High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were measured in the serum of 22 patients with systemic lupus erythematosus (SLE) and 101 of their first degree relatives. Four patients' sera (18%) were positive. Eight sera from relatives were strongly positive (7.9%). All 8 relatives came from different families, and only 3 of them were related to a positive positive proband. All 8 had clinical and/or other serological abnormalities, compared with only 30% of the aCL negative relatives (p less than 0.05). There were no reports or evidence of thrombosis, thrombocytopenia or spontaneous abortion among the aCL positive relatives. Our data indicate a strikingly higher incidence of aCL among relatives of lupus patients compared with controls. This may be associated with an increased incidence of abnormal clinical or serological findings in these individuals, and constitute a feature of a genetic predisposition to SLE.     

Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma

High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%–9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.     

Pathway inhibition: emerging molecular targets for treating glioblastoma

Insights into the molecular pathogenesis of glioblastoma have not yet resulted in relevant clinical improvement. With standard therapy, which consists of surgical resection with concomitant temozolomide in addition to radiotherapy followed by adjuvant temozolomide, the median duration of survival is 12-14 months. Therefore, the identification of novel molecular targets and inhibitory agents has become a focus of research for glioblastoma treatment. Recent results of bevacizumab may represent a proof of principle that treatment with targeted agents can result in clinical benefits for patients with glioblastoma. This review discusses limitations in the existing therapy for glioblastoma and provides an overview of current efforts to identify molecular targets using large-scale screening of glioblastoma cell lines and tumor samples. We discuss preclinical and clinical data for several novel molecular targets, including growth factor receptors, phosphatidylinositol-3 kinase, SRC-family kinases, integrins, and CD95 ligand and agents that inhibit these targets, including erlotinib, enzastaurin, dasatinib, sorafenib, cilengitide, AMG102, and APG101. By combining advances in tumor screening with novel targeted therapies, it is hoped that new treatment options will emerge for this challenging tumor type.     

Derivation of the children's head injury algorithm for the prediction of important clinical events decision rule for head injury in children

Background

A quarter of all patients presenting to emergency departments are children. Although there are several large, well‐conducted studies on adults enabling accurate selection of patients with head injury at high risk for computed tomography scanning, no such study has derived a rule for children.

Aim

To conduct a prospective multicentre diagnostic cohort study to provide a rule for selection of high‐risk children with head injury for computed tomography scanning.

Design

All children presenting to the emergency departments of 10 hospitals in the northwest of England with any severity of head injury were recruited. A tailor‐made proforma was used to collect data on around 40 clinical variables for each child. These variables were defined from a literature review, and a pilot study was conducted before the children''s head injury algorithm for the prediction of important clinical events (CHALICE) study. All children who had a clinically significant head injury (death, need for neurosurgical intervention or abnormality on a computed tomography scan) were identified. Recursive partitioning was used to create a highly sensitive rule for the prediction of significant intracranial pathology.

Results

22 772 children were recruited over 2½ years. 65% of these were boys and 56% were <5 years old. 281 children showed an abnormality on the computed tomography scan, 137 had a neurosurgical operation and 15 died. The CHALICE rule was derived with a sensitivity of 98% (95% confidence interval (CI) 96% to 100%) and a specificity of 87% (95% CI 86% to 87%) for the prediction of clinically significant head injury, and requires a computed tomography scan rate of 14%.

Conclusion

A highly sensitive clinical decision rule is derived for the identification of children who should undergo computed tomography scanning after head injury. This rule has the potential to improve and standardise the care of children presenting with head injuries. Validation of this rule in new cohorts of patients should now be undertaken.One million patients with head injuries attend emergency departments each year in the UK, of whom as many as 50% are children^1,2,3; this proportion is similar in the US, where there are 95 000 hospital admissions from childhood head injuries, at a cost of over US$ 1 billion per year.^4,5,6 In contrast with the high incidence of head injury, mortality is comparatively low (6–10 per 100 000), and as few as 1 in 500 of all people attending the emergency department have a fatal outcome.^7,8 Thus, although emergency physicians see a large number of patients with head injury, they rarely see patients who have life‐threatening intracranial complications after the injury.Over the past decade, several decision rules have been derived and validated using high‐quality methods to identify adults with a head injury who require computed tomography scanning.^{9,10,11,12,13,14} Although children account for as many as half of all head injuries, no such well‐derived multicentre clinical decision rules exist for children. The American Academy of Pediatrics in 1999^14a concluded that they could not advocate an evidence‐based computed tomography scanning strategy because of the poor quality of studies on children.¹⁵ In 2003, The National Institute of Clinical Excellence in the UK found that the quality of studies on childhood head injuries was so poor that they issued a clinical decision rule for children that was derived and validated only in adults.¹⁶Our aim was to derive a sensitive clinical decision rule for the management of children presenting with an acute head injury, which would identify children at high risk so as to undergo computed tomography scanning and allow the remaining patients to be discharged with no investigation.     

白细胞介素1及白细胞介素8在心肌缺血再灌注损伤中的动态演变及药物干预效果

目的:在心肌缺血再灌注损伤中,炎症细胞因子参与其过程的多个环节。实验拟验证白细胞介素1、白细胞介素8因子在此过程中的动态变化,并分析其与药物干预的关系。方法:实验于2005-10/2006-11在新乡医学院形态学实验室完成。①实验分组:选择健康Wistar成年大鼠70只,按随机数字表法分为3组:对照组(n=10)、模型组(n=30)和药物组(n=30)。后两组又分为缺血0.5h,再灌注2,4,8,12,24h6个时相点,每个时相点5只。对照组只设12h一个时相点作为总体对照。②实验方法:大鼠麻醉后,药物组在右股静脉注入甲泼尼龙(30mg/kg),对照组及模型组注入生理盐水(0.75mg/kg)。采用夹闭左冠状动脉前降支建立大鼠心肌缺血再灌注损伤模型。对照组只开胸不夹闭。③实验评估:在各时相点观察各组大鼠缺血再灌注后的心肌细胞改变;血清学检测白细胞介素1、白细胞介素8因子的动态表达。结果:①模型组缺血再灌注12h炎细胞浸润最显著,药物组炎细胞呈散在浸润。②模型组和药物组白细胞介素1、白细胞介素8因子质量浓度明显高于对照组[缺血再灌注8h为例,白细胞介素1分别为(99.21±14.37),(85.77±11.31),(21.87±10.32)ng/L;白细胞介素8分别为(794.85±24.07),(536.95±19.72),(103.94±11.59)ng/L,P<0.05],峰值分别在缺血再灌注4,8h;同时相点药物组白细胞介素1、白细胞介素8因子质量浓度明显低于模型组(P<0.05)。结论:白细胞介素1和白细胞介素8因子在心肌缺血再灌注损伤的炎症反应中发挥着重要作用;甲泼尼龙对缺血再灌注损伤心肌有保护作用。     

Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex

BACKGROUND: Epilepsy is a common neurologic complication of tuberous sclerosis complex (TSC) and it is often refractory to treatment. Therefore, treating physicians are often reluctant to discontinue antiepileptic drugs (AEDs) in individuals with TSC who have attained seizure remission. To our knowledge, seizure remission and AED discontinuation in children with TSC has not been studied. OBJECTIVE: To characterize seizure remission and AED discontinuation in children with TSC. METHODS: Retrospective medical record and neuroimaging analysis of 15 children with TSC and epilepsy who had seizure remission, with a subsequent trial of discontinuation of AED treatment. RESULTS: The seizure remission rate for the group of patients with TSC and epilepsy was 14.2%. From the group of 15 patients who had a remission, the absolute relapse rate was 26.7% after a mean follow-up of 5 years 7 months. Patients with sustained remission were more likely to have normal intelligence and only a few cortical or subcortical lesions on neuroimaging. CONCLUSIONS: The proportion of children with TSC and epilepsy who achieve seizure remission is small. Nevertheless, some do attain seizure remission, and AEDs may be successfully discontinued. Mild cerebral involvement is a general clinical marker for seizure remission. The relapse rate in those who have undergone a trial of discontinuation of AED therapy is comparable with the rate in the general pediatric population with epilepsy.