BACKGROUND & AIMS: Impotence affects 10 to 15% of the male population. Organic factors are recognized in 80% of cases. Intracavernosal injections of vasoactive agents (Virag) have provided advances in the physiopathologic understanding of impotence and provide new ways of treating this incapacity. However this option is inaffective in most organic casesarteriogenic, venogenic or disorders of smooth cavernous muscle. Vasoactive injections for many reasons are abandoned in about 40% of the cases.

Two kinds of surgical management can be performedmicrorevascularization in order to restore the arterial penile flow or to reduce penile venous flow during erection; implantation of penile prosthesis when other therapeutic possibilities are exhausted. Arterialization of the deep dorsal vein (DDV) appears to be the best procedure in arteriogenic and principally venous impotence. Erectile function in theses case is restored in 60% of our patients.

Two types of prostheses can be implantedsemi-rigid with an axial permanent rigidity and inflatable or hydraulic devices with a flaccid aspect after intercourse. These prostheses are technically successful in 75 to 90% of cases, but partner satisfaction does not match surgical success rates.

背景与目标： 阳影响了10％至15％的男性人口。在80％的病例中识别出有机因素。腔内注射血管活性剂（Virag）已在阳of的生理病理学理解上取得了进步，并提供了治疗这种无能的新方法。但是，此选项在大多数器质性动脉粥样硬化，静脉源性或海绵状平滑肌疾病中均无效。约有40％的病例因多种原因放弃了血管活性注射。

可以进行两种手术管理，以恢复勃起过程中的动脉阴茎流量或减少阴茎静脉血流量。当其他治疗方法用尽时，植入阴茎假体。深背静脉（DDV）的动脉化似乎是在动脉形成性和主要是静脉性阳ence中的最佳方法。在这种情况下，我们的患者中有60％恢复了勃起功能。

两种类型的假体可以半永久性植入，具有轴向永久性刚性，并且在性交后可植入具有松弛状态的充气或液压装置。从技术上讲，这些假体在75％至90％的病例中都是成功的，但伙伴的满意度与手术成功率不符。

BACKGROUND & AIMS: :Epidural blood patch (EBP) is an effective procedure for the treatment of spontaneous intracranial hypotension (SIH). Neurological compromise following EBP, although rare, is recognized as a serious potential complication. We describe a 33-year-old female patient in whom long-term bladder and bowel dysfunction developed following a small volume (10 mL) EBP to treat SIH. We also discuss the possible pathophysiological mechanisms related to this complication in the postprocedure setting.

背景与目标： ：硬膜外补血（EBP）是治疗自发性颅内低血压（SIH）的有效方法。 EBP后的神经功能损害虽然很少见，但被认为是严重的潜在并发症。我们描述了一名33岁的女性患者，在该患者中，小剂量（10 mL）EBP治疗SIH后会出现长期的膀胱和肠功能障碍。我们还将讨论与术后并发症相关的可能的病理生理机制。

BACKGROUND & AIMS: BACKGROUND:Ebstein anomaly is a rare and heterogeneous congenital heart defect affecting the tricuspid valve and right ventricular (RV) myocardium. Few studies have analysed the electrocardiographic features of Ebstein anomaly and none has addressed correlations with disease severity. METHODS:Patients with Ebstein anomaly who had undergone electrocardiography and cardiac magnetic resonance (CMR) within 6 weeks between 2001 and 2009 were included. Exclusion criteria were: associated congenital cardiac defect, previous RV myoplasty and/or reduction surgery, class I anti-arrhythmic drug therapy, and paced/pre-excited QRS. Standard electrocardiogram (ECG) findings were correlated with CMR-based RV measures and clinical profile. RESULTS:The mean age of the 63 study patients was 22 ± 13 years. An RV conduction delay (rsR' pattern in right precordial leads) was present in 45 patients (71%). The QRS duration correlated with anatomic RV diastolic volume (r = +0.56, P < 0.0001) and inversely with RV ejection fraction (EF; r = -0.62, P < 0.0001). The presence of QRS fractionation predicted greater atrialized RV volume (80 ± 31 vs. 45 ± 37 mL/m(2), P < 0.001). Normal QRS duration was associated with smaller anatomic RV diastolic volume (150 ± 57 vs. 256 ± 100 mL/m(2); P < 0.0001), higher RV EF (48 ± 6 vs. 34 ± 14%; P < 0.0001), higher oxygen consumption (VO(2)) at cardiopulmonary exercise (25.8 vs. 21.8 mL/kg/min, P = 0.05) and lower incidence of oxygen desaturation with exercise (25 vs. 65%, P = 0.02). CONCLUSION:Delayed and prolonged depolarization of the RV is common in patients with Ebstein anomaly. The QRS duration is a marker of RV enlargement and dysfunction. QRS fractionation is associated with a greater atrialized RV volume. A preserved surface ECG identifies a subset of patients with Ebstein anomaly with mild morphological and functional abnormalities and better clinical profile.

背景与目标： 背景：Ebstein异常是一种罕见的异质先天性心脏缺陷，会影响三尖瓣和右心室（RV）心肌。很少有研究分析Ebstein异常的心电图特征，没有研究解决疾病严重程度的相关性。
方法：纳入2001年至2009年之间6周内经历过心电图和心脏磁共振（CMR）检查的Ebstein异常患者。排除标准为：相关的先天性心脏缺陷，先前的RV肌成形术和/或复位手术，I类抗心律不齐药物治疗以及起搏/预激QRS。标准心电图（ECG）发现与基于CMR的RV测量和临床特征相关。
结果：63名研究患者的平均年龄为22±13岁。 RV传导延迟（右心前导联中的rsR'模式）存在于45例患者中（71％）。 QRS持续时间与解剖型RV舒张容积相关（r = 0.56，P <0.0001），与RV射血分数成反比（EF; r = -0.62，P <0.0001）。 QRS分馏的存在预示了较大的房颤RV量（80±31 vs. 45±37 mL / m（2），P <0.001）。正常QRS持续时间与较小的RV解剖解剖容积相关（150±57 vs. 256±100 mL / m（2）; P <0.0001），较高的RV EF（48±6 vs. 34±14％; P <0.0001） ，心肺运动时较高的耗氧量（VO（2））（25.8 vs. 21.8 mL / kg / min，P = 0.05）和较低的运动性氧脱饱和发生率（25 vs. 65％，P = 0.02）。
结论：Ebstein异常患者右室延迟和延长去极化是常见的。 QRS持续时间是RV增大和功能障碍的标志。 QRS分馏与较大的房颤RV量相关。保留的表面心电图可识别出具有轻度形态和功能异常以及更好的临床特征的一部分埃伯斯坦异常患者。

BACKGROUND & AIMS: :The objective of the study was to evaluate the association between peripheral venous disease (PVD) and arterial endothelial dysfunction (ED). Arterial and venous diseases have been always considered as two completely different entities, but the recent discovery of a relationship between arterial and venous thrombosis have challenged this assumption. ED, considered to be an early process in the pathophysiology of atherosclerotic disease, could represent a common pathogenetic background. We studied 39 healthy volunteers (median age: 34 years; men: 25.6%). PVD was diagnosed using ultrasound examination, arterial ED using flow-mediated dilation (FMD) and FMD normalized for the peak shear rate (nFMD). Compared with controls, participants with PVD had a lower FMD (15.2 versus 23.4%, P < 0.001) and nFMD (12.7 × 10(-3) versus 19 × 10(-3)/second, P < 0.001). People with the most clinically evident disease had the worst endothelial function. In conclusion, our findings, if confirmed in larger population, might corroborate the idea that venous and arterial disease could have common causes.

背景与目标： ：该研究的目的是评估周围静脉疾病（PVD）与动脉内皮功能障碍（ED）之间的关联。动脉和静脉疾病一直被认为是两个完全不同的实体，但是最近发现动脉和静脉血栓形成之间的关系挑战了这一假设。 ED被认为是动脉粥样硬化疾病病理生理的早期过程，可能代表了常见的致病背景。我们研究了39名健康志愿者（中位年龄：34岁；男性：25.6％）。使用超声检查诊断PVD，使用流介导的扩张（FMD）诊断动脉ED，并针对峰剪切速率（nFMD）归一化FMD。与对照组相比，PVD参与者的FMD较低（15.2比23.4％，P <0.001）和nFMD（12.7×10（-3）/ 19×10（-3）/秒，P <0.001）。临床上最明显的疾病的人的内皮功能最差。总之，我们的发现，如果在更大的人群中得到证实，可能证实静脉和动脉疾病可能是常见原因的观点。

BACKGROUND & AIMS: :Pathological examination of dementia with Lewy bodies patients identified the presence of abnormal α-synuclein (αSyn) aggregates in the presynaptic terminals. αSyn is involved in the regulation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Importantly, αSyn-transgenic mouse and postmortem examination of patients with Parkinson's disease have demonstrated the abnormal distribution of SNARE protein in presynaptic terminals. In this study, we investigated the effects of SNARE dysfunction on endogenous αSyn using Snap25(S187A/S187A) mutant mice. These mice have homozygous knock-in gene encoding unphosphorylatable S187A-substituted synaptosomal-associated protein of 25 kDa (SNAP-25). The mice displayed a significant age-dependent change in the distribution of αSyn and its Ser(129)-phosphorylated form in abnormally hypertrophied glutamatergic nerve terminals in the striatum. Electron-microscopic analysis revealed the abnormally condensed synaptic vesicles with concomitant mislocalization of αSyn protein to the periactive zone in the glutamatergic nerve terminals. However, the Snap25(S187A/S187A) mutant mouse harbored no abnormalities in the nigrostriatal dopaminergic neurons. Our present results suggest that SNARE dysfunction is the initial trigger of mislocalization and accumulation of αSyn, and probably is an important pathomechanism of α-synucleinopathies.

背景与目标： ：对路易体痴呆患者的病理检查发现突触前末梢存在异常的α-突触核蛋白（αSyn）聚集体。 αSyn参与可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合物的调节。重要的是，对帕金森氏病患者进行αSyn转基因小鼠和死后检查已证明，SNARE蛋白在突触前末端异常分布。在这项研究中，我们调查了Snapare功能障碍对使用Snap25（S187A / S187A）突变小鼠的内源性αSyn的影响。这些小鼠具有编码25kDa的不可磷酸化的S187A-取代的突触体相关蛋白的纯合敲入基因（SNAP-25）。小鼠在纹状体中异常肥大的谷氨酸能神经末梢中显示αSyn及其Ser（129）-磷酸化形式的分布具有明显的年龄依赖性。电子显微镜分析显示，异常浓缩的突触囊泡伴有αSyn蛋白向谷氨酸能神经末梢的活动区误定位。但是，Snap25（S187A / S187A）突变小鼠的黑质纹状体多巴胺能神经元中没有异常。我们目前的研究结果表明，SNARE功能障碍是αSyn错位和积累的最初诱因，并且可能是α-突触核蛋白病的重要发病机制。

BACKGROUND & AIMS: UNLABELLED:Endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are largely unknown. Statins might improve microvascular dysfunction in sepsis. The present study explores liver vascular abnormalities and the effects of statins in a rat model of endotoxemia. For this purpose, lipopolysaccharide (LPS) or saline was given to: (1) rats treated with placebo; (2) rats treated with simvastatin (25 mg/kg, orally), given at 3 and 23 hours after LPS/saline challenge; (3) rats treated with simvastatin (25 mg/kg/24 h, orally) from 3 days before LPS/saline injection. Livers were isolated and perfused and sinusoidal endothelial function was explored by testing the vasodilation of the liver circulation to increasing concentrations of acetylcholine. The phosphorylated endothelial nitric oxide synthase (PeNOS)/endothelial nitric oxide synthase (eNOS) ratio was measured as a marker of eNOS activation. LPS administration induced an increase in baseline portal perfusion pressure and a decrease in vasodilation to acetylcholine (sinusoidal endothelial dysfunction). This was associated with reduced eNOS phosphorylation and liver inflammation. Simvastatin after LPS challenge did not prevent the increase in baseline portal perfusion pressure, but attenuated the development of sinusoidal endothelial dysfunction. Treatment with simvastatin from 3 days before LPS prevented the increase in baseline perfusion pressure and totally normalized the vasodilating response of the liver vasculature to acetylcholine and reduced liver inflammation. Both protocols of treatment restored a physiologic PeNOS/eNOS ratio. CONCLUSION:LPS administration induces intrahepatic endothelial dysfunction that might be prevented by simvastatin, suggesting that statins might have potential for liver protection during endotoxemia.

背景与目标： 未加标签：内皮功能障碍可导致败血症相关的血管紊乱和器官衰竭。然而，败血症对肝窦窦内皮功能的影响在很大程度上尚不清楚。他汀类药物可能会改善败血症中的微血管功能障碍。本研究探讨了内毒素血症大鼠模型中的肝血管异常和他汀类药物的作用。为此，将脂多糖（LPS）或盐水给予以下动物：（1）用安慰剂治疗的大鼠； （2）在LPS /盐水刺激后3和23小时给予辛伐他汀（25mg / kg，口服）治疗的大鼠； （3）从LPS /盐水注射前3天开始，用辛伐他汀（25 mg / kg / 24 h，口服）治疗的大鼠。分离并灌注肝脏，并通​​过测试肝循环的血管舒张作用以增加乙酰胆碱的浓度来探索正弦内皮功能。测量磷酸化内皮一氧化氮合酶（PeNOS）/内皮一氧化氮合酶（eNOS）的比率作为eNOS活化的标志。 LPS给药引起基线门静脉灌注压力增加，乙酰胆碱（正弦血管内皮功能障碍）的血管舒张减少。这与减少的eNOS磷酸化和肝脏炎症有关。 LPS刺激后的辛伐他汀不能阻止基线门静脉灌注压力的升高，但可以减轻正弦血管内皮功能障碍的发展。 LPS前3天开始用辛伐他汀治疗可防止基线灌注压力增加，并使肝血管对乙酰胆碱的血管舒张反应完全正常化，并减轻肝脏炎症。两种治疗方案均恢复了生理性PeNOS / eNOS比率。
结论：LPS给药可引起辛伐他汀可预防肝内内皮功能障碍，这表明他汀类药物可能在内毒素血症期间具有保护肝脏的潜能。

BACKGROUND & AIMS: :The soya-derived phytoestrogen genistein has been suggested to be protective in cardiovascular diseases. In the present study, we have analysed whether chronic oral genistein might influence endothelial function in male SHRs (spontaneously hypertensive rats) via ERs (oestrogen receptors), changes in eNOS (endothelial NO synthase) activity and vascular O(2)(-) (superoxide) production. Rats (23-weeks old) were divided into the following groups: WKY (Wistar-Kyoto)-vehicle, SHR-vehicle, WKY-genistein (10 mg.kg(-1) of body weight.day(-1)); SHR-genistein; SHR-genistein-faslodex (ICI 182780; 2.5 mg.kg(-1) of body weight.day(-1)). Vascular expression of eNOS, caveolin-1 and calmodulin-1 were analysed by Western blotting, eNOS activity by conversion of [(3)H]arginine into L-[(3)H]citrulline and O(2)(-) production by chemoluminescence of lucigenin. In SHRs, after 5 weeks of treatment, genistein reduced systolic blood pressure and enhanced endothelium-dependent aortic relaxation to acetylcholine, but had no effect on the vasodilator responses to sodium nitroprusside. Compared with WKY rats, SHRs had up-regulated eNOS and down-regulated caveolin-1 and calmodulin-1 expression, increased NADPH-induced O(2)(-) production, but reduced eNOS activity. Genistein increased aortic calmodulin-1 protein abundance and eNOS activity, and reduced NADPH-induced O(2)(-) production in SHRs. The pure ERalpha and ERbeta antagonist faslodex did not modify any of the changes induced by genistein in SHRs, suggesting that these effects are unrelated to ER stimulation. In conclusion, genistein reduced the elevated blood pressure and endothelial dysfunction in SHRs. This latter effect appears to be related to increased eNOS activity associated with increased calmodulin-1 expression and decreased O(2)(-) generation.

背景与目标： 大豆来源的植物雌激素染料木黄酮已被建议在心血管疾病中具有保护作用。在本研究中，我们分析了慢性口服染料木黄酮是否可能通过ER（雌激素受体），eNOS（内皮型NO合酶）活性和血管O（2）（-）（超氧化物）生产。将大鼠（23周龄）分为以下几组：WKY（Wistar-Kyoto）车辆，SHR车辆，WKY-染料木黄酮（10 mg.kg（-1）体重.day（-1））； SHR-染料木黄酮; SHR-genistein-faslodex（ICI 182780; 2.5 mg.kg（-1）体重.day（-1））。通过蛋白质印迹分析eNOS，caveolin-1和钙调蛋白-1的血管表达，通过将[（3）H]精氨酸转化为L-[（3H）]瓜氨酸和通过生成O（2）（-）来分析eNOS活性。发光素的化学发光。在SHR中，经过5周的治疗，金雀异黄素降低了收缩压，增强了内皮依赖性的主动脉对乙酰胆碱的舒张作用，但对血管扩张剂对硝普钠的反应没有影响。与WKY大鼠相比，SHRs上调了eNOS，下调了Caveolin-1和calmodulin-1的表达，增加了NADPH诱导的O（2）（-）的产生，但降低了eNOS的活性。金雀异黄素增加主动脉钙调蛋白1蛋白的丰度和eNOS的活性，并减少NADPH诱导SHRs中的O（2）（-）生产。单纯的ERalpha和ERbeta拮抗剂faslodex并未改变染料木黄酮在SHRs中诱导的任何变化，表明这些作用与ER刺激无关。总之，金雀异黄素减轻了SHRs的血压升高和内皮功能障碍。后者的作用似乎与增加的钙调蛋白-1表达和减少的O（2）（-）生成有关的eNOS活性有关。

BACKGROUND & AIMS: :The role of the thyroid gland in glucose homeostasis remains incompletely understood. To get a better insight hypo-and hyperthyroid conditions were experimentally induced in rat and found severe defects in glucose homeostasis. While blood glucose level returned to normal level after 2.5 hr of oral glucose challenge in control rats the blood glucose level remained high even after 24 hr of glucose load in both hypo- and hyperthyroid rats. These experimentally manipulated rats displayed higher levels of liver glycogen (10.45-22.8-fold) and serum glutamic pyruvic transaminase (1.48-9.8-fold). Liver histology of hyperthyroid treated rats revealed hepatotoxicity. From the results it can be concluded that thyroid gland plays an important role in glucose homeostasis.

背景与目标： ：甲状腺在葡萄糖稳态中的作用仍未完全了解。为了更好地了解大鼠的甲状腺功能低下和甲状腺功能亢进症，并发现其体内葡萄糖稳态严重缺陷。在对照组大鼠口服葡萄糖2.5小时后血糖水平恢复到正常水平时，即使在甲状腺功能减退和甲状腺功能亢进的大鼠中，即使在葡萄糖加载24小时后，血糖水平仍保持较高水平。这些实验操作的大鼠显示出较高水平的肝糖原（10.45-22.8倍）和血清谷氨酸丙酮酸转氨酶（1.48-9.8倍）。甲亢治疗大鼠的肝脏组织学显示肝毒性。从结果可以得出结论，甲状腺在葡萄糖稳态中起重要作用。

BACKGROUND & AIMS: OBJECTIVE:Acute pulmonary hypertension may cause right ventricular (RV) contractile failure. While it has been assumed that restoration of normal loading conditions after acute pulmonary hypertension is sufficient for complete recovery of RV function, this has not been rigorously examined. The purpose of this study was to test the hypothesis that acute RV pressure overload produces RV contractile dysfunction that persists following restoration of control loading conditions. METHODS:We subjected 18 autonomically-blocked, chloralose-anesthetized, open-chest pigs to 1 h of pulmonary artery constriction to increase RV systolic pressure from 35 +/- 1 to 55 +/- 1 mmHg, followed by 2 h of measurements after pulmonary artery constriction release. We determined regional RV free wall function from pressure-segment length loops and preload recruitable stroke work relations, and global RV function from stroke work vs. end-diastolic pressure relations. RESULTS:As expected, RV free wall systolic shortening diminished during pulmonary artery constriction, but the endo/epi blood flow ratio, lactate uptake, and coronary venous pH were not significantly changed. Following release of pulmonary artery constriction, RV systolic and diastolic pressure returned to control values. Nonetheless, contractile dysfunction persisted, with depressed RV free wall systolic shortening (70 +/- 22% of control), RV regional external work (59 +/- 11% of control at control end-diastolic length), and global RV stroke work (56 +/- 14% of control at control end-diastolic pressure). Depressed regional work was due to a parallel, rightward shift of the preload recruitable stroke work relation. Five pigs identically instrumented but not subjected to pulmonary artery constriction showed no significant over 3 h. CONCLUSIONS:Acute pulmonary hypertension causes RV contractile dysfunction that persists at least 2 h after restoration of control loading conditions. Contractile dysfunction is not attributable to RV ischemia during pressure overload.

背景与目标： 目的：急性肺动脉高压可能导致右心室（RV）收缩衰竭。尽管已经假定急性肺动脉高压后恢复正常负荷状态足以使RV功能完全恢复，但尚未对此进行严格检查。本研究的目的是检验以下假设：急性RV压力超负荷会导致RV收缩功能障碍，并在控制负荷条件恢复后持续存在。
方法：我们对18头经氯醛糖麻醉的自闭式开胸猪进行了1小时的肺动脉收缩，以将RV收缩压从35 /-1增加到55 /-1 mmHg，然后在肺动脉进行2小时的测量收缩释放。我们从压力段长度环和预负荷可招募的卒中功关系中确定了区域RV无壁功能，并从卒中功与舒张末期压力关系中确定了整体RV功能。
结果：正如预期的那样，在肺动脉收缩期间右室游离壁收缩期缩短减少，但是内/外血流量比，乳酸摄取和冠状静脉pH没有明显变化。释放肺动脉收缩后，RV收缩压和舒张压恢复至控制值。然而，收缩功能障碍持续存在，右室游离壁收缩期缩短（控制区的70 /-22％），右室局部外部工作（在控制舒张末期的控制区为59 /-11％）和整体右室卒中工作持续存在（56）在对照舒张末期压力下为对照的14％）。较低的区域工作量是由于预载可招募中风工作关系的平行，向右移动。五只相同仪器但未经历肺动脉收缩的猪在3 h内无明显变化。
结论：急性肺动脉高压导致右室收缩功能障碍，在控制负荷恢复后至少持续2 h。压力超负荷期间收缩功能障碍不归因于RV缺血。

BACKGROUND & AIMS: PURPOSE:To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. EXPERIMENTAL DESIGN:Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m(2) every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction: control group A [bilirubin, AST, and AP < or = upper limit of normal (ULN)], mild dysfunction group B (bilirubin < or = ULN, ULN < AST < or = 2.5 x ULN, or ULN < AP < or = 5 x ULN), moderate dysfunction group C (ULN < bilirubin < or = 3.0 mg/dL, AST > 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. RESULTS:Dose escalation of single-agent oxaliplatin to 130 mg/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. CONCLUSIONS:Oxaliplatin at 130 mg/m(2) every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.

背景与目标： 目的：确定奥沙利铂在肝功能不全患者中的毒性，药代动力学和最大耐受剂量，并为该患者人群制定奥沙利铂剂量的正式指南。
实验设计：60例肝功能可变的成年癌症患者接受了静脉内注射。奥沙利铂每3周从60到130 mg / m（2）不等。根据肝功能障碍的程度将患者按总胆红素，天冬氨酸转氨酶（AST）和碱性磷酸酶（AP）的水平分为五个队列：对照组A [胆红素，AST和AP <或=正常上限（ ULN）]，轻度功能障碍B组（胆红素<或= ULN，ULN 2.5 x ULN或AP> 5 x ULN），严重功能障碍D组（胆红素> 3.0 mg / dL，任何AST和任何AP）和肝移植E组（任何胆红素，任何AST和任何AP）。在三名患者的队列中增加剂量，并测定尿液和血浆超滤液的铂浓度。
结果：在所有队列中，单药奥沙利铂的剂量递增都可耐受130 mg / m（2）。铂清除率与任何肝功能检查均不相关。在56例可诊断为喉癌和宫颈腺癌的可评估患者中，有2例的局部反应持续了3个月和5.5个月。
结论：在所有肝功能受损的患者中，每3周服用130 mg / m（2）的奥沙利铂具有良好的耐受性。肝功能不全的患者未提示降低单药奥沙利铂的剂量。

BACKGROUND & AIMS: :Our goal was to identify the role of poly(ADP-ribose) polymerase (PARP) in cerebrovascular dysfunction in Type 1 diabetes mellitus (T1D). In a first series of studies, rats were assigned to nondiabetic and diabetic (streptozotocin; 50 mg/kg IP) groups. Two to three months after injection of streptozotocin, we examine in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (adenosine diphosphate (ADP), acetylcholine and histamine) and -independent (nitroglycerin) agonists. After the initial examination of reactivity to the agonists, we treated pial arterioles acutely with an inhibitor of PARP (PJ-34; 1 microM), and then we again examined responses to the agonists. In a second series of studies, we examine superoxide production (lucigenin chemiluminescence) by parietal cortex tissue in nondiabetic and diabetic rats. We found that dilation of pial arterioles in response to ADP, acetylcholine and histamine, but not to nitroglycerin, was impaired in diabetic compared to nondiabetic rats. In addition, although PJ-34 did not alter responses in nondiabetic rats, PJ-34 alleviated T1D-induced impairment of NOS-dependent vasodilation. We also found that basal production of superoxide was increased in diabetic compared to nondiabetic rats and that PJ-34 decreased this basal production of superoxide. Our findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide via activation of PARP.

背景与目标： ：我们的目标是确定聚（ADP-核糖）聚合酶（PARP）在1型糖尿病（T1D）的脑血管功能障碍中的作用。在第一个系列研究中，将大鼠分为非糖尿病和糖尿病（链脲佐菌素； 50 mg / kg IP）组。注射链脲佐菌素后两到三个月，我们检查了小动脉对一氧化氮合酶（NOS）依赖性（二磷酸腺苷（ADP），乙酰胆碱和组胺）和非依赖性（硝酸甘油）激动剂的体内反应。初步检查与激动剂的反应性后，我们用PARP抑制剂（PJ-34; 1 microM）急性治疗了小动脉，然后再次检查了对激动剂的反应。在第二系列研究中，我们检查了非糖尿病和糖尿病大鼠顶叶皮质组织的超氧化物生成（荧光素化学发光）。我们发现，与非糖尿病大鼠相比，糖尿病患者对ADP，乙酰胆碱和组胺（而非对硝酸甘油）响应的小动脉小动脉扩张受到损害。此外，尽管PJ-34不会改变非糖尿病大鼠的反应，但PJ-34减轻了T1D诱导的NOS依赖性血管舒张功能受损。我们还发现，与非糖尿病大鼠相比，糖尿病患者的基础过氧化物含量增加，而PJ-34降低了基础过氧化物含量。我们的发现表明，T1D通过一种机制似乎削弱了NOS依赖性的脑小动脉反应性，该机制似乎与通过激活PARP形成超氧化物有关。

BACKGROUND & AIMS: :Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4 T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4 cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4 inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.

背景与目标： ：淋巴水肿是一种可怕的癌症治疗并发症。然而，尽管事实上有超过500万美国人受到这种疾病的影响，但淋巴水肿的病理学仍然未知，这限制了有效疗法的发展。这些研究的目的是确定炎症反应在淋巴水肿病理中的作用。使用小鼠模型的淋巴水肿，以及临床淋巴水肿标本，我们显示淋巴淤积导致CD4 T细胞炎症和T辅助2（Th2）分化。使用缺乏T细胞或CD4细胞的小鼠，我们表明这种炎症反应对于淋巴水肿的病理变化（包括纤维化，脂肪沉积和淋巴功能障碍）是必需的。此外，我们显示，使用白介素4（IL-4）或IL-13阻滞抑制Th2分化可通过减少组织纤维化并显着改善淋巴功能来防止淋巴水肿的发生和进展，而与淋巴管生成生长因子无关。我们显示，CD4炎症是淋巴水肿中组织纤维化和淋巴功能障碍的关键调节器，抑制Th2分化显着提高了淋巴功能，而与淋巴管生成细胞因子的表达无关。值得注意的是，预防和/或逆转在淋巴水肿中发生的病理组织改变的发展可能是该疾病的可行治疗策略。

BACKGROUND & AIMS: OBJECTIVE:This study examined the associations between respiratory symptoms and patterns of pulmonary dysfunction of 115 male roofing cement workers compared with 134 unexposed subjects. METHODS:A cross-sectional study was conducted. Environmental samplings and spirometry measurements were also collected. RESULTS:The exposed workers had higher respiratory dust exposure levels (0.65 mg/m3) compared with the unexposed groups (0.32 mg/m3). The exposed group had significantly higher prevalence than the unexposed group for shortness of breath (OR=2.19). The exposed group also had higher but insignificant prevalence of chronic cough (OR=1.34), chest tightness (OR=1.64), and wheezing (OR=1.89). The ventilatory respiratory function values (FEV1 and FVC) were slightly lower for the exposed group. CONCLUSION:An association between higher cement dust levels and a decline in ventilatory function among roofing fiber cement workers suggests that the respiratory health of roofing cement workers should be protected through policies or work standards.

背景与目标： 目的：本研究调查了115名男性屋面水泥工人与134名未暴露受试者的呼吸系统症状与肺功能障碍类型之间的关系。
方法：进行横断面研究。还收集了环境采样和肺活量测定法。
结果：暴露工人的呼吸粉尘暴露水平（0.65 mg / m3）高于未暴露组（0.32 mg / m3）。暴露组的呼吸困难患病率明显高于未暴露组（OR = 2.19）。暴露组的慢性咳嗽（OR = 1.34），胸闷（OR = 1.64）和喘息（OR = 1.89）的患病率也较高，但微不足道。暴露组的通气呼吸功能值（FEV1和FVC）略低。
结论：屋面纤维水泥工人中较高的水泥粉尘含量与通风功能下降之间存在关联，这表明应通过政策或工作标准保护屋面水泥工人的呼吸健康。

BACKGROUND & AIMS: BACKGROUND:In recent years the WTMM (wavelet transform modulus maxima) and MDFA (multifractal detrended fluctuation analysis) methods have become widely used techniques for the determination of nonlinear, multifractal heart rate (HR) dynamics. The purpose of our study was to compare multifractal parameters of heart rate calculated using both methods in a group of 90 patients with reduced left ventricular systolic function (rlvs group) and in a group of 39 healthy persons (nsr group). METHODS:For each subject from the rlvs group (LVEF < or =40%) and the nsr group, a 24-hour ECG Holter monitoring was performed. The width of the multifractal spectrum and global Hurst exponent were calculated by means of WTMM and MDFA methods for 5-hour daytime and nighttime subsets. RESULTS:The width of the multifractal spectrum was significantly lower and the Hurst exponent was significantly higher in rlvs group in comparison to nsr group both during diurnal activity and nocturnal rest according to MDFA and only during diurnal activity according to WTMM method. In both groups we observed significant differences of the multifractal spectrum width and the global Hurst exponent between the nighttime and daytime recordings. CONCLUSIONS:MDFA seems to be more sensitive as compared with WTMM method in differentiation between multifractal properties of the heart rate in healthy subjects and patients with left ventricular systolic dysfunction.

背景与目标： 背景：近年来，WTMM（小波变换模极大值）和MDFA（多重分形趋势波动分析）方法已成为广泛用于确定非线性，多重分形心率（HR）动力学的技术。我们研究的目的是比较90例左室收缩功能降低的患者（rlvs组）和39例健康人的组（nsr组）使用两种方法计算的心率的多重分形参数。
方法：对来自rlvs组（LVEF <或= 40％）和nsr组的每位受试者进行24小时ECG动态心电图监测。利用WTMM和MDFA方法，针对5小时的白天和夜间子集，计算了多重分形谱的宽度和整体赫斯特指数。
结果：根据MDFA，rlvs组的昼夜活动和夜间休息时，多重分形谱的宽度明显小于nsr组，Hurst指数显着较高；仅根据WTMM方法，在昼间活动时，多重分形谱的宽度较nsr组高。在两组中，我们观察到夜间和白天记录之间的多重分形谱宽度和全局赫斯特指数存在显着差异。
结论：与WTMM方法相比，MDFA在区分健康受试者和左室收缩功能不全患者的心率的多重分形特性方面似乎更为敏感。

BACKGROUND & AIMS: PURPOSE OF REVIEW:The autonomic nervous system has been implicated in the pathophysiology of chronic upper airway inflammatory disease for decades. We discuss the most recent literature with regard to autonomic nervous system dysfunction and chronic upper airway disease. RECENT FINDINGS:Recently, state of the art autonomic nervous system testing has demonstrated autonomic nervous system dysfunction in patients with chronic upper airway inflammatory disease. This dysfunction has been characterized as hypoadrenergic. SUMMARY:Autonomic nervous system dysfunction likely plays a role in chronic upper airway inflammatory disease. Further investigation may lead to a better understanding of the role of autonomic nervous system dysfunction in these disorders and, hence, opportunities for novel therapeutic modalities.

背景与目标： 审查目的：数十年来，自主神经系统已被纳入慢性上呼吸道炎性疾病的病理生理中。我们讨论有关自主神经系统功能障碍和慢性上呼吸道疾病的最新文献。
最近的发现：最近，最先进的自主神经系统测试已证明患有慢性上呼吸道炎性疾病的患者的自主神经系统功能异常。这种功能障碍的特征是肾上腺皮质功能低下。
摘要：自主神经系统功能异常可能在慢性上呼吸道炎性疾病中起作用。进一步的研究可能会导致对这些疾病中自主神经系统功能障碍的作用有更好的了解，因此，有可能寻求新的治疗方法。