TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme

SummaryPurpose In order to improve the survival of patients with a glioblastoma multiforme tumor (GBM), new therapeutic strategies must be developed. The use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing Ligand) seems a promising innovative therapy. The aim of this study was to quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2 and TRAIL on primary GBM specimens and to correlate this expression with survival.Experimental design Expression of TRAIL and TRAIL-receptors was assessed by immunohistochemistry, both quantitatively (% of positive tumor cells) and semi-quantitatively (staining intensity) within both the perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR of GBM tissue was performed to show expression of TRAIL receptor mRNA.Results Immunohistochemistry showed a slight diffuse intracytoplasmic and a stronger membranous staining for TRAIL and TRAIL receptors in tumor cells. Semi-quantitative expression of TRAIL showed a significantly higher expression of TRAIL in the perinecrotic zone than in the intermediate zone of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was positively correlated with survival (P=0.02). Multivariate analysis of TRAIL-R1 within the study group (n=62) showed that age, gender, staining intensity, antigenic load, % of TRAIL-R1 expression, were not statistically correlated with survival however radiotherapy was significantly correlated (multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity: P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058; radiotherapy: P=0.0001). Subgroup analysis of patients who had received radiotherapy (n=47) showed a significant association of % of TRAIL-R1 expression and the antigenic load of TRAIL-R1 with survival (multivariate analysis: P=0.036, respectively, P=0.023).Multivariate analysis of TRAIL-R2 staining intensity and antigenic load, within the study group (P=0.004, respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004), showed a significant association with survival. RT-PCR analysis detected a negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of astrocytic tumors (P=0.03).Conclusions TRAIL-R1 and TRAIL-R2 expression on tumor cells are independent prognostic factors for survival in patients with a glioblastoma multiforme. Both receptors could be targets for TRAIL therapy. As TRAIL-R2 is more expressed, in comparison with TRAIL-R1, on GBM tumor cells, TRAIL-R2 seems to be of more importance as a target for future TRAIL therapy than TRAIL-R1.     

臂丛神经根性损伤膈神经移位术对青壮年患者早期呼吸功能的影响

目的研究臂丛神经损伤膈神经移位术对青壮年患者早期呼吸功能的影响.方法对16例接受膈神经移位治疗的患者,在术前、术后（10 d）进行肺功能指标的比较,同时定期进行门诊随访,观察呼吸系统自觉症状程度.结果13例术后出现了不同程度的供氧不足症状,16例全部出现一侧膈肌抬高,术后第10天肺活量（VC）、肺活量预计值百分数（VC%）分别比术前减少37.98%和26.88%,两者差异有统计学意义（tvc=11.532、tvc%=0,P＜0.01）.其它项目如残气量（RV）较术前轻度下降,肺总量（TLC）下降值达到术前肺总量的36.49%,残气量/肺总量比值（RV/TLC%）较术前上升了4.75%,上述各指标的差值均有统计学意义.1 s用力呼气量/用力肺活量比值（FEV1/FVC）和术前比基本无改变,但其差值有统计学意义.膈神经移位右侧（10例）与左侧（6例）术前、术后肺活量比较差异有统计学意义.术后随访8个月～2年,所有患者均无明显呼吸困难和胸闷等症状.结论膈神经移位术后对青壮年患者肺容量有较大的丧失,肺通气功能减弱和小气道阻力增加,但其丧失程度在机体自身代偿耐受范围内,不会导致急剧发生的严重呼吸功能障碍.建议对右侧臂丛神经根性损伤的患者,术前进行严格的肺、心功能检查,避免发生较为严重的并发症.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

2016年四川省儿童青少年学生生长发育与营养状况分析

目的 描述并分析四川省儿童青少年学生的生长发育与营养状况。方法 采用多阶段随机整群抽样,抽取四川省12个城市的14772名7~18岁学生的学校体检数据进行了整理分析,按照《学龄儿童青少年营养不良筛查》评价生长迟缓、消瘦、超重及肥胖等学生营养状况。结果 四川省学生的身高、体重、BMI之间均随着年龄逐渐升高,各年龄段学生的平均身高、体重均低于全国平均身高。四川省儿童青少年营养不良检出率为10.11%,生长迟缓率、轻度消瘦、中重度消瘦检出率男生分别为2.33%、7.51%、3.12%,女生1.26%、4.32%、2.31%,男生高于女生。农村高于城市。营养过剩检出率为13.73%,超重、肥胖检出率男生高于女生,城市高于农村。且营养过剩检出率高于营养不良。结论 四川省儿童青少年平均身高、体重低于全国水平,其营养状况结果表明四川省儿童青少年学生特别是男生存在着消瘦与超重、肥胖的共存现象,这警醒在进行营养改善计划时,要防止营养过剩的发生。     

New England Medical Center Posterior Circulation Stroke Registry: I. Methods, Data Base, Distribution of Brain Lesions, Stroke Mechanisms, and Outcomes

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs before strokes, and 16% had only posterior circulation TIAs. Embolism was the commonest stroke mechanism accounting for 40% of cases (24% cardiac origin, 14% arterial origin, 2% had potential cardiac and arterial sources). In 32%, large artery occlusive lesions caused hemodynamic brain infarction. Stroke mechanisms in the posterior and anterior circulation are very similar. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes), while the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Infarcts that included the distal territory were twice as common as those that included the proximal or middle territories. Most distal territory infarcts were attributable to embolism. Thirty day mortality was low (3.6%). Embolic stroke mechanism, distal territory location, and basilar artery occlusive disease conveyed the worst prognosis.     

LATE TENSION PNEUMOCEPHALUS FOLLOWING FRONTAL CRANIOTOMY

Tension pneumocephalus is an uncommon but life-threatening complication of craniotomy which requires urgent diagnosis and treatment. It most often occurs perioperatively following subsequent anaesthesia using nitrous oxide. All previously reported postoperative cases followed posterior fossa or upper spinal cord surgery. Only two cases associated with frontal craniotomy have been reported since 1972, both occurring intraoperatively.     

脂联素与妊娠期糖尿病巨大儿发生关系的研究

妊娠期糖尿病孕妇中巨大儿发生率明显高于正常孕妇,巨大儿是妊娠期糖尿病最多见的围产儿并发症,高血糖-高胰岛素学说是其基本的发病机制.脂联素、瘦素、肿瘤坏死因子-α、胰岛素样生长因子、成纤维细胞生长因子-Ⅱ、胰岛素抵抗等因素的参与加剧了妊娠期糖尿病,同时这些因素也与胎儿的生长发育密切相关,其以各种方式参与了巨大儿的发生.其中,脂联素可能起着重要作用.脂联素是调节胰岛素和糖代谢的关键因子,而胎儿的生长发育受胰岛素和糖代谢的影响,因此,脂联素可能是调节胎儿宫内发育的候选因子之一.胎盘组织中存在脂联素基因的表达,妊娠期糖尿病孕妇胎盘脂联素基因mRNA表达水平显著降低,表明妊娠期糖尿病孕妇内分泌环境的变化不但严重地影响着胎盘基因的表达,而且能通过影响胎盘调节干扰胎儿的生长发育.     

Clinical outcomes and maternal perceptions of an updated model of perinatal care

BACKGROUND: Postpartum hospital stays seem likely to remain limited even under new laws which mandate that insurers cover 48-hour hospitalization after uncomplicated delivery. Clinicians, who are increasingly practicing in capitated arrangements, need better information to maximize clinical benefit to mothers and newborns using finite resources. OBJECTIVE AND INTERVENTIONS: This study's aim was to evaluate the clinical outcomes, patient perceptions, and costs of a revised model of perinatal care services. In this model, a new postpartum care center was established for routine follow-up of newborns within 48 hours after hospital discharge, educational efforts were shifted from the postpartum hospitalization to the prenatal period, and lactation consultant hours were increased. DESIGN AND PARTICIPANTS: Controlled, nonrandomized (double cohort) study that compared mothers and newborns with hospital stays of 48 hours or less during the Baseline Care (preintervention) study period (N = 344) with those under the Revised Care (postintervention) study period (N = 456). SETTING: The Hayward, California, medical center of Kaiser Permanente, a nonprofit health maintenance organization. DATA COLLECTION: Telephone interviews were attempted with all mothers 3 weeks after delivery. Data on rehospitalizations, emergency department (ED) and clinic visits, and costs during the first 14 postpartum days were collected from computerized databases and chart review. OUTCOME MEASURES: The combined clinical outcome was defined as any undesirable health event, including rehospitalization, an ED visit, or an urgent clinic visit by either the mother or newborn within the first 14 days postpartum, or breastfeeding discontinuation within the first 21 days postpartum. Maternal satisfaction and costs were also studied. RESULTS: Of 876 attempted interviews, 800 were completed (91%). Analyses were adjusted for age, race, education, parity, breastfeeding experience, and other relevant variables. Among the interviewed mother-newborn pairs, 45% in the Revised Care group experienced the combined clinical outcome, compared with 52% in the Baseline Care group. Newborns in the Revised Care group (29%) were significantly less likely to make urgent clinic visits during the first 14 days of life than those in the Baseline Care group (36%). There were no differences between groups in newborn ED visits or rehospitalizations, maternal clinical outcomes, or breastfeeding continuation. Mothers in the Revised Care group expressed higher satisfaction with the newborn's care, the amount of information they received about newborn care and breastfeeding, and the amount of help they received with breastfeeding. Planned hospital care, planned follow-up visits, and unplanned care costs decreased by $149 per delivery, while the new prenatal class and increased lactation consultant services cost $58 per delivery, for an estimated overall reduction in cost. CONCLUSIONS: We conclude that the revised model of perinatal care in this health maintenance organization medical center improved clinical outcomes and maternal satisfaction for low-risk mothers and newborns without increasing costs.