BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:To investigate whether preemptive administered lornoxicam changes perioperative platelet function during thoracic surgery. METHODS:A total of 20 patients scheduled for elective thoracic surgery were randomly assigned to receive either lornoxicam (16 mg, i.v.; n = 10) or placebo (n = 10) preoperatively. All patients underwent treatment of solitary lung metastasis and denied any antiplatelet medication within the past 2 weeks. Blood samples were drawn via an arterial catheter directly into silicone-coated Vacutainer tubes containing 0.5 mL of 0.129 M buffered sodium citrate 3.8% before, 15 min, 4 h and 8 h after the study medication was administered. Platelet aggregation curves were obtained by whole blood electrical impedance aggregometry (Chrono Log). RESULTS:Platelet aggregation was significantly reduced 15 min, 4 h and 8 h after lornoxicam administration compared to placebo (P < 0.05) for collagen, adenosine diphosphate and arachidonic acid as trigger substances. Adenosine diphosphate-induced platelet aggregation decreased by 85% 15 min after lornoxicam administration, and remained impaired for 8 h. CONCLUSION:Platelet aggregation assays are impaired for at least 8 h after lornoxicam application. Therefore perioperative analgesia by use of lornoxicam should be carefully administered under consideration of subsequent platelet dysfunction.

背景与目标： 背景与目的：探讨氯诺昔康在胸外科手术中是否能抢先使用围手术期血小板功能。
方法：总共20例计划进行择期胸外科手术的患者被随机分配为术前接受氯诺昔康（16 mg，i.v .; n = 10）或安慰剂（n = 10）。在过去的两周内，所有患者均接受了孤立性肺转移的治疗，并拒绝使用任何抗血小板药物。在施用研究药物之前，15分钟，4小时和8小时之后，通过动脉导管将血液样品直接抽取到装有0.5 mL 0.129 M柠檬酸钠3.8％的硅胶涂层的Vacutainer管中，该溶液的浓度为3.8％。通过全血电阻抗凝集法（Chrono Log）获得血小板聚集曲线。
结果：与安慰剂相比，氯诺昔康给药后15 min，4 h和8 h血小板聚集明显减少（P <0.05），其中胶原，腺苷二磷酸和花生四烯酸为触发物质。氯诺昔康给药后15分钟，二磷酸腺苷诱导的血小板凝集减少了85％，并持续受损8小时。
结论：氯诺昔康应用后至少8 h血小板聚集测定受损。因此，在考虑随后的血小板功能障碍时，应谨慎使用氯诺昔康围手术期镇痛。

BACKGROUND & AIMS: BACKGROUND:Nonsteroidal anti-inflammatory drug (NSAID) use may reduce the incidence of post-cardiothoracic surgery (CTS) atrial fibrillation (AF). The cerebrovascular and cardiovascular safety of using NSAIDs for post-CTS AF has not been determined. OBJECTIVE:To evaluate whether NSAIDs could reduce the incidence of post-CTS atrial fibrillation without increasing patients' risk of stroke or myocardial infarction (MI). METHODS:Patients (n = 555) undergoing CTS from the Atrial Fibrillation Suppression Trials I, II and III were evaluated in this nested cohort study. Demographic, surgical and medication use characteristics were prospectively collected as part of the AFIST trials. Endpoints included post-CTS atrial fibrillation, stroke, MI and the need for red blood cell transfusion. Multivariable logistic regression was used to control for potential confounders and calculate adjusted odds ratios with 95% confidence intervals. RESULTS:The population was 67.8 +/- 8.6 years old and 77.1% male with 127 (22.9%) patients receiving an NSAID postoperatively. Overall, 14.6% underwent valve surgery, 6.1% had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative beta-blockade and prophylactic amiodarone. NSAID use was associated with reductions in the adjusted odds of post-CTS atrial fibrillation (0.54 (0.32-0.90)) and the need for RBC transfusions (0.63 (0.41-0.97)). No elevation in the odds of developing stroke (1.10 (0.21-5.66)) or MI (1.70 (0.40-7.10)) was observed. LIMITATIONS:Patients were not randomized to receive NSAIDs versus a control. We may not have had adequate power to evaluate stoke or MI in this analysis. CONCLUSIONS:NSAIDs decreased the odds of developing post-CTS atrial fibrillation, further supporting the hypothesis of inflammation as a trigger for post-CTS atrial fibrillation. The need for RBC transfusions was also reduced with NSAID use. We may have been underpowered to evaluate stroke or MI incidence, but the qualitative elevations in these variables suggest more safety data is needed before NSAIDs can be routinely recommended.

背景与目标： 背景：非甾体类抗炎药（NSAID）的使用可以减少心动胸外科手术（CTS）后心房纤颤（AF）的发生。尚未确定将NSAID用于CTS后AF的脑血管和心血管安全性。
目的：评估非甾体抗炎药是否可以降低CTS后房颤的发生率，而又不增加患者发生中风或心肌梗塞（MI）的风险。
方法：在这项嵌套队列研究中，对来自房颤抑制试验I，II和III的接受CTS的患者（n = 555）进行了评估。作为AFIST试验的一部分，前瞻性地收集了人口统计学，手术和药物使用特征。终点包括CTS后的心房纤颤，中风，心肌梗死以及是否需要输注红细胞。多变量逻辑回归用于控制潜在的混杂因素，并以95％的置信区间计算调整后的优势比。
结果：该人群为67.8 /-8.6岁，男性为77.1％，其中127名（22.9％）术后接受NSAID治疗。总体而言，进行瓣膜手术的比例为14.6％，先前房颤的比例为6.1％，心力衰竭的比例为12.6％，术后进行了β受体阻滞剂和预防性胺碘酮的比例分别为84.0％和44.1％。使用NSAID可以降低CTS后房颤的调整几率（0.54（0.32-0.90））和需要进行RBC输血（0.63（0.41-0.97））。没有观察到发展中风（1.10（0.21-5.66））或MI（1.70（0.40-7.10））的几率升高。
局限性：与对照组相比，患者没有被随机分配接受NSAIDs治疗。在此分析中，我们可能没有足够的能力来评估卒中或心肌梗塞。
结论：NSAIDs降低了CTS后房颤发生的可能性，进一步支持了炎症假说是CTS后房颤触发的假设。 NSAID的使用也减少了对RBC输血的需要。我们可能没有足够的能力来评估中风或MI发生率，但是这些变量的定性升高提示，在常规推荐使用NSAID之前，需要更多的安全性数据。

BACKGROUND & AIMS: :Many drugs have the potential to cause drug-induced liver injury (DILI); however, underlying mechanisms are diverse. The concept of adverse outcome pathways (AOPs) has become instrumental for risk assessment of drug class effects. We report AOPs specific for immune-mediated and drug hypersensitivity/allergic hepatitis by considering genomic, histo- and clinical pathology data of mice and dogs treated with diclofenac. The findings are relevant for other NSAIDs and drugs undergoing iminoquinone and quinone reactive metabolite formation. We define reactive metabolites catalyzed by CYP monooxygenase and myeloperoxidases of neutrophils and Kupffer cells as well as acyl glucuronides produced by uridine diphosphoglucuronosyl transferase as molecular initiating events (MIE). The reactive metabolites bind to proteins and act as neo-antigen and involve antigen-presenting cells to elicit B- and T-cell responses. Given the diverse immune systems between mice and dogs, six different key events (KEs) at the cellular and up to four KEs at the organ level are defined with mechanistic plausibility for the onset and progression of liver inflammation. With mice, cellular stress response, interferon gamma-, adipocytokine- and chemokine signaling provided a rationale for the AOP of immune-mediated hepatitis. With dogs, an erroneous programming of the innate and adaptive immune response resulted in mast cell activation; their infiltration into liver parenchyma and the shift to M2-polarized Kupffer cells signify allergic hepatitis and the occurrence of granulomas of the liver. Taken together, diclofenac induces divergent immune responses among two important preclinical animal species, and the injury pattern seen among clinical cases confirms the relevance of the developed AOP for immune-mediated hepatitis.

背景与目标： ：许多药物都有可能引起药物性肝损伤（DILI）；但是，潜在的机制是多种多样的。不良结局途径（AOP）的概念已成为评估药物类别影响的工具。通过考虑用双氯芬酸治疗的小鼠和狗的基因组，组织学和临床病理数据，我们报告了特异性针对免疫介导的和药物超敏性/过敏性肝炎的AOP。该发现与其他非甾体抗炎药和正在经历亚氨基醌和醌反应性代谢产物形成的药物有关。我们定义了由CYP单加氧酶和嗜中性粒细胞和Kupffer细胞的髓过氧化物酶以及尿苷二磷酸葡萄糖醛糖苷转移酶产生的酰基葡萄糖醛酸苷作为分子引发事件（MIE）催化的反应性代谢产物。反应性代谢物与蛋白质结合并充当新抗原，并涉及抗原呈递细胞以引发B细胞和T细胞反应。考虑到小鼠和狗之间的免疫系统各不相同，在细胞水平上定义了六个不同的关键事件（KE），在器官水平上定义了多达四个KE，并且对于肝脏炎症的发生和发展具有机理上的合理性。对于小鼠，细胞应激反应，干扰素γ，脂肪细胞因子和趋化因子信号传导为免疫介导的肝炎的AOP提供了理论依据。对于狗，先天和适应性免疫反应的错误编程导致肥大细胞激活。它们浸润到肝实质中，并转移到M2极化的Kupffer细胞，这表示过敏性肝炎和肝肉芽肿的发生。综上所述，双氯芬酸在两种重要的临床前动物物种之间诱导不同的免疫反应，临床病例中观察到的损伤模式证实了已开发的AOP与免疫介导的肝炎的相关性。

BACKGROUND & AIMS: BACKGROUND:In up to 70%-80% of patients with a suspected non-steroidal anti-inflammatory drug hypersensitivity (NSAIDH), challenge tests with the culprit drug yield negative results. On the other hand, there could be a NSAIDH overdiagnosis when anaphylaxis is the clinical manifestation. We hypothesize that some negative NSAID challenge tests and an overdiagnosis of NSAIDH occur in patients with food-dependent NSAID-induced hypersensitivity (FDNIH). METHODS:We studied 328 patients with a suspected acute NSAIDH. FDNIH was diagnosed in patients meeting all the following: (1) tolerance to the food ingested more temporally closed before the reaction, later the episode, (2) respiratory or cutaneous symptoms or anaphylaxis related to NSAID, (3) positive skin prick test to foods and/or specific IgE to food allergens (Pru p 3, Tri a 19, Pen a 1) involved in the reaction, and (4) negative oral provocation test to the culprit NSAID. RESULTS:199 patients (60%) were diagnosed with NSAIDH and 52 (16%) with FDNIH. Pru p 3 was involved in 44 cases (84.6%) and Tri a 19 in 6 cases (11%). FDNIH subjects were younger (p < .001), with a higher prevalence of rhinitis (p < .001) and previous food allergy (p < .001), together with a higher proportion of subjects sensitized to pollens (p < .001) and foods (p < .001). Using just four variables (Pru p 3 sensitization, Tri a 19 sensitization, anaphylaxis, and any NSAID different from pyrazolones), 95.3% of cases were correctly classified, with a sensitivity of 92% and specificity of 96%. CONCLUSION:Evaluation of FDNIH should be included in the diagnostic workup of NSAIDH.

背景与目标： 背景：在高达70％-80％的怀疑患有非甾体类抗炎药超敏反应（NSAIDH）的患者中，使用该罪魁祸首药物进行的激发试验得出阴性结果。另一方面，当过敏反应为临床表现时，可能存在NSAIDH过度诊断。我们假设在食物依赖性NSAID引起的超敏反应（FDNIH）患者中发生了一些阴性的NSAID挑战试验和NSAIDH的过度诊断。
方法：我们研究了328例疑似急性NSAIDH的患者。在满足以下所有条件的患者中诊断出FDNIH：（1）对反应前，后发作更短暂地进食的食物具有耐受性，（2）与NSAID相关的呼吸或皮肤症状或过敏反应，（3）皮肤点刺试验阳性食物和/或与反应有关的食物过敏原的特定IgE（Pru p 3，Tri a 19，Pen a 1），以及（4）对罪魁祸首NSAID的口服刺激试验为阴性。
结果：199例患者（60％）被确诊为NSAIDH，52例（16％）被诊断为FDNIH。 Pru p 3涉及44例（84.6％），Tri a 19涉及6例（11％）。 FDNIH受试者年龄较小（p <.001），鼻炎患病率较高（p <.001），既往食物过敏（p <.001）以及对花粉敏感的受试者比例较高（p <.001）和食物（p <.001）。仅使用四个变量（Pru p 3致敏，Tri a 19致敏，过敏反应以及与吡唑啉酮不同的任何NSAID），正确分类了95.3％的病例，敏感性为92％，特异性为96％。
结论：FDAIH的评估应包括在NSAIDH的诊断检查中。

BACKGROUND & AIMS: BACKGROUND:NSAIDs appear to moderately reduce prostate cancer risk. However, evidence is limited on whether NSAIDs protect against prostate cancer mortality (death from prostate cancer among men without a cancer history) and case fatality (death from prostate cancer among men with prostate cancer), and whether benefits are consistent in white and black men. This study investigated associations of aspirin and non-aspirin (NA) NSAID use with prostate cancer incidence, mortality, and case fatality in a population-based cohort of white and black men. METHODS:We included 6,594 men (5,060 white and 1,534 black) from the Atherosclerosis Risk in Communities study without a cancer history at enrollment from 1987 to 1989. NSAID use was assessed at four study visits (1987-1998). Cancer outcomes were ascertained through 2012. Cox proportional hazards regression was used to estimate adjusted HRs, overall and by race. RESULTS:Aspirin use was not associated with prostate cancer incidence. However, aspirin use was inversely associated with prostate cancer mortality [HR, 0.59; 95% confidence interval (CI), 0.36-0.96]. This association was consistent among white and black men and appeared restricted to men using aspirin daily and/or for cardiovascular disease prevention. Aspirin use was inversely associated with case fatality (HR, 0.45; 95% CI, 0.22-0.94). NA-NSAID use was not associated with these endpoints. CONCLUSIONS:Aspirin use was inversely associated with prostate cancer mortality and case fatality among white and black men. IMPACT:If confirmed by additional studies, benefits of aspirin for preventing prostate cancer mortality may need to be factored into risk-benefit calculations of men considering an aspirin regimen.

背景与目标： 背景：NSAIDs似乎可适度降低前列腺癌的风险。但是，关于NSAID是否能预防前列腺癌的死亡率（无癌症病史的男性死于前列腺癌）和病死率（前列腺癌的男性死于前列腺癌），以及白人和黑人的益处是否一致，目前的证据有限。 。这项研究调查了阿司匹林和非阿司匹林（NA）NSAID的使用与白人和黑人人群中前列腺癌的发生率，死亡率和病死率之间的关系。
方法：我们纳入了从1987年至1989年入组的无动脉粥样硬化史的来自社区动脉粥样硬化风险研究的6,594名男性（5,060名白人和1,534名黑人）。在四次研究访问（1987年至1998年）中评估了NSAID的使用。在2012年之前确定癌症的结局。使用Cox比例风险回归法估算总体和种族的调整后HR。
结果：阿司匹林的使用与前列腺癌的发病率无关。然而，阿司匹林的使用与前列腺癌的死亡率呈负相关[HR，0.59； H。 95％置信区间（CI），0.36-0.96]。白人和黑人男性之间的这种联系是一致的，并且似乎仅限于每天使用阿司匹林和/或预防心血管疾病的男性。阿司匹林的使用与病死率成反比（HR，0.45； 95％CI，0.22-0.94）。 NA-NSAID的使用与这些端点无关。
结论：阿司匹林的使用与白人和黑人男性的前列腺癌死亡率和病死率成反比。
影响：如果通过其他研究证实，在考虑使用阿司匹林方案的男性的风险收益计算中，可能需要考虑阿司匹林预防前列腺癌死亡的益处。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the efficacy and safety of oxaprozin in comparison with diclofenac in patients with periarthritis pain of the shoulder previously unsuccessfully treated with nonsteroidal anti-inflammatory drugs other than diclofenac and oxaprozin. METHODS:In this open, multicentre, randomised, controlled study, eligible patients with periarthritis of the shoulder were randomised to receive either oxaprozin 1200 mg once daily (n = 49) or diclofenac 50 mg three times daily (n = 47). The treatment period was 15 +/- 1 days. The study was planned on a hypothesis of equivalence between the two study drugs. The primary study endpoint was the change from baseline at day 15 in the patient-assessed shoulder pain score. Secondary efficacy variables included investigator-assessed shoulder function, patient-assessed quality of life on the Short-Form-36 (SF-36) Acute Health Survey and both patients' and investigators' overall assessment of efficacy. RESULTS:At day 15, the mean changes in shoulder pain score from baseline in the oxaprozin and diclofenac groups were -5.85 +/- SD 4.62 and -5.54 +/- SD 4.41, respectively. The difference between the two groups was not statistically significant, confirming the hypothesis of the study that oxaprozin is as effective as diclofenac. Investigator-assessed shoulder function improved in both groups but more so in the oxaprozin group (p = 0.028 at day 15). Quality of life as measured by SF-36 total score was also improved in both treatment groups, with a trend toward greater improvement in the oxaprozin group. Furthermore, a significantly more favourable effect on the SF-36 'mental health' item was observed in oxaprozin compared with diclofenac-treated patients at day 15 (p = 0.0202). As assessed by investigators, the overall efficacy of oxaprozin was superior to that for diclofenac at visit 3 (8 +/- 1 days) (p = 0.0067). Patients also assessed the overall efficacy of oxaprozin as superior to that of diclofenac at visits 3 (8 +/- 1 days) (p = 0.0235) and 4 (15 +/- 1 days) (p = 0.0272). Only six adverse events, all of which were mild or moderate in intensity and occurred in four diclofenac recipients, were observed in the study. CONCLUSIONS:As expected, once-daily oxaprozin proved to be as effective as diclofenac three times daily in reducing the primary efficacy variable of patient-assessed shoulder pain score in patients with periarthritis of the shoulder refractory to previous treatments with other NSAIDs. Oxaprozin was shown to be superior to diclofenac in improving shoulder function and was considered by investigators and patients to have greater overall efficacy than diclofenac. In addition, oxaprozin showed a trend toward superior results in improving patients' quality of life compared with diclofenac. A trend towards better tolerability results for oxaprozin compared with diclofenac was also noted.

背景与目标： 目的：评价奥沙普嗪与双氯芬酸相比，以前用双氯芬酸和奥沙普嗪以外的非甾体类抗炎药治疗失败的肩周炎患者的疗效和安全性。
方法：在这项开放性，多中心，随机，对照研究中，将符合条件的肩周炎患者随机接受每日一次1200毫克奥沙普嗪（n = 49）或每天三次3次（n = 47）双氯芬酸50 mg。治疗期为15±1天。这项研究是根据两种研究药物之间的等效性假设进行计划的。主要研究终点是患者评估的肩痛评分与第15天基线相比的变化。次要功效变量包括研究者评估的肩部功能，36型简表（SF-36）急性健康调查中患者评估的生活质量以及患者和研究者对功效的总体评估。
结果：在第15天，奥沙普嗪和双氯芬酸组的肩膀疼痛评分相对于基线的平均变化分别为-5.85 /-SD 4.62和-5.54 /-SD 4.41。两组之间的差异无统计学意义，证实了该研究的假设，即奥沙普嗪与双氯芬酸一样有效。在两组中，研究者评估的肩部功能均得到改善，但在奥沙普嗪组中则更为明显（第15天时p = 0.028）。在两个治疗组中，以SF-36总评分衡量的生活质量也得到了改善，而在oxaprozin组中有改善的趋势。此外，在第15天，与双氯芬酸治疗的患者相比，在奥沙普嗪中观察到对SF-36“心理健康”项目的明显更有利的影响（p = 0.0202）。根据研究人员的评估，在第3次就诊（8 /-1天），奥沙普嗪的总体疗效优于双氯芬酸（p = 0.0067）。患者在第3（8 /-1天）（p = 0.0235）和第4（15 /-1天）（p = 0.0272）的访视中也评估了奥沙普嗪的总体疗效优于双氯芬酸。在这项研究中，仅观察到了六种不良事件，全部为轻度或中度强度，并发生在四名双氯芬酸接受者中。
结论：如预期的那样，每天一次的奥沙普嗪被证明与双氯芬酸一样有效，每天三次，可降低以前用其他NSAID治疗的难治性肩周炎患者的患者评估的肩痛评分的主要疗效变量。奥沙普嗪在改善肩部功能方面显示出优于双氯芬酸，并且被研究者和患者认为比双氯芬酸具有更高的总体疗效。此外，与双氯芬酸相比，奥沙普嗪在改善患者生活质量方面显示出趋向于优异结果的趋势。还发现与双氯芬酸相比，奥沙普嗪具有更好的耐受性的趋势。

BACKGROUND & AIMS: BACKGROUND:Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for arthritis but cause gastrointestinal injury. Bovine colostrum is a rich source of growth factors and is marketed as a health food supplement. AIMS:To examine whether spray dried, defatted colostrum or milk preparations could reduce gastrointestinal injury caused by indomethacin. METHODS:Effects of test solutions, administered orally, were examined using an indomethacin restraint rat model of gastric damage and an indomethacin mouse model of small intestinal injury. Effects on migration of the human colonic carcinoma cell line HT-29 and rat small intestinal cell line RIE-1 were assessed using a wounded monolayer assay system (used as an in vitro model of wound repair) and effects on proliferation determined using [3H]thymidine incorporation. RESULTS:Pretreatment with 0.5 or 1 ml colostral preparation reduced gastric injury by 30% and 60% respectively in rats. A milk preparation was much less efficacious. Recombinant transforming growth factor beta added at a dose similar to that found in the colostrum preparation (12.5 ng/rat), reduced injury by about 60%. Addition of colostrum to drinking water (10% vol/vol) prevented villus shortening in the mouse model of small intestinal injury. Addition of milk preparation was ineffective. Colostrum increased proliferation and cell migration of RIE-1 and HT-29 cells. These effects were mainly due to constituents of the colostrum with molecular weights greater than 30 kDa. CONCLUSIONS:Bovine colostrum could provide a novel, inexpensive approach for the prevention and treatment of the injurious effects of NSAIDs on the gut and may also be of value for the treatment of other ulcerative conditions of the bowel.

背景与目标： 背景：非甾体类抗炎药（NSAIDs）对关节炎有效，但会引起胃肠道损伤。牛初乳是生长因子的丰富来源，可作为保健食品的补充品销售。
目的：研究喷雾干燥，脱脂初乳或乳制品是否可以减少消炎痛对胃肠道的伤害。
方法：使用吲哚美辛抑制大鼠胃部损伤模型和吲哚美辛小鼠小肠损伤模型检查口服溶液的效果。使用受伤的单层测定系统（用作伤口修复的体外模型）评估了对人结肠癌细胞系HT-29和大鼠小肠细胞RIE-1迁移的影响，并通过[3H]确定了对增殖的影响胸苷掺入。
结果：用0.5或1毫升初乳制剂预处理可分别在大鼠中减少30％和60％的胃损伤。牛奶制品的功效要差得多。以与初乳制品中所发现的剂量（12.5 ng /大鼠）相似的剂量添加重组转化生长因子β，可减少约60％的伤害。在小肠损伤的小鼠模型中，将初乳添加到饮用水中（10％vol / vol）可以防止绒毛缩短。添加牛奶的准备是无效的。初乳增加了RIE-1和HT-29细胞的增殖和细胞迁移。这些影响主要归因于分子量大于30 kDa的初乳成分。
结论：牛初乳可以为预防和治疗非甾体抗炎药对肠道的伤害提供一种新颖，廉价的方法，也可能对肠其他溃疡性疾病的治疗有帮助。

BACKGROUND & AIMS: After colectomy with ileorectal anastomosis (IRA) for treatment of familial adenomatous polyposis (FAP), the rectal mucosa remains, with the risk of malignant change. Locoregional (rectal) sulindac has been applied, with initial higher-dose therapy and subsequent low-dose maintenance therapy to minimise side-effects. The dose-finding study with sulindac suppositories started with a dose of 300 mg sulindac daily per patient over 6 weeks. Depending on proctoscopical evaluation of regression of polyposis, sulindac doses were reduced in predefined steps. Ten of 15 patients developed a complete remission following 42 weeks of treatment, while the rest had partial remission. Responses were recorded 6-24 weeks after beginning sulindac treatment. After 36 weeks, 13/15 patients received 25-50 mg sulindac daily. An increase in the number of partial remissions after 42 weeks of treatment at doses of 100 mg sulindac daily may indicate the first approach to a reduced dose between 100 mg to 25 mg sulindac daily, but may also point to the importance of long-term treatment rather than dose-intense therapy.

背景与目标： 结肠切除术与回肠直肠吻合术（IRA）一起治疗家族性腺瘤性息肉病（FAP）后，直肠粘膜仍然存在，有发生恶变的风险。已应用局部（直肠）舒林酸，并采用了最初的大剂量治疗和随后的小剂量维持治疗，以最大程度地减少副作用。使用舒林酸栓剂的剂量查找研究始于每位患者在6周内每天服用300毫克舒林酸的剂量。根据对息肉消退的镜检评估，舒林酸的剂量可按预定步骤减少。 15位患者中有10位在治疗42周后完全缓解，其余患者部分缓解。开始舒林酸治疗后6-24周记录反应。 36周后，有13/15的患者每天接受25-50 mg舒林酸。每天接受100 mg舒林酸的剂量治疗42周后部分缓解的数量增加可能表明第一种减少每天100 mg至25 mg舒林酸剂量的方法，但也可能表明长期治疗的重要性而不是剂量密集型疗法。

BACKGROUND & AIMS: BACKGROUND:Statins and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced risk of colorectal cancer (CRC) in some studies. The objective of this study was to quantify the relative risk of inflammatory bowel disease (IBD) as a risk factor for CRC and to estimate whether this risk may be modified by long-term use of NSAIDs or statins. METHODS:The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study of incident colorectal cancer in northern Israel and controls matched by age, sex, clinic, and ethnicity. Personal histories of IBD and medication use were measured by structured, in-person interview. The relative risk of IBD and effect modification by statins and NSAIDs were quantified by conditional and unconditional logistic regression. RESULTS:Among 1921 matched pairs of CRC cases and controls, a self-reported history of IBD was associated with a 1.9-fold increased risk of CRC (95% confidence interval [CI], 1.12-3.26). Long-term statin use was associated with a reduced risk of both IBD-associated CRC (odds ratio [OR] = 0.07; 95% CI, 0.01-0.78) and non-IBD CRC (OR = 0.49; 95% CI, 0.39-0.62). Stratified analysis suggested that statins may be more protective among those with IBD (ratio of OR = 0.14; 95% CI, 0.01-1.31; P = .51), although not statistically significant. NSAID use in patients with a history of IBD was suggestive of reduced risk of CRC but did not reach statistical significance (OR = 0.47; 95% CI, 0.12-1.86). CONCLUSIONS:The risk of CRC was elevated 1.9-fold in patients with IBD. Long-term statin use was associated with reduced risk of CRC in patients with IBD.

背景与目标： 背景：在一些研究中，他汀类药物和非甾体抗炎药（NSAID）与降低结直肠癌（CRC）的风险有关。这项研究的目的是量化炎症性肠病（IBD）作为CRC的危险因素的相对风险，并估计长期使用NSAID或他汀类药物是否可以改变这种风险。
方法：结肠直肠癌的分子流行病学研究是一项基于人群的病例对照研究，研究对象是以色列北部地区的结肠直肠癌，并按年龄，性别，诊所和种族进行了对照。 IBD的个人病史和药物使用情况是通过结构化的面对面访谈来衡量的。 IBD的相对风险以及他汀类药物和非甾体抗炎药对效应的影响通过有条件和无条件逻辑回归进行定量。
结果：在1921对配对的CRC病例和对照中，IBD的自我报告病史与CRC风险增加1.9倍相关（95％置信区间[CI]，1.12-3.26）。长期使用他汀类药物与IBD相关CRC（比值比[OR] = 0.07; 95％CI，0.01-0.78）和非IBD CRC（OR = 0.49; 95％CI，0.39- 0.62）。分层分析表明，他汀类药物在IBD患者中可能具有更好的保护作用（OR = 0.14； 95％CI，0.01-1.31； P = .51），尽管无统计学意义。有IBD病史的患者使用NSAID提示CRC风险降低，但未达到统计学意义（OR = 0.47； 95％CI，0.12-1.86）。
结论：IBD患者的CRC风险升高了1.9倍。长期使用他汀类药物可降低IBD患者的CRC风险。

BACKGROUND & AIMS: BACKGROUND:Noxious cutaneous stimuli enhance spinal excitability. The behavioral correlate to this response is found in the rat formalin test, in which formalin injection into the hindpaw evokes signs of nociception (flinching and licking of the injected paw) with acute (phase 1) and delayed-hyperalgesic (phase 2) components.

METHODS:The effect of intrathecal morphine (a mu agonist), U50488H (a kappa agonist), ST-91 (an alpha 2 agonist), L-PIA (an adenosine A1 agonist), and ketorolac (a nonsteroidal antiinflammatory drug, or NSAID), were examined in rats undergoing the formalin test. Spinal interactions between ketorolac and the mu, kappa, alpha 2, and adenosine A1 agonists were assessed using isobolographic analysis.

RESULTS:Morphine and ST-91 caused a dose-dependent suppression of phase 1 and phase 2 of the formalin test, while U50488H and L-PIA had little effect on phase 1, but caused dose-dependent depression of phase 2. Intrathecal ketorolac inhibited the phase 2 response, but had limited effect on phase 1. The isobolographic analysis revealed a significant synergy (with fractional dose ratios of less than 1) between ketorolac and morphine or ST-91 for phase 1 and phase 2, but only an additive interaction was found between ketorolac and L-PIA or U50488H.

CONCLUSIONS:These observations offer systematic support for the powerful interaction between NSAIDs and opioids and certain other analgesics in clinical pain states. These studies also demonstrate that spinal synergy is not a common property of all interactions. Thus, the NSAID synergy appears to occur with agents that exert a concurrent action both pre- and postsynaptic to the primary afferents.

背景与目标： 背景：有害的皮肤刺激可增强脊柱兴奋性。在大鼠福尔马林试验中发现了与该反应相关的行为，其中将福尔马林注射到后爪中会引起具有急性（阶段1）和延迟性痛觉过敏（阶段2）成分的伤害感受（被注射的爪子畏缩和舔动）。

方法：鞘内注射吗啡（μ激动剂），U50488H（κ激动剂），ST-91（α2激动剂），L-PIA（腺苷A1）的作用激动剂）和酮咯酸（一种非甾体类抗炎药，NSAID）已在接受福尔马林测试的大鼠中进行了检查。用等效线描记法分析了酮咯酸与mu，κ，α2和腺苷A1激动剂之间的脊髓相互作用。

结果：吗啡和ST-91引起剂量依赖性抑制作用福尔马林测试的第1和第2阶段，而U50488H和L-PIA对第1阶段影响不大，但引起剂量依赖性的第2阶段抑制。鞘内注射酮咯酸可抑制第2阶段的反应，但对第1阶段的作用有限。等效线描图分析显示，对于1期和2期，酮咯酸和吗啡或ST-91之间具有显着的协同作用（分数剂量比小于1），但在酮咯酸和L-PIA或U50488H之间仅发现了加性相互作用。
结论：这些观察结果为NSAID和阿片类药物以及某些其他镇痛药在临床疼痛状态下的强大相互作用提供了系统的支持。这些研究还表明，脊柱协同并不是所有相互作用的共同属性。因此，NSAID协同作用似乎与对初级传入神经突触前和突触后同时发挥作用的药物发生。