Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

Neurocritical Care - For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral...     

银杏竹鼠肌肉成分对小鼠智力、体力的影响

目的：观察银杏竹鼠肌肉成分对小鼠智力体力的影响。方法：小鼠随机分为七组，通过喂饲银杏竹鼠肌肉干粉连续一个月，用小鼠低温游泳存活时间实验，耐缺氧实验及跳台和记忆获得障碍实验分别记录低温游泳存活时间，缺氧存活时间及第一次错误潜伏期和跳台错误次数。结果：各竹肉组小鼠与普通饲料（ＮＳ）组，普肉组，护宝液组比较，均可明显延长小鼠低温游泳存活时间和缺氧存活时间（Ｐ＜０．０５），与洋参丸组相当（Ｐ＞０．０５），竹肉大／超组小鼠跳台错误次数均减少（Ｐ＜０．０５），竹肉超组小鼠第一次错误潜伏期延长（Ｐ＜０．０５），竹肉大组小鼠第一次错误潜伏期有延长趋势，但无统计学意义。结论：口服银杏竹鼠肌肉成分可增强小鼠学习记忆能力，增强小鼠体质，提高小鼠生活质量。这一结果也提示银杏竹鼠肌肉成分很有可能成为极有应用前景和开发前景的保健食品。     

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.     

Femoral shaft fractures in children

We report our experience with elastic stable intramedullary titanium nailing (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31 children (20 boys), median age 6 (4-11) years, with ESIN for 29 closed and 2 grade I open femoral shaft fractures. We reviewed 30 children clinically after median 1.5 (1-3) years. Their median hospital stay was 6 (2-20) days. All fractures were radiographically united at a median of 7 (5-9) weeks. The nails were removed in 29 children after a median of 22 (6-38) weeks postoperatively. At follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10 degrees of internal rotational deformity in 1 child. No angular deformity had occurred. Elastic stable intramedullary nailing seems to be a safe method for the treatment of femoral shaft fractures in children between 4 and 11 years of age.     

Intravenous Lidocaine Relieves Spinal Cord Injury Pain: A Randomized Controlled Trial

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing.

Results: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction >= 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick.     

慢性束缚应激对大鼠行为及前额叶皮质细胞外信号调节激酶磷酸化的影响

目的 探讨慢性束缚应激模型大鼠的行为及前额叶皮质中磷酸化细胞外信号调节激酶（ERK1／2）表达的变化。方法 将雄性SD大鼠随机分为正常对照组和束缚应激组，每组8只。将束缚应激组大鼠放入特制的束缚器中限制其活动，6k／d，连续21d。比较应激前后大鼠旷场行为和Morris水迷宫行为学的改变，用蛋白免疫印迹技术和免疫组织化学方法观察应激后大鼠前额叶皮质P—ERK1／2表达的变化，并与正常对照组比较。结果 （1）行为学改变：应激后，束缚应激组大鼠的水平活动度[（4265±864）mm]少于正常对照组[（8562±502）mm]，中央停留时间[（39．1±4．3）s]长于正常对照组[（24．6±1．6）s]，均P〈0．01；束缚应激组大鼠在Morris水迷宫实验的目标象限活动时间[（57．2±1．7）s]和穿越站台次数[（2．0±0．8）次]均少于正常对照组[分别为（70．7±3．6）s和（6．2±1．0）次；均P〈0．01]。（2）p-ERK1／2蛋白水平：应激后束缚应激组吸光度（A）值[（0．767±0．006）]低于正常对照组[（0．813±0．015）；P〈0．05]。（3）p-ERK1／2阳性细胞数：应激后束缚应激组[（76±5）个]少于正常对照组[（110±14）个；P〈0．05]，且树突染色浅淡。结论 慢性心理应激明显影响动物的活动度和记忆能力；前额叶皮质中p-ERK1／2表达的减少，提示ERK信号转导通路可能参与了应激发生的机制。