Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

Down syndrome (DS) patients have an increased risk of developing pulmonary hypertension (PH). Increased plasma levels of asymmetric dimethylarginine (ADMA) may contribute to vascular dysfunction in adults with idiopathic pulmonary hypertension. Our goal was to test the hypothesis that DS patients with PH have higher plasma levels of ADMA than DS patients without PH. DS patients with definitive PH (n = 6) and DS patients with no evidence of PH (n = 12) were studied. Plasma levels of arginine, ADMA, and nitrite/nitrate (NOx; stable metabolites of nitric oxide (NO)) were measured. Plasma arginine concentration was lower (p < 0.05) in PH patients (23 ± 11 μM) versus non-PH patients (46 ± 24 μM). Plasma ADMA concentration was higher (p < 0.005) in PH patients (18.0 ± 4.2 μM) versus non-PH patients (8.6 ± 5.9 μM). Plasma NOx was lower (p < 0.05) in PH patients (4.5 ± 1.7 μM) versus non-PH patients (8.5 ± 7.3 μM). These results are consistent with ADMA contributing to lower NO production in DS patients with PH and suggest that ADMA levels may be a potential biomarker for PH in DS patients.     

Are stable postoperative biliary atresia patients really stable?

 Transforming growth factor-beta 1 (TGF β-1) is an important mediator of liver-cell proliferation and replication that is implicated in hepatic fibrosis (HF). Hepatic stellate cells (HSC) are activated by TGF β-1 and are the main precursor cells involved in fibrogenesis. The correlation between serum TGF β-1, activated HSC in liver-biopsy specimens, and liver biochemistry was investigated to determine the value of TGF β-1 as an indicator of clinical status in postoperative biliary atresia (BA) patients. Thirty-two postoperative BA patients (mean age 11.2 ± 2.8 years) and 13 normal controls (mean age 10.3 ± 3.7 years) were studied. Based on average liver function test (LFT) results over a 3-month period immediately prior to this study, the BA patients were divided into group I (anicteric, normal LFT; n = 10); group II (anicteric, elevated liver transaminases; n = 12), and group III (jaundiced end-stage liver fibrosis awaiting liver transplantation; n = 10). Serum TGF β-1 was determined using ELISA. Liver-biopsy specimens were examined with antibody against TGF β-1 and α-smooth muscle actin (SMA) antibody for detection of activated HSC. Serum TGF β-1 was significantly higher in groups I (11.4 ± 3.7 ng/ml; P < 0.01) and II (23.3 ± 11.3 ng/ml; P < 0.001) than in group III (3.0 ± 1.5 ng/ml) and controls (4.5 ± 2.5 ng/ml) despite normal LFT in group I. The 3 subjects with the highest serum TGF β-1 in group II had bile lakes. Biopsies from groups I and II were strongly positive for TGF β-1 in hepatocytes and Kupffer cells and for activated HSC detected by SMA compared with group III and controls. Because serum TGF β-1 and activated HSC are only present during active fibrosis, we conclude that there is progressive fibrogenesis even in seemingly normal postoperative BA patients. In particular, bile lakes should be regarded as a key sign of progressive HF, the presence of which should be regarded with extreme caution. We suggest that serum TGF β-1 could be used as an accurate indicator of progressive fibrogenesis in postoperative BA patients. Accepted: 14 April 2000     

Distal splenorenal shunt with splenopancreatic disconnection for portal hypertension in biliary atresia

This study evaluated the long-term effects of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) on portal hypertension (PH) in biliary atresia (BA) patients. Five patients with BA underwent DSRS-SPD at the age of 3.3 to 8.5 years. They had been free from jaundice after hepatic portoenterostomy (HPE); however, they gradually developed gastroesophageal varices and hypersplenism. Portal venous pressure after anastomosis was 37.2 ± 6.1 cmH₂O, as high as that before anastomosis (37.8 ± 3.3 cmH₂O). Postoperatively, liver function tests became worse within 2 weeks; however, they returned to preoperative levels within 1 month without any further treatment. No patient developed a significant encephalopathy throughout the observed period. During follow-up of 4 to 12 years, the shunt was patent in all patients. Spleen size decreased after operation. Abdominal-wall venous dilatation completely disappeared in two of four patients. The platelet counts gradually increased and were significantly higher 3 years (126.6 ± 59.3 × 10³/mm³) after DSRS-SPD than preoperative values (66.0 ± 24.2 × 10³/mm³). White blood cell counts showed no significant changes. No patient developed a gastrointestinal hemorrhage postoperatively, although three had had repeated hemorrhages before the operation. Two patients showed disappearance of varices endoscopically at 2 years and 7 months after DSRS-SPD, respectively, but had recurrent varices at 7 and 11 years, respectively. The endoscopic findings regarding varices 3 to 7 years after DSRS-SPD were as follows: decreased number (80%); decreased length (40%); improvement of form (20%); improvement of fundamental color (60%); disappearance of red-color sign (100%); disappearance of gastric varices (75%); and disappearance of acute gastric mucosal lesions (100%). Although one patient later underwent liver transplantation because of progression of liver cirrhosis, all five are doing well. From these results, DSRS-SPD may prove to be a safe and feasible procedure for intrahepatic PH after HPE for BA and may improve gastroesophageal varices and hypersplenism on long-term follow-up. Accepted: 13 July 1998     

The relationship between procollagen-III-peptide and the severity of esophageal varices in children with biliary atresia after Kasai operation

Biliary atresia (BA) is a common cause of infantile cholestasis. Disease progression leads to intra hepaticfibrosis, and thus to the development of PH and EV. Our objective has been to study the relationship between procollagen-III-peptide (PIIIP) and the severity of EV in children with BA after Kasai operation. Children below 15 years of age (n=29) with BA after a Kasai operation were evaluated for EV by endoscopy. Healthy (n=26) children of the same age and sex distribution who participated in the hepatitis B vaccination program served as the controls. Serum PIIIP was determined by radioimmunoassay. The BA patients were classified on the basis of severity of EV (Paquet's classification) into three groups: group 1 (n=15) had grade 0, group 2 (n=8) grade 1–2, and group 3 (n=6) grade 3–4 EV. In group 3, serum PIIIP (2.9 ± 1.3 IU/ml) was significantly higher than in group 2 (1.5 ± 0.4 IU/ml) (P < 0.05). Serum PIIIP levels were increased in group 2 compared with group 1 (1.2 ± 0.4 IU/ml) and in group 1 compared with the control group (1.2 ± 0.2 IU/ml), but this difference was not significant. PIIIP levels increased with severity of the EV in the BA patients. Hence, high PIIIP levels may serve as a non invastive indicator of EV developing in postoperative BA patients. Accepted: 8 January 2001     

Plasma endothelin-1 levels in patients with biliary atresia: possible role in development of portal hypertension

BACKGROUND: Biliary atresia (BA) is a severe neonatal liver disease characterized by progressive extrahepatic biliary tract and intrahepatic inflammatory process. Hepatic fibrosis and portal hypertension (PH) still occur despite the disappearance of jaundice following successful hepatic portoenterostomy. Endothelin-1 (ET-1) is a potent vasoconstrictor and has been reported to stimulate hepatic collagen synthesis. The aim of this study was to demonstrate the potential role of ET-1 in the pathogenesis of the progressive inflammation, fibrosis and PH in BA. METHODS: Thirty pediatric patients with biliary atresia post-hepatic portoenterostomy and 12 healthy children were examined. The ET-1 level was determined by commercially available enzyme-linked immunosorbent assay kits. RESULTS: Endothelin-1 levels were elevated in the patients compared with those of the controls (5.45+/-3.34 vs. 2.74+/-2.17 pg/ml, P = 0.01). Moreover, patients with PH also had greater levels of ET-1 than those without PH (6.73+/-3.27 vs. 3.26+/-2.2 pg/ml, P = 0.004). Patients with abnormal transaminase enzymes had significantly higher ET-1 levels than those with normal enzymes (6.43+/-3.33 vs. 3.17+/-2.1 pg/ml, P = 0.01). In the jaundice-free group, endothelin-1 levels were elevated in the patients with PH compared with those without PH (5.93+/-2.15 vs. 2.88+/-2.1 pg/ml, P = 0.02). CONCLUSIONS: Our findings showed elevation of plasma ET-1 levels in patients with BA, especially in those with PH. ET-1 levels were also higher in patients with elevated transminase enzymes as well as in the jaundice-free group with PH. ET-1 might play a role in the pathogenesis of the progressive inflammation, fibrosis and PH in BA.     

Long-term follow-up of patients with biliary atresia successfully treated with hepatic portoenterostomy. The importance of sequential treatment

The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range 10.7–22.5 years; mean 15.4±0.7 years) treated with hepatic portoenterostomy (HPE) and jaundice-free for more than 10 years without liver transplantation (LT) is analyzed retrospectively. Eight of these patients subsequently required LT (age at LT 12.8±0.5 years, range 10.5–15.2 years); 3 children (aged 11.6, 13.2 and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding associated with other signs of severe disease and are now candidates for LT; and among the 7 asymptomatic patients (age range 11.2–22.5 years; mean 15.9±2.1 years), 5 had sonographic and biochemical signs of moderate portal hypertension (PH). In order to analyze whether the age at transplantation influences the survival of children transplanted for BA, we also reviewed the outcome of 71 BA patients transplanted at our hospital between 1986 and 1996. All the children older than 10 years at the time of LT were alive; only patients younger than 10 years died following LT (n= 15). We conclude that the natural outcome of extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases successfully treated with HPE. In our experience, the results of sequential treatment with HPE and LT were excellent.     

Plasma vascular endothelial growth factor level is a predictor of the severity of postoperative capillary leak syndrome in neonates undergoing cardiopulmonary bypass

 Capillary leak syndrome (CLS), characterized by extravascular fluid accumulation and significant organ dysfunction, is a serious complication in children undergoing cardiopulmonary bypass (CPB). We examined the relationship between plasma vascular endothelial growth factor (VEGF) levels and severity of CLS. The kinetics of VEGF in the plasma of 11 neonates and 7 older children undergoing CPB were investigated, correlating plasma VEGF levels and CLS clinical presentation. The degree of postoperative CLS was quantified by measuring parameters of extracellular volume and end-organ dysfunction. A chest-wall soft-tissue-width index (CSTWI) was designed in order to standardize the extracellular fluid accumulation. Most CLS parameters were significantly more prominent in the neonatal patients. Low plasma VEFG levels (>35 pg/ml) were found in 3 neonatal control patients and all but, sample from the older group patient. The neonates had significantly higher preoperative VEGF plasma levels (684.4 ± 559.1 pg/ml, P = 0.02), which decreased during the operation to levels below 35 pg/ml and increased again 24 h postoperatively to levels significantly higher than in the older patients (484 ± 270.3 pg/ml, P = 0.001). Multilinear regression analysis found preoperative VEGF levels to independently correlate with CLS as represented by CSTWI (P < 0.01, r = 0.726). Both the occurrence of post-CPB CLS and plasma VEGF levels pre- and postoperatively were thus higher in neonates than in children. Plasma VEGF level is a predictor of the severity of postoperative CLS. Accepted: 1 March 2000     

α-Glutathione-s-transferase as a new sensitive marker of hepatocellular damage in biliary atresia

 Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. α-Glutathione-s-transferase (α-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum α-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 ± 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum α-GST was determined using a specific ELISA. Tissue α-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum α-GST was significantly higher in group II (20.7 ± 8.4 ng/ml) than in groups I (4.7 ± 1.3 ng/ml) and III (8.0 ± 1.2 ng/ml) (P < 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens α-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III α-GST was only found in regenerative nodules. We conclude that α-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of α-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.     

The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease

Kawasaki disease (KD) is associated with coronary artery injury. Studies have shown that the endothelial progenitor cell (EPC) participates in the process of arterial repair. Data have been reported that the number of EPC increased significantly in the subacute phase of KD. However, until now, there are no data about the functions of EPC in KD patients. The present study was designed to further investigate the number and functions of EPC in KD. Ten KD patients in the acute phase and ten healthy volunteers were recruited and attributed to the KD group and control group, respectively. The circulating CD34/kinase insert domain-containing receptor double positive cells were evaluated in the two groups using flow cytometry. In vitro assays were used to measure the functions of EPC, including proliferation, adhesion, and migration activities. The plasma levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were also assessed in both groups. The number of EPC in the KD group was significantly higher than that of the control group (0.021 ± 0.007% vs. 0.014 ± 0.003%, P < 0.05). The migratory response of EPC was significantly decreased in the KD group, compared with that of the control group (5.50 ± 1.78 vs. 3.40 ± 1.35 cells/high power field, P < 0.01). Similarly, the proliferative and adhesive activities of EPC in the KD group were also decreased (0.47 ± 0.08 vs. 0.66 ± 0.07, P < 0.01; 6.5 ± 2.12 vs. 11.2 ± 2.04 cells/high power field, P < 0.01). The plasma NO, TNF-α, and hs-CRP levels in the KD group were higher than those of the control group (54.10 ± 11.78 vs. 38.80 ± 11.10 μmol/l, P < 0.01; 48.20 ± 7.42 vs. 37.00 ± 11.12 pg/ml, P < 0.05; 87.10 ± 30.18 vs. 5.30 ± 3.37 mg/l, P < 0.01). The number of circulating EPC positively correlated with the level of NO (r = 0.92, P < 0.001), and the functions of EPC negatively correlated with the levels of TNF-α and hs-CRP, respectively. In Kawasaki disease, the number of EPC was enhanced and the functions of EPC were attenuated. The two-way regulation of circulating EPC in KD patients may be associated with the disorders of cytokines or messengers in KD patients.     

Pre-operative time course changes in liver function tests in biliary atresia: Its usefulness in the discrimination of biliary atresia in early infancy

In order to investigate the possibility of early discrimination of extrahepatic biliary atresia from other cholestatic diseases, a series of results of liver function tests in infants with cholestatic diseases were reviewed. The results of routine liver function tests (LFT) recorded in patients' charts were reviewed within 12 weeks after birth in 47 infants with extrahepatic biliary atresia (BA), 10 infants with neonatal hepatitis (NH) and 130 age-matched control infants (CO) without cholestatic diseases. The mean of each test value for each week after birth was derived from the actual data examined in each infant. No differences were observed between BA and CO in the levels of aminotransferases within 2 weeks after birth. Total bilirubin and direct bilirubin levels were significantly different between BA and CO within 1 week after birth (16.1 ± 3.2 mg/dL vs 11.1 ± 4.5 mg/dL, 4.6 ± 2.6 mg/dL vs 0.7 ± 0.3 mg/dL, respectively) The direct bilirubin-total bilirubin ratio exceeded 25% within the first week in BA. The individual values of direct bilirubin (DB) exceeded 2 mg/dL within the first week in all infants with BA, while none of the individual values exceeded 1.6 mg/dL in CO. Gamma-glutamyl transpeptidase levels were significantly different between BA and CO at 4 weeks (432 ± 272 IU/L vs 79 ± 43 IU/L) and thereafter; and were significantly different between BA and NH at 6 weeks (314 ± 232 IU/l vs 69 ± 58 IU/L) and thereafter. These data suggest that the determination of direct bilirubin within 1 week after birth can detect extrahepatic biliary atresia patients from those with physiologic jaundice, and γ-glutamyl transpeptidase levels may discriminate BA from NH at no later than 6 weeks of age.     

Beneficial effect of a traditional herbal medicine (inchin-ko-to) in postoperative biliary atresia patients

 Inchin-ko-to (ICKT) prevents Fas-mediated liver injury. This study evaluates the effect of ICKT on conventional markers of liver function (LF) and liver fibrosis in 18 postoperative biliary atresia (BA) patients aged 3 to 23 years with elevated glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), γ-glutamyl transpeptidase (γGTP) but normal serum total bilirubin (T-Bil) levels. ICKT (0.15 g/kg per day) was administered orally for 1 year. Serum GOT, GPT, γGTP, total bile acids (TBA), and T-Bil as markers of LF and hyaluronic acid (HA), prolyl hydroxylase (PH), procollagen III peptide (PIIIP), and type IV collagen as markers of liver fibrosis were measured before and after treatment in each patient and compared statistically. All patients tolerated ICKT well, and there were no side effects. The percentage of subjects who improved after ICKT was 45% for serum GOT, 72% for GPT, 72% for γGTP, 72% for TBA, 67% for HA, 40% for PH, 50% for PIIIP, and 23% for type IV collagen. Changes in the mean values of all serum markers were statistically significant (P < 0.01). It is concluded that long-term administration of ICKT in postoperative BA patients improves liver status as assessed by markers of LF and fibrosis. Accepted: 22 September 2000     

Suppression of elevated plasma interleukin-8 levels due to total ischemia and reperfusion of the small intestine by luminal perfusion with fetal bovine serum

 A previous study demonstrated that continuous enteric luminal perfusion of fetal bovine serum (FBS) protects the small intestine from total ischemia/reperfusion injury (IRI) and increases the intestinal mass. In this study, we further investigated the changes in plasma interleukin-8 (IL-8) level caused by total ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8 levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and then reperfusion was instituted. Luminal perfusion of FBS was conducted via an osmotic minipump connected to the stomach through a fine polyethylene tube, starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked immunosorbent assay. The results were compared among the FBS-treated and untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia to 6 h after initiation of reperfusion (P < 0.05) with a peak of 641.5 ± 36.9 pg/ml in the untreated group and 471.6 ± 42.2 pg/ml in the treated group. Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of total ischemia and 1 h after initiation of reperfusion (P < 0.05). The results suggest that FBS might play a role in the treatment of total IRI of the small intestine. Accepted: 21 March 2001     

Oxidative stress profile in the post-operative patients with biliary atresia

Background and purpose  Many post-operative patients with biliary atresia (BA) suffer from liver dysfunction, such as chronic inflammation even without jaundice after a Kasai’s hepatic portoenterostomy. Methods  The presence and degree of oxidative stress were evaluated in the post-operative patients with BA. Twelve outpatients who underwent a Kasai’s hepatic portoenterostomy were evaluated. The active oxygen products, the rate of bioantioxidant, the markers of oxidative stress, and the degree of hepatic oxidative stress were examined by immunohistochemical staining of biopsied specimens. Results  All of the oxidative stress markers in the post-operative patients with BA increased in comparison to those in the controls. Moreover, 8-OHdG immunohistochemical staining was positive in 84 ± 4.8% in hepatic cells in the portal area in the post-operative patients with BA. Conclusion  The post-operative patients with BA were under increased oxidative stress, even if their liver dysfunction was mild without jaundice. Antioxidant therapy might be necessary to decrease of oxidative stress in the post-operative patients with BA.     

Relationships between OPG,RANKL, bone metabolism,and bone mineral density in biliary atresia

Purpose  Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) have been implicated in osteoclastogenesis. However, the relationship between the OPG–RANKL system and bone status in biliary atresia (BA) has not, as yet, been clarified. Thus, the aim of this study has been to evaluate the relationship between the OPG–RANKL system and bone mineral metabolism in patients with BA. Methods  Fifty patients with BA and 13 healthy controls were investigated. The mean age of BA patients and controls was 7.3 ± 0.6 and 8.0 ± 1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was determined by dual energy X-ray absorptiometry. Results  Biliary atresia patients had significantly elevated serum OPG levels compared with controls (4.0 ± 0.3 vs. 3.0 ± 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with jaundice were higher than in those without jaundice (4.6 ± 0.4 vs. 3.6 ± 0.4 pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA patients than in controls (2.9 ± 0.2 vs. 1.2 ± 0.7 pmol/L, P = 0.001). In addition, serum RANKL levels were increased in BA patients with jaundice compared to those without jaundice, but this difference was not statistically significant (3.2 ± 0.3 vs. 2.7 ± 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA patients were not significantly different from those in the healthy controls, whereas the serum CTX levels were elevated in BA patients compared with the controls (0.4 ± 0.1 vs. 0.2 ± 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA children with jaundice was significantly lower than that of BA children without jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum levels of OPG (r = −0.452, P < 0.001). Conclusion  Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss. Presented at the 30th American Society for Bone and Mineral Research (ASBMR) annual meeting, Montreal, Quebec, Canada, 12–16 September 2008.     

Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn—a prospective randomized controlled trial

Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ±0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion.     

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-α), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-α, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 ± 6.1 years, weight for height ratio 89 ± 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 ± 15% of predicted at D0 to 51 ± 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 ± 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 ± 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 ± 17 mg/l to 4 ± 7 mg/l (P < 0.05), elastase 62 ± 29 μg/l to 45 ± 18 μg/l (P < 0.02), orosomucoid acid 1.25 ± 0.11 g/l to 0.80 ± 0.15 g/l (P < 0.001), and TNF-α 37 ± 14 pg/ml to 29 ± 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-α (P < 0.02). Conclusion The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation. Received: 6 August 1998 and in revised form: 23 November 1998 / Accepted: 23 November 1998     

Clinical significance of c-kit expression in biliary atresia

The aim of the present study was to examine the clinical significance of c-kit expression in biliary atresia (BA) using formalin-fixed, paraffin-embedded sections from 21 patients with BA. Patients were divided into group I (n = 8) with good liver function; group II (n = 8) with moderate liver dysfunction; and group III (n = 5) with severe liver dysfunction. Choledochal cysts (CDC, n = 5) and normal liver samples (NL, n = 4) served as controls. The results were analyzed and compared among the groups. Most c-kit ⁺ cells were present in the portal tracts, and their numbers in BA were significantly higher than in the controls (11.12 ± 1.64 vs 2.15 ± 0.15 [mean ± standard error], P = 0.02, BA vs CDC; 11.12 ± 1.64 vs 1.66 ± 0.52, P = 0.03, BA vs NL). Clinical correlation revealed a significantly higher number of c-kit ⁺ cells in group III versus group I (18.10 ± 3.62 vs 8.86 ± 2.51, P = 0.02). These results suggest that c-kit overexpression is associated with an adverse clinical outcome in BA. Accepted: 1 November 2000     

Plasma endothelin-1 and nitrate levels in Down’s syndrome with complete atrioventricular septal defect-associated pulmonary hypertension: a comparison with non-Down’s syndrome children

Children with Down’s syndrome (DS)-associated complete atrioventricular septal defect (AVSD) have rapid and aggressive development of pulmonary vascular disease when compared with non-Down’s syndrome (ND) children. We aimed to evaluate the role of plasma endothelin-1 (ET-1) and nitrate levels in DS children with complete AVSD-associated pulmonary hypertension (PH) and compare this to ND patients. The study included 20 patients (11 males, nine females) who had complete AVSD associated with PH. Comparisons were made between DS patients (n = 12) aged 4 to 8 months (median 5 months) and ND patients (n = 8) aged 4 to 12 months (median 7 months). Blood samples were drawn from the inferior vena cava, pulmonary artery, pulmonary vein, and aorta. The plasma ET-1 concentrations of the two groups were compared to the peripheral venous and arterial ET-1 levels, and pulmonary vein nitrate was compared to the peripheral arterial nitrate levels of ten healthy infants. The mean pulmonary artery (PA) pressure and pulmonary vascular resistance (Rp) were significantly higher in the DS group than ND patients, and the pulmonary blood flow (Qp) in ND patients was higher than DS patients. There were no differences between the two study groups in regard to plasma ET-1 and nitrate levels obtained from matched sampling sites. The plasma ET-1 and nitrate levels were significantly higher in both study groups compared to the control subjects. The plasma ET-1 and nitrate levels in DS patients with PH were not different when compared to those of ND patients.     

Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters

Biliary atresia (BA) is a neonatal obliterative cholangiopathy of unknown etiology. Despite the Kasai procedure, hepatic fibrosis and portal hypertension (PH) still occur. Interleukin-8 (IL-8) is an important mediator of inflammation and immune response in human disease. The objective of this study was to investigate the potential role of IL-8 in the pathogenesis of the progressive, sclerosing, inflammatory process and fibrosis in BA. A total of 60 pediatric patients with BA and 15 healthy children were evaluated. The mean ages of BA patients and controls were 6.3±0.6 and 6.7±1.1 years, respectively. The patients were classified into two groups according to their clinical outcomes: patients with jaundice (total bilirubin ±25.5 mol/l) and patients without jaundice (total bilirubin <25.5 mol/l). The IL-8 levels in serum samples were determined by commercially available enzyme-linked immunosorbent assay. Serum IL-8 levels were higher in the BA patients than in healthy children (236.2±60.1 vs. 34.5±12.1 pg/ml, P<0.001). Patients with jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Serum IL-8 levels in the jaundice group were significantly higher than in those without jaundice (516.5±130.0 vs. 49.3±10.4 pg/ml, P<0.0005). Furthermore, patients with PH had higher IL-8 levels than those without PH (378.1±102.2 vs. 106.6±48.4 pg/ml, P<0.005). In the jaundice-free group, IL-8 levels were elevated in patients with PH compared with those without PH (79.0±17.4 vs. 19.7±5.8 pg/ml, P<0.005). The present study demonstrated elevation of serum IL-8 levels in children with BA. Serum IL-8 levels were also higher in patients with jaundice compared with patients without jaundice. These findings suggest that IL-8 may play a significant role in the pathogenesis of BA.