Investigation of serum bile acids; seven patients with Alagille syndrome

To clarify whether an abnormal bile acid pattern has a role in the pathogenesis of Alagille syndrome, we compared serum bile acid patterns in seven with Alagille syndrome with those of patients with congenital biliary atresia (CBA), neonatal hepatitis (NH) and normal infants.Of the seven patients with Alagille syndrome, four patients were younger and three were older than 1 year. The mean total serum bile acid level in the infants was higher than in older subjects. There was a dissociation between the levels of serum total bile acid and bilirubin in three of the seven cases. The mean total bile acid levels in serum were in the following decreasing order: CBA, Alagille syndrome, NH and controls.The ratio of cholate to chenodeoxycholate in the younger patients with Alagille syndrome was significantly higher than CBA (P<0.001). However, no specific bile acid pattern was found in Alagille syndrome by high-performance liquid chromatography (HPLC).Abbreviations TBA total bile acids - FBA free bile acids - conj-BA conjugated bile acids - C/CDC ratio of cholate to chenodeoxycholate - G/T ratio of glycine conjugates to taurine conjugates - GPT glutamic pyruvic transaminase - CBA congenital biliary atresia - NH neonatal hepatitis - HPLC high performance liquid chromatography - GCA glycocholate - TCA taurocholate - GCDCA glycochenodeoxycholate - TCDCA taurochenodeoxycholate     

Studies on the conjugating activity of bile acids in children

The unconjugated and conjugated bile acid levels in sera of 98 normal children and nine normal adults were measured by high performance liquid chromatography. The results showed that the mean total bile acid level was high, 11.0 +/- 8.7 mumol/liter (1 SD) during the neonatal period (0-4 wk) and then gradually decreased with age. The ratio of the concentration of conjugated bile acids to total bile acids in serum was as high as 90% or more in infants under 1 yr of age and slowly decreased with age. The mean ratio of cholic acid to chenodeoxycholic acid was high (1.7 +/- 1.1) during the neonatal period but decreased after 3 months to the adult level (0.4 +/- 0.2). The mean ratio of glycine conjugated bile acids to taurine conjugated bile acids was 3.0 +/- 3.1 during the neonatal period and the ratio during the 1st month of life was significantly lower than that after that period with little further change at any age. The mean ratio of the concentration of secondary bile acids to primary bile acids showed significantly lower values in infants less than 1 yr of age. The main bile acid was glycocholic acid in the neonatal period but after 1-3 months glycochenodeoxycholic acid predominated. With age, the serum bile acid pattern which was characteristic in infancy gradually approached that of adults.     

Sulfated and nonsulfated bile acids in urine of patients with biliary atresia: analysis of bile acids by high-performance liquid chromatography

To elucidate urinary bile acid patterns in patients with biliary atresia (BA), 15 sulfated and nonsulfated bile acids in urine were separately measured by high-performance liquid chromatography. This relatively simple technique for fluorescence detection utilizes the enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) to reveal urinary bile acid patterns. By this method, recovery rates of sulfated and nonsulfated bile acids in urine were satisfactory, and this analysis was shown to be applicable to clinical situations. In 10 patients with BA, the mean level of total bile acids in urine (23.35 +/- 18.51 mumol/day) was seven times higher than the mean level in eight normal infants (3.05 +/- 2.05 mumol/day). In the infants with BA, the mean level of total sulfated bile acids was about half of the total bile acid level. The main components of urinary nonsulfated bile acids in BA were glycocholic acid (6.21 +/- 5.55 mumol/day) and taurocholic acid (2.28 +/- 1.33 mumol/day), whereas the main components of the urinary sulfated bile acids were glycochenodeoxycholic acid (4.58 +/- 6.97 mumol/day) and taurochenodeoxycholic acid (3.67 +/- 3.54 mumol/day). Chenodeoxycholic acid, which is relatively toxic to the liver, may more easily be conjugated with sulfate and, hence, excreted into urine at a faster rate than cholic acid. Marked individual variations in urinary bile acid patterns were observed not only in BA patients but also in normal controls.     

Pancreatic Hormone Changes in Infantile Obstructive jaundice

Metabolic disturbances of pancreatic hormones in obstructive jaundice in infancy were evaluated experimentally and clinically. In our experimental study, using young rats, the level of plasma insulin (IRI) gradually increased after ligation of the common bile duct. These levels were a little lower than those in the non-treated controls. The level of plasma glucagon (IRG) incerased remarkably 4 weeks after ligation of the common bile duct. Clinically, there were no significant differnces in the levels of IRI and IRG among normal controls and cases of neonatal hepatitis and congenital biliary atresia (CBA). In CBA patients, these levels can be correlated with the progression of hepatic fibrosis; an increase in IRG and a decrease in teh IRI/IRG mol ratio was noticed in patients with grade III of hepatic fibrosis. These indicate that, in obstructive jaundice in infancy, the more severe the hepatic damage due to obstructive jaundice, the higher the level of plasma glucagon concentration will rise.     

Studies on the Enterohepatic Circulation of Bile Acids in Infancy and Childhood

To elucidate the enterohepatic circulation of bile acids in hepatobiliary disorders, the present author measured the fasting cholic acid levels in serum and followed up the changes of the levels after MCT milk administration. The subjects were 17 cases of neonatal hepatitis, 24 cases of congenital biliary atresia (CBA), 19 cases of other hepatobiliary disorders and 117 normal children. The serum cholic acid levels in the neonatal period were significantly high, which suggested a physiological cholestasis in neonates which gradually decreased with age. The mean level in CBA was rather higher than that in neonatal hepatitis but showed overlap of the levels. The patterns of changes of serum cholic acid levels in MCT milk test were classified into 6 types which were respectively characteristic of each disorders according to varied disturbance of the enterohepatic circulation of bile acids. This MCT milk test may be useful in making a differential diagnosis of various hepatobiliary disorders, especially neonatal hepatitis and CBA.     

Duodenogastric bile reflux is common in cystic fibrosis

BACKGROUND: Patients with cystic fibrosis (CF) have a high incidence of gastroesophageal reflux disease, but few cases of mucosal injury are reported. Duodenogastric reflux has not been studied in CF but has been suggested to have a pathogenic role in producing alkaline injury to the esophageal mucosa. The aim of this study was to analyze the presence of duodenogastric reflux in patients with CF. PATIENTS AND METHODS: Ten patients with CF and 7 healthy volunteers participated in the study. Gastroduodenal manometry and intragastric perfusion were performed in all subjects. Gastric perfusate was analyzed for bilirubin and bile acids. Only patients and controls exhibiting normal migrating motor complexes were evaluated. RESULTS: Eight patients with CF had normal motility recordings and had significantly higher gastric bilirubin levels compared with healthy subjects (P = 0.003). The bilirubin concentration was associated with bile acid regurgitation in five patients with CF. All bile acids were conjugated with a high glycine/taurine ratio and low levels of secondary bile acids. Small amounts of keto bile acids were found in two patients. CONCLUSION: The patients with CF had an increased incidence of duodenogastric reflux compared with healthy subjects. The bile acid composition was typical for CF with low levels of secondary bile acids. Although high bile acid concentration was found in the duodenogastric reflux in most patients with CF, the less toxic profile of the bile acids might possibly contribute to the low frequency of Barrett's esophagus in CF.     

Unconjugated, Glycine-conjugated, Taurine-conjugated Bile Acid Nonsulfates and Sulfates in Urine of Young Infants with Cholestasis

ABSTRACT. A direct assay system for conjugated bile acids using an enzymatic procedure and high-performance liquid chromatography was used for the analysis of urinary bile acid profiles in young infants with intrahepatic cholestasis (idiopathic neonatal hepatitis syndrome) or extra-hepatic biliary atresia. The major urinary bile acids were cholate and chenodeoxycholate conjugates, but a small amount of deoxycholate and 3β-hydroxy-5-cholenate conjugates were detected. Although there was no significant difference in total bile acid excretion between patients with intrahepatic cholestasis and extrahepatic biliary atresia, mean ratios of cholate to chenodeoxycholate and sulfated to total urinary bile acids were different between the two groups examined (5.63±2.83 vs. 2.50±1.25, p <0.05, 15.8±9.9 vs. 34.5±9.9%, p < 0.005). The proportion of taurine-conjugated chenodeoxycholate in the sulfate fraction to the total bile acid was lower in intrahepatic cholestasis, compared with that in biliary atresia (7.7±7.5 vs. 22.7±7.8 %, p < 0.005). The greater ratio of cholate to chenodeoxycholate and the reduced excretion of sulfated urinary bile acids in intrahepatic cholestasis was due to decreased taurine-conjugated chenodeoxycholate sulfate excretion.     

Systolic time intervals in anemic children with or without congestive heart failure

Systolic time intervals (STI) were measured from simultaneous high speed recordings of electrocardiogram, phonocardiogram, and carotid artery trace in 47 children of anemia with or without congestive heart failure (CHF), and in 20 healthy normal children. Group I comprised 20 healthy controls with a mean Hb level of 13.65±0.73 gm percent, group II of 37 anemic children with a mean Hb level of 7.3±1.01 gm percent, without any evidence of CHF: Group III of 10 severely anaemic children with a mean Hb level of 2.75±0.82 gm percent with overt CHF. Electromechanical systole (QS2) pre-ejection period (PEP), left ventricular ejection time (LVET) and the ratio of PEP/LVET were studied and compared in various groups. PEP/LVET ratio was found to be 0.265±0.04, 0.363±0.07 and 0.407±0.06 in groups I, II, III cases respectively. The mean PEP/LVET ratio was significantly prolonged in groups II and III when compared with group I (p<.001). Further mean PEP/LVET ratio was significantly greater in group III subjects when compared with group II patients (p<.001). Thus it seems that LV dysfunction sets in early in cases of anemic children and as the severity of anemia increases. left ventricular dysfunction proportionately increases, ultimately resulting in congestive heart failure.     

Alterations of serum bile acid profile in breast-fed infants with prolonged jaundice

Serum bile acid conjugates in breast-fed infants with prolonged jaundice were analyzed by a newly developed procedure using high-performance liquid chromatography with fluorescence labeling. Major bile acids were cholate and chenodeoxycholate conjugates. Some of the breast-fed jaundiced infants had high levels of serum bile acid conjugates (greater than 25 mumol/L), but the mean levels of individual bile acid conjugates found in jaundiced breastfed infants were not significantly different from those in breast-fed infants without jaundice. The glycine- to taurine-conjugated bile acid ratio in breast-fed jaundiced infants was significantly lower than in breast-fed nonjaundiced infants or bottle-fed nonjaundiced infants. In breast-fed infants, the portion of taurine-conjugated bile acids increased in proportion to serum bilirubin levels. These findings suggest that alteration in conjugated bile acid patterns of breast milk jaundice is related to an increased enterohepatic circulation of bile acids as well as bilirubin in infants fed on breast milk that contains high amounts of taurine.     

Unconjugated, glycine-conjugated, taurine-conjugated bile acid nonsulfates and sulfates in urine of young infants with cholestasis

A direct assay system for conjugated bile acids using an enzymatic procedure and high-performance liquid chromatography was used for the analysis of urinary bile acid profiles in young infants with intrahepatic cholestasis (idiopathic neonatal hepatitis syndrome) or extra-hepatic biliary atresia. The major urinary bile acids were cholate and chenodeoxycholate conjugates, but a small amount of deoxycholate and 3 beta-hydroxy-5-cholenate conjugates were detected. Although there was no significant difference in total bile acid excretion between patients with intrahepatic cholestasis and extrahepatic biliary atresia, mean ratios of cholate to chenodeoxycholate and sulfated to total urinary bile acids were different between the two groups examined (5.63 +/- 2.83 vs. 2.50 +/- 1.25, p less than 0.05, 15.8 +/- 9.9 vs. 34.5 +/- 9.9%, p less than 0.005). The proportion of taurine-conjugated chenodeoxycholate in the sulfate fraction to the total bile acid was lower in intrahepatic cholestasis, compared with that in biliary atresia (7.7 +/- 7.5 vs 22.7% +/- 7.8%, p less than 0.005). The greater ratio of cholate to chenodeoxycholate and the reduced excretion of sulfated urinary bile acids in intrahepatic cholestasis was due to decreased taurine-conjugated chenodeoxycholate sulfate excretion.     

EXCRETION OF BILE ACIDS IN ERYTHROBLASTOSIS FOETALIS

The excretion pattern of intramuscularly injected cholic acid-24–¹⁴C was studied for 4 days after the injection in 10 cases of erythro-blastosis (EB). Seven patients with EB and raised serum conjugated bilirubin excreted 3643% of the injected isotope in the urine, whereas the amounts of isotope in the faeces varied greatly. In 3 cases without raised serum conjugated bilirubin less isotope was recovered in the urine and always more than 10% of injected isotope was recovered in the faeces. Cholic acid-24–¹⁴C was excreted essentially unchanged in all cases but in conjugated form. In all cases of EB the urine was found to contain bile acids, chiefly cholic acid. The infants with EB associated with cholestasis excreted 4.8–132.3 μmol of these acids per day; the corresponding values in the absence of cholestasis being 0.4–0.9 μmol per day. In the infants with physiological jaundice the excretion ranged from less than 0.01 to 0.7 μmol per day; the correspondign values in the 2 patients with hyperbilirubinaemia were about 0.2 μmol per day. The infants with EB associataed with cholestasis were found to excrete as large amounts of bile acids in the urine as the infants with intrahepatic cholestasis. These findings strongly suggest that increased serum conjugated bilirubin, irrespective of the patho-genesis of the liver damage, is associated with an impaired bile acid excretion to the intestine. EB without increased serum conjugated bilirubin did not seem to alter the bile acid metabolism, since the urinary excretion of cholic acid and chenodeoxycholic acid in these cases was practically the same as in jaundiced newborn infants.     

生物标记物粪便胆汁酸的测定在过敏性紫癜患儿诊治中的意义

目的 探讨生物标记物粪便胆汁酸浓度在过敏性紫癜(HSP)患者中的变化及其在诊治中的临床意义。方法 选取2014~2016年确诊为HSP的19例患儿为HSP组,另选取27例健康儿童为健康对照组。采集HSP组患儿急性期、恢复期及健康对照组儿童粪便标本,应用液相质谱技术检测各组儿童粪便胆汁酸水平。结果 HSP组患儿恢复期胆酸水平均高于健康对照组和HSP组急性期 (P < 0.016)。HSP组患儿恢复期鹅脱氧胆酸水平高于健康对照组 (P < 0.016)。HSP组患儿急性期和恢复期脱氧胆酸、石胆酸水平均低于健康对照组 (分别P < 0.05、P < 0.016)。各组间熊去氧胆酸水平比较差异均无统计学意义 (P > 0.05)。结论 HSP患儿急性期粪便次级胆汁酸脱氧胆酸和石胆酸低于健康对照组,这可能与HSP的发病或转归有关。     

Bile acid malabsorption in cystic fibrosis with and without pancreatic insufficiency

Serum conjugated cholic acid (CCA) and conjugated chenodeoxycholic acid (CCDCA) fasting levels were measured in 30 children with cystic fibrosis (CF) without liver involvement, and mean levels were not significantly different from control values. In seven children (four with partially corrected pancreatic insufficiency and three without pancreatic insufficiency) serum levels of both primary bile acids (BAs) were also measured after the ingestion of a standard liquid meal; the values were then compared with those for total and fractional fecal BA excretion. The CCA mean peak increase was significantly reduced in patients with pancreatic insufficiency (p less than 0.01), as well as in those without pancreatic insufficiency (p less than 0.05), as compared to controls. The CCDCA mean peak increase was reduced only in patients with pancreatic insufficiency (p less than 0.01). Fecal results confirmed serum data, showing a significantly increased excretion of cholic and deoxycholic acids in patients without pancreatic insufficiency as compared to controls (p less than 0.02), despite a similar total BA excretion. In patients with pancreatic insufficiency, total fecal BA levels were markedly increased compared to control values (p less than 0.001); the fecal percentage of chenodeoxycholic and lithocholic acids was greater than that recorded in patients without pancreatic insufficiency (p less than 0.05), in agreement with the different behaviour of serum CCDCA postprandial curves for the two groups of patients. The results are consistent with selective malabsorption of cholic acid in CF, independent of the presence of pancreatic insufficiency; they confirm the usefulness of serum BA postprandial determinations in measuring BA malabsorption.     

PLASMA CONJUGATED CHOLIC ACID IN PREMATURE AND TERM NEWBORNS AND YOUNG INFANTS

ABSTRACT. Tikanoja, T., Tikanoja, S. and Simell, O. (Children's Hospital, University of Helsinki, Helsinki, Finland). Plasma conjugated cholic acid in premature and term newborns and young infants. Acta Paediatr Scand, 70:491,.–Bile acid handling by neonates, both premature (Group 1, mean gestational age 34.3 weeks; Croup II, 36,6 weeks) and full-term (Group HI, 40.2 weeks) and by 3-month-old infants (Group IV) was assessed by measuring plasma concentrations of conjugated cholic acid (CCA) before and at successive intervals after feeds. The prefeeding CCA concentrations were highest in Group I (log mean 8.2; range 1.8–28.6 μmol/1) and lower in Groups II (7.5; 2.6–22.4 umol/1), III (5.1; 2.1–11.1 μ0mol/1), and IV (2.2; 0.5–6.1 μmol/1). The mean postprandial increments correlated with maturity: the rises for Groups I-IV were 3.7, 4.3, 1.0 and 0.7 μmol/1, respectively. Peak values were consistently reached at 30 min after the start of the feed, i.e., strikingly earlier than in older children and adults. After the peaks the return to prefeeding levels occurred rapidly in Groups II-IV but more slowly in the most premature infants (Group I). The rapid postprandial rise may be due to many factors, e.g., passive jejunal absorption, immature hepatic-clearing mechanisms, or rapid transit of bile acids to the ileum. Hence, measurements of postprandial plasma bile acids would appear ill-suited for detection of disturbed ileal function in young infants. The high concentrations in healthy newborns suggest that caution is necessary in interpreting plasma bile acid concentrations during the first few weeks of life, especially in premature infants.     

Development of Bile Acid Metabolism in Neonates during Perinatal Period | Part 2. Mass screening of congenital biliary atresia by radioimmunoassay using dried blood spot

Inour country, congenital biliary atresia (CBA) has occurred in approximately 1 of 10,000 live births, but its prognosis has been extremely poor. In the mass screening of this disease, glycocholic acid (GCA) or chenodeoxycholic acid (CDCA) level in dried blood spots on filter paper in5-day-old neonates was determined by radioimmunoassay (RIA).
To determine GCA in dried blood spots on filter paper, the procedures in this experiment were modified using commercial kit for serum.
The mean GCA level of controls (n=391) was 5.88±4.28 nM/ml and that of CBA (n=22) was 14.1 ±3.1 nM/ml. On the other hand the mean CDCA level of controls (n=86) was 5.86 ±3.07 pM/l disc that of CBA (n=22) was 30.0 ±35.9 pM/l disc. When the criterion is assumed to be more than 16 nM/ml of GCA level or 10 pM/l disc of CDCA level, false negative diagnoses of CBA are 31.8% and 18.2% respectively. On the other hand false positive diagnoses of CBA are 6.9% and 3.5% respectively. It was thought that false negative diagnosis on mass screening with GCA level would decrease using fresh dried blood spot within 2 weeks after taking blood.
In 22 CBA cases, the GCA levels in dried blood spots on filter paper were not always parallel with the CDCA levels.     

Measurement of serum total bile acid levels in long-term postoperative follow-up of patients with congenital bile-duct dilatation

 Serum total bile acid levels (STBA), a sensitive indicator of cholestasis, were measured during the long-term postoperative period in patients with congenital bile-duct dilatation (CBDD) (choledochal cyst) and the factors contributing to elevation of STBA were analyzed in 44 patients. Their ages at operation ranged from 1 month to 16 years. A STBA level over 12 nmol/ml on two or more measurements during outpatient follow-up was considered abnormal. Patients were classified into three groups: group 1, STBA, 12–50 nmol/ml; group 2, STBA ≥ 50 nmol/ml; group N, STBA normal. In 19 patients (43.2%) STBA was normal. Of the 25 patients (56.8%) with elevated STBA, groups 1 and 2 comprised 12 (27.3%) and 13 patients (29.5%), respectively. The mean age in group N was 5.1 ± 4.2 years, which was higher than in groups 1 (2.6 ± 2.3) and 2 (2.3 ± 2.5 years) (P < 0.05). Preoperative STBA and total bilirubin were higher in group 2 (79.2 ± 75.1 nmol/ml resp. 5.2 ± 4.2 mg/dl) than in groups N (20.1 ± 32.6, 1.3 ± 1.4) and 1 (22.8 ± 37.2, 1.4 ± 1.0) (P < 0.05). Preoperative alkaline phosphatase and gamma-glutamyl transpeptidase were higher in group 2 (1,006 ± 872 IU/l, 452 ± 326 IU/l) than in group N (573 ± 371, 205 ± 238) (P < 0.05). Histologic findings on liver biopsy showed fibrosis in 38.5% of group 2 patients, which was significantly higher than in groups N (15.8%) and 1 (16.7%) (P < 0.05). Cholestasis was detected in 41.7% of group 1 and 61.5% of group 2 patients, compared to 10.5% of group N patients (P < 0.05). Postoperative elevation of STBA may thus persist in more than one-half of patients with CBDD, and is likely to occur in patients of young age who have severe cholestasis or liver fibrosis preoperatively. Further investigations may be required in regard to the development of postoperative complications. Accepted: 7 February 2001     

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.     

Excessive fecal taurine loss predisposes to taurine deficiency in cystic fibrosis

Elevation of the ratio of glycine: taurine-conjugated bile acids (G/T ratio) is thought to contribute to fat malabsorption in cystic fibrosis (CF). The cause, extent, and reversibility of taurine deficiency in CF were assessed using balance studies in 6 subjects (ages 8-14 years) who were supplemented with taurine (0.24-2.4 mmol/kg/24 h) for 1 week. Taurine reduced the G/T ratio both in serum and duodenal juice in all children. The mean fecal taurine loss in CF subjects [10.8 mumol/kg/24 h +/- 9.9 (SD), range 0.9-27.9] was much greater than that in controls (less than 0.1 mumol/kg/24 h, n = 4) and approximated the dietary taurine intake (mean 14.6 +/- 4.4 mumol/kg/24 h, n = 12). Absorption of an oral taurine load appeared to be normal in CF. Excessive fecal taurine loss appears to predispose CF children to bile acid taurine deficiency, a deficiency that can be corrected by oral taurine supplements.     

Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs'negative haemolytic anaemia

We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs'negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum γ-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1β-hydroxylated bile acids, especially lβ,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid (25.5-67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1β-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of Δ⁴-3-oxo bile acids is increased. Familial intrahepatic cholestasis, Coombs'negative haemolytic anaemia, 1β-hydroxylated bile acids, unsaturated ketonic bile acids     

Relation Between Red Cell Distribution Width and Clinical Outcome After Surgery for Congenital Heart Disease in Children

Recent studies have reported a strong association between increased red cell distribution width (RDW) and the risk of adverse outcomes for adults with heart failure. This study investigated the association between preoperative RDW and postoperative clinical outcomes for children with cardiac disease. The relation between preoperative RDW and the length of postoperative stay was tested with 688 consecutive children undergoing surgery for congenital heart disease (CHD). The RDW was significantly higher in patients who died during the postoperative hospital stay (mean, 18.34?±?4.69 vs 16.12?±?2.84; p?=?0.004). The risk of postoperative death was five times higher for patients with an RDW of 16% or more. In the general study population, RDW correlated with the intensive care unit (ICU) stay (p?<?0.0001) and with the total hospital stay in the local population (p?<?0.0001). The correlation between RDW and ICU stay was stronger for patients with acyanotic CHD (p?<?0.0001) than for those with cyanotic CHD (p?=?0.0007), and for the subpopulation of patients with acyanotic CHD and normal hemoglobin level (p?<?0.0001) than for anemic patients with acyanotic CHD (p?=?0.025). Preoperative RDW is a strong predictor of an adverse outcome in children undergoing surgery for CHD, especially in nonanemic patients, for whom it reflects an underlying inflammatory stress.