特发性肾病综合征患儿尿液外泌体miR-194-5p水平及其临床价值

目的探讨特发性肾病综合征(idiopathic nephrotic syndrome,INS)患儿尿液外泌体miR-194-5p水平及其作为辅助诊断标志物的临床价值。方法收集101例INS患儿和98例性别、年龄相匹配的健康儿童尿液标本,采用实时荧光定量PCR(qRT-PCR)检测miR-194-5p在尿液外泌体中的含量;ROC曲线、相关性分析等评估其对INS患儿的诊断价值。结果 INS组尿液外泌体miR-194-5p水平明显高于健康人对照组[2.420(0.650,9.515)fmol/L vs 0.360(0.220,0.653)fmol/L,U=1 552,P0.01],且其中44例患者在治疗缓解后明显下降[0.975(0.375,4.358)fmol/L vs 0.320(0.145,0.523)fmol/L,W=708,P0.01];伴有高尿蛋白的INS患儿miR-194-5p水平明显高于伴有低尿蛋白患儿[8.430(7.225,13.070)fmol/L vs 2.130(1.180,3.090)fmol/L,U=0,P0.01];miR-194-5p诊断INS的ROC曲线下面积(AUC~(ROC))为0.843(95%CI:0.789～0.897)。相关性分析显示,INS患儿尿液外泌体miR-194-5p与血清清蛋白(r=-0.300)水平呈负相关,与血清总胆固醇(r=0.278)、24 h尿蛋白(r=0.296)呈正相关(P均0.01)。结论 INS患儿尿液外泌体miR-194-5p含量明显升高,与24 h尿蛋白、血清清蛋白和胆固醇水平密切相关,有望作为辅助诊断儿童INS的非侵入性分子标志物。     

精神分裂症患者白细胞中循环miRNA的表达及其临床意义

目的探讨白细胞中循环miRNA在精神分裂症SZ的表达水平及其诊断价值。方法收集90例SZ患者作为疾病组,90例双相情感障碍(BPAD)患者作为病例对照组,90例体检健康者作为健康对照组,采用实时荧光定量PCR检测各组白细胞中8个miRNA(miR-31-5p、miR-99b-5p、miR-107、miR-134-5p、miR-487b-3p、miR-181b-3p、miR-431-5p和miR-433-5p)的表达水平,并进行统计学分析,以验证差异表达的miRNA;绘制受试者工作曲线(ROC)曲线,建立人工神经网络(ANN)诊断模型,并分析其诊断价值。结果 SZ患者存在6个显著低表达的miRNA,其ROC曲线下面积(AUCROC)分别为miR-31-5p:0.931,miR-487b-3p:0.887,miR-99b-5p:0.869,miR-431-3p:0.763,miR-134-3p:0.756,miR-107:0.721;在ANN模型中,最优模型的AUCROC为0.960,敏感性86.7%,特异性95.6%。结论白细胞中6个差异表达的miRNA可能作为SZ诊断的非侵袭性生物学标志物,而ANN诊断模型可以提高miRNA对SZ的诊断价值。     

结直肠癌组织miR-485-5p，miR-1207-3p和miR-590-3p水平表达与临床病理特征及生存的相关性研究

目的　研究 miR-485-5p,miR-1207-3p和 miR-590-3p在结直肠癌演进过程中的表达变化。方法　选取 2019年 1月～ 2020年 1月承德市中心医院病理科归档资料齐全完整的 84例结直肠癌组织石蜡标本和距离癌组织边缘 5cm的癌旁组织石蜡标本。采用免疫组织化学法及荧光定量 PCR法检测以直肠组织制作的标本 miR-485-5p,miR-1207-3p和 miR-590-3p,分析 miR-485-5p,miR-1207-3p和 miR-590-3p在结直肠癌组织演进过程中的表达变化。结果　癌组织 miR-485-5p(3.25±0.32 fmol/L),miR-1207-3p(1.45±0.14 fmol/L)和 miR-590-3p(2.63±0.26 fmol/L)表达均低于癌旁组织 (7.65±0.76 fmol/L,5.81±0.58 fmol/L,8.95±0.89 fmol/L),差异有统计学意义（ t=48.900,66.970, 62.470,均 P＜ 0.05)。Ⅲ～Ⅳ期、中、低分化、有淋巴结转移、有肝转移患者 miR-485-5p,miR-1207-3p和 miR-590-3p表达分别低于Ⅰ～Ⅱ期、高分化、无淋巴结转移、无肝转移患者,差异有统计学意义（ t/F=21.338～ 52.835, 均 P＜ 0.05）。死亡组患者 miR-485-5p（1.52±0.15 fmol/L）,miR-1207-3p（0.50±0.05 fmol/L）和 miR-590-3p（1.15±0.11 fmol/L）均低于存活组（4.98±0.49 fmol/L,2.40±0.24 fmol/L,4.11±0.41 fmol/L）,差异具有统计学意义（t=27.820,31.370, 28.520,均 P＜ 0.05）。 ROC曲线分析显示,三项联合曲线下面积、敏感度和特异度分别为 0.823,86.30%和 87.32%;miR-485-5p分别为 0.699,85.78%和 86.41%;miR-1207-3p分别为 0.768,85.59%和 71.14%;miR-590-3p分别为 0.719,83.62%和 87.62%,三项联合诊断价值大于单独检测。 miR-485-5p,miR-1207-3p和 miR-590-3p之间相关性分析显示, miR-485-5p与 miR-12073p呈正相关（ r=0.457,P=0.005）;miR-485-5p与 miR-590-3p呈正相关（ r=0.314,P=0.003）;miR-1207-3p与 miR590-3p呈正相关（ r=0.332,P=0.002）。结论　血清 miR-485-5p,miR-1207-3p和 miR-590-3p水平联合检测对诊断结直肠癌、判断恶化程度有一定临床价值,且可能作为结直肠癌患者潜在的预后标志物。     

儿童原发性肾病综合征患者尿液外泌体miR-23b-3p水平变化及其临床意义

目的检测尿液外泌体miR-23b-3p在儿童原发性肾病综合征(nephrotic syndrome,NS)患者中的水平,评估其作为NS辅助诊断指标的临床价值。方法收集2017年3～11月在解放军东部战区总医院住院并确诊的98例NS患儿(NS组)和南京医科大学附属儿童医院95例年龄、性别相匹配的健康儿童(对照组)的晨尿标本及临床资料。实时荧光定量PCR (quantitative real-time PCR,qRT-PCR)方法检测miR-23b-3p在尿液外泌体中的含量。应用受试者工作特征曲线(receiver operating characteristic curve,ROC)、相关性分析等评估其作为儿童NS诊断指标的临床价值。结果 miR-23b-3p在NS组尿液外泌体中的浓度明显高于对照组[13.44(4.47,31.40)fmol/L vs 3.94(2.76,7.15)fmol/L,差异有统计学意义,U=1 899,P0.000 1],且在治疗缓解后显著下降[10.62(4.38,37.72)fmol/L vs 2.84(1.53,4.92)fmol/L,W=695,P0.000 1]。miR-23b-3p诊断NS的ROC曲线下面积(AUC)为0.796(95%CI:0.734～0.858),敏感度为84.7%,特异度为64.2%。相关性分析显示,NS患儿尿液外泌体miR-23b-3p与血清总蛋白(r=-0.377)、清蛋白(r=-0.309)水平呈显著负相关,与血清总胆固醇(r=0.266)、三酰甘油(r=0.318)呈显著正相关,差异均具有统计学意义(均P0.01)。结论 miR-23b-3p在NS患儿尿液外泌体中的含量显著升高,且在治疗缓解后明显降低,有望作为儿童NS辅助诊断和治疗效果监测的潜在指标。     

循环microRNA-193簇对乳腺癌的筛查价值

目的探讨循环microRNA-193(miR-193)家族对乳腺癌(BC)的筛查价值。方法检索GEO数据库并分析miR-193簇的表达。收集45例健康人对照及130例乳腺癌患者血清样本,RT-qPCR检测各组血清miR-193簇的表达水平。ROC曲线分析miR-193簇对BC的筛查效能。结果在筛选阶段,GEO数据集分析结果表明,BC患者血清中miR-193a-5p与miR-193b表达降低且具有良好的诊断效能;RT-qPCR结果显示,与对照组相比,BC患者血清中miR-193簇成员(miR-193a-3p,-5p和miR-193b-5p)的含量均显著降低(P均0.01)。在验证阶段,miR-193a-5p和miR-193b-5p的AUC~(ROC)分别为0.888(95%CI:0.808～0.969)和0.954(95%CI:0.902～1.000),而二者联合筛查的AUC~(ROC)为0.982(95%CI:0.966～0.999)。结论血清miR-193a-5p和miR-193b-5p可以作为BC的筛查标志物,二者联合显著提高筛查效能,具有较好的临床应用潜能。     

2型糖尿病及其微血管并发症患者血清miR-342-5p和miR-423-5p水平测定及临床意义

目的检测2型糖尿病(T2DM)及其微血管并发症患者血清miR-342-5p、miR-423-5p及氧化脂蛋白水平,分析其潜在的临床意义。方法用实时荧光定量PCR检测50例T2DM、T2DM微血管并发症患者及体检健康者血清miR-342-5p和miR-423-5p表达水平;ELISA法检测其ox-LDL,ox-Lp(a),β2-GPⅠ-ox-LDL,β2-GPⅠ-Lp(a)的含量;生化分析仪测定相关生化指标。结果与健康对照组血清miR-342-5p和miR-423-5p表达水平[分别为0.144(0.027,0.487)fmol/L;1.480(0.676,2.580)fmol/L]比较,T2DM患者[0.234(0.103,1.241)fmol/L(U=779,P0.01);3.398(1.742,7.351)fmol/L(U=606,P0.01)]和T2DM微血管并发症患者[0.300(0.102,2.760)fmol/L(U=731,P0.01);3.886(2.021,9.430)fmol/L(U=488,P0.01)]表达水平显著上升。miR-342-5p和miR-423-5p对T2DM患者诊断的ROC曲线下面积(AUCROC)分别为0.688(95%CI:0.586~0.791)和0.758(95%CI:0.664~0.851),对T2DM微血管并发症患者分别为0.702(95%CI:0.600~0.803)和0.801(95%CI:0.716~0.886);T2DM和T2DM微血管并发症患者ox-LDL、ox-Lp(a)、β2-GPⅠ-ox-LDL、β2-GPⅠ-Lp(a)水平亦显著高于健康对照组(P均0.05)。Spearman秩相关分析显示,miR-342-5p和miR-423-5p与FPG、ox-LDL、ox-Lp(a)、β2-GPⅠ-ox-LDL、β2-GPⅠ-Lp(a)呈显著正相关(P均0.05)。结论 miR-342-5p和miR-423-5p可能作为T2DM及其微血管并发症的辅助诊断指标。     

miR-181b-3p在胃癌患者血清中的表达及其靶基因预测

目的 研究血清miR-181 b-3 p检测在胃癌诊断中的价值.方法 采用反转录-聚合酶链反应(RT-PCR)法检测35例胃癌患者(研究组)和45例健康志愿者(对照组)血清中miR-181b-3p的相对表达水平,并比较不同年龄、性别、临床及病理学特征胃癌患者血清中的miR-181b-3p相对表达水平.绘制受试者工作特征(ROC)曲线计算曲线下面积,评价miR-181b-3p对胃癌的诊断效能.结合miRDB、miRWalk、TargetScan和DIANA TOOLS数据库预测miR-181b-3p的靶基因,并绘制蛋白互作网络图.结果 与对照组比较,研究组血清中miR-181b-3p的相对表达水平明显升高,差异有统计学意义(t=7.943,P<0.05).未/低分化程度、有淋巴结转移、TNM分期Ⅲ～Ⅳ期胃癌患者血清中miR-181 b-3 p相对表达水平明显高于中/高分化程度、无淋巴结转移、TNM分期Ⅰ～Ⅱ期胃癌患者,差异有统计学意义(t=3.509、P<0.001,t=3.080、P=0.004,t=2.641、P=0.013).血清miR-181b-3p检测诊断胃癌的ROC曲线下面积为0.886(95％CI:0.815～0.956),灵敏度为68.8％,特异度为91.1％.miR-181b-3p预测靶基因所编码蛋白质间相互作用关系较复杂.结论 血清miR-181b-3p在胃癌患者中表达上调,且能够有效区分胃癌患者和健康人群,有望作为诊断胃癌的生物标志物.     

血清中miR-34b-3p和SERPINA1在子宫内膜异位症中的表达及临床意义

目的 探讨血清中微小RNA-34b-3p(miR-34b-3p)和丝氨酸蛋白酶抑制剂A1(SERPINA1)在子宫内膜异位症中的表达及临床意义。方法 前瞻性纳入2021年5月至2022年6月同济大学附属第一妇婴保健院收治的行腹腔镜手术的子宫内膜异位症患者98例为子宫内膜异位症组。同期选取同济大学附属第一妇婴保健院住院行腹腔镜手术的卵巢良性囊肿患者和体检中心体检健康的女性各100例分别为卵巢囊肿组和对照组。采用实时荧光定量PCR检测血清中miR-34b-3p的表达,采用酶联免疫吸附试验检测血清中SERPINA1的表达,Pearson相关分析miR-34b-3p和SERPINA1的相关性,采用受试者工作特征(ROC)曲线评价miR-34b-3p和SERPINA1在子宫内膜异位症中的诊断价值。结果 子宫内膜异位症组患者血清中miR-34b-3p的表达为0.46±0.11,明显低于对照组和卵巢囊肿组(2.32±0.43、2.81±0.57),血清中SERPINA1的表达为(143.86±36.72) pg/mL,明显高于对照组和卵巢囊肿组[(34.56±7.53)、(28.13±6.49) p...     

星形细胞瘤患者癌组织和血清miR 497表达下降及其临床意义

摘要：目的：检测星形细胞瘤患者癌组织和血清中miR-497的表达水平及治疗前后血清miR-497的变化,探讨其作为分子标志物的可能性。 方法：采集8例星形细胞瘤患者癌组织、4例癌旁组织、3例正常脑组织以及133例治疗前患者的（WHO Ⅱ级55例、Ⅲ级45例和IV级33例）血清样本,用实时荧光定量RT-PCR法检测miR-497含量,并以80例年龄、性别匹配的健康人作对照。对其中14例患者进行术前、术后血清miR-497含量的比较,ROC曲线分析miR-497对星形细胞瘤的诊断价值。 结果：miR-497在癌组织中的表达量明显低于癌旁组织和正常脑组织 (F=13.78,P<0.05),在患者血清中的浓度也显著降低［（112.69±54.58） fmol/L vs （254.32±142.12） fmol/L,t=10.31,P<0.01］。用于星形细胞瘤诊断的miR 497 ROC曲线下面积（AUC^ROC）为0.894 (95% CI, 0.853～0.935),敏感性为82%,特异性为90%。血清miR 497在患者术后明显上升［术后（165.69± 56.87） fmol/L vs 术前（93.77±38.50） fmol/L,t=3.92,P<0.01。 结论: 星形细胞瘤患者癌组织和血清miR-497低表达,miR-497有望作为该病诊断及预后评价的检测指标。     

基于miR-106b-5p调控CCND1基因研究幽门螺杆菌促进食管癌细胞增殖的功能机制

目的 研究幽门螺杆菌(Hp)感染通过miR-106b-5p/细胞周期蛋白D1(CCND1)途径促进食管癌细胞增殖的作用机制。方法 收集手术切除的食管癌组织46份,检测Hp感染情况及miR-106b-5p、CCND1的表达水平。培养食管癌TE-1细胞株,分别给予不处理、Hp感染、转染阴性对照(NC)序列、转染miR-106b-5p模拟物、转染NC序列同时加入Hp菌液、转染miR-106b-5p模拟物同时加入Hp菌液处理,分别作为对照组、Hp组、miR-NC组、miR-106b-5p组、miR-NC+Hp组、miR-106b-5p+Hp组,检测细胞增殖情况、细胞周期及miR-106b-5p、CCND1的表达水平。结果 Hp阳性的食管癌组织中miR-106b-5p的表达水平低于Hp阴性的食管癌组织,CCND1的表达水平高于Hp阴性的食管癌组织,差异有统计学意义(P<0.05)。食管癌组织中miR-106b-5p与CCND1的表达水平呈负相关(r=-0.414,P=0.004);Hp组TE-1细胞的A₄₉₀水平、细胞周期S期及G2/M期比例、CCND1的表达水平高于...     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.