medium conditioned by peripheral blood leukocytes (PHA-LCM), but it was invariably ineffective in improving growth values. Recombinant HuGM-CSF supported the growth of granulocyte-macrophage colonies in 15 of 16 cases. The overall incidence (mean +/- SEM) of CFU-GM in cultures containing rHuGM-CSF (5 ng/ml) was significantly higher than the one found in cultures stimulated with PHA-LCM (40 +/- 15 vs. 17 +/- 7, p less than 0.05). Upon culture with rHuGM-CSF (5 ng/ml), in 5 of 15 patients de novo colony formation was observed (8 +/- 4) and in 4 of 15 patients CFU-GM growth (129 +/- 33) fell within normal range. Doses of rHuGM-CSF higher than 5 ng/ml did not result in a further increase of MDS-derived colony formation. It is concluded that rHuGM-CSF (a) does not improve the growth of CFU-GEMM, CFU-Mk, and BFU-E; (b) may completely restore the growth of CFU-GM in a subgroup of MDS patients; (c) while ineffective in improving anemia and thrombocytopenia, its in vivo in MDS may correct leukopenia through an effect at the level of granulocyte-macrophage progenitor cell compartment, at least in a subset of highly responsive patients.
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PMID:Growth of human hematopoietic colonies from patients with myelodysplastic syndromes in response to recombinant human granulocyte-macrophage colony-stimulating factor. 265 96

Although immune mechanisms are known to be partially responsible for the thrombocytopenia of patients infected with HIV-1, an understanding of the mechanism underlying this disorder is incomplete. A casual observation that bone marrow biopsies of HIV-infected individuals seem to exhibit an unusually large number of denuded megakaryocyte nuclei (DN-MK) prompted a study comparing MK of 20 HIV-seropositive individuals with those of 10 patients with HIV-negative idiopathic thrombocytopenic purpura and 10 hematologically normal subjects. In normal marrows the number of DN-MK average 2.1 +/- 0.5 SE per 10 low power field. In patients with ITP the average number was 6.5 +/- 1.4 SEM, whereas HIV-ITP marrows had an average of 42.5 +/- 3.7 SEM. Electron microscopy of AIDS megakaryocytes exhibited ballooning of the peripheral zone to an extent not seen by us in any other myelodysplastic syndromes. These observations support the concept that the pathophysiology affecting MK/platelets in HIV-infection should not be equated with the destructive process underlying other immune thrombocytopenias.
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PMID:Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1). 275 19

The effects of nafazatrom on leukocyte function in vitro and in vivo were related to its ability to salvage ischemic myocardium in an occlusion-reperfusion model of myocardial injury in the anesthetized dog. Nafazatrom (0.4-75 microM) produced dose-related inhibition in vitro of neutrophil aggregation, superoxide anion generation, arachidonic acid metabolism, and, to a lesser extent, the release of beta-glucuronidase. In contrast, nafazatrom (0.4-37.5 microM) did not substantially influence platelet aggregation or the platelet metabolism of arachidonic acid. In vivo nafazatrom (10 mg/kg, po) reduced infarct size from 58 +/- 3% of the risk area (mean +/- SEM, n = 9) in control dogs to 23 +/- 2% of the risk area (n = 9, P less than 0.01). Nafazatrom also reduced the incidence of accompanying arrhythmias. Nafazatrom-induced myocardial salvage was not associated with any hemodynamic changes; moreover, it was independent of platelets, since thrombocytopenia did not prevent nafazatrom from exerting a protective effect. Measurements of the neutrophil-specific myeloperoxidase enzyme in ischemic myocardium indicate that the smaller infarct size in dogs treated with nafazatrom is accompanied by diminished leukocyte infiltration. Thus, the ability of nafazatrom to inhibit neutrophil function in vitro and cell infiltration in vivo may underly its myocardial-protective effects.
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PMID:Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. 298 18

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t1/2 lambda 1 of 9.8 +/- 1.2 (SEM) min and mean t1/2 lambda z of 64.1 +/- 8.9 (SEM) min. The large variation observed in t1/2 lambda z was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t1/2 lambda z or the area under the curve. This may be due to a failure to monitor active metabolites of mitomycin C; other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or the small number of courses associated with thrombocytopenia (less than 100,000/mm3). Our study indicates that an interaction of drug dose and treatment course may be associated with increasing t1/2 lambda z; the renal clearance contributes a small component of mitomycin C elimination; metabolites of mitomycin C cannot be detected by the present HPLC technique; and routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.
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PMID:Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma. 310 86


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