Antipyrine elimination and hepatic microsomal enzyme activity in patients with liver disease

Induction of hepatic monooxygenases reflected by 7-ethoxycoumarin O-deethylase has been proposed to be associated with the initiation of liver damage. This study investigated a possible correlation between 7-ethoxycoumarin O-deethylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase and benzypyrene hydroxylase activity in liver biopsy specimens of 31 patients with liver disease and antipyrine elimination, an in vivo parameter of hepatic monooxygenase activity. No correlation was found between the enzyme activities and antipyrine clearance or half-life. When microsomal enzyme activities were compared with the formation rate of 4-hydroxyantipyrine, 3-methylhydroxyantipyrine, and norantipyrine, a correlation was found only between benzo[alpha]pyrene hydroxylase and 3-methylhydroxyantipyrine (r = 0.89; p less than 0.0005). There was also a correlation between 7-ethoxycoumarin O-deethylase and reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase (0.56; p less than 0.05). Our data suggest that antipyrine elimination is not related to 7-ethoxycoumarin O-deethylase activity in liver disease. However, the formation rate of antipyrine metabolites, rather than antipyrine half-life and clearance, may correlate with the activity of certain microsomal enzymes.     

Pulmonary aspects of chronic liver disease and liver transplantation

A vast spectrum of pulmonary pathologic conditions occurs in association with chronic liver diseases, and clinically important manifestations, such as arterial hypoxemia, can result. Both pulmonary vascular and parenchymal abnormalities can contribute to the dysfunction, as evidenced by results of pulmonary function tests and gas exchange studies. The clinical implications of identifying such pulmonary problems range from alleviation of symptoms, especially dyspnea, to comprehensive assessment of patients before and after liver transplantation. Physicians should be aware of these potential pulmonary disorders that can complicate liver disease and liver transplantation so that management of affected patients can be improved.     

干细胞移植治疗肝病的研究现状

学术背景：常规的内科保肝治疗效果不佳，原位肝移植仍然是治疗终末期肝病最有效的措施，但肝源缺乏、费用昂贵、移植排斥反应及长期应用免疫抑制剂引起并发症等成为限制其广泛应用的主要原因。干细胞移植有利于受损肝组织修复，能够代偿部分肝功能，已成为治疗肝病的一种新方法。 目的：介绍干细胞移植治疗肝病的研究现状。 检索策略：由该论文的研究人员应用计算机检索Pubmed 2002-01／2007-12的相关文献，检索词“transplantation of stem cell，liver disease，hepatic disease”，并限定文献语种为“English”。同时计算机检索中国知识资源总库CNKI2002-01/2007—12的相关文献，检索词“干细胞移植，肝病”，并限定文献语种为中文。共检索到125篇文献，对资料进行初审，纳入标准：①文章内容与干细胞移植应用于肝病的治疗相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准：重复研究或Meta分析类文章。 文献评价：文献的来源主要是通过对干细胞移植治疗肝病方面内容进行汇总分析，其中36篇相关度较高，对完全符合标准的30篇作为参考文献进行综述。进一步查找全文，2篇为综述，其余均为临床或基础实验研究。 资料综合：①干细胞移植动物实验：采用不同方法建立肝损伤动物模型，对成模动物以不同途径进行不同种类的干细胞移植实验，移植后行肝脏组织学检查及检测转氨酶和白蛋白等肝功能指标，结果显示干细胞移植能够改善肝功能，修复肝脏组织结构，减轻肝脏损伤。②干细胞移植用于临床治疗：多项通过干细胞移植治疗终末期肝病和难治性肝病患者的研究表明，干细胞移植后患者症状缓解，肝功能和凝血功能明显好转，治疗时间缩短，改善预后，且无严重并发症出现。③干细胞移植相关并发症及其应用     

干细胞移植治疗肝病的研究现状

学术背景:常规的内科保肝治疗效果不佳,原位肝移植仍然是治疗终末期肝病最有效的措施,但肝源缺乏、费用昂贵、移植排斥反应及长期应用免疫抑制剂引起并发症等成为限制其广泛应用的主要原因.干细胞移植有利于受损肝组织修复,能够代偿部分肝功能,已成为治疗肝病的一种新方法.目的:介绍干细胞移植治疗肝病的研究现状.检索策略:由该论文的研究人员应用计算机检索 Pubmed 2002-01/2007-12的相关文献,检索词"transplantation of stem cell,liver disease,hepatic disease",并限定文献语种为"English".同时计算机检索中国知识资源总库CNKI 2002-01/2007-12的相关文献,检索词"干细胞移植,肝病",并限定文献语种为中文.共检索到125篇文献,对资料进行初审,纳入标准:①文章内容与干细胞移植应用于肝病的治疗相关.②同一领域选择近期发表或在权威杂志上发表的文章.排除标准:重复研究或Meta分析类文章.文献评价:文献的来源主要是通过对干细胞移植治疗肝病方面内容进行汇总分析,其中36篇相关度较高,对完全符合标准的30篇作为参考文献进行综述.进一步查找全文,2篇为综述,其余均为临床或基础实验研究.资料综合:①干细胞移植动物实验:采用不同方法建立肝损伤动物模型,对成模动物以不同途径进行不同种类的干细胞移植实验,移植后行肝脏组织学检查及检测转氨酶和白蛋白等肝功能指标,结果显示干细胞移植能够改善肝功能,修复肝脏组织结构,减轻肝脏损伤.②干细胞移植用于临床治疗:多项通过干细胞移植治疗终末期肝病和难治性肝病患者的研究表明,干细胞移植后患者症状缓解,肝功能和凝血功能明显好转,治疗时间缩短,改善预后,且无严重并发症出现.③干细胞移植相关并发症及其应用评价:行干细胞移植治疗肝病患者的临床研究,未经合理的多中心、大样本、随机对照实验设计,其治疗效果不确切,至今仍存在不同观点,且移植后可出现病毒感染及肝静脉梗阻等并发症,以及干细胞的致瘤性,均限制了其应用.结论:尽管目前多项干细胞移植用于治疗肝病患者的临床研究均已取得一些疗效,但有报道认为其对肝损伤无明显改善,且产生相关并发症,同时仍存在一定问题.因此需要合理设计,并进行随机对照来确证以往研究结果的可靠性,使其成为治疗肝病的一个安全有效措施,从而排除质疑,推进其临床应用.     

肝移植术后脂肪肝的超声表现

目的探讨肝移植术后脂肪肝的超声声像图表现。方法对437例接受原位肝移植手术,术后常规腹部超声检出脂肪肝患者的声像图表现进行分组,对均匀弥漫性脂肪肝组与非均匀性脂肪肝组患者的血流动力学异常表现进行分析。结果超声检出肝移植术后脂肪肝36例(36/437,8.2%),其中非均匀性脂肪肝10例(10/36,27.8%),均匀弥漫性脂肪肝26例(26/36,72.2%)。非均匀性脂肪肝组10例中7例发生血流动力学异常;均匀弥漫性脂肪肝组26例中仅4例发生血流动力学异常,非均匀性脂肪肝组患者血流动力学异常的发生率明显高于均匀性脂肪肝组(P0.05)。结论肝移植术后脂肪肝患者的超声表现以均匀弥漫性脂肪肝为主;非均匀性脂肪肝更多表现出血流动力学异常。     

Oxygen kinetics during liver transplantation: The relationship between delivery and consumption

In anesthetized humans, oxygen consumption is independent of oxygen delivery above a critical threshold. Below this critical level, lactic acid is a marker of anaerobic metabolism and tissue oxygen debt, and heralds a supply dependency of oxygen consumption. The goal of this study was to determine whether a threshold value for oxygen delivery below which oxygen consumption becomes supply dependent can be identified in patients with normal, impaired, or absent liver function. Measurements were made in 34 surviving patients (group 1) and in 16 nonsurvivors with sepsis and postoperative liver graft failure (group 2). Hemodynamic measurements and blood samples were taken 10 minutes after introduction of anesthesia, 10 minutes after cross-clamping, and 10 minutes after reperfusion of the new liver. At these time points, we measured blood lactate, cardiac output, and arterial and mixed venous oxygen contents in order to calculate oxygen consumption and oxygen delivery. In both groups, cardiac output, oxygen delivery, and oxygen consumption decreased during the anhepatic phase and increased after unclamping of the inferior vena cave. Lactate increased in both groups during surgery, but was significantly higher in nonsurvivors (6.6 ± 0.4 mmol/L) than in survivors (4.6 ± 0.1 mmol/L) (P <.05). With similar changes for oxygen delivery and oxygen consumption during increased lactate levels we could not identify a clear supply dependency of oxygen consumption in survivors and nonsurvivors during liver transplantation. We conclude that the interpretation of blood lactate levels during circulatory shock can be biased due to a reduced lactate clearance in patients with impaired liver function, unrelated to the status of the relationship between oxygen delivery and consumption. Moreover, elevated blood lactate after liver transplantation predicts postoperative complications and death.     

Treatment options for osteoporosis in chronic liver disease patients requiring liver transplantation

As patient life expectancy rises after liver transplantation, osteoporosis becomes a significant contributor to morbidity and mortality. Patients who undergo liver transplant have an increased risk of bone fractures secondary to osteoporosis, relative to the general population. Risk factors (pre- and posttransplant) include treatment with steroids, alcohol abuse, smoking, poor nutritional status, immobility, reduced muscle mass, menopause, and hypogonadism. The role of cholestatic liver disease is well recognized, but as of yet, the underlying etiology is unknown. The role of immunosuppressants is also evident, but their exact contribution remains to be established. Currently, there are no established therapies for osteoporosis secondary to liver transplantation. Most of the therapeutic options have been extrapolated from usual treatment options for osteoporosis in the general population. It is reasonable to attempt to lower steroid dosages, especially with the availability of new and more potent immunosuppressants such as mycophenolate mofetil and tacrolimus. Potentially, high-risk patients could be identified early with BMD screening. Preventive measures could be instituted and patients could be monitored more closely for objective signs of osteoporosis, such as decline in BMD and early fractures. Calcium and vitamin D supplementation may be helpful in those with deficiencies or poor nutritional intake, as well as in women older than 25 years. The role of bisphosphonates and hormone replacement therapy remains equivocal as studies in transplant patients are currently lacking. Risk versus benefit must be weighed on an individual basis. Lifestyle measures should be instituted in all patients if possible.     

Antipyrine clearance and metabolite formation: the influence of liver volume and smoking

The influence of liver volume and cigarette smoking on antipyrine clearance and metabolite formation was studied in seventeen volunteers (eight smokers, nine non-smokers). Inter-test coefficient of variation of liver volume (as determined by ultrasound) was 6.3%. The mean antipyrine clearance was 49.3 +/- 18.3 ml min-1 and when normalized for liver volume 36.1 +/- 10.1 ml min-1 l-1. The antipyrine clearance per unit volume of liver was significantly higher in smokers (43.0 +/- 10.5 ml min-1 l-1), than in non-smokers (30.0 +/- 4.6 ml min-1 l-1) (P less than 0.01). No significant difference was found between the two groups as to the excreted amounts of 4-hydroxyantipyrine (OHA), norantipyrine (NORA), and 3-hydroxymethylantipyrine (HMA). Normalized for liver volume the mean clearances for production (Clm) of these metabolites were significantly higher in the group of smokers than in the group of non-smokers. The greatest change was observed for OHA formation. However, analysis of variance showed that the differences in the percentages of change of the mean Clm of these metabolites in the two groups are not significant.     

肝移植术后不同通气模式对血流动力学和氧动力学影响的差异

目的:肝移植患者术后常需短期机械通气辅助支持,对比分析不同机械通气方式对肝移植术后患者血流动力学及氧动力学指标的影响.方法:选择 2006-01/12于解放军第四五八医院行背驮式肝移植的患者11例,患者对实验及治疗方案均知情同意,且得到医院伦理道德委员会批准.经漂浮导管、桡动脉导管进行持续心输出量、肺动脉压及动脉血压监测.随机交替使用容量控制通气和同步间歇指令通气加压力支持通气,观察两种通气模式下血流动力学指标及氧动力学指标的变化.结果:11例患者全部进入结果分析.同步间歇指令通气加压力支持通气模式下患者的气道停顿压明显低于容量控制通气模式(P < 0.05),两组通气模式下患者其他血流动力学指标及氧动力学指标差异并无显著性意义(P > 0.05).结论:同步间歇指令通气加压力支持通气模式可作为肝移植术后患者呼吸支持和脱机过渡较为理想的通气模式.     

终末期肝病患者肝移植术前肺功能的改变

目的 探讨终末期肝病患者肝移植术前的肺功能情况.方法 选择在我院等待肝移植的154例终末期肝病患者为研究对象,测定其肺通气功能、小气道功能及弥散功能,并对其术前肺功能损害情况进行分析.结果 154例患者中出现肺功能异常140例(90.9%),140例弥散功能均减低;其次表现为限制性通气功能减低(42.8%,66/154)和小气道功能减低(37.7%,58/154),少数为阻塞性通气功能减低(28.6%,44/154).结论 终末期肝病患者肺功能异常较常见,肝移植术前肺功能检查对评价肺功能受损程度及对术后呼吸道管理具有一定参考价值.

Abstract：

Objective To assess the pulmonary function before liver transplantation in patients with end-stage liver disease. Methods One hundred and fifty-four patients with end-stage liver disease, who were waiting for liver transplantation in our hospital, were enrolled into the study. The pulmonary ventilation function,small airway function and diffusion capacity were measured and analyzed respectively. Results Among 154 subjects,140 (90. 9%, 140/154) patients had abnormal pulmonary function, shown as pulmonary diffusing capacity reduction;followed by restrictive ventilatory function reduction (42. 8% ,66/154) and small airway function reduction (37. 7%, 58/154 ), the least common manifestation was obstructive ventilatory function reduction (28.6 % ,44/154 ). Conclusion Abnormal pulmonary function in patients with end-stage liver disease is common, and the pulmonary function tests before liver transplantation has certain referential value for pulmonary function damage evaluation and postoperatively respiratory tract management.     

肝移植治疗脾功能亢进相关终末期肝病

背景：肝移植已成为治疗脾亢相关终末期肝病最理想的方法,行肝移植过程中保留脾脏,是否会出现移植后脾功能亢进相关问题,目前尚无统一的认识。目的：观察肝移植治疗脾功能亢进相关终末期肝病移植后脾功能的恢复过程。方法：纳入肝移植治疗终末期肝病患者63例,按有无脾功能亢进分为脾亢组和非脾亢组。比较两组移植后血小板计数、彩超测定脾脏上下径、厚度、门静脉直径及随访15个月的结果。结果与结论：纳入患者63例,死亡8例,55例进入结果分析。其中,肝移植并行切脾者4例,仅1例存活。脾亢组移植手术结束时血小板较移植前明显降低,移植后3d降至最低,而后逐渐上升,移植后7d明显增加（P〈0.05）,稳定至15个月;非脾亢组血小板移植后5d降至最低,17d达到移植前水平,两组比较差异均有显著性意义（P〈0.05）。移植后7d脾脏上下径及厚度开始明显减小（P〈0.05）,3个月脾静脉直径明显减小（P〈0.05）,至15个月稳定,患者均无门静脉高压曲张静脉破裂出血史。说明肝移植过程中若无绝对切除脾脏的适应症,应尽量保留脾脏。     

肝移植治疗脾功能亢进相关终末期肝病

背景:肝移植已成为治疗脾亢相关终末期肝病最理想的方法,行肝移植过程中保留脾脏,是否会出现移植后脾功能亢进相关问题,目前尚无统一的认识。目的:观察肝移植治疗脾功能亢进相关终末期肝病移植后脾功能的恢复过程。方法:纳入肝移植治疗终末期肝病患者63例,按有无脾功能亢进分为脾亢组和非脾亢组。比较两组移植后血小板计数、彩超测定脾脏上下径、厚度、门静脉直径及随访15个月的结果。结果与结论:纳入患者63例,死亡8例,55例进入结果分析。其中,肝移植并行切脾者4例,仅1例存活。脾亢组移植手术结束时血小板较移植前明显降低,移植后3d降至最低,而后逐渐上升,移植后7d明显增加(P<0.05),稳定至15个月;非脾亢组血小板移植后5d降至最低,17d达到移植前水平,两组比较差异均有显著性意义(P<0.05)。移植后7d脾脏上下径及厚度开始明显减小(P<0.05),3个月脾静脉直径明显减小(P<0.05),至15个月稳定,患者均无门静脉高压曲张静脉破裂出血史。说明肝移植过程中若无绝对切除脾脏的适应症,应尽量保留脾脏。     

Cyclosporine kinetics in renal transplantation

The pharmacokinetics of cyclosporine were evaluated in 41 recipients of a cadaveric renal transplant. Cyclosporine was taken by mouth (mean dose 14 mg/kg) on one study day and was intravenously infused over 2 hours (mean dose 4.7 mg/kg) on the next study day. Cyclosporine was extracted from whole blood and analyzed by HPLC. After intravenous infusion, cyclosporine exhibited multicompartmental behavior. The mean (+/- SD) terminal disposition rate constant was 0.065 +/- 0.036 hours-1 and the harmonic mean t 1/2 was 10.7 hours. The harmonic mean total body clearance of cyclosporine was 5.73 ml/min/kg and the mean apparent volume of distribution was 4.5 +/- 3.6 L/kg. The absorption of oral cyclosporine was slow and incomplete. Peak blood cyclosporine concentrations (means = 1,103 ng/ml) were reached between 1 and 8 hours after oral dosing (means = 4 hours). The mean relative bioavailability was 27.6% +/- 20%. Oral bioavailability was less than 10% in 17% of our subjects. The absorption and clearance of cyclosporine were highly variable. We conclude that the variability in the kinetics of cyclosporine makes trough blood level monitoring essential in the management of patients who receive renal transplants.     

Antipyrine clearance in pneumonia

Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was 31.4 +/- 7.6 ml/min (X +/- SD). Fourteen and 28 days later during convalescence, clearance values were higher (47.8 +/- 18.9 and 49.2 +/- 15.0 ml/min, respectively). We conclude that microsomal hepatic drug metabolism in adults is impaired during pneumonia.     

氧疗对肝移植围手术期患者肺动脉压及氧动力学的影响及护理

目的 探讨背驮式肝移植围手术期氧疗对患者肺动脉压和氧动力学的影响及总结给氧护理要点。方法 2006年6月～2007年10月对10例肝移植患者实施氧疗，在病情稳定时停用呼吸机，观察患者在停止氧疗60min前后血流动力学变化情况。结果 患者吸氧期间比停止吸氧后60min平均肺动脉压（mPAP）明显降低（P〈0．01），氧分压（PaO2）明显升高（P〈0．001）。结论 背驮式肝移植围手术期吸氧可降低患者肺动脉压和提高PaO2。给氧过程应调节好氧流量，并观察用氧后病情的变化。     

Indications and optimal terms of liver transplantation in chronic diffuse hepatic disease

Patients with chronic diffuse hepatic disease (CDHD) take a great part in structure of morbidity of adult population. Problem of treatment of patients with hepatic cirrhosis (HC) is still very important. Main contingent of these patients who need hepar transplantation consists from HC patients with various ethiology, cholestatic diseases, inborn metabolism disturbances and hepatic tumors. At present in the world there is a tendency to early performing of operation while decompensation of other organs and systems still do not exist. When there is diagnosis of inborn metabolism disturbance indication to ortotopic transplantation of hepar (OTH) are put at the same time with verification of diagnosis. In case of HC urgency of OTH depends on stage of disease (system assessment of severity of hepatic insufficiency by 'hild-Pugh, MELD), response of patients on therapy and frequency of hospitalizing. Performance of OTH makes possible to prolongate of patients' life and significantly improve its quality.     

成人间活体肝移植治疗终末期肝病

目的探讨成人间活体肝移植治疗终末期肝病的方法及技术要点。方法回顾性分析2000年9月—2004年9月成人间活体肝移植9例患者的临床资料。其中,左半肝(第、、段,包括肝中静脉)移植3例,右半肝(第、、、段,不包括肝中静脉)移植6例。结果9例供体无手术死亡,平均手术时间(6.2±1.4)h;术中出血300~1200ml;术后胆漏1例,切口脂肪液化1例;随访6~12个月,无远期并发症,全部于术后1~2个月恢复工作。受体手术时间5~11h;采用改良方法重建移植肝流出道、显微技术重建肝动脉、端端吻合重建胆道;术中出血800~7000ml;移植物冷缺血时间(1.9±0.5)h;无肝期时间(98±26)min;移植物重量与受体体重比为(1.20±0.26)%。受体术后并发腹腔内局限性胆漏1例;死亡1例,长期存活8例。结论成人间活体肝移植是解决供肝短缺、治疗终末期肝病的有效方法,同时能相对保证供体的安全;管道重建是手术成功的关键。     

终末期肝病模型评分的完善与肝移植预后

终末期肝病模型（MELD）评分作为一种预测终末期肝病患者待肝期内短期死亡危险新的评价系统,相对于Child．Turcutte—Pugh（CTP）评分和美国器官共享网络（UNOS）评分具有更加客观、准确的优点。然而,其缺陷与不足经过众多的临床研究逐渐加以证实。本文就国内外学者对MELD评分系统的争论与完善以及MELD评分是否同样能应用于对肝移植术后的存活起到准确预测效果进行综述。