Functional studies on c.1347C>T,a polymorphism modulating phenotypic outcome in X-linked adrenoleukodystrophy

Tijdschrift voor Kindergeneeskunde -     

F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study

Studies on baboons and preliminary observations in three patients with sickle cell anemia (SS) suggested that high doses of pulse administered recombinant human erythropoietin (rHuEPO) stimulate F-reticulocyte production. We now report on the administration of rHuEPO in a double- blind format to ascertain frequency of response and potential precipitation of side effects. Ten patients were enrolled, but one was discontinued due to the indication of a blood transfusion. Of the other nine, five received rHuEPO in escalating doses (from 400 to 1,500 U per kg twice daily [BID] per week), alternating with a placebo, in blinded fashion. The second group, consisting of four patients, followed an identical protocol (except starting dose was 1,000 U/Kg, BID per week) and were iron supplemented during treatment. The criterion of response was a transient doubling (as a minimum) of the steady-state F- reticulocyte level. We found that none of the five patients in the first group responded to rHuEPO, and two of them became iron deficient, as judged by a significant decrease in ferritin. Of the second group, four patients responded with F-reticulocyte increases. In three patients, open label administration of rHuEPO confirmed the effect. We observed seven painful episodes during this study, two during the EPO administration and five during the placebo arm. Three patients were phlebotomized because the hemoglobin level increased 1.5 g/dL more than steady-state levels. Of the six patients followed-up by percent dense cell determinations, one exhibited increased levels during periods of the treatment, whereas the other five showed no change. No anti-rHuEPO antibodies were detected. We conclude that rHuEPO can stimulate F- reticulocyte response in some patients with sickle cell anemia, without apparent negative clinical side effects. The state of iron stores may be critical. Whether higher doses of rHuEPO and/or a different regimen might induce sustained F cells and fetal hemoglobin increases remains to be determined.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

新型降脂药物PCSK9抑制剂在动脉粥样硬化心血管疾病的研究现状

动脉粥样硬化是许多心血管疾病的早期病理改变,脂质代谢紊乱是动脉粥样硬化性心血管疾病（ASCVD）最重要的危险因素之一。前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9） 是血脂调节的关键因子,可以通过与低密度脂蛋白受体（LDLR）结合,降解LDLR从而阻止低密度脂蛋白的清除,导致低密度脂蛋白胆固醇（LDL-C）水平升高,增加心血管疾病的风险。PCSK9也参与炎症细胞因子的生成、内皮功能障碍和动脉粥样硬化斑块的形成。多项研究显示,PCSK9是治疗ASCVD的一个有希望的新靶点。PCSK9抑制剂是目前治疗高胆固醇血症的新型药物。本文就PCSK9抑制剂在动脉粥样硬化中的作用及药物研究进展做一综述,为临床用药提供参考。