BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量，疗效和副作用。符合条件的患者被转诊到姑息治疗计划，并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后，每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化，在之前的24小时内有四个或更少的抢救剂量，并且疼痛等级为无或轻度。如果连续96个小时保持这些标准，CIVI被认为等于CSCI。进入了57名患者，其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段，越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr，平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次，而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83，0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米，第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7，2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告，需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量，都有足够的疼痛控制，并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明，静脉注射和南卡罗来纳州当作为连续输注给药时，大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： : 交感神经的维持性疼痛可以通过交感神经传出和传入伤害性纤维之间的触感相互作用来介导，也可以通过儿茶酚胺诱导的伤害性神经末梢的激活来介导。我们在此报告了一名患有交感持续疼痛的患者的C伤害感受器的单纤维记录，其中交感神经阻滞反复消除了双腿的持续疼痛。我们根据八种C纤维的机械响应性和与活动有关的传导速度减慢 (在0.125Hz下20个脉冲的0.5/-1.1与7.1/-2.0 ms的潜伏期增加)，将它们分类为机械敏感的伤害感受器。强烈的内源性交感神经爆发后，两根C纤维被激活，延迟数秒; 在将去甲肾上腺素 (10 microl，0.05%) 注射到其神经支配区域后，它们也被兴奋约3分钟。在这两种纤维中，记录了通过注射低pH溶液 (磷酸盐缓冲液，pH 6.0，10μl) 而延长的活化以及前列腺素E2注射后它们的热响应的敏化，证明了它们的传入性质。此外，对于机械不敏感的伤害感受器，它们的活性依赖性减慢是典型的。我们得出的结论是，内源性释放的儿茶酚胺可以激活敏感的机械不敏感伤害感受器，从而可能导致交感疼痛。没有发现交感传出和伤害性传入纤维之间的触觉相互作用的证据。

BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.

背景与目标： : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链，p56lck，p59fyn，ZAP-70，PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少，但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比，接受治疗的患者中大多数信号分子的强度相对不受影响，但低于未经治疗的惰性患者。然而，在患者中表达每种信号分子的T细胞总数减少，而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中，T细胞对PHA的反应降低，但对PPD的反应降低。结果表明，尽管信号分子发生了一些变化，T细胞数量减少，但在用氟达拉滨和阿仑单抗治疗后，总体T细胞功能可能长期保持良好。

BACKGROUND & AIMS: :Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available. Most SCCHN tumors overexpress the epidermal growth factor receptor (EGFR). This is a tyrosine kinase membrane receptor and has a clear implication in angiogenesis, tumor progression and resistance to different cancer treatments. Cetuximab is a monoclonal antibody that binds to EGFR and alters the tyrosine kinase-mediated signal transduction pathway. The drug is active in colon cancer and is currently being tested in SCCHN patients. For locally advanced disease, cetuximab/radiotherapy combination has demonstrated a benefit in survival when compared with radiotherapy alone as radical treatment. Cetuximab is an active treatment in platin-refractory patients with recurrent/metastatic disease.

背景与目标： : 手术和放疗是头颈部鳞状细胞癌 (SCCHN) 患者的标准治疗选择。化疗和放化疗是局部晚期疾病的新选择，尤其是不可切除肿瘤患者的诱导化疗。在复发/转移性疾病和进展为基于铂的方案后，除了最佳支持治疗外，目前尚无其他治疗方法。大多数SCCHN肿瘤过表达表皮生长因子受体 (EGFR)。这是一种酪氨酸激酶膜受体，对血管生成，肿瘤进展和对不同癌症治疗的抵抗力具有明确的意义。西妥昔单抗是一种与EGFR结合并改变酪氨酸激酶介导的信号转导途径的单克隆抗体。该药物在结肠癌中具有活性，目前正在SCCHN患者中进行测试。对于局部晚期疾病，与单纯放疗相比，西妥昔单抗/放疗联合治疗在生存方面具有益处。西妥昔单抗是对复发/转移性疾病的铂难治性患者的积极治疗。

BACKGROUND & AIMS: AIM:To research possible associations between previous exposure to specific torture techniques and prevalent pain in the head and face, back, and feet. METHODS:221 refugees, 193 males and 28 females, previously exposed to torture in their home country, were subject to a clinical interview at a rehabilitation clinic for torture victims. The interview focused on exposure to torture and somatic symptoms prevalent at examination. RESULTS:The mean number of times imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean duration from initial imprisonment to final release was 3.7 years; and the mean duration from final release to preliminary interview was 8.4 years. The most frequent physical torture method reported was beating (92.3%) and the main mental torture method was deprivation (84.6%). Pain in the head and face was found to be strongly associated with torture against head and face (OR 3.89, 95% CI 1.49-10.20) and with the cumulative number of physical torture methods exposed to. Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12). Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the strongest predictor for pain in the feet was general abuse of the whole body (OR 5.64, 95% CI 1.93-16.45). CONCLUSION:In spite of many factors being potentially co-responsible for prevalent pain, years after the torture took place it presents itself as strongly associated with specific loci of pain, with generalized effects, and with somatizing.

背景与目标：

BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： : 脊髓NMDA受体激活后过度兴奋可能导致慢性疼痛。天然衍生的哺乳动物肽组织蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物 [Ser1] 组织蛋白 (SHG) 可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型 (CCI) 诱发神经病理性疼痛。鞘内注射SHG可显着减轻由CCI引起的痛觉过敏和异常性疼痛，几乎使反应正常化。这些结果表明，天然肽组织粒蛋白可能是神经性疼痛管理的新型辅助手段。

BACKGROUND & AIMS: :Wound healing is a complex process resulting from an interplay of processes including coagulation, inflammation, angiogenesis, and epithelialization. The chemokine family has been shown to contain members that are potent regulators of many of these pathways. Because we have previously shown that chemokines "pool" in biologic wound dressings, we studied the levels of CXC and CC chemokines, along with key inflammatory mediators, serially from a group of patients undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had marked clinical healing of their ulcers (median 63.3% reduction in size) with two of 10 completely healed. Wound fluids extracted from dressings showed high levels of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward increases in the ratio of the sums of the angiogenic versus angiostatic CXC chemokines (p = 0.082) in the tissues collected from the center of the ulcers during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted for the most changes in wound fluid angiogenic chemokines, with significant differences both as compared with baseline levels and with patients' plasma level noted at various time points between weeks 0 and 8. The level of angiostatic chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell most significantly between weeks 0 and 3 as compared with plasma levels. The observed shift toward angiogenic CXC chemokines suggests that effective healing in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a state more conducive to epithelialization,characteristic of the proliferative phase of wound healing. CC chemokines were also elevated at baseline in the wound fluid samples as compared with the patients' plasma levels. Macrophage inflammatory protein-1 (3 and regulated on activation, normal T expressed and secreted (RANTES) levels decreased with healing, whereas there were significant increases in the tissue levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or = 0.05 for both). Coincident with these changes was a steady increase in the ratio of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center tissues, which also correlated with healing (p < 0 .05) as compared with a decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids. These findings suggest that advanced wound care techniques help move the ulcer from a chronic inflammatory state into one more characteristic of the late inflammatory/early proliferative phase of wound healing. Chemokines may play a critical role in the pathogenesis of chronic venous ulcers through their effects on angiogenesis and/or the progression of inflammatory reactions at the site of injury.

背景与目标： 伤口愈合是一个复杂的过程，由凝血、炎症、血管生成和上皮形成等过程的相互作用产生。趋化因子家族已被证明包含许多这些途径的有效调节剂。因为我们以前已经表明趋化因子在生物伤口敷料中 “聚集”，所以我们连续研究了一组接受慢性静脉腿部溃疡治疗的患者的CXC和CC趋化因子以及关键炎症介质的水平。8周后，所有患者的溃疡临床愈合明显 (中位63.3% 缩小)，其中10例中有2例完全愈合。从敷料中提取的伤口液显示出高水平的血小板因子-4和干扰素-γ 诱导蛋白，在伤口闭合期间从溃疡中心收集的组织中，血管生成与血管抑制CXC趋化因子 (p = 0.082) 的总和比率呈增加趋势。中性粒细胞激活肽-2和interleukin-8占伤口流体血管生成趋化因子的最大变化，与基线水平和患者血浆水平相比，在第0周和第8周之间的不同时间点存在显着差异。与血浆水平相比，血管抑制趋化因子，干扰素y诱导蛋白10和血小板活化4的水平在第0周和第3周之间下降最明显。观察到的向血管生成CXC趋化因子的转变表明，慢性静脉功能不全溃疡的有效愈合似乎使溃疡床 “移至” 更有利于上皮形成的状态，这是伤口愈合增生期的特征。与患者血浆水平相比，伤口液体样品中的CC趋化因子在基线时也升高。巨噬细胞炎性蛋白-1 (3) 和受激活调节，正常T表达和分泌 (RANTES) 水平随愈合而降低，而在治疗的前4周内，单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1 a的组织水平显着增加 (两者p <或 = 0.05)。与这些变化同时发生的是，interleukin-1 R/interleukin-1受体拮抗剂蛋白的比例在溃疡中心组织，与溃疡边缘的比率降低相比，这也与愈合相关 (p <0.05)，和伤口液体中的双相反应。这些发现表明，先进的伤口护理技术有助于将溃疡从慢性炎症状态转移到伤口愈合的晚期炎症/早期增生期的另一个特征。趋化因子可能通过其对血管生成的影响在慢性静脉溃疡的发病机理中发挥关键作用和/或损伤部位炎症反应的进展。

BACKGROUND & AIMS: :Several molecular-targeted therapeutics have been tested in clinical trials for the treatment of head and neck squamous cell carcinoma (HNSCC). Of these, therapeutics targeting the epidermal growth factor receptor (EGFR) have been studied most extensively and some agents have demonstrated measurable clinical effectiveness. However, molecular studies designed to define HNSCC patient subcohorts of likely responders to EGFR-targeted therapy have not identified molecular signatures that correlate with clinical response. Here, the authors summarise the relevant clinical findings and highlight reported molecular correlative studies for EGFR-targeted therapeutics for HNSCC. The authors focus especially on molecular markers evaluated for association with clinical response and include data from EGFR-targeted clinical studies in other cancer sites that they anticipate will be of interest to the head and neck cancer research and treatment communities.

背景与目标： : 几种分子靶向疗法已在治疗头颈部鳞状细胞癌 (HNSCC) 的临床试验中进行了测试。其中，针对表皮生长因子受体 (EGFR) 的疗法已被最广泛地研究，并且一些药物已证明可测量的临床有效性。然而，旨在定义可能对EGFR靶向治疗有反应的HNSCC患者亚组的分子研究尚未确定与临床反应相关的分子特征。在这里，作者总结了相关的临床发现，并重点报道了针对HNSCC的EGFR靶向治疗的分子相关研究。作者特别关注评估与临床反应相关的分子标志物，并包括来自其他癌症部位的EGFR靶向临床研究的数据，他们预计头颈癌症研究和治疗社区将对此感兴趣。

BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.

背景与目标： : 周围神经性疼痛是一种独特的慢性疼痛形式，困扰多达50% 的艾滋病患者。这项初步研究的目的是检查冰按摩减轻神经性疼痛和改善睡眠质量的效果，并确定进行更大规模研究的可行性。使用了重复测量设计。这三种治疗方法包括冰按摩，干毛巾按摩和在场。连续抽样选择33例患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但随着时间的推移，冰按摩和毛巾按摩的疼痛强度有所降低，这表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标：

BACKGROUND & AIMS: :The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

背景与目标： 内脏疼痛的感知是一个复杂的过程，涉及脊髓和高阶脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节剂，但肠道细菌是否在内脏敏感性中起作用尚待确定。我们使用无菌小鼠 (GF) 评估内脏敏感性，脊髓基因表达和与疼痛相关的大脑结构。GF小鼠表现出内脏超敏反应，并伴有脊髓中Toll样受体和细胞因子基因表达的增加，这通过出生后用常规定植 (CC) 的微生物群定植而标准化。在GF小鼠中，前扣带回皮层 (ACC) 和导水管周围灰色 (涉及疼痛处理的区域) 的体积分别减少和扩大，并且ACC的树突状变化明显。这些发现表明，正常的内脏疼痛感需要肠道菌群。

BACKGROUND & AIMS: BACKGROUND & AIMS:Some patients with chronic hepatitis B virus (HBV) infection progress to hepatocellular carcinoma (HCC). However, the long-term effect of nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS:Therefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis. RESULTS:Of 785 consecutive HBV carriers between 1998 and 2008, 117 patients who received NA therapy and 117 patients who did not, were selected by eligibility criteria and propensity score matching. Factors associated with the development of HCC were analyzed. In the follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors significantly associated with the incidence of HCC, as determined by Cox proportional hazards models, include higher age (hazard ratio, 4.36 [95% confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62], p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS:NA therapy reduced the risk of HCC compared with untreated controls. Higher serum levels of HBcrAg and BCP mutations are associated with progression to HCC, independent of NA therapy.

背景与目标：

BACKGROUND & AIMS: :The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

背景与目标： : 已在50例与癌症相关的严重疼痛患者中评估了使用固定在常规16号硬膜外导管上的皮下植入门静脉系统的可行性。该技术允许以8-12小时的间隔经皮硬膜外施用吗啡以控制疼痛。植入的平均持续时间为12周，而原位保留的最长时间为36周。由于各种原因，必须删除五个门户。由于导管阻塞 (六次) 和门静脉阻塞 (两次)，注射系统有八次阻塞。当更换导管或门静脉时，这些患者继续获得出色的镇痛效果。在尸体中，使用22号Huber点针或一次性针 (25号) 模拟300注射，并通过光学和扫描电子显微镜检查注射物。两种类型的针头都会导致颗粒污染，推荐的Huber点针头会更大。

BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

背景与目标： : 美国 (20世纪70年代1985年) 和瑞士 (1988-1993) 的精神科医生和心理治疗师合法使用MDMA作为处方药，以提高心理治疗的有效性。早期报告表明，它在治疗创伤相关疾病中很有用。最近，第一个完成的MDMA辅助心理治疗PTSD的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理治疗在治疗耐药的PTSD患者中的安全性和有效性; 我们的随机，双盲，活性安慰剂对照试验招募了12名患者接受低剂量 (25 mg，加12.5 mg补充剂量) 或全剂量MDMA (125 mg，加62.5 mg补充剂量)。MDMA在三个实验课程中进行，并散布在每周的非基于药物的心理治疗课程中。使用的结果指标是临床医生管理的PTSD量表 (CAPS) 和创伤后诊断量表 (PDS)。在基线，第二次和第三次MDMA疗程 (治疗结束) 后三周以及2个月和1年随访时对患者进行评估。我们发现MDMA辅助心理治疗可以在临床环境中安全施用。未发生与药物相关的严重不良事件。尽管有临床和统计学上显着的自我报告 (PDS) 改善 (p = 0.066)，但我们没有看到CAPS评分的统计学显着降低 (p = 0.014)。在1年的随访中，CAPS评分进一步提高。此外，三个MDMA会话比两个更有效 (p = 0.016)。