肝胰十二指肠器官簇移植(附一例报道)

目的探讨肝胰十二指肠联合移植术治疗1例原发性肝癌合并胰头转移的疗效。方法2004年9月,对1例原发性肝癌合并胰头转移的患者行病肝、全胰腺十二指肠、远端胃及脾脏切除后,进行肝胰十二指肠原位器官簇移植。结果移植术后胰腺功能恢复正常,未应用胰岛素维持;术后1周肝功能恢复正常。患者目前已存活5个月,肝脏和胰腺功能均正常,未发生排斥反应,未见肿瘤复发迹象,一般情况好。结论肝胰十二指肠器官簇移植为上腹部晚期恶性肿瘤患者提供了延长生命的机会,同时更为晚期肝病伴有胰腺功能不良患者的彻底治愈探索出新的手术术式。     

肝胰十二指肠器官簇移植外科技术

2004年9月1例原发性肝癌合并胰头转移的患者在我院接受肝胰十二指肠器官簇移植，整块切除全肝、胆囊、十二指肠、胰腺、脾脏、胃大部和部分上段空肠，进行了血管和消化道重建。移植后胰腺功能正常，未应用胰岛素维持。术后第4d肠道功能恢复，术后1周肝功能恢复正常；术后16d时因腹腔内出血行剖腹探查血肿清除术，同时对感染伤口进行减张缝合，愈合良好；术后2月时出现不全性肠梗阻症状，保守治疗后好转。患者目前已存活5个月，肝脏和胰腺功能均正常，痊愈出院。肝胰十二指肠器官簇移植术的成功为上腹部晚期恶性肿瘤患者提供了延长生命的机会，同时为晚期肝病伴有胰腺功能不良患者的彻底治愈探索出新的手术方式。     

上腹部器官簇移植治疗多脏器恶性肿瘤手术方式探讨

上腹部器官簇移植受者5例，其中男性4例，女性1例；胰腺癌肝转移3例，肝癌胰腺及腹腔淋巴结转移2例。5例患者分别于2004年5月至2005年4月接受上腹部器官簇移植治疗，切除脏器包括全胃、肝脏、胰腺、脾脏、十二指肠及部分空肠，移植器官簇包括肝脏、胰腺、十二指肠及部分空肠。所有患者均于术后4～6h清醒，8～14h撤除呼吸机；术后第3～7d从SICU转回普通病房开始康复治疗。AST、ALT及TB等肝功能指标在术后1周趋于正常水平；C-肽、血淀粉酶、血清胰岛素水平在1～2周内达到正常范围。目前，除1例患者出现肿瘤复发外，其余病例一般情况良好。肝胰十二指肠器官簇移植具有肿瘤根治彻底、器官功能替代全面的特点，是上腹部多脏器恶性肿瘤的有效治疗方法。     

应用肝肾胰十二指肠联合切取供肝的动脉分配与肝移植术后动脉并发症的关系(附11例报告)

目的 探讨应用肝肾胰十二指肠联合切取方法获得的器官簇中的供肝进行肝移植,其中各器官动脉的分配及重建方式与肝移植术后动脉并发症的关系,以期更加合理安全地分配利用供体器官,减少相关术后并发症的发生.方法 分析11例肝肾胰十二指肠联合切取器官簇的动脉分配及重建方式对肝移植效果的影响.结果 11例供肝未发现变异肝动脉,于肝固有动脉和胃十二指肠动脉分叉处获得Carrol袢.其中1例因动脉长度不足行动脉搭桥,术后动脉血栓形成行二次移植,其余动脉重建吻合顺利,术后恢复良好；另1例患者术后5个月死于肺感染,其余患者移植肝功能恢复良好.结论 肝肾胰十二指肠联合切取时,受者必须保留足够的动脉长度,器官切取组与受者手术组保持及时准确的沟通,器官分配时肝组保留胃十二指肠和肝固有动脉Carrol袢,吻合时采用严格的显微外科血管吻合技术是避免发生术后肝动脉并发症的关键.此种方式获得的供肝可以在不影响肾脏、胰腺等多器官利用的前提下完成肝脏移植手术.     

成功的上腹部器官簇移植1例：供体器官的切取及修整

目的探讨上腹部多器官移植中器官簇的切取、修整、血管整形方法及移植效果。方法供体器官簇获取采用腹部多器官联合切取，腹主动脉、肠系膜上静脉、胆管及十二指肠同时灌注降温。器官簇肠系膜上动脉和腹腔干分别与供体髂内、外动脉吻合，通过髂总动脉与受体腹主动脉吻合。受体为胰腺囊腺癌并肝内转移患者，行上腹部肝、胆、胰、脾、十二指肠、全胃、空肠上段及大小网膜切除，接受肝、胰、十二指肠器官簇移植。结果移植后器官簇存活及功能良好，肝、胰功能均在术后4天恢复正常，患者现已完全康复，未出现明确并发症。结论获取质量良好的上腹部器官簇及合理血管整形，是保证移植效果的前提；上腹部器官簇移植是治疗上腹局部晚期肿瘤的有效方法。     

肝胰十二指肠器官簇移植五例治疗分析

目的总结肝胰十二指肠器官簇移植术后并发症发生和器官功能恢复情况。方法对5例终末期肝病合并2型糖尿病患者进行肝胰十二指肠器官簇移植．术中保留受体胰和全消化道．行单纯肝切除术后,予以肝胰十二指肠器官簇移植。结果5例患者术程均顺利,手术时间9。16h,术中出血1600～3000ml。术后1例出现肺部感染;1例出现移植物抗宿主病（GVHD）并肺部感染;1例出现急性肾功能衰竭。5例患者均未出现肠瘘、吻合口瘘、胆道并发症、急慢性排斥反应及胰腺炎。5例患者丙氨酸转氨酶、天冬氨酸转氨酶及总胆红素等肝功能指标在术后1周趋于正常水平：C肽、血糖水平在1。2周达到正常范围。术后经2～23个月的随访,除1例因GVHD死亡外,其余4例患者肝功能均维持正常．无需外援性胰岛素即可维持血糖稳定。结论肝胰十二指肠器官簇移植在技术上具有可行性,是一种治疗多器官病变的有效方法。     

上腹部器官簇移植手术方式的探讨

目的探讨上腹部器官簇移植治疗多脏器恶性肿瘤的可行性及临床效果。方法上腹部器官簇移植受者2例,其中男、女各1例;均为胰腺癌肝转移患者。2例患者分别于2004年5月和8月接受上腹部器官簇移植治疗,切除脏器包括全胃、肝脏、胰腺、脾脏、十二指肠及部分空肠,移植器官簇包括肝脏、胰腺、十二指肠。其中1例胰腺肿物侵犯肠系膜上动脉（SMA）,切断SMA后,其远端与右髂总动脉吻合重建血供。结果2例患者于术后4h及5h清醒,8h及10h后撤除呼吸机;术后第3天及第5天从外科加强治疗病房转至普通病房。肝功能指标在手术1周后趋于正常;胰腺功能在10d内达到正常范围。1例患者存活12个月,死于肿瘤复发;另1例术后恢复平稳,术后20d自动出院。结论肝胰十二指肠器官簇移植为上腹部局部多脏器恶性肿瘤提供了一种手术上可行并具有一定疗效的治疗方法。     

上腹部器官簇移植供体器官的切取及修整

目的 探讨上腹部多器官移植中器官簇的切取、修整、血管整形方法及移植效果.方法 5例供体器官簇的获取均采用腹部多器官联合切取,腹主动脉、肠系膜上静脉、胆道及十二指肠同时灌注降温.供体器官簇的肠系膜上动脉和腹腔干分别与取自供体的髂内、外动脉预先行端端吻合,再通过髂总动脉与受体腹主动脉单口端侧吻合（动脉“搭桥”）.受体行上腹部肝、胆、胰、脾、十二指肠、全胃、空肠上段及大小网膜切除,接受肝、胰、十二指肠器官簇移植.结果 5例患者移植术后器官簇存活及功能均良好,肝胰功能均在术后1周左右恢复正常.其中2例患者分别于术后第2天、第3天出现十二指肠空肠吻合口瘘,经再次手术后治愈.目前,除1例患者于术后3个月肿瘤复发、肺转移,死于全身衰竭外;其余4例患者移植物功能良好,现均已存活达6个月.结论 获取质量良好的上腹部器官簇及适当的血管整形,是保证移植效果的前提;上腹部器官簇移植是治疗上腹多脏器恶性肿瘤的有效治疗方法.     

上腹部器官簇移植的消化道重建与术后处理

目的探讨上腹部器官簇移植术中消化道重建和手术后处理的方法。方法回顾性分析中山大学附属第一医院于2004年5月为1例胰腺癌合并多发性肝脏转移患者成功实施的亚洲首例上腹部器官簇移植资料。结果术中切除了患者的肝脏、胆囊、胰腺、十二指肠及近端部分空肠、全胃、脾脏、大小网膜等脏器。采用Roux-en-Y方式进行消化道重建:供体十二指肠近端封闭,受体近端空肠与供体十二指肠水平部吻合,吻合口下方35cm处切断受体空肠,断端远端口与食管行端侧吻合,近端口与距离食管吻合口50cm的空肠行端侧吻合。十二指肠腔内置减压管自受体空肠引出体外,Roux-en-Y吻合口远端空肠造瘘置营养管。术后应用生长抑素控制胰液分泌,尽早使用肠内营养,延迟拔除胃管及十二指肠减压管。患者术后恢复顺利,第3天移植胰腺内分泌功能已发挥作用,移植肝脏功能基本正常;消化道功能恢复顺利,第4天肠道排气排便,逐渐恢复至普通饮食;术后1个月除出现腹泻症状外,无其他并发症出现,肝功能及胰腺外分泌功能各项指标均正常。结论上腹部器官簇移植的成功为消化道重建及其手术后处理提供了经验。     

肝胰十二指肠器官簇移植术后的免疫抑制治疗

目的探讨肝胰十二指肠器官簇移植术后的免疫抑制治疗的合理用药方案。方法收集本中心共实施的10例肝胰十二指肠器官簇移植手术病例,其中5例为上腹部肿瘤伴腹腔多发转移病灶患者接受了肝脏、胰腺及上消化道全切除术后行器官簇移植,5例乙型肝炎后肝硬化失代偿期合并2型糖尿病患者予以单纯肝切除术后行器官簇移植。10例患者均采用巴利昔单抗＋他克莫司＋激素＋霉酚酸酯四联免疫抑制方案,对患者的临床资料进行回顾性分析。结果10例患者手术顺利,术后肝脏、胰腺及十二指肠功能恢复良好。5例肿瘤患者最长存活326d,3例死于多器官功能衰竭,2例死于肿瘤复发。5例肝硬化合并糖尿病患者除1例于术后4周死于移植物抗宿主病（GVHD）外,其余4例均存活,最长生存时间已超过21个月。随访期内及至患者死亡,10例患者均未发生排斥反应。结论采用巴利昔单抗＋他克莫司＋激素＋霉酚酸酯四联免疫抑制方案可以有效预防肝胰十二指肠器官簇移植术后排斥反应的发生。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.