BACKGROUND & AIMS: OBJECTIVE:In the absence of immunodeficiency, only microchimerism (<0.1%) has been achieved in human fetal recipients or nonhuman primates following in utero hematopoietic cell transplantation (IUHCT). We hypothesized that enhanced long-term engraftment might be more reliably achieved in microchimeric systems if higher levels of chimerism existed during development of adaptive immunity. To evaluate this hypothesis, we stimulated the donor cells with vascular endothelial growth factor (VEGF) and stem cell factor (SCF) prior to IUHCT in a chimerism-resistant murine strain combination. METHODS:Donor Balb/c marrow was cultured in media with or without VEGF and SCF supplementation for 12 hours prior to IUHCT into B6 fetuses at 14 days postcoitum (dpc). Donor cell phenotype, homing, and chimerism were assessed at short and long-term time points and transplanted animals received skin allografts at 8 weeks. RESULTS:In pretreated allogeneic recipients, early chimerism rates were more than double that of controls (71% vs 33%, p = 0.01). These differences were associated with higher numbers of pretransplant donor cell colony-forming cells without change in donor cell homing. Despite prolonged skin allograft survival for pretreated recipients compared with controls (mean survival = 20.8 vs 8.2 days, p < 0.001), long-term engraftment was unchanged. CONCLUSIONS:These findings demonstrate that higher levels of early chimerism in recipients of cytokine-stimulated marrow result in improved short-term chimerism and tolerance. Future studies are needed to confirm the existence of a "threshold" level of chimerism necessary to sustain long-term engraftment.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia.

METHODS:Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation.

RESULTS:A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies.

CONCLUSION:The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.

背景与目标： 简介 : 在1982至1989之间，有46例患者插入了用于胃食管反流的Angelchik假体。11名患者 (24%) 随后切除了假体，除一名患者外，所有患者均因顽固性吞咽困难。
方法 : 对36名原始患者进行问卷调查，其中32例进行了钡棉花糖吞咽研究。
结果 : 在原位假体的患者中，有很大比例的患者 (26例中的20例) 有吞咽困难的症状。在棉花糖吞咽的客观评估中，通过时间明显慢于年龄匹配的对照组 (P <0.01)，但与先前的插入后研究相比，随着时间的变化没有显着恶化。
结论 : angelchik假体在很大一部分患者中引起长期吞咽困难，四分之一的患者严重到必须将其切除。因此，不建议继续使用。

BACKGROUND & AIMS: Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1 receptor activation, the implications of A2 receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A2 receptor blockade in the presence of complete A1 receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A2 receptors can enhance synaptic transmission. A2 receptor blockade by the A2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A1 receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A1 receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A2 antagonist 8-SPT (8-(p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A2 receptors play no significant role in the maintenance phase of LTP. Selective A2a receptor activation did not alter the field EPSP. Similarly, selective blockade of the A2a receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A2 receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A2b receptor.

背景与目标： 尽管据报道，由于激动剂介导的腺苷A1受体激活，神经传递减少，但A2受体激活对突触传递的影响尚未得到很好的探讨。我们检查了腺苷A2受体在大鼠横海马切片中Schaffer collateral-CA1途径之间的神经传递功效中的作用。在完全A1受体抑制的存在下，A2受体阻断导致场兴奋性突触后电位 (EPSP) 斜率响应于低频测试脉冲 (0.033Hz) 的可逆降低，表明A2受体可以增强突触传递。A2拮抗剂DMPX (3,7-二甲基-1-炔基黄嘌呤) 对A2受体的阻断阻止了破伤风诱导的EPSP长期增强 (LTP) 的诱导。相反，在A1受体阻滞期间未观察到对LTP诱导的这种作用。我们还研究了在CPT持续阻断A1受体期间DMPX对LTP诱导的影响。在这种情况下，与单独在CPT存在下诱导的LTP相比，LTP显着降低。使用高度极性的A2拮抗剂8-SPT (8-(对磺苯基) 茶碱) 发现了类似的结果，表明DMPX对LTP的作用不是由于对细胞内中间体的直接作用。如果在破伤风后45分钟使用DMPX，则表明A2受体对LTP表达没有影响在LTP的维持阶段没有重要作用。选择性A2a受体激活不会改变EPSP。同样，选择性阻断A2a受体不会干扰破伤风诱导的LTP。神经元放电速率的增加会导致细胞外腺苷浓度的升高。这些结果表明，A2受体可能在诱导中起重要作用，尽管不是维持海马LTP，并且该作用可能是由A2b受体介导的。

BACKGROUND & AIMS: :A survey of pediatric otolaryngologists about voice disorders in children suggests that approximately 1% of children examined were noted to have voice problems, and in only one fifth of these children (0.2%) were the voice problems related to professional use of the voice, such as singing. Direct flexible laryngoscopy was the sole method of examination for 80% of the children examined by these pediatric specialists. Voice therapy for 6 months was generally recommended (88%). The survey represents an estimated clinical experience of > 160,000 children per year, and it achieved a response rate of 40% of pediatric otolaryngologists (48/120). Results suggest that the use of video and stroboscopy for examination of the pediatric voice would enhance understanding and assure correct diagnosis and treatment.

背景与目标： : 对儿童耳鼻喉科医生进行的一项关于儿童语音障碍的调查表明，大约1% 的被检查儿童有语音问题，其中只有5分之1儿童 (0.2%) 的语音问题与专业使用语音有关，例如唱歌。直接柔性喉镜检查是由这些儿科专家检查的80% 儿童的唯一检查方法。通常建议语音治疗6个月 (88%)。该调查代表了每年> 160,000名儿童的估计临床经验，并且达到了小儿耳鼻喉科医生的40% (48/120)。结果表明，使用视频和频闪镜检查小儿语音将增强理解并确保正确的诊断和治疗。

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: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.

背景与目标： : 受损的轴突在哺乳动物中枢神经系统 (CNS) 中无法长距离再生不是由于中枢神经元无法再生，而是由于CNS组织环境的非宽松性质。例如，在周围神经内良好生长的再生CNS轴突不能穿透成熟的CNS组织超过约1毫米。最近的证据表明，这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在此报告，植入成年大鼠兴奋性毒性病变纹状体的人类端脑神经母细胞可以逃避或中和成年CNS环境的这种抑制作用，并沿主要有髓纤维束延伸轴突，距离可达约20毫米。可以看到轴突沿着纹状体-黑质和皮质-脊髓束的路径伸长，到达黑质，桥脑核和颈脊髓，这是纹状体和皮质投射神经元的正常目标。这些植入物。

BACKGROUND & AIMS: PURPOSE:Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. DESIGN AND METHODS:We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we asked the professional to recommend the appropriate forms of long-term care. RESULTS:Although the professional respondents used the full spectrum of options offered to them, some professionals tended to favor the sector they worked in. Advanced practice nurses recommended day care and homemaking more and adult foster care less. Gerontologists used skilled nursing-facility placement more actively and rehabilitation, homemaking, and home health care less actively. Geriatricians and primary care physicians both favored rehabilitation and skilled nursing-facility care and were both less enthusiastic about assisted living, homemaking, and informal care, but the geriatricians favored day care more than did the primary care physicians. Registered nurses were highly supportive of assisted living, adult foster care, homemaking, and home health care, and they opposed skilled nursing-facility care. Social workers were less likely than other participants to endorse rehabilitation and adult foster care. IMPLICATIONS:Because consumer preference should be a major factor in making long-term-care decisions, many consumers need information about what options may best fit their situation. In the absence of empirical data on which types of long-term care work best for whom, consumers have to rely on expert judgment-but that judgment varies. Clients should be aware that an expert's background (as defined by discipline and work situation) may affect his or her recommendations. Each discipline appears to have its own set of experiences and beliefs that may influence recommendations.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

背景与目标：

BACKGROUND & AIMS: :Like other thalamic nuclei, the primate pulvinar is considered not to have long-range intrinsic connections, either excitatory or inhibitory. Injections of biotinylated dextran amine (BDA) in the medial pulvinar, however, reveal retrogradely filled neurons up to 2.0 mm from the injection edge. Serial section reconstruction (n = 18) confirmed that retrogradely filled neurons projected to the injection site and showed that they had additional long-range collaterals within the posterior pulvinar. Arrays of small, beaded terminations occurred in multiple foci along the collaterals. Terminal arrays were up to 1.0 mm in length; foci were separated by about 0.7 mm. Somata were large (average area = 220 microm2), and dendritic arbors were radiate and also large (about 1.0 mm in diameter), but without either the appendages of classical interneurons or the hairlike spines characteristic of radiate pulvinocortical projection neurons. Double labeling for BDA and parvalbumin (PV) or BDA and gamma-aminobutyric acid (GABA) indicated that these large neurons were positive for both PV and GABA. Double labeling for PV and GABA, or PV and glutamic acid decarboxylase 67 (GAD67) revealed a small number of similarly large neurons in the posterior pulvinar that were positive for both substances. Thus, we propose that these neurons are a novel class of inhibitory interneuron, longer range than the classic thalamic local circuit interneurons. Future questions include how these neurons relate to other inhibitory systems and specific postsynaptic populations and whether they are located preferentially within the posterior pulvinar, possibly related to the multimodal character of this thalamic region.

背景与目标： : 与其他丘脑核一样，灵长类脉冲被认为不具有兴奋性或抑制性的远距离内在联系。然而，在内侧髓中注射生物素化的葡聚糖胺 (BDA) 显示出从注射边缘到2.0毫米的逆行填充的神经元。连续切片重建 (n = 18) 证实，逆行填充的神经元投射到注射部位，并显示它们在后牙髓内有其他远距离侧支。沿侧支的多个病灶中出现了一系列小的串珠末端。末端阵列的长度可达1.0毫米; 病灶间隔约0.7毫米。躯体很大 (平均面积 = 220 microm2)，树突状乔木辐射且也很大 (直径约1.0毫米)，但没有经典中间神经元的附属物或辐射的皮质投射神经元的毛状刺特征。BDA和小白蛋白 (PV) 或BDA和 γ-氨基丁酸 (GABA) 的双重标记表明，这些大神经元对PV和GABA均为阳性。对PV和GABA或PV和谷氨酸脱羧酶67 (GAD67) 的双重标记显示，后牙髓中少量类似的大神经元对两种物质均呈阳性。因此，我们建议这些神经元是一类新型的抑制性中间神经元，其范围比经典的丘脑局部电路中间神经元更长。未来的问题包括这些神经元与其他抑制系统和特定的突触后种群之间的关系，以及它们是否优先位于后牙髓内，这可能与该丘脑区域的多模式特征有关。

BACKGROUND & AIMS: :A number of groups have developed libraries of siRNAs to identify genes through functional genomics. While these studies have validated the approach of making functional RNAi libraries to understand fundamental cellular mechanisms, they require information and knowledge of existing sequences since the RNAi sequences are generated synthetically. An alternative strategy would be to create an RNAi library from cDNA. Unfortunately, the complexity of such a library of siRNAs would make screening difficult. To reduce the complexity, longer dsRNAs could be used; however, concerns of induction of the interferon response and off-target effects of long dsRNAs have prevented their use. As a first step in creating such libraries, long dsRNA was expressed in mammalian cells. The 250 nt dsRNAs were capable of efficiently silencing a luciferase reporter gene that was stably transfected in MDA-MB-231 cells without inducing the interferon response or off-target effects any more than reported for siRNAs. In addition, a long dsRNA expressed in the same cell line was capable of silencing endogenous c-met expression and inhibited cell migration, whereas the dsRNA against luciferase had no effect on c-met or cell migration. The studies suggest that large dsRNA libraries are feasible and that functional selection of genes will be possible.

背景与目标： : 许多小组已经开发了sirna文库，以通过功能基因组学鉴定基因。尽管这些研究已经验证了制作功能性RNAi文库以了解基本细胞机制的方法，但由于RNAi序列是合成生成的，因此它们需要现有序列的信息和知识。另一种策略是从cDNA创建RNAi文库。不幸的是，复杂性的文库sirna将筛选困难.为了降低复杂性，可以使用更长的dsrna; 然而，对干扰素反应的诱导和长dsrna的脱靶效应的担忧阻止了它们的使用。作为创建此类文库的第一步，长dsRNA在哺乳动物细胞中表达。250 nt dsrna能够有效地沉默在MDA-MB-231细胞中稳定转染的荧光素酶报告基因，而不会比sirna所报道的更多诱导干扰素应答或脱靶效应。此外，在同一细胞系中表达的长dsRNA能够沉默内源性c-met表达并抑制细胞迁移，而针对荧光素酶的dsRNA对c-met或细胞迁移没有影响。研究表明，大型dsRNA文库是可行的，并且基因的功能选择将是可能的。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: The clinical outcome of treatment using conical crown-retained dentures was evaluated. Of the initial 25 patients provided with 26 conical crown-retained dentures, 18 patients with 18 restorations could be examined after a time ranging between 73 and 92 months. Of the eight restorations lost, four had been changed as a result of factors that might have been related to the prosthodontic care. Most of the patients were very satisfied with the restorations both functionally and esthetically and found their chewing comfort to be better after treatment with conical crown-retained dentures. However, 50% of the patients reported speech problems related to treatment. Technical failures were not insignificant but were treatable. The survival rate after 73 to 92 months was 78.3%.

背景与目标： 评估了使用锥形冠保留义齿治疗的临床结果。在最初提供26个圆锥形冠保留义齿的25例患者中，可以在73至92个月的时间内检查18例具有18个修复体的患者。在丢失的八个修复物中，有四个由于可能与口腔修复有关的因素而被更改。大多数患者在功能和美学上都对修复体感到非常满意，并发现在使用圆锥形冠保留义齿治疗后，其咀嚼舒适度更好。然而，50% 患者报告了与治疗相关的言语问题。技术故障并非微不足道，但可以治愈。73 ~ 92个月后的生存率为78.3%。

BACKGROUND & AIMS: Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

背景与目标： 依托泊苷产生拓扑异构酶II的可逆抑制，导致DNA裂解，从而具有抗肿瘤作用。这种机制表明，持续治疗的时间越长，抗肿瘤作用就越大。在本研究中，对29例年龄> 或 = 65岁的非霍奇金淋巴瘤 (NHL) 患者进行了低剂量口服依托泊苷长期治疗的治疗和不良反应的研究，这些患者的标准化疗无效或难治性。这些患者尽可能长时间地接受依托泊苷50 mg/d的剂量。继续治疗直到白细胞计数降低至 <或 = 2,000/microL或血小板计数降低至 <或 = 5 × 10(4)/microL。根据治疗效果的世卫组织标准，29例患者中有6例 (20.7% 例) 完全缓解，13例 (44.8% 例) 部分缓解，缓解率为65.5%。> or = 3级的不良反应包括白细胞减少24例 (82.8%) 和贫血7例 (24.1%)。由于白细胞减少 (粒细胞计数 <或 = 1,000/microL)，将八名患者与依托泊苷联合给予粒细胞集落刺激因子 (g-csf)。鉴于其良好的主观耐受性，低的严重不良反应发生率和良好的活性，长期连续给予单药口服依托泊苷代表了对老年NHL患者的有用治疗。

BACKGROUND & AIMS: OBJECTIVE:The authors' goal was to test the hypothesis that the antidepressant effect of total sleep deprivation can be maintained by initially avoiding sleep during a supposedly "critical" time period in the early morning.

METHOD:They studied 33 inpatients with major depression, melancholic type, all of whom responded positively to total sleep deprivation. Twelve of the patients were men and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00 midnight, which then was shifted back by 1 hour each day until a sleep time of 11:00 p.m. to 6:00 a.m. was reached.

RESULTS:Twenty (61%) of the 33 patients who responded to total sleep deprivation with an improved state of mood maintained this improvement during sleep phase advance therapy. Drug-free and medicated patients did not differ from each other.

CONCLUSIONS:The rapid amelioration of mood observed with total sleep deprivation can be preserved with a succeeding phase shift of the sleep period.

背景与目标： 目的 : 作者的目标是检验以下假设: 完全睡眠剥夺的抗抑郁作用可以通过最初在清晨的一个所谓的 “关键” 时期避免睡眠来维持。
方法 : 他们研究了33名患有抑郁症，忧郁型的住院患者，他们都对完全睡眠不足有积极的反应。12名患者为男性，21名患者为女性; 他们的平均年龄为46.7岁 (SD = 13.7)。完全睡眠剥夺后，患者开始从下午5:00到午夜12:00的睡眠计划，然后每天向后转移1小时，直到达到下午11:00上午6:00的睡眠时间。
结果 : 33名对完全睡眠剥夺有改善的情绪状态有反应的患者中有20名 (61% 名) 在睡眠阶段提前治疗期间保持了这种改善。无药物和药物治疗的患者彼此之间没有差异。
结论 : 完全睡眠剥夺所观察到的情绪迅速改善可以通过睡眠期的后续相移来保持。

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：