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Mixed medulloblastomatous tumours are known to comprise several histological characteristics. A three year old boy is reported with a tumour containing elements of medulloblastomatous, rhabdomyosarcomatous and melanotic tissues.  相似文献   
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Objectives To study the frequency of insulin resistance (IR) in endometrial cancer patients, its relation to the clinical course of the disease and DNA damage, and to evaluate possible approaches to the pharmacological correction of IR in the patients studied.Methods The signs of insulin resistance syndrome and its association with the clinical and pathological features of the disease and DNA damage in somatic cells (micronucleus frequency in peripheral blood lymphocytes) and endometrial normal and tumor tissue (alkaline unwinding) were determined in 99 endometrial cancer patients.Results The frequency of insulin resistance syndrome counted on the basis of fasting plasma glucose and insulin concentrations according to Duncan et al. is equal to 0.35 (95% CI 0.24–0.46), or 35%, in endometrial cancer patients who do not have a history of diabetes mellitus. Patients with well- or moderately differentiated endometrial adenocarcinomas (mostly type I) had statistically significantly higher basal and stimulated plasma insulin and C-peptide concentrations than patients with poorly differentiated endometrial adenocarcinomas or rarely encountered tumors of the endometrium (primarily type II). Interestingly, the level of fasting insulinemia positively correlates with disease stage and with local and regional tumor dissemination only in the group of patients with well- or moderately differentiated endometrial adenocarcinomas. On the other hand, hyperinsulinemia and other hormonal-metabolic disturbances typical of insulin resistance syndrome do not increase the probability of DNA damage of somatic cells (according to the data of micronucleus test). In addition, no association between hormonal-metabolic disturbances and the degree of DNA unwinding in tumor and visually unchanged endometrium was found.Conclusion Thus, insulin resistance/hyperinsulinemia is associated with a more aggressive course of the disease in certain groups of the patients but—in contrast to excessive estrogenic stimulation—does not result in increased genotoxic damage in tumor and normal tissues. The data obtained once more confirm the need for treatment and prevention measures aimed at correcting hormonal-metabolic disturbances in endometrial cancer patients and groups at risk of this disease. Such an approach might include use of antidiabetic biguanides, thiazolidinediones (glitazones), and statins.  相似文献   
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BACKGROUND: In clinical practice, HLA matching is generally applied to minimize the incidence of graft rejection after transplantation. Recently, graft rejection has been directly associated with the presence of preformed alloreactive T cells before transplantation. Despite this knowledge, assays to rapidly quantify preformed alloreactivity are not available for use in a clinical setting. In this study, such an assay was developed and evaluated in a large cohort to correlate alloreactive T-cell reactivity with HLA matching. METHODS: Stimulator peripheral blood mononuclear cells were prestained with CD45-fluorescein isothiocyanate antibody and mixed with responder peripheral blood mononuclear cells. Activation-induced cytokine secretion was blocked using brefeldin A. After 6 hr, functionally active alloreactive responder CD4 and CD8 T cells were quantified among fluorescein isothiocyanate-negative cells by their expression of interferon-gamma on flow cytometry. RESULTS: Directly alloreactive CD4 and CD8 T cells among both stimulators and responders were easily distinguished after 6 hr of stimulation without being affected by bystander activation. Among 128 paired combinations, 23.4% of individuals had alloreactive CD8 T cells, 15.7% had alloreactive CD4 T cells, and 12.5% had alloreactivity in both T-cell subpopulations. Alloreactive T cells decreased from circulation within a few days after transplantation. In line with well-known clinical observations that associate HLA matching with graft outcome, the number of HLA-A and -B mismatches correlated with alloreactive CD8 T-cell frequencies in the whole study population, whereas it did not predict alloreactivity on an individual basis. CONCLUSION: Alloreactive T cells may rapidly be quantified after 6 hr of stimulation. Thus, the flow cytometric approach may be applied in a clinical setting to facilitate the individualization of immunosuppressive therapy and studies on the identification of patients who are at increased risk to develop graft rejection.  相似文献   
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Paracetamol (acetaminophen) is generally considered to be the analgesic of choice for patients undergoing oral anticoagulant therapy. Occasionally, however, interactions have been reported with therapeutic doses of the analgesic, e.g. if the drug is taken for a longer period of time. The mechanism of this interaction is not clearly understood. We investigated the effects of paracetamol and its toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) on in vitro vitamin K-dependent gamma-carboxylase (VKD-carb) and vitamin K epoxide reductase (VKOR) activities. Paracetamol had no effect in either enzymatic reactions. NAPQI, on the other hand, appeared to interfere with VKD carb activity via two mechanisms; 1) oxidation of the cofactor vitamin K-hydroquinone, 2) inactivation of the enzyme. The inactivation, in micromolar ranges, is not reversible and may be the result of covalent binding of NAPQI with functional amino acids. NAPQI also inhibited VKOR, but at higher concentrations. Unexpectedly, N-acetylcysteine was found to inhibit VKOR activity at concentrations that are obtained during rescue therapy of paracetamol intoxication. We conclude that, the potentiation of the oral anticoagulant effect by paracetamol is likely to result from NAPQI-induced inhibition of enzymes of the vitamin K cycle, particularly VKD-carb.  相似文献   
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Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.e. medrogestone) 17alpha-hydroxyprogesterone derivatives (i.e. chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate), 19-norprogesterone derivatives (i.e. nomegestrol, promegestone, trimegestone, nesterone), 19-nortestosterone derivatives norethisterone (NET), lynestrenol, levonorgestrel, desogestrel, gestodene, norgestimate, dienogest) and spironolactone derivatives (i.e. drospirenone). Some of the synthetic progestins are prodrugs, which need to be metabolized to become active compounds. Besides the progestogenic effect, which is in common for all progestins, there is a wide range of biological effects, which are different for the various progestins and have to be taken into account, when medical treatment is considered.  相似文献   
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OBJECTIVE: Our objective was to study the pharmacokinetics of R - and S -acenocoumarol in a subject who was highly sensitive to the anticoagulant effect of acenocoumarol. The subject was found to be heterozygous for CYP2C9*3. METHODS: The plasma pharmacokinetics of the acenocoumarol enantiomers was established after an oral dose of 8 mg of racemic acenocoumarol. Urine was collected to establish the formation clearance of the 6- and 7-hydroxy metabolites of R - and S -acenocoumarol. RESULTS: The pharmacokinetics of S -acenocoumarol in this subject differed greatly (oral clearance, 6%-10%; half-life of elimination, 400%-500%) from the values of a [wt/wt] control and from population values. R -acenocoumarol clearance was at the lower level of population values. The apparent formation clearances of the metabolites were low-approximately 10% of control activity for the hydroxylations (6- and 7-) of S -acenocoumarol and for the 7-hydroxylation of R -acenocoumarol. The rate of the 6-hydroxylation of R -acenocoumarol was about 50% of control values. CONCLUSION: The presence of even one copy of CYP2C9*3 reduces profoundly the metabolic clearance of S -acenocoumarol. As a result the first-pass effect of elimination is abolished and the maintenance time is increased. S -Acenocoumarol, which is normally clinically inactive, will now exert main anticoagulant activity.  相似文献   
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