User experiences, preferences and choices relating to functional electrical stimulation and ankle foot orthoses for foot-drop after stroke

Objectives

To explore experiences, preferences and choices relating to the use of ankle foot orthoses (AFOs) and functional electrical stimulation (FES) for foot-drop by people who have suffered a stroke and their carers, with the aim of informing clinical decision-making.

Design

Semi-structured interviews explored individual experiences through a phenomenological approach. The Interpretative Phenomenological Analysis framework was used to enable organisation and interpretation of qualitative interview data.

Setting

Participants who had used both transcutaneous FES and one of several types of AFO were recruited from a single FES clinic.

Participants

Nine people who had suffered a stroke and four carers were recruited purposively, including people between 2 and 9 years post stroke, with different degrees of difficulty in walking.

Results

Participants described experiences, preferences and choices relating to AFO and FES use. All but one person expressed a preference for FES use and related this to being able to move the ankle more freely; walk more normally, safely and independently; and greater comfort. Several people also used AFOs when the FES equipment failed, when travelling and near water. One person rationed their use of FES on a daily basis due to allergic reactions.

Conclusions

The consensus in this sample demonstrated positive and negative experiences of both FES and AFO use. Participants weighed up the pros and cons, and despite predominant preferences for FES, many also used AFOs due to some drawbacks of FES. Further research and development are required to reduce drawbacks and further explore users’ experiences.     

CC趋化因子受体4及其抑制剂研究进展

CC趋化因子受体4（CCR4）是G蛋白偶联受体家族成员之一,由包含7次跨膜结构域的多肽链组成,表达于多种细胞或组织中。CCR4通过与其内源性配体CCL17、CCL22及CKLF1作用介导多种炎症反应,尤其在哮喘发生和发展的病理过程中起重要作用,因此可能是某些炎性疾病、特别是哮喘的潜在治疗靶点。本文对CCR4及其抑制剂的研究进展做一综述。     

Phase I/II trial of non-cytotoxic suramin in combination with weekly paclitaxel in metastatic breast cancer treated with prior taxanes

Purpose

Suramin, a polysulfonated naphthylurea, inhibits the actions of polypeptide growth factors including acidic and basic fibroblast growth factors (aFGF and bFGF), which confer broad spectrum chemotherapy resistance. We hypothesized that suramin at non-cytotoxic doses in combination with weekly paclitaxel would be well tolerated and demonstrate anti-tumor activity.

Methods

Women with metastatic breast cancer who had been previously treated with a taxane in the adjuvant or metastatic setting were eligible. The primary objective of the phase I was to determine the dose of intravenous (IV) weekly suramin that resulted in plasma concentrations between 10 and 50?umol/l over 8?C48?h (or the target range) in combination with IV 80?mg/m² of weekly paclitaxel. The primary objective of the phase II trial was to determine the anti-tumor activity of the dosing regimen defined in phase I. Therapy was continued until disease progression or development of unacceptable toxicity.

Results

Thirty-one patients were enrolled (9: phase I; 22: phase II). In phase I, no dose-limiting toxicities were observed. Pharmacokinetics during the first cycle showed suramin concentrations within the target range for 21 of 24 weekly treatments (88?%). In phase II, the objective response rate (ORR) was 23?% (95?% CI 8?C45?%), the median progression-free survival was 3.4?months (95?% CI 2.1?C4.9?months), and the median overall survival was 11.2?months (95?% CI 6.6?C16.0?months).

Conclusions

Non-cytotoxic doses of suramin in combination with weekly paclitaxel were well tolerated. The efficacy was below the pre-specified criteria required to justify further investigation.     

负载抗原的DC与CIK共培养对耐药乳腺癌细胞的杀伤作用

目的:观察负载抗原的树突状细胞(dendritic cell,DC)与细胞因子诱导的杀伤细胞(cytokine-induced killer cell,CIK)对高表达P-糖蛋白(P-glycoprotein,P-gp)的多药耐药(multidrug resistance,MDR)人乳腺癌MCF-7/ADR细胞的杀伤作用。方法:提取健康人外周血单个核细胞,常规诱导出CIK及DC;制备MCF-7/ADR细胞冻融抗原后冲击DC,并与CIK共培养作为实验组(冻融物DC-CIK组),未负载抗原的DC与CIK共培养作为对照组(DC-CIK组),同时设单独培养的CIK组或DC组作为空白对照组。流式细胞术分析细胞的表型及P-gp表达,ELISA法测定细胞上清中IL-12、IFN-γ水平,MTT法检测对MCF-7/ADR及MCF-7细胞株的杀伤活性。结果:冻融物DC-CIK组、DC-CIK组细胞增殖活性均大于CIK组(P<0.05)。冻融物DC-CIK组对MCF-7/ADR、MCF-7细胞的杀伤活性在效靶比10∶1、20∶1、40∶1时分别为(44.29±1.39)%、(58.24±3.52)%、(68.9±2.83)%和(33.51±2.18)、(40.43±2.3)%、(44.62±1.19)%,均高于DC-CIK组及CIK组(P<0.05);冻融物DC-CIK组对MCF-7/ADR耐药细胞株的杀伤活性高于非耐药细胞株MCF7(P<0.05);而对于非耐药株MCF-7细胞的杀伤活性,冻融物DC-CIK组和DC-CIK组之间差异无统计学意义(P>0.05)。结论:DC与CIK共培养细胞增殖活性和细胞毒活性均强于CIK,经冻融抗原冲击的DC与CIK共培养可以显著提高对MCF-7/ADR耐药细胞株的杀伤活性。     

Carotenoids and the risk of developing lung cancer: a systematic review

BACKGROUND: Carotenoids are thought to have anti-cancer properties, but findings from population-based research have been inconsistent. OBJECTIVE: We aimed to conduct a systematic review of the associations between carotenoids and lung cancer. DESIGN: We searched electronic databases for articles published through September 2007. Six randomized clinical trials examining the efficacy of beta-carotene supplements and 25 prospective observational studies assessing the associations between carotenoids and lung cancer were analyzed by using random-effects meta-analysis. RESULTS: The pooled relative risk (RR) for the studies comparing beta-carotene supplements with placebo was 1.10 (95% confidence limits: 0.89, 1.36; P = 0.39). Among the observational studies that adjusted for smoking, the pooled RRs comparing highest and lowest categories of total carotenoid intake and of total carotenoid serum concentrations were 0.79 (0.71, 0.87; P < 0.001) and 0.70 (0.44, 1.11; P = 0.14), respectively. For beta-carotene, highest compared with lowest pooled RRs were 0.92 (0.83, 1.01; P = 0.09) for dietary intake and 0.84 (0.66, 1.07; P = 0.15) for serum concentrations. For other carotenoids, the RRs comparing highest and lowest categories of intake ranged from 0.80 for beta-cryptoxanthin to 0.89 for alpha-carotene and lutein-zeaxanthin; for serum concentrations, the RRs ranged from 0.71 for lycopene to 0.95 for lutein-zeaxanthin. CONCLUSIONS: beta-Carotene supplementation is not associated with a decrease in the risk of developing lung cancer. Findings from prospective cohort studies suggest inverse associations between carotenoids and lung cancer; however, the decreases in risk are generally small and not statistically significant. These inverse associations may be the result of carotenoid measurements' function as a marker of a healthier lifestyle (higher fruit and vegetable consumption) or of residual confounding by smoking.     

两种微创治疗方法在盘源性腰痛治疗中的应用

目的比较水冷式双极射频纤维环成形术和椎间盘内电热疗法治疗盘源性腰痛的临床效果及其并发症。方法 80例盘源性腰痛患者,随机分为A、B两组,每组40例,分别采用水冷式双极射频纤维环成形术和椎间盘内电热疗法进行治疗,观察两组患者手术前后VAS疼痛评分、Oswestry功能障碍指数评定的功能状态以及手术并发症等情况变化。结果经两种微创方法治疗后,两组患者疼痛评分均明显降低,功能状态显著改善,无严重并发症发生。结论水冷式双极射频纤维环成形术和椎间盘内电热疗法均能快速缓解患者疼痛,显著改善患者功能状态,并发症少,两者都是治疗盘源性腰痛的安全、有效的方法。     

Breast cancer patients' clinical outcome measures are associated with Src kinase family member expression

Background:

This study determined mRNA expression levels for Src kinase family (SFK) members in breast tissue specimens and assessed protein expression levels of prominent SFK members in invasive breast cancer to establish associations with clinical outcome. Ki67 was investigated to determine association between SFK members and proliferation.

Methods:

The mRNA expression levels were assessed for eight SFK members by quantitative real-time PCR. Immunohistochemistry was performed for c-Src, Lyn, Lck and Ki67.

Results:

mRNA expression was quantified in all tissue samples. SRC and LYN were the most highly expressed in malignant tissue. LCK was more highly expressed in oestrogen receptor (ER)-negative, compared with ER-positive tumours. High cytoplasmic Src kinase protein expression was significantly associated with decreased disease-specific survival. Lyn was not associated with survival at any cellular location. High membrane Lck expression was significantly associated with improved survival. Ki67 expression correlated with tumour grade and nuclear c-Src, but was not associated with survival.

Conclusions:

All eight SFK members were expressed in different breast tissues. Src kinase was highest expressed in breast cancer and had a negative impact on disease-specific survival. Membrane expression of Lck was associated with improved clinical outcome. High expression of Src kinase correlated with high proliferation.     

From the Cover: The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles

Asthma often worsens at night. To determine if the endogenous circadian system contributes to the nocturnal worsening of asthma, independent of sleep and other behavioral and environmental day/night cycles, we studied patients with asthma (without steroid use) over 3 wk in an ambulatory setting (with combined circadian, environmental, and behavioral effects) and across the circadian cycle in two complementary laboratory protocols performed in dim light, which separated circadian from environmental and behavioral effects: 1) a 38-h “constant routine,” with continuous wakefulness, constant posture, 2-hourly isocaloric snacks, and 2) a 196-h “forced desynchrony” incorporating seven identical recurring 28-h sleep/wake cycles with all behaviors evenly scheduled across the circadian cycle. Indices of pulmonary function varied across the day in the ambulatory setting, and both laboratory protocols revealed significant circadian rhythms, with lowest function during the biological night, around 4:00 AM, uncovering a nocturnal exacerbation of asthma usually unnoticed or hidden by the presence of sleep. We also discovered a circadian rhythm in symptom-based rescue bronchodilator use (β2-adrenergic agonist inhaler) whereby inhaler use was four times more likely during the circadian night than day. There were additive influences on asthma from the circadian system plus sleep and other behavioral or environmental effects. Individuals with the lowest average pulmonary function tended to have the largest daily circadian variations and the largest behavioral cycle effects on asthma. When sleep was modeled to occur at night, the summed circadian, behavioral/environmental cycle effects almost perfectly matched the ambulatory data. Thus, the circadian system contributes to the common nocturnal worsening of asthma, implying that internal biological time should be considered for optimal therapy.

Asthma is characterized by bronchial hyperreactivity leading to airway inflammation, bronchoconstriction, and symptoms of “chest tightness.” It has been recognized for hundreds of years that asthma severity generally increases at night, producing what had historically been termed “nocturnal asthma.” For instance, in 1698, the physician Sir John Floyer recognized from his own experience that “at first waking, about one or two of the Clock in the Night, the Fit of the Asthma more evidently begins” (1). Nocturnal worsening of asthma occurs in as many as 75% of patients with asthma, equating to 20 million people in the United States alone (2–6). The variation across the day and night in peak expiratory flow (PEF) can be as much as 50% (7, 8). Also, the highest rate of asthma exacerbations leading to respiratory failure or death occurs across the night (3, 9, 10). Therefore, understanding the mechanisms underlying the daily variability in asthma severity could have major diagnostic and therapeutic implications.Behavioral and environmental factors are known to affect asthma severity, including exercise, air temperature, pollution, the sleep/wake cycle (11), changes in posture (12), and the sleeping environment (13). However, it is also possible that the endogenous circadian timing system contributes to nocturnal worsening of asthma (14). The circadian system—composed of the central circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus and circadian oscillators in most organs and tissues of the body—orchestrates ∼24-h rhythms in physiology and behavior (15). This endogenous timing system may influence the pulmonary and inflammatory system via the autonomic nervous system (16), humoral factors (17), and/or local molecular clocks (18, 19).We tested the hypothesis that the circadian system, independent of sleep and other behavioral and environmental factors, contributes to the nocturnal worsening of asthma in humans.