Development of Bile Acid Metabolism in Neonates during Perinatal Period Part 1: Bile acid levels in sera of Mothers, fetuses and neonates

To eluidate the development of bile acid metabolism in neonates during the perinatal period, the present author measured the bile acid levels in amniotic fludis and sera of mothers, umbilical cords and neonates. The subjects were 166 samples of amniotic fluids and sera of mothers, umbilical cords and neonates (at 2 days, 1 week, 2 weeks, 3 weeks and 4 weeks of life). The bile acid levels in amniotic fluids were measured by radioimmunoassay (RIA) and the levels in sear were measured by high-performance liquid chromatography (HPLC). Total chenodeoxycholic acid (unconjugated chenodeoxycholic acid (free CDC), glycochenodeoxycholic acid (GCDCA) and taurochenodeoxycholi acid (TCDCA)) were predominant in amniotic fluids and sera of early neonates before 1 week of life. Total bile acid (TBA) levels gradually increased for 4 weeks after birth. The mean glycine to taurine (G/T) conjugation ratio of bile acids of mothers was higher than that of umbilical cords and early neonates before 1 week of life. The mean conjugation rate of bile acids in sera of neonates at 1 week after birth was higher than that of mothers and umbilical cords. There were distinct individualities in TBA levels, the presene of lithocholic acid (LCA), total cholic acid to total chenodeoxycholic acid (CA/CDCA) ratio and G/T ratio at the same age, and in bile acid patterns in the same pair of mothers and umbilical cords.     

Infantile Liver Giant Cells: Immunohistological Study of Their Proliferative State and Possible Mechanisms of Formation

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1.22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non–giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation. Received May 6, 1998; accepted July 23, 1998.     

Menetrier'S Disease in Children: Report of a Case and Review of the Pediatric Literature

A case of Menetrier's disease (giant hyperplasia of the gastric mucosa) in a 2-day-old infant is presented. The lesion was primarily confined to the gastric antrum. It resulted in outlet obstruction and necessitated partial gastrectomy. The pertinent literature is critically evaluated, and probably only 2 of the 9 previously reported cases of Menetrier's disease in children qualify fully.     

Liver retransplantation with external biliary diversion for progressive familial intrahepatic cholestasis type 1: a case report

Abstract:  PFIC1, originally described as "Byler disease," is characterized by cholestatic feature and chronic diarrhea. Many patients require LT for the cure, but intractable diarrhea and prolonged growth retardation after LT are serious complications limiting the ultimate outcome of LT for this disease. EBD has recently been shown to be a promising and effective treatment. Recently, we successfully treated a five-yr-old boy with PFIC1 employing EBD after re-transplantation. The patient received LDLT at the age of one yr. Six months after initial transplantation, he developed repeated attacks and diarrhea followed by the development of liver dysfunction and ascites. Liver biopsy at three yr after LDLT revealed the features of chronic graft rejection. With a diagnosis of chronic graft rejection with liver failure, we performed a repeat LDLT with EBD in which the jejunal loop used for hepaticojejunostomy was taken out of the body surface through the abdominal wall. Ten months after surgery, he is doing well, having no attack of diarrhea.     

Syndromatic Paucity of Interlobular Bile Ducts: Hepatic Histopathology of the Early and Endstage Liver

Morphologic findings of the liver in syndromatic paucity of intrahepatic bile ducts (SPIHBD) during infancy include paucity of interlobular bile ducts, features of “giant cell hepatitis,” dilated lymphatics and veins in the portal tract, perisinusoidal fibrosis, and bile duct epithelial changes with a concentric layering of mesenchymal cells around bile ducts reminiscent of renal dysplasia. The latter change is characteristic of SPIHBD. Although the disease is characterized by paucity of bile ducts, morphometric studies show paucity of interlobular bile ducts in less than half of the patients during infancy. Reduced numbers of portal tracts and increased percentage of portal tracts devoid of bile ducts are more constant findings. It was impossible to predict from the early biopsy which patients would develop more severe portal fibrosis. Later in the disease portal fibrosis is variable and unevenly distributed, being more severe near the hilum regardless of the prior performance of a Kasai-type operation or the state of patency of the extrahepatic bile ducts. Hypoplasia of the extrahepatic bile ducts is the usual finding in SPIHBD, but if atresia of extrahepatic bile ducts is associated with intrahepatic paucity of bile ducts, the hepatic histopathology is that of PIHBD. Recognition of PIHBD would avoid unwarranted surgical procedures.     

Histologic Features of the Liver in Type Ia Glycogen Storage Disease: Comparative Study between Different Age Groups and Consecutive Biopsies

In this report, the histologic criteria for the diagnosis of type Ia glycogen storage disease (GSD) in a wide age range were studied. Liver needle biopsies of 44 patients with type Ia GSD confirmed by enzyme analysis were re-evaluated and compared. Fatty change, nuclear hyperglycogenation (NH), and fibrosis were examined and graded. The second biopsies of 14 patients were also evaluated and compared with the first ones. The patients were grouped according to age: group I: <1 year (18 cases), group II: 1–5 years (19 cases), group III: >5 years (7 cases). A mosaic pattern was detected in all biopsies. The amount of fibrosis in group I was less than that in the other two groups. The fatty change in group I was more prominent. There was not much difference in the amount of NH between age groups. In comparing the two different biopsies of 14 patients, the amount of fibrosis was found to be increased in 7 cases. NH was also increased in a different group of 7 patients. These findings were both statistically significant. The amount of fatty change was minimal in most of the cases. Fibrosis is associated with types III, IV, VI, IX, and X GSD. Our results support previous studies stating that fibrosis may also be present and varies in extent in type I GSD. Fatty change as large lipid vacuoles and NH may not be seen in many cases of type I GSD. Therefore, histologic criteria for the diagnosis of GSD may not be specific, and enzyme analysis should be performed. Received March 14, 2001; accepted February 8, 2002.     

单纯性肥胖患儿非酒精性脂肪肝病与胰岛素抵抗

目的探讨单纯性肥胖(肥胖)儿童发生非酒精性脂肪肝病(NAFLD)的情况及与胰岛素抵抗(IR)、血脂、体质量指数(BMI)、腰臀比(WHR)的关系。方法选择肥胖儿童90例,年龄2.5～14.3岁。其中NAFLD 24例(NAFLD组),无NAFLD 66例(无NAFLD组)。另选35例年龄、性别与其相匹配的健康儿童为健康对照组。清晨空腹测量其体质量、身高、腰围和臀围,计算BMI和WHR,同时静脉采血检测其血清胰岛素(FINS)、糖(FBG)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和ALT、AST等,计算稳态模型胰岛素抵抗指数(HOMA-IR=FINS×FBG/22.5),并做肝胆等部位超声检查。结果 NAFLD占肥胖儿童的26.67%;NAFLD组儿童BMI、WHR最高,其次为无NAFLD组,差异均有统计学意义(Pa<0.001);3组儿童FINS和HOMA-IR值差异均有统计学意义(Pa<0.001),NAFLD组最高,其次为无NAFLD组,均明显高于健康对照组,但FBG无明显差异;NAFLD组血清TG、LDL-C和TC水平明显高于无NAFLD组和健康对照组(Pa<0.01);HOMA-IR值与BMI、WHR、血TG、LDL-C呈正相关(r=0.402、0.256、0.239、0.180,P=0.000、0.004、0.008、0.046);BMI、WHR诊断NAFLD的受试者工作特征(ROC)曲线下面积分别为0.805和0.765(Pa=0.000)。结论肥胖儿童NAFLD的发生与IR,血TG、LDL-C、TC升高及BMI、WHR增高关系密切,BMI、WHR对儿童肥胖NAFLD具有一定的诊断价值。控制体质量,减少腰围,可减轻IR,阻止NAFLD的发生、发展。     

Congenital Polyvalvular Disease: A Review

This review outlines the morphologic and pathogenetic characteristics of congenital polyvalvular disease. Two cases are used for exemplification. The macroscopic and histologic features of the valves as well as associated cardiac lesions and clinical syndromes are described, followed by a discussion of morphogenesis of this disease.     

PERSPECTIVES IN PEDIATRIC PATHOLOGY: Progressive Familial Intrahepatic Cholestasis: A Personal Perspective

Progressive familial intrahepatic cholestasis (PFIC), originally described as “Byler disease” in an Amish kindred, has been distinguished from other forms of cholestatic liver disease in childhood by clinical findings, clinical–laboratory observations, and morphologic studies in biopsy, hepatectomy, and autopsy specimens. Correlation with genetic analyses has permitted both more precise definition of PFIC and distinctions within PFIC. Two types of PFIC now are recognized: PFIC-1, resulting from mutations in a gene called FIC1 (familial intrahepatic cholestasis, type 1), and PFIC-2, resulting from mutations in a gene called BSEP (bile salt export pump). Other forms of PFIC may yet be identified. The roles of FIC1 and BSEP in the secretion of bile acids into bile and in the post-secretory modification of bile are under study. Received September 1, 1999; accepted October 16, 1999.     

婴儿肠道菌群与分娩方式、喂养方式及胆汁淤积性肝病的关系

目的分析分娩方式和喂养方式对健康婴儿肠道菌群的影响,探讨肠道相关分子微生态在胆汁淤积性肝病中的作用及意义。方法收集37例健康婴儿(其中阴道分娩21例,剖宫产16例;母乳喂养15例,人工喂养22例)及84例胆汁淤积性肝病婴儿粪便,提取粪便中细菌DNA并测量A260值;应用实时荧光定量PCR反应测定粪便中双歧杆菌、乳酸杆菌及大肠杆菌3种代表菌的数量。结果阴道分娩婴儿与剖宫产婴儿比较,母乳喂养婴儿与人工喂养婴儿比较,粪便标本中细菌DNA A260值和3种代表菌数量差异均无统计学意义(Pa>0.05)。健康对照组与胆汁淤积性肝病组粪便标本中细菌的DNA A260值分别为(1.94±0.47)g.L-1和(0.40±0.09)g.L-1,2组比较差异有统计学意义(t=8.91,P=0.00);健康对照组与胆汁淤积性肝病组3种细菌数(lg拷贝数/g湿便)的对数值比较差异均有统计学意义(双歧杆菌9.49±0.59 vs 7.68±0.57;t=15.96,P=0.00;乳酸杆菌8.58±0.32 vs 8.16±0.70;t=3.46,P=0.00;大肠杆菌6.87±0.67 vs 7.26±0.86;t=-2.41,P=0.02)。结论不同的分娩方式、喂养方式对婴儿期肠道菌群无影响;胆汁淤积性肝病婴儿肠道菌群与健康婴儿不同,粪便中细菌总量减少,双歧杆菌及乳酸杆菌数量明显减少,大肠杆菌的数量则明显增多,提示肠道菌群失调与婴儿胆汁淤积性肝病的发生、发展有一定关系。     

急性淋巴细胞白血病患儿化疗肝损伤相关因素及治疗效果

目的探讨小儿急性淋巴细胞白血病(ALL)化疗肝损伤的发生率、相关因素及预后,并观察保肝药物的临床疗效。方法回顾性分析61例ALL患儿,统计其化疗肝损伤总体发生率及肝损伤程度构成比,不同性别、年龄、危险度分型、化疗阶段化疗肝损伤发生率及肝损伤程度的异同,化疗时存在感染及输血的患儿化疗肝损伤发生率的差别,化疗肝损伤后应用保肝药与未用保肝药物对预后的影响有无差异,各组差异比较采用χ2检验。结果 61例患儿中发生化疗肝损伤49例,其发生率为80%。其中轻度肝损伤占23%,中度肝损伤占39%,重度肝损伤占18%。不同性别、年龄、危险度分型化疗肝损伤发生率比较,差异无统计学意义(Pa>0.05)。不同化疗阶段肝损伤发生率差异有统计学意义(P<0.05),巩固治疗期较其他化疗阶段化疗肝损伤发生率明显偏低(P<0.005)。化疗中发生感染、输血可增高化疗肝损伤发生率(Pa<0.05)。应用保肝药与未用保肝药对化疗肝损伤预后的影响差异有统计学意义(P<0.05)。结论小儿ALL化疗肝损伤发生率较高。化疗肝损伤的发生率与患儿年龄、性别、危险度分型等因素无显著相关。化疗并感染是化疗肝损伤的高危因素,化疗输血也与化疗肝损伤相关,应用保肝药可显著提高化疗肝损伤的治愈率。     

Defects of the central nervous system in Finland: III. Disease and drugs in pregnancy

The matched pair system of the Finnish Register of Congenital Malformations was used to search for association between defects of the central nervous system (CNS), and maternal diseases and/or drug consumption during pregnancy. The study material consisted of 710 cases with CNS defects and their controls. Significant associations were found for the following conditions: influenza, threatened abortion, depressive state, toxemia of pregnancy, diabetic mothers, and for the consumption of the following drugs: salicylates, pyrazolones/anilines, euphoristic analgesics, sympathomimetics, barbiturates, and cough medicines. 259 cases with polydactyly and their controls were also compared, with a view to demonstrating what biases might be introduced by the case-control method. After utilizing the possibilities of this design for examining the above mentioned significant associations, the factors to be seriously considered were reduced to the following ones: influenza, depressive state, toxemia of pregnancy, diabetic mothers and cough medicines.     

Castleman's Disease in Childhood and Adolescence: Report of a Case and Review of Literature

Cases of Castleman's disease, a disorder affecting lymphoid organs, which is largely benign in nature, are rare in the pediatric period. This report describes one such case, occurring in a 5-year-old boy, and reviews the published cases of Castleman's disease presenting in childhood and adolescence. The purpose of this review was to compare the features of this disease process in children with the much fuller documentation that exists for Castleman's disease in adults. In children, Castleman's disease usually presents in the abdomen, chest (mediastinum or lung hilum), or neck and may be either asymptomatic or present with systemic symptoms of which anemia and fever are the most frequent. The disease is curable by surgical excision.