The impact of hepatic xanthine oxidase and xanthine dehydrogenase activities on liver function in chronic cholestasis.

Activities of hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XD), serum liver enzymes, and reduced glutathione (GSH) were determined in livers of chronic cholestatic rats. The common bile duct was ligated (CBDL) and rats were randomized to either an untreated group or to treatment with allopurinol, a competitive XO inhibitor, or received a tungsten-supplemented diet to inactivate XO and XD, or received antioxidants vitamin C and vitamin E. One group underwent only sham laparotomy. After 4 weeks, in untreated CBDL animals serum aspartate aminotransferase and bilirubin concentrations were significantly elevated and hepatic GSH was significantly decreased when compared with the sham-operated group. Histochemical and enzymatic determinations of XD and XO showed a significant increase in hepatic XO activity after CBDL. Treatment with allopurinol and a tungsten-supplemented, molybdenum-free diet significantly attenuated serum liver enzymes, hepatic XO activity, and improved hepatic GSH levels, whereas vitamins C and E had a positive effect only on hepatic GSH levels. Our results support the hypothesis that cholestasis-induced hepatocellular injury is partially triggered by oxidative processes derived from increased hepatic XO activity. Inhibition and inactivation of XO exerts a hepatocellular protective effect in chronic cholestasis.

Bunk beds--a still underestimated risk for accidents in childhood?

UNLABELLED: A retrospective analysis of 218 bunk-bed accidents and a random sample survey with 991 family interviews were performed in order to establish guidelines for bunk-bed accident prevention. Falls from the top bed during sleep (35.1%) or while playing (34.4%) and falling off the ladder (23.2%) are the leading causes of bunk-bed accidents. Of the 218 children, 91 (41.7%) had sustained major injuries, including 3 polytrauma, 7 skull fractures, 44 cerebral concussions, 33 long bone fractures, 2 Lisfranc injuries, and 2 lacerations of the spleen. Of these accidents, 58.3% resulted in minor injuries with 18 fractures in other locations than the long bones or cranial vault, 89 contusions and sprains, 18 skin lacerations and 2 tooth fractures. A total of 23.8% of the accidents occurred in children under 3 years of age. The random sample survey demonstrated that in relation to age groups of children 30.8% (0%-45.8%) of families interviewed had been using bunk beds, with peaks at 3 years (29.8%), 7 years (36.5%) and 11 years (45.8%) of age. Of these bunk beds, 75.3% were equipped with side-rails, 57.3% had placed carpets alongside the bunk bed and 43.0% had used night lights. CONCLUSION: There is only one recommendation: no bunk beds!!!

The effect of vitamin C and vitamin E supplementation on bacterial translocation in chronic portal hypertensive and common-bile-duct-ligated rats.

In rats with chronic portal hypertension (PH) and common bile duct ligation (CBDL), significant ileal bacterial overgrowth, translocation of indigenous intestinal bacteria, a decrease in hepatic and ileal reduced glutathione (GSH) and an increase in ileal mucosal lipid peroxidation occur. alpha-Tocopherol (vitamin E) and ascorbic acid (vitamin C) treatment attenuated the incidence of bacterial translocation, improved hepatic and ileal GSH levels and decreased ileal mucosal lipid peroxidation. These results suggest that in chronic PH and CBDL oxidative processes in the liver and intestine play an important role for bacterial translocation.

Allopurinol reduces bacterial translocation, intestinal mucosal lipid peroxidation, and neutrophil-derived myeloperoxidase activity in chronic portal hypertensive and common bile duct-ligated growing rats.

Bacterial translocation (BT) from the gastrointestinal tract has been thought to play a role in the pathogenesis of septic complications in patients with chronic portal hypertension (PH) and obstructive jaundice. The purpose of this study was to investigate the incidence of BT and to assess the role of intestinal mucosal malondialdehyde (MDA) levels as an indicator of lipid peroxidation and polymorphonuclear neutrophil-derived myeloperoxidase (MPO) in chronic portal hypertensive and common bile duct-ligated rats. Twenty male rats were subjected to sham laparotomy (SL), 20 rats to calibrated portal vein constriction (PH), 20 rats to common bile duct ligation (CBDL), and 10 rats served as a nonoperated control group (NOP). After 4 wk, 10 animals of each operated group received 50 mg/kg allopurinol intraperitoneally, at 24 h, and again 2 h prior to estimation of BT, intestinal mucosal MDA, and MPO activities. In the NOP and SL groups, BT to the mesenteric lymph nodes (MLN) and spleen was present. In PH and in CBDL rats, BT to liver, portal vein, peritoneum, and caval vein occurred. Allopurinol treatment attenuated the frequence of BT in PH and decreased BT in CBDL rats significantly (p < 0.05). Ileal mucosal MDA levels (nanomoles/g) in untreated rats increased from 45.1 +/- 7.9 in SL to 98.2 +/- 9.1 in PH and to 102.2 +/- 11 in CBDL rats (p < 0.01). In the allopurinol groups the increase of MDA to 49.1 +/- 1.3 in PH, and 66.2 +/- 2.2 in CBDL was significantly lower (p < 0.01). MPO activity (units/g) in the ileal mucosa increased in untreated rats from 319 +/- 129 after SL to 866 +/- 104 after PH and to 1016 +/- 104 after CBDL (p < 0.01). Allopurinol significantly attenuated MPO activity to 369 +/- 44 in PH, and to 372 +/- 60 in CBDL animals (p < 0.01). In PH and CBDL rats significant BT, intestinal mucosal lipid peroxidation, and polymorphonuclear neutrophil-derived MPO activity occurred. Allopurinol reduced BT and improved intestinal mucosal MDA and MPO activities, suggesting that there might be an association between BT and intestinal mucosal lipid peroxidation.

Allopurinol and glutamine attenuate bacterial translocation in chronic portal hypertensive and common bile duct ligated growing rats.

BACKGROUND: Spontaneous bacterial infections and septicaemia result in morbidity and mortality in patients with portal hypertension and obstructive jaundice. AIM: The aim of this study in rats was to investigate the incidence of bacterial translocation in portal hypertension and obstructive jaundice, and to evaluate the effects of allopurinol and glutamine. METHODS: Rats were subjected to sham laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). Animals of each group were either treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and allopurinol and glutamine. RESULTS: After four weeks, significant bacterial translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and myeloperoxidase activity (MPO) released from activated neutrophils were also significantly increased (p < 0.01). Allopurinol and glutamine in PH and CBDL rats improved bacterial translocation, and decreased MDA and MPO values (p < 0.01). CONCLUSION: In PH and CBDL rats significant bacterial translocation, ileal mucosal lipid peroxidation, and neutrophil derived MPO activity occurred. Allopurinol and glutamine significantly reduced bacterial translocation, as well as ileal mucosal MDA and MPO activities.

Bacterial translocation in chronic portal hypertensive and common bile duct-ligated growing rats.

Spontaneous bacteremias and infectious complications occur in patients with chronic portal hypertension (PH) and obstructive jaundice, and most of these infections are caused by indigenous intestinal bacteria translocating to regional lymph nodes and the systemic circulation. The aim of this study was to investigate bacterial translocation (BT) at two stages: (1) isolated chronic PH; and (2) obstructive jaundice. Four-week-old male rats were either subjected to sham laparotomy (SL) or to pH or common bile duct ligation (CBDL). After 4 weeks, animals were weighed and the portal pressure was measured. Samples from the portal vein (PV), vena cava, liver, spleen, mesenteric lymph nodes (MLN), and ileum were obtained for bacteriologic cultures. Specimens from the liver, jejunum, and ileum were taken for histologic examination. Portal pressure increased from 7.4±0.3 to 20.5±0.6 mmHg in PH and CBDL animals (P <0.01). Bacterial cultures obtained from the ileum showed significant bacterial overgrowth (P <0.01) in pH and CBDL rats (1.3±0.8 × 10(4) after SL; 1.2±0.6 × 10(5) in PH and 1.9±0.6 × 10(6) in CBDL). BT occured in 10% of SL animals to the MLN and spleen. In PH animals 23% positive cultures were found, almost all due to BT to the PV, vena cava, and liver. CBDL resulted in a BT rate of 47%, mainly by translocation to the PV, liver, and MLN (P <0.05 vs. SL). Histomorphologically, the jejunum and ileum were normal in all three groups. These results suggest that in growing PH and CBDL rats intestinal bacterial overgrowth with significant BT occurs, and the incidence of BT seems to be related to the amount of bacteria colonizing the intestinal tract.

[Long-term follow-up of infants with pathological gastroesophageal reflux]. / Langzeitkontrollen bei Säuglingen mit pathologischem gastroösophagealen Reflux.

Between 1981 and 1984 330 infants with suspected gastroesophageal reflux (GER) were investigated by combined esophageal manometry and pH-monitoring. GER of 283 patients with a manometric reflux time more than 1% was classified as pathologic. After one year of conservative therapy a follow-up-study mainly by 24-hour-pH-monitoring could be performed in 108 patients. Two thirds (76 out of 108) still showed a pathological GER. In the age of about two years follow-up-investigation in 41 patients showed in one third of them (13 out of 41) a pathological GER. 5.4% of all investigated children (18 out of 330) hat to be operated because of complicated GER. Follow-up has been performed in 24 children over five years with manometry and/or pH-monitoring and/or barium swallow and/or endoscopy with biopsy. After one year of conservative therapy more than two thirds of them (19 out of 24), after two years one third (eight out of 24) showed a pathological GER. In a few cases (four out of 24) the pathological GER disappeared spontaneously in the age of four to five years. In the age of 1.5 to three years six children had to be operated because of complicated GER. We conclude from this study that a spontaneous healing of pathological GER occurs in about two thirds of the patients older than one year. In about 8% (two out of 24) a pathological GER persists over the fifth year of life representing a permanent risk of GER complications.

[Problems of gastroesophageal reflux in childhood]. / Probleme des gastro-ösophagealen Refluxes im Kindesalter.

Gastro-esophageal reflux is common in infancy. However, in most of those children reflux disappears spontaneously at the end of the first year or during the second year of life. Thus, the authors suggest the hypothesis that gastro-esophageal reflux in infancy represents a delay in maturation of central structures for the motor function of the esophagus. Therefore conservative therapy during infancy is the treatment of choice for most of the infants. Additional factors however, such as severe cerebral or neurological damage, esophageal atresia, failure to growth and esophagitis make an early operative intervention often necessary. Likewise operative therapy is the treatment of choice in older children with symptoms of esophagitis or stenosis. Different diagnostic procedures are discussed briefly.