猪尾导管连接化疗药盒实现肝脏肿瘤多重化疗的可行性研究

目的 探讨使用猪尾造影导管与单一化疗药盒连接实现肝脏肿瘤多重化疗的可行性及初步疗效。资料与方法 对30例晚期肝脏恶性肿瘤患者采用经股动脉穿刺、腹腔动脉内植入猪尾导管与皮下埋置药盒并序贯化疗，统计手术成功率、并发症及临床疗效。结果 30例手术全部成功，发生切口延迟愈合1例。术后随访28例，经影像学复查对比，病变缩小7例，稳定12例，进展9例。随访期间12例患者死亡，术后生存期42d-10个月，中位生存期6个月。另外16例患者至今存活，已达术后2-16个月。结论 采用猪尾造影导管置于腹腔动脉并与化疗药盒相连接，能够对晚期肝脏恶性肿瘤实现多重化疗，技术上简单可行，并发症少，初步疗效令人满意。     

Effect of portal infusion of hypertonic saline on neurons in the dorsal motor nucleus of the vagus in the rat

Effects of hepatoportal osmo-receptive (or sodium-receptive) afferents on neurons within the dorsal motor nucleus of the vagus (DMV) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Responses of 56 spontaneously active neurons to antidromic stimulation of the ventral trunk of the subdiaphragmatic vagus were recorded in the left DMV. Among them, 35 neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve (inhibitory neurons), except two neurons that were slightly excited. Effects of portal infusion of 3.6% NaCl were examined on 26 inhibitory neurons. Sixteen neurons increased their discharge rates and one neuron decreased its discharge rate in response to portal infusion of hypertonic saline. Thirty-five DMV neurons responded to electrical stimulation of the dorsal trunk of the subdiaphragmatic vagus were inhibited by electrical stimulation of the hepatic branch of the vagus. Four neurons were excited by this stimulation. Relatively smaller number of neurons (5 out of 22 inhibitory neurons) increased their discharge rates in response to portal infusion of hypertonic saline. In conclusion, the response of DMV neuron observed in this experiment was characterized by increasing the frequency of spike discharges in response to portal infusion of hypertonic saline. However, these neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve. These results suggest that the hepatoportal osmoreceptive afferents may be conveyed to the DMV via inhibitory synapses.     

Percutaneous aspiration and ethanol sclerotherapy of symptomatic hepatic cysts

Nineteen patients with 49 symptomatic non-neoplastic non-parasitic simple hepatic cysts were subjected to ultrasonographically guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. Small cysts were treated twice, the large ones three times at the same sitting. The volume of alcohol per injection varied from 20 to 100 ml, depending on the size of the cyst. A cure was usually achieved with one ethanol sclerotherapy treatment. Only minor side effects such as transient pain and temperature elevation occurred. Forty-seven of the 49 cysts could be treated adequately, and did not recur during a follow-up period af 12–40 months. The results indicate that aspiration an and ethanol sclerotherapy is the treatment of choice in patients with symptomatic non-neoplastic simple hepatic cysts or polycystic liver disease. Correspondence to: A. Leinonen     

Profile of etodolac: Pharmacokinetic evaluation in special populations

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (C_max) averaged 15.9 g/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t_1/2) was 6 to 7 hours. There were no apparent differences in C_max, the time at which C_max occurred (t_max), area under the serum concentration/time curve (AUC_0–24), or t_1/2 between groups of young men (n=20), elderly men (n=24), and elderly men with osteoarthritis (n=20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in C_max, t_max, AUC_0–24 or t_1/2 between groups of normal subjects (n=10) and patients with mild-to-moderate renal impairment (n=10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p<0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter t_max in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.Die pharmakokinetischen Parameter von Etodolac, einem neuen, nichtsteroidalen entzündungshemmenden Therapeutikum, wurden an gesunden Probanden, an Patienten mit Leber- und Nierenleiden und an Älteren Patienten untersucht. Orale Etodolac Gaben wurden von den 28 gesunden Probanden schnell resorbiert. Nach einer einmaligen Dosis von 200 mg betrug nach 1,2 Stunden die durchschnittliche maximum Serumkonzentration (C_max) 15,9 g/ml, wobei mehr als 99% des Medikaments an das Serumprotein gebunden war. Clearance erfolgte hauptsÄchlich über die Niere. Die mittlere Eliminationshalbwertszeit (t_1/2) variierte zwischen 6 und 7 Stunden. In Bezug auf C_max, dem Zeitpunkt an dem C_max auftrat (t_max), FlÄche unter der Serumkonzentrationskurve (AUC_0–24) und t_1/2 wurden keine offensichtliche Unterschiede festgestellt zwischen der Gruppe junger MÄnnern (n=20), Älterer MÄnner (n=24) und Älteren MÄnnern mit Osteoarthritis (n=20) nach einer einmaligen Etodolac-Gabe oder nach 7 tÄgiger subchronischer Dosierung. Es bestanden auch keine Anzeichen einer Kumulation. ZusÄtzlich wurden auch keine Unterschiede in C_max, t_max, AUC_0–24 und t_1/2 zwischen der Gruppe gesunder Probanden (n=10) und der Patientengruppe mit leichten bis mÄigen NierenfunktionsschÄden (n=10) beobachtet. Im mittleren Serumspiegel des nicht gebundenen Medikaments in Patienten im Endstadium der Nierenerkrankung, die mit Langzeitdialyse behandelt wurden, konnte kein Unterschied im Vergleich zu gesunden Probanden festgestellt werden, obwohl der mittlere Serumspiegel für proteingebundenes Etodolac in den Patienten etwas niedriger lag als in gesunden Probanden. Der einzige signifikante Unterschied (p<0.05) zwischen Patienten mit stabilisierter Leberzirrhose und gleichaltrigen Probanden war eine etwas kürzere t_max in den Zirrhosepatienten (1,1 versus 1,4 Stunden). Diese Ergebnisse beweisen, dakeine Notwendigkeit vorliegt, die Etodolac-Dosierung für diese Risikogruppen zu modifizieren.Se comparó la farmacocinética de etodolac, un fármaco antiinflamatorio no esteroide nuevo, en sujetos normales y en pacientes con enfermedad renal y hepática y en pacientes ancianos. Etodolac administrado por vía oral a 28 sujetos normales fue rápidamente absorbido. A las 1,2 horas siguientes a la administración de una dosis de 200 mg, la concentración sérica máxima (C_max) alcanzó un promedio de 15,9 g/ml, con más del 99% del fármaco unido a la proteína sérica. La eliminación fue principalmente hepática. La vida media (t_1/2) fue 6–7 horas. No se observaron diferencias en C_max, en el tiempo en el cual se produjo C_max, en el área bajo la curva de concentración sérica/tiempo (ABC_0–24) ni en t_1/2 entre los grupos de hombres jóvenes (n=20), de hombres ancianos (n=24) y de hombres ancianos con osteoartritis (n=20), después de la administración de una dosis Única o después de 7 días de administración subcrónica de etodolac. Además, no hubo evidencia de acumulación. Tampoco se registraron diferencias en C_max, t_max, ABC_0–24 o t_1/2 entre los grupos de sujetos normales (n=10) y los pacientes con insuficiencia renal leve a moderada (n=10). Los pacientes con nefropatía terminal que estaban recibiendo hemodiálisis crónica tuvieron las mismas concentraciones séricas medias de fármaco libre que los sujetos normales, a pesar de que las concentraciones séricas medias de etodolac unido a proteina fueron levemente inferiores que en los sujetos normales. La Única diferencia significativa (p<0,05) entre los pacientes con cirrosis hepática estable y los sujetos normales de edad similar fue t_max ligeramente inferior en los sujetos cirróticos (1,1 vs 1,4 horas). Estos hallazgos sugieren que no es necesario modificar la dosis de etodolac para su uso en estos grupos de alto riesgo.La pharmacocinétique de l'étodolac, un anti-inflammatoire non stéroÏdien, a été comparé chez des sujets normaux et des patients présentant des affections rénales et hépatiques, et chez des malades âgés. Chez 28 sujets normaux, la résorption d'étodolac administré par voie orale a été rapide. Dès 1,2 heure suivant l'absorption d'une dose de 200 mg, la moyenne des concentration sériques maximales (C_max) était de 15,9 g/ml, plus de 99% pour cent du médicament étant liés aux protéines sériques. La clairance se fait surtout par voie hépatique. La demivie moyenne (t_1/2) était de 6 à 7 heures. Il n'y avait aucune différence apparente en ce qui concerne C_max, le temps d'apparition de C_max (t_max), l'aire sous la courbe concentration sérique/temps (AUC_0–24) ni t_1/2 entre les groupes d'hommes jeunes (n=20), d'hommes âgés (n=24), et d'hommes âgés atteints d'arthrose (n=20) à la suite d'une dose unique d'étodolac ou après 7 jours d'administration subchronique. De plus, aucune accumulation n'a été constatée. D'autre part, aucune différence de C_max, t_max, AUC_0–24 ni t_1/2 n'a été notée entre les groupes de sujets normaux (n=10) et de malades présentent des altérations rénales légères ou modérées (n=10). Les malades en insuffisance rénale terminale soumis à l'hémodialyse chronique ont présenté une concentration sérique moyenne de médicament libre analogue à celle des sujets normaux, mais la moyenne des taux sériques d'étodolac lié aux protéines était légèrement inférieure à celle observée chez les sujets normaux. La seule différence significative (p<0.05) entre les malades présentant une cirrhose hépatique stable et des sujets normaux appariés quant à l'âge était représentée par un t_max légèrement plus court chez les cirrhotiques (1,1 contre 1,4 heure). Ces données permettent de penser qu'aucune modification posologique de l'étodolac ne serait nécessaire pour ces groupes à haut risque.La farmacocinetica dell'etodolac, un nuovo farmaco anti-infiammatorio non steroidale è stata messa a confronto in gruppi normali, in pazienti affetti da malattia rénale ed epatica ed in pazienti anziani. In 28 soggetti normali l'etodolac somministrato oralmente è stato rapidamente assorbito. Dopo 1.2 ore dall'ingestione di una dose di 200 mg la massima concentrazione di siero (Cmax) presentava un valore medio di 15,9 mg/ml, con più del 99% del farmaco legato alla proteina del siero. La clearance era soprattutto a livello epatico. L'emivita media (t1/2) era di 6–7 ore. Non vi sono state evidenti differenze medie nei valori di concentrazione massima (Cmax), tempo (Tmax) al quale si aveva la Cmax, nella curva dell'area sotto concentrazione di siero/tempo (AUCo-24) oppure nel valore dell'emivita media (t1/2) tra gruppi di uomini giovani (n=20), uomini anziani (n=24) e anziani con osteoartrite (n=20), dopo una dose singola di etodolac o dopo 7 giorni di somministrazione subcronica. Inoltre non vi sono stati segni di accumulo. Per di più non vi sono state differenze nei valori di Cmax, tmax, AUCo-24 o t1/2 tra gruppi di soggetti normali (n=10) e pazienti con alterazioni renali da leggere a moderate (n=10). I pazienti con malattia renale all'ultimo stadio che ricevevano emodialisi cronica presentavano la stessa concentrazione media di siero di farmaco libero dei soggetti normali, anche se i livelli medi di siero di etodolac legato alle proteine erano leggermente inferiori a quelli di soggetti normali. L'unica differenza significativa (p<0.05) tra pazienti con cirrosi epatica stabile e soggetti normali della stessa età era nei tmax leggermente più brevi nei soggetti cirrotici (1.1. contro 1.4 ore). Questi risultati suggeriscono che nessuna alterazione del dosaggio di etodolac sarebbe necessaria in questi gruppi ad alto rischio.     

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (H _{O 2}) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. H _{O 2} did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.(Masaki E, Yasuda N, Tanifuji Y et al.: Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs. J Anesth 3: 118–122, 1989)     

215例急性和亚急性重型肝炎临床特征对比性分析

目的进一步了解急性重型和亚急性重型肝炎（简称急重和亚急重）患者的临床特征，以及它们之间的异同。方法收集和整理215例急重和亚急重住院患者的临床资料，使用X^2检验、t检验、回归分析等方法进行相关的统计学分析。结果①乙型肝炎病毒感染仍是急重和亚急重型肝炎的主要病因，均占30％以上。抗结核药物是药物性急重和亚急重肝炎的首要原因；②急重和亚急重患者肝性脑病发生率分别为78．13％和43．05％，差异有统计学意义（P〈0．001）；③急重患者的平均凝血酶原活动度低于20％，而亚急重患者平均凝血酶原活动度低于30％；④急重患者发生率前三位的并发症分别为肝性脑病、电解质紊乱及脑水肿；而亚急重则分别为腹水、电解质紊乱及肝性脑病；⑤急重和亚急重患者的病死率与病情最重时PT、WBC及中性粒细胞比例均呈正相关，而与PTA、TC均呈负相关；亚急重还与病情最重时TB、BLA及CRE呈正相关，与CHE、TG、PLT、ALB呈负相关。结论①急重和亚急重患者无论在好发年龄、肝性脑病发生率、肝性脑病出现时间，还是在凝血功能异常、预后与实验室指标等方面差异较大，属两个独立的疾病；②对于无肝性脑病的急重和亚急重患者，严重的凝血功能异常是一个重要的灵敏和特异性指标。     

Differences between human and mouse alpha‐fetoprotein expression during early development

Alpha‐fetoprotein (AFP) is the major serum protein during development. AFP is one of the earliest proteins to be synthesised by the embryonic liver. The synthesis of AFP decreases dramatically after birth and only trace amounts are expressed in the adult liver. The tissue distribution of AFP in early human embryogenesis has not been defined. We have studied the expression pattern of AFP mRNA in human and mouse embryos by in situ hybridisation. In humans, AFP is expressed in the hepatic diverticulum at 26 d postovulation as it differentiates from the foregut endoderm (i.e. in the most primitive hepatocytes). It is also expressed in the endoderm of the gastrointestinal tract and in the yolk sac at this age. AFP is subsequently expressed in the mesonephros and transiently in the developing pancreas. In the mouse, no expression of AFP was observed in the mesonephros but other sites of expression were similar. Thus AFP has a distinct temporospatial expression pattern during the embryonic period and this differs between human and mouse species. It is interesting that AFP is expressed by tumours such as primitive gastrointestinal, renal cell and pancreatic tumours as well as those of hepatocyte origin. This distribution reflects the sites of AFP expression during development.     

大鼠肝抑素纯化及其生物活性的检测

用ＳｅｐｈａｄｅｃＧ－５凝胶过滤层析法，进一步纯化具肝抑素生物活性的大鼠肝蛋白质粗提品，以分离的大鼠再生肝的肝细胞为靶细胞，体外检测各洗脱峰浓缩物对肝细胞增殖的制率结果证明，Ｅ峰浓缩物的抑制作用最强，其活性比为粗提品的２０倍，ＳＤＳ聚丙烯酰胺电泳图及蛋白质迁移率测定表明，该浓缩物的主要成分为分子量１３．５ｋＤ的多肽。本研究对大鼠肝抑素做了初步纯化，验证了该物质在肝再生中起重要调控作用的生物效应。     

Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe

A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Small and medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42: 662–666, 1992.