BACKGROUND & AIMS: :A 47-year-old man presented with abdominal pain, neck stiffness, severe transient hypertension and unusually dark urine. Cerebrospinal fluid investigations and angiography confirmed the diagnosis of a subarachnoid haemorrhage. Porphyrin studies on the patient and his family demonstrated that the family has acute intermittent porphyria. This is the second case report of an acute hepatic porphyria presenting with a subarachnoid haemorrhage. Acute transient hypertension during the attack of porphyria caused the rupture of an intracranial arterial aneurysm.

背景与目标： ：一名47岁的男子出现腹痛，颈部僵硬，严重的短暂性高血压和异常黑尿。脑脊液检查和血管造影证实了蛛网膜下腔出血的诊断。对患者及其家人的卟啉研究表明，该家庭患有急性间歇性卟啉症。这是第二例急性肝卟啉症伴蛛网膜下腔出血的报道。卟啉症发作期间的急性短暂性高血压引起颅内动脉瘤破裂。

BACKGROUND & AIMS: :The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P < 0.01) and volume (P < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after IH exposure. CIH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth.

背景与目标： ：这项研究的目的是评估阻塞性睡眠呼吸暂停（OSA）相关的慢性间歇性缺氧（CIH）是否影响肺癌的进展，并阐明肺癌小鼠模型的相关机制。 CIH组中的C57 / BL6小鼠在诱导肿瘤后暴露于间歇性缺氧2周，并与对照小鼠（室内空气）进行比较。测量缺氧诱导因子1α（HIF-1α），血管内皮生长因子（VEGF）和转移相关基质金属蛋白酶（MMP）。用western blot检测HIF-1α，Wnt /β-catenin，核因子红系2相关因子2（Nrf2）和哺乳动物靶标雷帕霉素-ERK等几种缺氧相关途径蛋白的表达水平。 CIH组的肿瘤数目（P <0.01）和肿瘤体积（P <0.05）增加。 CIH处理后，MMP-2的活性增强。 CIH组的VEGF水平显着升高（p <0.05）。 IH暴露后，β-catenin和Nrf2易位至细胞核，Wnt /β-catenin信号传导的下游效应子水平升高。 CIH增强了肺癌小鼠模型中肿瘤的增殖和迁移特性。 ß-catenin和Nrf2似乎是肿瘤生长的关键介质。

BACKGROUND & AIMS: :Decompression stress and exposure to hyperoxia may cause a reduction in transfer factor of the lung for carbon monoxide and in maximal aerobic capacity after deep saturation dives. In this study lung function and exercise capacity were assessed before and after a helium-oxygen saturation dive to a pressure of 2.5 MPa where the decompression rate was reduced compared with previous deep dives, and the hyperoxic exposure was reduced by administering oxygen intermittently at pressures of 50 and 30 kPa during decompression. Eight experienced divers of median age 41 years (range 29-48) participated in the dive. The incidence of venous gas microemboli was low compared with previous deep dives. Except for one subject having treatment for decompression sickness, no changes in lung function or angiotensin converting enzyme, a marker of pulmonary endothelial cell damage, were demonstrated. The modified diving procedures with respect to decompression rate and hyperoxic exposure may have contributed to the lack of changes in lung function in this dive compared with previous deep saturation dives.

背景与目标： ：减压应力和高氧暴露可能导致一氧化碳的肺转移因子减少，并导致深度饱和潜水后最大有氧运动能力降低。在这项研究中，在氦氧饱和度潜水至2.5 MPa的压力之前和之后评估了肺功能和运动能力，与以前的深潜相比，减压率降低了，而在200℃的压力下间歇地给氧减少了高氧暴露减压期间为50和30 kPa。八名经验丰富的潜水员，中位数年龄为41岁（29-48岁），参加了此次潜水。与以前的深潜相比，静脉气体微栓塞的发生率低。除一名接受减压病治疗的受试者外，未证明肺功能或血管紧张素转换酶（肺内皮细胞损伤的标志物）发生变化。与以前的深度饱和潜水相比，在减压和高氧暴露方面经过改进的潜水程序可能导致该肺功能缺乏变化。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Alemtuzumab may be effective in Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma, but is associated with severe hematologic toxicity and infections. This study investigated whether low-dose subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical responses similar to those obtained with the standard regimen, but with less toxicity. DESIGN AND METHODS:Fourteen SS patients were enrolled: 11 had relapsed/refractory disease and three had untreated SS with high counts of circulating Sézary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on day 3, then 15 mg on alternating days; circulating SC were evaluated after the fourth 15 mg dose and treatment was interrupted in the presence of counts <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days) was administered to the remaining patients, with SC counted before every injection, until a reduction to values of <1,000/mm (3). RESULTS:The median SC count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical response, with three complete responses (21.4%). After a median follow-up of 16 months, the median time-to-treatment failure is 12 months. Infectious complications occurred in 28.6% of patients, all included in the group treated with 15 mg. No patient in the group treated with 10 mg developed hematologic toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells occurred after the first cycle. INTERPRETATION AND CONCLUSIONS:Subcutaneous alemtuzumab at very low doses (10 mg maximum per administration), given for a short period based on SC levels, has a good toxicity profile, high response rate and causes durable remissions in SS patients with high tumor burden in the peripheral blood.

背景与目标： 背景与目的：Alemtuzumab可能对Sézary综合征（SS），侵袭性皮肤T细胞淋巴瘤有效，但与严重的血液学毒性和感染有关。这项研究调查了低剂量皮下注射alemtuzumab是否可以诱导血液学，免疫学和临床反应，与标准治疗方案相似，但毒性较小。
设计与方法：招募了14例SS患者：11例复发/难治性疾病和3例未经治疗的SS，其循环中的Sézary细胞（SC）数量高。四名患者在第1天接受3 mg阿仑珠单抗，在第3天接受10 mg，然后每隔一天接受15 mg；在第四个15 mg剂量后评估循环SC，并在计数<1,000 / mm的情况下中断治疗（3）。其余患者服用减少剂量的药物（第1天为3 mg，隔天则为10 mg），每次注射前都要对SC进行计数，直至降至<1,000 / mm（3）。
结果：中位SC计数下降了95.5％。总体而言，有12/14例患者（85.7％）达到了临床缓解，其中3例完全缓解（21.4％）。中位随访16个月后，中位治疗失败时间为12个月。感染并发症发生在28.6％的患者中，所有患者均接受15 mg治疗。用10 mg治疗的组中没有患者出现血液学毒性或感染。在第一个周期后，循环的NK，B和CD3 CD8细胞得以早期恢复。
解释和结论：根据SC水平在短期内给予非常低剂量的皮下注射alemtuzumab（每次给药最大10 mg），具有良好的毒性特征，高响应率，并导致具有高肿瘤负担的SS患者持久缓解。外周血。

BACKGROUND & AIMS: PURPOSE:To evaluate the primary success and short-term patency associated with a new 4-F sheath-compatible self-expanding nitinol stent after failed conventional angioplasty of distal popliteal and infrapopliteal lesions in severe lifestyle-limiting claudication (LLC) and chronic critical limb ischemia (CLI). MATERIALS AND METHODS:Between May 2003 and July 2005, 35 patients with Rutherford category 3-5 disease (16 patients with CLI, 19 patients with LLC) underwent percutaneous transluminal angioplasty (PTA) and stent implantation. Indications for stent placement were residual stenosis, flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical investigation, color-flow and duplex Doppler ultrasonography, and digital subtraction angiography were performed. Technical success, primary patency at 6 months, clinical improvement as defined by Rutherford with clinical and hemodynamic measures, and complications were evaluated. RESULTS:A total of 22 patients underwent distal popliteal artery stent placement and 13 underwent tibioperoneal artery stent placement. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 82%. The mean resting ankle-brachial index at baseline was 0.50 +/- 0.16 and significantly increased to 0.90 +/- 0.17 at 12-24 hours after intervention and 0.82 +/- 0.24 at latest follow-up (P < .001 for both). The sustained clinical improvement rate was 80% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 100%. The rate of major complications was 17%. CONCLUSIONS:Infrapopliteal application of the new nitinol stent is a safe, feasible, and effective method with good short-term patency rate in the treatment of severe LLC and chronic CLI.

背景与目标： 目的：评估在严重的生活方式限制性lau行（LLC）和慢性危重肢体的远侧pop和in下病变的常规血管成形术失败后，与新型4-F鞘相容性自扩张镍钛合金支架相关的主要成功和短期通畅性缺血（CLI）。
材料与方法：2003年5月至2005年7月，对35例卢瑟福3-5型疾病患者（16例CLI患者，19例LLC患者）进行了经皮腔内血管成形术（PTA）和支架植入术。支架置入的指征是残余狭窄，限流夹层或PTA后的弹性后座力。在干预前后，以及在6个月的随访期间，进行了临床研究，彩色流和双工多普勒超声检查以及数字减影血管造影。评估了技术成功率，6个月时的通畅性，卢瑟福定义的临床改善以及临床和血液动力学指标以及并发症。
结果：总共22例患者接受了pop骨远端动脉支架置入术，其中13例接受了胫腓骨动脉支架置入术。所有患者均成功进行了支架植入。放置支架后，研究组在6个月时的主要累积通畅率为82％。基线时平均静息踝臂指数为0.50 /-0.16，干预后12-24小时显着增加至0.90 /-0.17，最新随访时为0.82 /-0.24（两者均P <.001）。在六个月的随访中，持续的临床改善率为80％。大截肢的6个月肢体抢救率为100％。主要并发症发生率为17％。
结论：新的镍钛合金支架在眼下应用是治疗严重LLC和慢性CLI的一种安全，可行，有效的方法，具有良好的短期通畅率。

BACKGROUND & AIMS: :Medical therapy to improve symptoms, stabilise the underlying vascular disease and improve lower limb outcomes is an important and effective adjunct to lifestyle modification and surgical or endovascular interventions in patients with IC. Randomised placebo controlled trials have shown that the phosphodiesterase III inhibitor cilostazol 100mg bid improves pain-free and maximum walking distance, as well as quality of life, in a range of patients with intermittent claudication in whom there is no evidence of tissue necrosis or rest pain. This review summarises the evidence from 8 pivotal trials of cilostazol involving over 2000 patients with intermittent claudication treated for up to 6 months. There is comparatively less evidence to support the use of other treatment modalities for relief of symptoms in intermittent claudication, but there is considerable interest in therapeutic angiogenesis to promote new vessel formation and enhance collateralisation of the lower limb using recombinant growth factor proteins or gene transfer strategies. The rationale for therapeutic angiogenesis is discussed, together with the most recent results from randomised trials in patients with peripheral arterial disease.

背景与目标： ：改善症状，稳定潜在的血管疾病和改善下肢预后的医学治疗是IC患者生活方式改变以及外科或血管内干预的重要而有效的辅助手段。随机安慰剂对照试验表明，磷酸二酯酶III抑制剂西洛他唑100mg bid可以改善一系列间歇性lau行患者的无痛和最大步行距离以及生活质量，这些患者没有组织坏死或休息疼痛的迹象。这篇综述总结了西洛他唑的8项关键试验的证据，这些试验涉及2000例间歇性lau行患者，治疗时间长达6个月。相对较少的证据支持使用其他治疗方式来缓解间歇性lau行中的症状，但是对于使用重组生长因子蛋白或基因转移策略来促进新血管形成并增强下肢的侧支作用的治疗性血管生成具有相当大的兴趣。讨论了治疗性血管生成的原理以及外周动脉疾病患者随机试验的最新结果。

BACKGROUND & AIMS: BACKGROUND:Malaria in pregnancy has adverse effects on maternal and child health. Intermittent preventive treatment (IPTp) with three doses of Sulfadoxine/Pyrimethamine is an effective preventive measure for malaria in pregnancy. However, 24.0% of women use this prophylactic regimen in Ebonyi State. Previous studies have focused on the level of uptake with less attention given to factors influencing uptake. Therefore, we examined the predictors of IPTp uptake in the last pregnancy among women in Ebonyi State, Nigeria. METHODS:This was a community-based cross-sectional study among 340 women of reproductive age selected using multistage sampling technique. A semi-structured interviewer administered questionnaire was used to collect data on socio-demographic characteristics of respondents, IPTp uptake and reasons for not taking IPTp. Adherence was judged adequate if three or more doses of IPTp were taken, otherwise inadequate. Data were analyzed using descriptive statistics, Chi- square test and logistic regression model at 5% level of significance. RESULTS:Mean age of respondents was 28.8 ± 5.2 years, 96.5% were married, 19.4% had tertiary education, and 11.2% were from polygamous family. Uptake of IPTp was 74.2%. The level of IPTp uptake was 12.5 and 41.0% among women with no formal and tertiary education respectively. A similar pattern of IPTp uptake was observed among women from monogamous (38.0%) and polygamous (39.5%) families. Women education, husband education and family type were associated with uptake of IPTp, however only husband education remained a predictor of uptake. Women whose husband had secondary education (aOR = 4.1, 95%CI: 1.66-10.06) and tertiary education (aOR = 4.8, 95%CI: 1.76-12.90) were more likely to have IPTp uptake than those whose husbands had below secondary education. CONCLUSION:Adequate IPTp uptake among women in their last pregnancy was below WHO recommendation. Intervention aimed at improving couple's education could facilitate increase in IPTp uptake in Ebonyi State.

背景与目标： 背景：怀孕期间的疟疾会对母婴健康产生不利影响。三种剂量的磺胺多辛/乙胺嘧啶的间歇性预防性治疗（IPTp）是预防疟疾的有效措施。但是，在埃博尼州，有24.0％的妇女使用了这种预防性治疗方案。先前的研究集中在摄取水平上，较少关注影响摄取的因素。因此，我们检查了尼日利亚埃邦伊州妇女最后一次妊娠中IPTp摄取的预测因子。
方法：这是一项基于社区的横断面研究，对使用多阶段抽样技术选择的340名育龄妇女进行了研究。使用半结构性访调员管理的问卷来收集有关受访者的社会人口统计学特征，IPTp摄入量和不服用IPTp的原因的数据。如果服用三剂或更多剂量的IPTp，则判断粘附性足够，否则不足。使用描述性统计，卡方检验和逻辑回归模型对数据进行了分析（显着性水平为5％）。
结果：受访者平均年龄为28.8±5.2岁，已婚的比例为96.5％，大专以上学历的比例为19.4％，一夫多妻制家庭的比例为11.2％。 IPTp的吸收率为74.2％。没有受过正规和高等教育的妇女中IPTp摄取水平分别为12.5％和41.0％。在一夫一妻制（38.0％）和一夫多妻制（39.5％）家庭的妇女中观察到了类似的IPTp吸收模式。妇女的教育，丈夫的教育和家庭类型与IPTp的摄取有关，但是只有丈夫的教育仍然是摄取IPTp的指标。丈夫受过中等教育（aOR = 4.1，95％CI：1.66-10.06）和高等教育（aOR = 4.8，95％CI：1.76-12.90）的女性比丈夫受过中等教育的女性更有可能接受IPTp 。
结论：上次妊娠妇女的足够IPTp摄取低于WHO的建议。旨在改善夫妇的教育水平的干预措施可以促进埃博尼州IPTp摄入量的增加。

BACKGROUND & AIMS: :Sporotrichosis is a subcutaneous and exceptionally deep mycosis caused by a dimorphic fungus, Sporothrix schenckii. Itraconazole is a triazole derivative leading to good results in the treatment of sporotrichosis. Patients with cutaneous sporotrichosis proven with mycological tests (direct examination and culture) were enrolled. All patients underwent laboratory tests (at baseline and on a monthly basis) and received oral itraconazole 400 mg/day for one week with a 3-week break (pulses); thereafter the drug was administered as pulses until clinical and mycological cure was achieved. Five patients with sporotrichosis were enrolled, 4 with cutaneous lymphangitic form and one with fixed cutaneous form. Clinical and mycological cure was achieved in 4/5 cases (80%), with a mean number of pulses of 3.5. No patient had side effects and no laboratory test abnormalities occurred. Intermittent or pulsed itraconazole was effective in treating cutaneous sporotrichosis. It may be considered as a new treatment choice that entails an important reduction in total medication use.

背景与目标： ：Sporotrichosis是由双态真菌Schenothrix schenckii引起的皮下和极深的真菌病。伊曲康唑是一种三唑衍生物，在孢子体增生症的治疗中具有良好的疗效。入选经真菌学检查（直接检查和培养）证实的皮肤孢子虫病患者。所有患者均接受实验室检查（在基线和每月进行），并接受口服伊曲康唑400 mg /天，为期一周，中断3周（脉冲）；此后以脉冲形式给药直至达到临床和真菌学治愈。招募了5例孢子体增生症患者，其中4例为皮肤淋巴管炎形式，而1例为皮肤固定形式。临床和真菌学治愈率达到4/5例（80％），平均脉搏数为3.5。没有患者有副作用，也没有发生实验室检查异常。间歇或脉冲伊曲康唑可有效治疗皮肤孢子虫病。它可以被认为是一种新的治疗选择，它可以显着减少总用药量。

BACKGROUND & AIMS: :Vascularized tumors are exposed to intermittent hypoxia, that is, hypoxia followed by periods of reoxygenation. Abnormal structure and dysfunction of tumor blood vessels are responsible for these conditions. These repeated short periods of hypoxia concern tumor cells as well as endothelial cells. However, the effects of intermittent hypoxia are poorly understood. The aim of this study was to investigate the effects of intermittent hypoxia on endothelial cells and particularly on HIF-1alpha, a central actor in adaptive response to hypoxia. For that, endothelial cells were exposed to four repeated cycles of 1-h hypoxia followed by 30 min of reoxygenation. We showed that repeated cycles of hypoxia/reoxygenation induced a modification in HIF-l alpha phosphorylation pattern: a progressive increase in HIF-1alpha phosphorylated form was observed during the hypoxic periods. Activation of p42/p44, Akt and PKA was observed in parallel. PKA was shown to be involved in the phosphorylation of HIF-lalpha under intermittent hypoxia, while p42/p44 and Akt were not. As HIF-1 activity is often associated with enhanced cell survival, a better knowledge of the effects of intermittent hypoxia on endothelial cells and the highlight of particular mechanisms induced by intermittent hypoxia are essential to understand the behavior of endothelial cells during neo-angiogenesis.

背景与目标： ：血管化肿瘤暴露于间歇性缺氧，即缺氧，随后进行复氧。肿瘤血管的异常结构和功能异常是造成这些疾病的原因。这些反复的缺氧短时间涉及肿瘤细胞以及内皮细胞。但是，对间歇性缺氧的影响了解甚少。这项研究的目的是研究间歇性缺氧对内皮细胞，特别是对HIF-1alpha的影响，HIF-1alpha是对缺氧的适应性反应的主要参与者。为此，将内皮细胞暴露于四个重复的1小时缺氧循环，然后再进行30分钟的复氧。我们显示了缺氧/复氧的重复周期诱导了HIF-1α磷酸化模式的修饰：在缺氧期间观察到HIF-1α磷酸化形式的逐步增加。并行观察到p42 / p44，Akt和PKA的激活。在间歇性缺氧条件下，PKA参与了HIF-1α的磷酸化，而p42 / p44和Akt则不参与。由于HIF-1活性通常与提高的细胞存活率相关，因此，了解间歇性缺氧对内皮细胞的影响以及了解间歇性缺氧引起的特定机制的重要性，对于理解新血管生成过程中的内皮细胞行为至关重要。

BACKGROUND & AIMS: BACKGROUND:The intermittent Pringle's maneuver (IPM) is conducted mainly during the procedure of hepatectomy to control intraoperative blood loss (IBL), but it has been questioned since improvement of surgical technology and intraoperative management. Hence, we conducted a systematic review and meta-analysis to validate the clinical value of IPM. MATERIALS AND METHODS:Eligible studies that were designed to evaluate the IPM in the procedure of hepatectomy were searched for on PubMed, Medline, and other databases from establishment of the database to October 2019. The primary endpoints were IBL and intraoperative blood transfusion (IBT). The risk ratio (RR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS:A total of 16 studies with six randomized controlled trials (RCTs) were enrolled in this meta-analysis, including 1,770 cases in the IPM group and 1,611 cases in the non-IPM group. Overall, there were no significant differences between the IPM and non-IPM groups in the amount of IBL and the incidence of IBT (RR = 0.96, 95% CI 0.67-1.37, P = 0.82), which was also confirmed in the subgroups of RCTs (P > 0.05). However, subgroup analyses showed that for patients with colorectal liver metastasis (CRLM), the amount of IBL was generally higher in the IPM group than in the non-IPM group, and the incidence of IBT was significantly higher in the IPM group (RR = 7.17, 95% CI 1.91-26.94, P = 0.004). In addition, no significant differences were observed in terms of postoperative complications between the two groups (all P > 0.05). CONCLUSION:With the current data, we concluded that IPM had lost its value in patients with CRLM, although it remained controversial in patients with hepatocellular carcinoma.

背景与目标： 背景：间歇性普林格尔手术（IPM）主要在肝切除术中进行，以控制术中失血（IBL），但自从手术技术和术中管理水平不断提高以来，人们一直对此提出质疑。因此，我们进行了系统的综述和荟萃分析，以验证IPM的临床价值。
材料与方法：从建立数据库到2019年10月，在PubMed，Medline和其他数据库中搜索旨在评估肝切除术中IPM的合格研究。主要终点是IBL和术中输血（IBT） 。使用具有95％置信区间（CI）的风险比（RR）来确定效应大小。
结果：本荟萃分析共纳入16项研究，包括6项随机对照试验（RCT），其中IPM组为1,770例，非IPM组为1,611例。总体而言，IPM组和非IPM组之间的IBL量和IBT的发生率没有显着差异（RR = 0.96，95％CI 0.67-1.37，P = 0.82），这在以下亚组中也得到了证实RCT（P> 0.05）。但是，亚组分析显示，对于结直肠肝转移（CRLM）患者，IPM组的IBL含量通常高于非IPM组，IPM组的IBT发生率明显更高（RR = 7.17，95％CI 1.91-26.94，P = 0.004）。此外，两组在术后并发症方面均未观察到显着差异（均P> 0.05）。
结论：根据目前的数据，我们得出结论，尽管IPM在CRLM患者中失去了价值，但在肝细胞癌患者中仍然存在争议。

BACKGROUND & AIMS: :Androgen deprivation therapy (ADT) is still a mainstay of treatment for advanced prostate cancer. Continuous ADT causes considerable patient morbidity including sexual dysfunction, poor mood and physical capacity, changes in body composition and health-care-related costs. Intermittent ADT has been used as an approach to ADT monotherapy to limit morbidity by enabling cyclical recovery of serum testosterone levels. To date, a number of well-performed randomized controlled trials and meta-analyses have demonstrated statistically insignificant differences in oncological outcomes between intermittent and continuous ADT monotherapy. Sexual outcomes, morbidity profiles and cost-savings favour intermittent therapy in most randomized trials, but the benefit for clinical practice is unclear. Despite the growing body of evidence, the optimal administration regime for ADT has not been clearly established and incorporation of adjunctive upfront treatments such as chemotherapy and novel anti-androgen agents has further hampered progress. Recommendations by authoritative urological and oncological societies regarding the use of intermittent ADT are limited. The potential benefits of reduced morbidity for a particular patient must be considered in light of the possible oncological outcomes. Although the oncological changes associated with intermittent ADT are controversial, intermittent ADT does seem to provide symptomatic benefit in patients compared with continuous ADT. However, careful selection of suitable patients is crucial.

背景与目标： ：雄激素剥夺疗法（ADT）仍然是晚期前列腺癌的主要治疗手段。连续的ADT会导致相当大的患者发病率，包括性功能障碍，情绪低下和身体能力差，身体成分发生变化以及与医疗相关的费用。间歇性ADT已被用作ADT单药治疗的一种方法，可通过周期性恢复血清睾丸激素水平来限制发病率。迄今为止，许多性能良好的随机对照试验和荟萃分析显示，间歇性和连续性ADT单一疗法在肿瘤学结局方面统计学上无显着差异。在大多数随机试验中，性结局，发病率概况和成本节约有利于间歇治疗，但临床实践的益处尚不清楚。尽管有越来越多的证据，但尚未明确确定ADT的最佳给药方案，而辅助性前期治疗（如化学疗法和新型抗雄激素剂）的纳入进一步阻碍了进展。权威泌尿科和肿瘤学学会对间歇性ADT的使用建议是有限的。必须根据可能的肿瘤学结果考虑降低特定患者发病率的潜在益处。尽管与间歇性ADT相关的肿瘤学变化是有争议的，但与连续性ADT相比，间歇性ADT确实对患者提供了症状上的益处。但是，仔细选择合适的患者至关重要。

BACKGROUND & AIMS: AIMS & OBJECTIVES:The aim of the current study was to explore factors that hinder or promote adherence to clean intermittent self-catheterization (CISC) procedures in adults. BACKGROUND:Clean intermittent self-catherization is associated with favourable patient outcomes, but adherence to the procedure is not addressed in the international literature. METHODS:Relevant factors were explored in two studies. The first study (n = 10) addressed mastery and short-term adherence, whereas the second study (n = 20) addressed long-term adherence in these patients. Determinants of patient adherence were derived from pre-structured interviews with patients, using a content-analysis procedure. RESULTS:A list of 16 determinants of mastery and short-term adherence and a list of 12 determinants of long-term adherence was found. Most of these determinants were found in both older (>or=65 years of age) and younger patients. However, five determinants of mastery and short-term adherence and six determinants of long-term adherence were specific to patients under the age of 65. CONCLUSION:Our findings give a first insight into CISC adherence. General determinants of adherence relate to knowledge, complexity of the procedure, misconceptions, fears, shame, motivation and quality and continuity of professional care. Furthermore integrating CISC in everyday life can be difficult. In younger patients, availability of materials, physical impairments and resistance to a sickness role can further compromise adherence. RELEVANCE TO CLINICAL PRACTICE:Issues of knowledge, fears, motivation and potential psychological impact of performing CISC should be addressed prior to deciding on CISC and instructing patients. Follow-up care should be improved to include re-evaluations of skills, discussing adherence, integrating CISC in daily activities and general coping issues.

背景与目标： 目的和目标：本研究的目的是探讨阻碍或促进成人清洁间歇性自导管（CISC）手术依从性的因素。
背景：干净的间歇性自我凯瑟琳化与良好的患者预后相关，但国际文献中未提及对手术的依从性。
方法：在两项研究中探讨了相关因素。第一项研究（n = 10）针对精通和短期依从性，而第二项研究（n = 20）针对这些患者的长期依从性。患者依从性的决定因素是使用内容分析程序从与患者进行的预先结构化访谈中得出的。
结果：找到了掌握和短期坚持的16个决定因素的清单和长期坚持的12个决定因素的清单。这些决定因素大多数是在年龄较大（>或= 65岁）和年轻患者中发现的。但是，掌握和短期依从性的五个决定因素以及长期依从性的六个决定因素特定于65岁以下的患者。
结论：我们的发现为CISC的依从性提供了第一见解。依从性的一般决定因素涉及知识，程序的复杂性，误解，恐惧，羞耻，动机以及专业护理的质量和连续性。此外，将CISC整合到日常生活中可能很困难。在较年轻的患者中，材料的可获得性，身体上的损伤和对疾病的抵抗力可能会进一步损害依从性。
与临床实践的关系：在决定进行CISC和指导患者之前，应解决执行CISC的知识，恐惧，动机和潜在的心理影响等问题。应当改善后续护理，包括重新评估技能，讨论依从性，将CISC纳入日常活动和一般应对问题。

BACKGROUND & AIMS: :Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to benzene or toluene alone suggests that, at the doses used in this study, toluene can enhance benzene-induced clastogenic or aneugenic bone marrow injury. These findings exemplify the importance of studying the effects of binary chemical interactions in animals exposed to lower exposure concentrations of benzene and toluene on benzene metabolism and clastogenicity. The relevance of these data on interactions for humans exposed at low benzene concentrations can be best assessed only when the mechanism of interaction is understood at a quantitative level and incorporated within a biologically based modeling framework.

背景与目标： ：苯是重要的工业化学品。在某些水平上，已发现苯会在人类中产生再生障碍性贫血，全血细胞减少，骨髓小球性贫血和遗传毒性作用。细胞色素P450单加氧酶和髓过氧化物酶代谢为氢醌，苯酚和其他代谢物会导致苯毒性。细胞色素P450的其他异质底物可以改变苯的代谢。在高浓度下，甲苯已显示出抑制苯代谢和苯诱导的毒性的作用。本研究调查了在较低和间歇性共同暴露下暴露于苯和甲苯的遗传毒性。通过全身吸入将小鼠暴露于空气，50 ppm苯，100 ppm甲苯，50 ppm苯和50 ppm甲苯或50 ppm苯和100 ppm的空气中，每天吸入6小时/天，持续8天（在15天的时间内）。甲苯。与暴露于空气的对照组相比，暴露于50 ppm苯的小鼠的微核多色红细胞（PCE）的频率增加（2.4倍），尿代谢产物（t，t-粘康酸，对苯二酚和s-苯基巯基尿酸）的含量增加。 。苯与100 ppm甲苯的共同暴露导致尿液代谢产物水平相似，但微核PCE的频率增加了3.7倍。苯与50 ppm甲苯的共同暴露导致微核频率的升高与100 ppm甲苯的相似，这与单独暴露于50 ppm的苯没有显着差异。两种共同暴露-50 ppm苯与50或100 ppm甲苯-均导致CYP2E1活性显着升高，而单独暴露于苯或甲苯后并未发生。暴露于50 ppm苯和/或100 ppm甲苯后，全血谷胱甘肽（GSH）水平同样降低，而同时暴露于50 ppm苯和100 ppm甲苯则显着降低GSSG水平并增加GSH / GSSG比。与仅暴露于苯或甲苯的小鼠相比，苯和甲苯共同暴露后微核PCE的发生频率更高，这表明，在本研究中使用的剂量下，甲苯可以增强苯诱导的可致瘤性或非成因性骨髓损伤。这些发现证明了研究动物中二元化学相互作用对苯和甲苯的较低暴露浓度对苯代谢和致突变性的影响的重要性。仅当在定量水平上理解相互作用机理并将其纳入基于生物学的建模框架中时，才能最好地评估这些数据对与低苯浓度暴露的人的相互作用的相关性。

BACKGROUND & AIMS: :The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients' resistant to standard treatments.

背景与目标： ：睡眠呼吸暂停低通气综合症（SAHS）涉及间歇性缺氧，通过将动物模型暴露于振荡的PO2模式进行实验性重现。在这两种情况下，慢性间歇性缺氧（CIH）暴露都会导致颈动脉体（CB）过度活化，从而增加对脑干的输入，这会引起交感神经亢进，随后是由于CB去神经支配而导致的高血压。 CB在化学感受器细胞中具有多巴胺（DA）受体作为DA-2自身受体。目的是检查阻断DA-2受体是否可以降低CIH产生的CB超敏反应，从而最大程度地减少与CIH相关的影响。多潘立酮（DOM）是一种选择性外周DA-2受体拮抗剂，它不穿越血脑屏障，用于检查其对暴露于CIH（30天）的大鼠的作用。测量动脉压，CB分泌活性和全身体积描记法。在CIH的最后15天内，急性或长期给药的DOM逆转了CIH产生的高血压，其作用与CB失神经获得的类似。 DOM在对照动物中略微降低了血压，并且在对照或CIH动物中不影响低氧通气反应。没有观察到不良反应。 DOM被用作胃肠动力药和止吐药，可能是SAHS患者对标准疗法产生抗药性的高血压治疗机会。