The caffeine metabolic ratio as an index of xanthine oxidase activity in clinically active and silent celiac patients.

BACKGROUND: The xanthine oxidoreductase system has been identified as one of the main sources of free radicals responsible for various forms of tissue injury. Because the intestinal villi are an important location of this enzyme, it was of interest to study the role of xanthine oxidase in gluten-sensitive celiac enteropathy, associated with characteristic villous atrophy. Measured by a noninvasive method, the ratio of caffeine metabolites excreted in the urine after a caffeine challenge had previously been shown to be indicative of the total xanthine oxidase activity of the patient. METHODS: The study involved 22 children with gluten-challenged celiac disease, exhibiting subtotal villous atrophy in specimens from the third intestinal biopsy in accordance with ESPGHAN criteria. Ten of the patients displayed overt clinical symptoms (active form), whereas 12 had no symptoms (silent form). Urinary caffeine metabolites were determined by high-pressure liquid chromatography. The total in vivo xanthine oxidase activity was expressed as the caffeine metabolite index. RESULTS: In patients with active celiac disease the xanthine oxidase activity index was considerably higher, whereas in those with silent disease it was significantly lower than the control value. A significant negative correlation was shown between the index indicative of xanthine oxidase activity and the serum iron level of the patients. CONCLUSIONS: Activation of xanthine oxidase may play a role in the pathogenesis of active celiac disease with definite malabsorption, gastrointestinal symptoms, and anemia. The caffeine test reflects the difference in the pathogenetic mechanism leading to the mucosal lesion and clinical symptoms of active and silent forms of celiac disease.

Coeliac disease: always something to discover.

The authors present more than 20 years' experience with coeliac disease, with a summary of their published studies. Hair shaft characteristics were determined by scanning electron microscopy. Hair diameter was significantly lower and cuticular erosion scores higher in those who were not on gluten-free diets as compared to controls, showing a tendency towards normal values following start of gluten-free diets. Proton-induced X-ray emission showed significantly lower zinc content of the hair shaft in the group with acute coeliac disease and after a short-term diet, which approached the normal range only after a year-long diet. The serum prolactin levels in healthy controls and in coeliac patients on the diet were within normal limits, whereas in children with coeliac disease taking gluten in their meals, a significant hyperprolactinaemia was found. The erythrocyte glutathione content of coeliac children was elevated, and the glutathione disulfide level was significantly decreased, as compared to values in normal controls. The erythrocyte glutathione disulfide level and glutathione disulfide/erythrocyte glutathione ratio in coeliac children also differed from those in children with iron deficiency. With genotyping, the DQB1*0201/2 (p < 0.00001) and DR3 (p < 0.00001), DR7 (p < 0.01) alleles showed significant positive association with the disease.

Serial cholangiographic appearances in recurrent pyogenic cholangitis.

From December 1982 to December 1991, cholangiograms were obtained in 227 patients with recurrent pyogenic cholangitis. Cholangiographic abnormalities included biliary dilation, calculi, sludge, excessive branching, and arrowhead formation of intrahepatic ducts and biliary strictures. In 21 patients, previous evidence of biliary ascariasis was seen. Repeat cholangiograms were performed in 55 patients in a follow-up period of 18.0 +/- 1 months. Of these patients, 12 treated conservatively continued to get recurrent cholangitis and revealed worsening abnormalities on repeat cholangiograms. Another 25 patients had successful endoscopic sphincterotomy and extraction of biliary calculi. These patients remained free of symptoms on follow-up, with significant resolution of abnormalities on repeat cholangiograms. The remaining 18 patients with failed surgical or endoscopic interventions continued to get recurrent episodes of cholangitis and worsening of abnormalities on repeat cholangiograms. This retrospective study indicates that the natural course of recurrent pyogenic cholangitis is a progressive, destructive cholangiopathy. Ascaris lumbricoides invasion of the biliary tree is an initiating event in a sub-group of patients.

Worm extraction and biliary drainage in hepatobiliary and pancreatic ascariasis.

From December 1989 to March 1992, 50 (32%) of 156 patients with hepatobiliary and pancreatic ascariasis underwent various endoscopic interventional procedures. Endoscopic intervention was performed when patients did not respond to energetic symptomatic treatment within the first few days of hospitalization (n = 45) or when worms had not moved out of the ducts into the duodenum at 3 weeks (n = 5). Worm extraction was successful in all 18 patients from the ampullary orifice and in 34 (89.5%) of 38 patients from the bile or pancreatic duct. In five patients with pyogenic cholangitis, endoscopic nasobiliary drainage was performed to decompress the bile ducts. After worm extraction/nasobiliary drainage, 41 (91%) of the 45 patients with biliary disease (n = 42) or acute pancreatitis (n = 3) had rapid relief of symptoms. Three patients developed complications related to endoscopy, including cholangitis (n = 2) and hypotension (n = 1).

Biliary abnormalities associated with extrahepatic portal venous obstruction.

We prospectively studied 21 consecutive patients with extrahepatic portal venous obstruction for evidence of biliary tract disease. Two patients were first seen with extrahepatic cholestasis; another had recurrent cholangitis. All three patients with clinically manifest biliary disease were adults. Another five patients had icterus on clinical examination. Liver function tests revealed elevated bilirubin levels in 14 patients (66.6%), elevated alkaline phosphatase levels in 17 (80.9%) and elevated serum ALT levels in 8 (38.0%). Endoscopic retrograde cholangiography revealed abnormal findings in 17 patients (80.9%). The changes involved the common bile duct (66.6%) more often than they did the hepatic bile ducts (38.1%). Cholangiographic abnormalities included strictures (52.4%), caliber irregularity (23.8%), segmental upstream dilatation (42.8%), ectasia (9.5%), collateral veins causing extraluminal bile duct impressions (14.3%), displacement of ducts (9.5%), angulation of ducts (4.7%) and pruning of intrahepatic ducts (9.5%). The pathogenesis of such cholangiographic abnormalities is unknown. However, possible factors in such changes include collateral veins bridging the blocked portal vein, causing bile duct impressions; fibrous scarring of porta hepatis, causing angulation of bile duct; and ischemic injury to bile duct, leading to stricture formation and caliber irregularity. Biliary disease is important in the clinical outcome of patients with extrahepatic portal venous obstruction because variceal sclerotherapy has prolonged the life expectancies of such patients.

Percutaneous drainage versus albendazole therapy in hepatic hydatidosis: a prospective, randomized study.

BACKGROUND: Recently, drug treatment and percutaneous drainage have been used successfully when treating hepatic hydatid cysts. Until now, there is no published study comparing the relative safety and efficacy of these two forms of treatment. METHODS: In a prospective study, 33 hepatic hydatid cysts were randomly distributed to receive percutaneous drainage (10), albendazole (10 mg.kg-1.day-1 for 8 weeks) plus percutaneous drainage (12), and albendazole alone (11). Patients were serially assessed by clinical and biochemical examinations, ultrasonography, and hydatid serology. RESULTS: On serial ultrasonography, cysts attained heterogeneous echopattern in 18, uniform echogenicity in 11, and disappearance in 3. All 22 cysts treated with percutaneous drainage and only 2 (18.2%) cysts treated with albendazole alone reduced in size and change in echopattern (P < 0.01). Maximum size reduction was observed in cysts treated with a combination of percutaneous drainage and albendazole (P < 0.05). Complications observed with drainage were cyst infection in 2 patients, fever in 3, cyst biliary rupture in 1, and urticaria in 2. These were managed successfully without any mortality. Three patients who received albendazole developed reversible elevation of liver cell enzymes. CONCLUSIONS: It was concluded that percutaneous drainage with albendazole therapy is an effective form of management for hepatic hydatid cysts.

Hepatitis C virus antibodies in acute and chronic liver disease in India.

The prevalence of serum antibodies to hepatitis C virus was assessed by an enzyme-linked immunosorbent assay in patients with epidemic non-A, non-B hepatitis (14), sporadic non-A, non-B hepatitis (42), chronic hepatitis (14) and cirrhosis (26). None of the patients with epidemic non-A, non-B hepatitis (14) and acute self-limiting sporadic non-A, non-B hepatitis without prior parenteral exposure (38) tested positive for hepatitis C virus antibody. Based on epidemiologic features, hepatitis E virus is presumably the etiologic agent for both these entities. Hepatitis C virus (HCV) antibody was positive in none of the patients with cryptogenic chronic hepatitis (11) and in 2(8%) patients with cryptogenic cirrhosis (25). It was concluded that cryptogenic chronic hepatitis and cirrhosis in India may be caused by alternative viral agents of the non-A, non-B type or by hepatotoxins to which the population may be exposed. Of 8 patients with prior parenteral exposure (transfusions 6, needle pricks 2) 5 (62.5%) patients tested positive for HCV antibody. HCV antibody was detected in 1 (25%) patient with acute self-limiting, parenterally transmitted non-A, non-B hepatitis and in 4 (100%) patients with chronic parenterally transmitted non-A, non-B hepatitis.

Oddi's sphincter motor activity in patients with recurrent pyogenic cholangitis.

Oddi's sphincter motor activity was studied in 15 healthy subjects and 15 patients with recurrent pyogenic cholangitis. No significant difference was found in the common bile duct pressures, the Oddi's sphincter basal pressures or the amplitude, frequency and duration of phasic contractions between the controls and patients. However, a significant difference was found in the percentage of antegrade and retrograde phasic wave sequences between the two groups. In control patients 64.0% +/- 5.3% of phasic wave sequences were antegrade, and 20% +/- 3.6% were retrograde. In patients with recurrent pyogenic cholangitis, 37% +/- 3.6% of phasic wave sequences were antegrade, and 42% +/- 5.5% were retrograde. No significant difference was found in the percentage of simultaneous phasic wave sequences (16% +/- 1.5% vs. 18.5% +/- 2.8%, respectively) between the two groups. In all, five (33%) patients with recurrent pyogenic cholangitis had abnormal propagation of phasic contractions of Oddi's sphincter (retrograde phasic wave sequences greater than 50%), two (13%) patients had elevated Oddi's sphincter basal pressures (greater than 40 mm Hg) and one (7%) patient had increased frequency of Oddi's sphincter phasic contractions (more than 9/min). Six of the 15 patients had evidence of papillitis on duodenoscopy. We believe papillitis could induce motor abnormalities in these patients, thus resulting in delayed biliary drainage and recurrent attacks of cholangitis.

Sonographic findings in gallbladder ascariasis.

Invasion of the adult roundworm, Ascaris lumbricoides, into the gallbladder is rare and was seen in 14(2.1%) of the 665 cases with hepatobiliary ascariasis. The diagnosis was suggested in all 13 cases in which sonography was performed and in 5 of the 11 cases at endoscopic retrograde cholangiography. Sonographic findings included a nonshadowing, long, echogenic structure in the form of a coil, an echogenic strip with central anechoic tube, an echogenic structure extending across the gallbladder giving it a septate appearance, and characteristic erratic, nondirectional, zig-zag movements of these echogenic structures in the gallbladder. Serial sonograms accurately predicted spontaneous exit of the worm. Pregnancy and anomalous origin of the cystic duct directly from the papilla of Vater facilitated worm invasion into the gallbladder. We conclude that real-time sonography offers a simple, rapid approach for the diagnosis and follow-up of patients, whereas endoscopic retrograde cholangiography has limited diagnostic value in this disorder.

Determination of hair trace elements in childhood celiac disease and in cystic fibrosis.

Applying proton-induced X-ray emission authors investigated the hair trace element contents in 10 children with acute celiac disease after 3 to 6 and 12 months long gluten-free diet; in 9 children with cystic fibrosis and in a control group (6 children) of the same age. There was no difference in Cu, Fe, Ca, Cl values between the examined groups. The Zn contents of the hair are significantly low in the group with acute celiac disease after a short-term diet and also in the group with cystic fibrosis, the data approach the normal range only after a year's diet. The significant rise of hair potassium contents is well indicated in patients with acute celiac disease and this rise may be due to the destruction of cell cuticles. In case of cystic fibrosis there is no significant rise of hair potassium value.

Decrease in the antioxidant capacity of red blood cells in children with celiac disease.

The erythrocyte glutathione metabolism of 11 children with acute celiac disease (CD), 11 children under gluten free diet with CD and 5 children with cow's milk allergy was compared to that of 11 children with nutritive iron deficiency and to 22 healthy children as controls. Erythrocyte glutathione (GSH) content of celiac children was elevated and the glutathione disulfide (GSSG) level was significantly decreased as compared to normal controls. Erythrocyte GSSG/GSH ratio in acute CD differed also from the one in iron deficiency. In vitro oxidative load of acetylphenylhydrazine proved the impaired glutathione stability of the erythrocytes in acute CD and cow's milk allergy. A parallel rise of methemoglobin and hemichrome level of blood cells was seen. Further on, the selenium content of the red blood cells of CD patients decreased. All alterations of the erythrocyte tended to normalize during the dietetic period. These data suggest a reduced protective capacity of erythrocytes in CD and in cow's milk allergy in childhood against oxidizing stresses.

[Selenium levels in erythrocytes of children with celiac disease]. / Coeliakiás gyermekek vörösvértest szelén szintjének vizsgálata.

Selenium is the component of the glutationperoxidase one of the most important enzymes in the antioxidant protection of the organism. In preliminary studies the authors found in celiac children increased sensitivity to oxidative stress and biochemical changes referring to decreased activity of glutationperoxidase enzyme. Therefore the selenium content of washed erythrocytes has been determined with fluorimetry in 24 celiac children kept on gluten containing diet and 25 on gluten-free diet. In gluten loading the selenium level was significantly lower than in the healthy control group. The selenium value rose at a small degree in the erythrocytes of celiac children kept on gluten-free diet but did not reach the lower limit of the physiological value. On the basis of these results the malabsorption of selenium was found to play also an important role in the decreased protecting capacity against oxidative stress effects in celiac diseases of childhood. The necessity of supplementing the trace element is raised.

The importance of cow's milk protein intolerance in chronic diarrhoea of children.

A survey is given of the cases diagnosed as cow's milk protein intolerance in the last 5 years. The diagnosis was established on the basis of the regression of clinical symptoms after elimination from the diet of cow's milk and their recurrence after milk challenge. In more than half of the cases intestinal biopsy was carried out; three patients were rebiopsied after milk challenge. Intestinal biopsy is indicated solely in cases when the exclusion of coeliac disease is necessary for the correct diagnosis.

[Incorporation of H3 uridine in chick embryo skin cultured in media containing histones]. / Incorporazione di urinina H3 in espianti di cute di embrione di pollo coltivati con istoni.

In this paper the authors have carried out further research on the differentiation of six-day limb skin from chick embryos cultured in vitro in mediam containing histones. When 3H-uridine is added to this modified medium, a decrease of 3H-uridine uptake and incorporation is observed. The authors conclude that in their system the histones not only interfere with the regulation of genetic transcription by inhibiting DNA-dependent RNA synthesis, but they also change cellular permeability.

Renal tubular ferritin-uptake, a consequence of the increased glomerular permeability, during the benign and malignant course of renal hypertension in rats.

Tubular uptake of ferritin given intravenously was studied in the right and left kidneys of 74 Goldblatt-hypertensive rats. Previous observations pointed out the pathologically enhanced permeability of glomerular barrier as the cause of the phenomenon. It was assumed, that the extent of tubular areas taking up ferritin, refers to the number of damaged glomeruli. The process was characterized semiquantitatively by planimetric measurements and determination of the non-hemin iron concentration in the renal cortical tissue. A more frequent and extensive tubular ferritin-uptake (and glomerular damage) was bilaterally recorded in the kidneys of malignant hypertensive rats in comparison to the benign ones. The development of the phenomenon in the clamped kidneys, being defended from high blood pressure, suggests a humoral factor behind the enhanced glomerular permeability. Saline intake has a beneficial effect on the glomerular damage similar to the hypertensive angiopathy.