An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect

Multimerin is a massive soluble, multimeric protein found in platelets and endothelial cells. Recent studies identified multimerin as a specific coagulation factor V binding protein, complexed with platelet, but not plasma, factor V. These findings led us to investigate individuals with inherited factor V deficiencies for possible multimerin abnormalities. Platelet proteins were evaluated using immunoassays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, immunoprecipitation, and direct binding studies. Patients with factor V Quebec, a disorder with abnormal platelet factor V, had a quantitative deficiency in multimerin (n = 11 tested; mean, 12.5%; range, 5% to 27% of the normal pool; normal range, 45% to 214%) with a normal multimer pattern. Quantitative and qualitative abnormalities were detected in their platelet factor V. An unrelated patient who was deficient in platelet and plasma factor V had normal platelet multimerin. The levels of platelet beta- thromboglobulin, von Willebrand factor, thrombospondin, and fibrinogen antigen were normal in the factor V Quebec patients. However, proteins with abnormal mobility were detected in their platelet lysate and releasate, and their platelet thrombospondin, von Willebrand factor, and fibrinogen showed evidence of proteolytic degradation. Platelet counts of the factor V Quebec patients ranged from mildly thrombocytopenic to low normal (mean, 159 x 10(9)/L; range, 104 to 198 x 10(9)/L). In addition, their platelets failed to aggregate in response to 6 to 10 micromol/L epinephrine despite normal numbers of platelet alpha 2-adrenergic receptors. These data indicate that patients with factor V Quebec have an inherited bleeding disorder distinct from other platelet disorders and associated with multiple abnormalities, including multimerin deficiency, abnormal platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen, and an epinephrine aggregation defect.     

Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602)

Of 1,036 children with newly diagnosed non-T, non-B acute lymphoblastic leukemia (ALL) and a demonstrated cytogenetic abnormality treated on the frontline Pediatric Oncology Group (POG) therapeutic trial 8602, there were 33 patients with trisomy 21 as the sole abnormality. Of these 33, 14 had Down syndrome (DS). Although the non-DS (NDS) trisomy 21 cases tended to be older than the DS cases, there were no other significant differences in clinicobiologic features nor in treatment outcomes between the DS and NDS groups, nor between the entire trisomy 21 group and the other chromosome abnormality group. Among NDS patients with +21 and one additional abnormality, +X, +16, -20, and structural abnormalities involving 6q or 12p were common findings. Kaplan-Meier event-free survival (EFS) curves showed a 4-year EFS of 80% (SE, 12%) in NDS trisomy 21 cases, 71% (SE, 22%) in DS cases with trisomy 21 as the sole abnormality, and 69% (SE, 2%) in cases with other chromosome abnormalities. Trisomy 21 as a sole acquired abnormality in NDS patients suggests a good prognosis.     

Double bypass for inoperable pancreatic malignancy at laparotomy: postoperative complications and long-term outcome

INTRODUCTION

Between 4% and 13% of patients with operable pancreatic malignancy are found unresectable at the time of surgery. Double bypass is a good option for fit patients but it is associated with high risk of postoperative complications. The aim of this study was to identify pre-operatively which patients undergoing double bypass are at high risk of complications and to assess their long-term outcome.

METHODS

Of the 576 patients undergoing pancreatic resections between 2006 and 2011, 50 patients who underwent a laparotomy for a planned pancreaticoduodenectomy had a double bypass procedure for inoperable disease. Demographic data, risk factors for postoperative complications and pre-operative anaesthetic assessment data including the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) and cardiopulmonary exercise testing (CPET) were collected.

RESULTS

Fifty patients (33 men and 17 women) were included in the study. The median patient age was 64 years (range: 39–79 years). The complication rate was 50% and the in-hospital mortality rate was 4%. The P-POSSUM physiology subscore and low anaerobic threshold at CPET were significantly associated with postoperative complications (p=0.005 and p=0.016 respectively) but they were unable to predict them. Overall long-term survival was significantly shorter in patients with postoperative complications (9 vs 18 months). Postoperative complications were independently associated with poorer long-term survival (p=0.003, odds ratio: 3.261).

CONCLUSIONS

P-POSSUM and CPET are associated with postoperative complications but the possibility of using them for risk prediction requires further research. However, postoperative complications following double bypass have a significant impact on long-term survival and this type of surgery should therefore only be performed in specialised centres.     

雷洛昔芬对绝经后猴子冠状动脉粥样硬化的影响

已证实雷洛昔芬在骨和胆固醇代谢中起雌激素激动剂的作用，而在乳腺和子宫起雌激素拈抗剂的作用：本文研究雷洛昔芬是否具有雌激素激动剂作用，是否能预防冠状动脉粥样硬化，并与传统的结合雌激素治疗的疗效相比较。卵巢切除（即手术绝经）的短尾猴，喂食会导致冠状动脉粥样硬化的食物，然后分别以安慰剂、雷洛昔芬每日1mg、     

Clinical Features of Crohn''s Disease in Ireland

Irish men and women are at equal risk of developing Crohn's disease. Age at diagnosis (12--mean 30.5-75 yr) and duration of symptoms before diagnosis (1--mean 35.7-444 months) are similar to those for Crohn's disease in other countries. The proportion of patients with macroscopic involvement of the large bowel at diagnosis (68%) is increasing and this is probably a true increase. At the same time the incidence of perianal disease is probably decreasing. Extraintestinal manifestations probably occur more frequently than previously recognized. Crohn's disease and psoriasis, which occurred in 7% of the patients, are probably associated disorders.     

中国与澳大利亚老年冠心病患者左冠状动脉病变特点的对比研究

目的探讨中国南京和澳大利亚悉尼地区的老年冠心病患者左冠状动脉病变是否存在种族和性别差异。方法经冠状动脉造影确诊的冠心病患者,年龄≥60岁,中国南京地区黄种人入选1442例(男性72.0%)为中国组,澳大利亚悉尼当地白种人同期入选1309例(男性65.6%)为澳大利亚组。从左冠状动脉病变率和Gensini积分,左前降支(LAD)和左回旋支(LCX)各段及主要分支病变率及狭窄程度进行比较。结果2组男性患者左冠状动脉病变率显著高于同组女性(P<0.05),但2组患者左冠状动脉的Gensini积分无显著的性别差异(P>0.05)。中国组LAD和LCX近中段的病变率以及LAD和LCX各段及分支(除LCX远段外)的狭窄程度均显著高于澳大利亚组(P<0.001)。结论中国组与澳大利亚组在冠心病危险因素、左冠状动脉病变的分布、狭窄程度和Gensini积分方面存在种族差异。中国组较澳大利亚组具有更严重的左冠状动脉病变,而且没有明显的性别差异。