Safety and immunogenicity of a combined vaccine against hepatitis A and B in patients with autoimmune hepatitis.

Patients with autoimmune hepatitis (AIH) are a group at risk of disease exacerbation or relapse of the underlying disease should they fall ill with infectious hepatitis A (HAV) or B (HBV). Therefore, it seems appropriate to protect this group of persons against HAV and HBV disease by vaccination. An open study evaluated the safety, reactogenicity and immunogenicity of a combined HAV and HBV vaccine in 10 patients with AIH (6 patients aged 1-15 years and four patients aged 16+ years). The vaccine was administered using a three-dose vaccination schedule (0, 1 and 6 months). The vaccine course was well tolerated, safe and did not aggravate the clinical course of the underlying disease. Patients responded with 100% seroconversion for antibody to the HAV vaccine component and geometric mean antibody concentration (GIVIC) comparable to healthy cohorts. Response to the HBV component antigen was comparable to previous reports of HBV vaccination in immune compromised individuals with lower GMC than observed in healthy populations. One month after the third vaccine dose (month 7), all six vaccinees in the 1-15 years age group developed protective levels of anti-HBs as compared to two of the four vaccinees in the 16+ years age group.

[Budd-Chiari syndrome and TIPS--twelve years' experience]. / Budduv-Chiariho syndrom a TIPS--12 let zkuseností.

BACKGROUND: Massive thrombosis of hepatic veins is clinically the most serious type of Budd-Chiari syndrome (BCS). Ischemic impairment is the basic problem in case of acute or fulminate course of BCS. Restitution of blood drainage within the liver is a key therapeutic approach in such situation. In chronic course of the disease, symptoms of portal hypertension as ascites, G1 bleeding or hepatorenal syndrome are more common. The portosystemic shunt leads both to blood outflow restitution and to the decrease of portal hypertension. TIPS is a promising method due to minimal perioperative risk for the patient in critical situation and also due to its easiness of use. The aim of our study was to determine the clinical outcome in patients with BCS treated by TIPS in a retrospective analysis. METHODS AND RESULTS: During 12 years 23 patients with intraparenchymal thrombotic occlusion of hepatic veins were treated using TIPS, 17% were children, only 4 patients (17%) were men, the median age was 33.3 years (range 13 to 75 years). One third of the procedures was performed as urgent. In 2/3 of patients thrombosis developed in relation to myeloproliferative syndrome, in nearly 1/3 the origin of thrombosis was not detected. In 2 patients a defect of coagulation was revealed. In the first 11 patients the bare stent was used, the consecutive 12 patients received the ePTFE covered stent (stentgraft). Six patients died during follow-up: I due to fulminate liver failure, 2 due to liver failure caused by acute shunt occlusion, 1 due to the progression of the underlying hematooncological disease; the reason of death in 2 patients was not known. One patient was treated by OLTx during follow-up. The 17 surviving patients are in good condition with good shunt function although they need anticoagulant therapy and intermittent reinterventions. The average period between revisions was 2-3 years, 2 patients had no revision of TIPS for 4 years. The use of ePTFE covered stents had no effect on the number of early occlusions (approx. 18%), the occurrence of late stenoses and occlusions was substantially decreased (p=0.04, log-rank test). CONCLUSIONS: Standing on this experience we consider TIPS, in accordance with literature data, an advantageous therapeutic approach in Budd-Chiari syndrome caused by massive liver vein thrombosis. If the follow up treatment is rigorous, the TIPS usually ensures the necessary perfusion and the function of the liver So it may spare the patients of objectionable liver transplantation.

[Examination of gastric emptying rate by means of 13C-octanoic acid breath test. Methods of the test for adults and results of the investigation of healthy volunteers]. / Stanovení rychlosti evakuace zaludku pomoci dechového testu s 13C-oktanovou kyselinou. Metodika testu pro dospelé a výsledky vysetrení zdravých dobrovolníku.

BACKGROUND: 13C-octanoic acid breath test (13C-OABT) is a simple, safe and non-invasive technique for measuring gastric emptying. However, the method has not been standardized yet. Aim of the study was to work up, introduce and evaluate our own method of the 13C-OABT for adults. METHODS AND RESULTS: Ten healthy volunteers entered the study (5 men, 5 women, mean age 32 years, 50 % Helicobacter pylori positive). Standard test meals (with 100 mg 13C-sodium octanoate) were used three times within 3 weeks. The same solid meal (1,178 kJ) for Tests 1 and 2 contained scrambled egg (+ 3 g oil), white bread (40 g), butter (10 g) and distilled water (200 ml). Semi-solid meal (1,020 kJ) for Test 3 contained milk pudding (200 g) and distilled water (200 ml). Duplicate breath samples were obtained before and every 15 minutes after eating the test meal during 255 minutes. Altogether 1,080 breath samples were analysed twice (isotope ratio mass spectrometry, AP2003 Analytical Precision, UK). To assess the half-life of elimination (t1/2 E), we modelled the process of elimination with the incomplete gamma-function, which has a convenient form for the empiric plotting of breath test data. Mean t1/2E was 136+/-10 minutes (Test 1), 134+/-14 (Test 2) and 123+/-16 minutes (Test 3). Clinical reproducibility of 13C-OABT in particular persons was 98.2% (18 breath samples series), 90.8 % (15 samples) and 87.1% (9 breath samples series). There was a significant correlation between Test 1 and Test 2 results (r=0.887, p<0.0001). Mean difference of duplicate breath sample analysis was 1.460 % (in 540 pairs), mean baseline one-day analysis difference was 0.0982 (99.9274% accuracy). In healthy volunteers, normal range of t1/2E is 110-160 minutes for solids and 91-155 minutes for semisolid test meal. Using our own computed mean time of intermediate metabolism of 13C-octanoic acid (76.5+/-7.5 minutes), gastric emptying half-time is 33.5-83.5 minutes for solids and 14.5-78.5 minutes for semisolid test meal in healthy volunteers. CONCLUSIONS: The 13C-OABT is accurate non-invasive method for gastric emptying measurement.

Endoscopic retrograde cholangiopancreatography in childhood.

ERCP was performed in 19 children and adolescents aged 4 to 16 years. In 13 children the examination was done under general anesthesia, in 6 cases with the usual premedication using dolsin and atropine. Indications for examination were unclear abdominal pain with occasional amylase elevation, in 3 patients status after an abdominal injury. In 16 patients the examination clarified the complaints by detecting organic disease of the gallbladder or the pancreas. ERCP is an important procedure in the event of uncertain diagnosis in children and adolescents and, if the indication is correct, and the technique good, is well tolerated by the patients.

Serum soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) in healthy school aged children and adults.

The aim of this study was to map normal levels of serum soluble isoforms of adhesion molecules in relation to age and sex in the group of school-aged children. sICAM-1, sVCAM-1 and sE-selectin were determined in the group of 158 normal children subdivided into two subgroups; 6-10 years (68 children, median age 8 years) and 11-15 years (90 children, median age 12 years) and in 70 normal adult blood donors (25 females and 45 males, median age 46 years). The levels of sICAM-1 and sE-selectin fell down significantly over the age range 6-15 years, while the level of sVCAM-1 was remained. Age-related normal ranges were established using correlation analysis and were expressed as the 5%-95% percentiles intervals: sICAM-1 206.8-486.8 ng/ml, sE-selectin 36.7-153.2 ng/ml in the group of 6-10 years old children, sICAM-1 184.1-354.0 ng/ml, sE-selectin 29.9-114.1 ng/ml in group of 11-15 years old children. The levels of sVCAM-1 were 359.6-822.0 ng/ml and were constant within the examined age interval from 6 to 15 years. The influence of sex was also assayed and it was not statistically significant in any age category tested. Normal ranges of sICAM-1 (60.2-218.4 ng/ml), sE-selectin (8.3-116.9 ng/ml) and sVCAM-1 (338.0-1148.0 ng/ml) were established for adult population of healthy blood donors using the same methods.

[Transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of symptomatic portal hypertension]. / Transjugulární intrahepatální portosystémový zkrat (TIPS) pri lécbe symptomatické portálni hypertenze.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is the creation of a percutaneous portosystemic anastomosis which is used as an alternative method of surgical portosystemic shunts and endoscopic treatment in the therapy of complications of portal hypertension. The objective of the present work was to summarize experience with TIPS in 100 patients. METHODS AND RESULTS: In 1992-1995 the authors treated 100 patients with symptomatic portal hypertension by TIPS. To create the shunt in 84% patients a spiral Z stent was used, in the remainder a Wallstent. In 86% patients the indication for TIPS was haemorrhage associated with portal hypertension and in 14% refractory ascites. TIPS was implemented in 98% patients. The pressure in the portal vela was not reduced on average to 58% of the original value. Haemorrhage was not stopped in one of 7 patients. Haemorrhage from varices reappeared in 7% patients indicated on account of repeated haemorrhage and was always associated with the finding of chronic stenosis of the shunt. The mortality in conjunction with the procedure was 4%, the mortality within 30 days after operation was 8%. Uncontrollable encephalopathy developed in 3% of the patients. Primary patency of the shunt created by the spiral Z stent was 85% after 6 months, after 12 months 72% and thus does not differ from primary patency when Wallstents are used, as reported in the literature. CONCLUSIONS: TIPS is an effective method to reduce the pressure in the portal vein in portal hypertension. The main limiting factor of the method is stenosis of the shunt due to hyperplasia of the neointima. Stenoses of the shunt can be effectively dilated by percutaneous balloon angioplasty.

[Diabetes and celiac disease]. / Diabetes a celiakie.

Celiac sprue is permanent lifelong intolerance of gluten which in some sensitive individuals leads to an inflammation of various grades followed by atrophy of jejunum mucosa. Diagnosis of celiac sprue is based on proof of histopathological changes in jejunum mucosa as a result of presence of gluten in food. In recent years, serum endogenous myosin and tissue transglutaminase antibodies were used in a diagnostic algorithm. We distinguish active, silent, latent, and potential celiac sprue. Simultaneous incidence of type I diabetes mellitus and celiac sprue has been documented in a range of studies. Both diseases have common immunology and genetic characters. Prevalence of celiac sprue in patients with type I diabetes is several times higher compared to prevalence of this disease in the population. There is the prevalence of celiac sprue 3.6-5.1% in children with type I diabetes mellitus in the Czech Republic, silent form of the disease is the most frequent one. An effect of a strict gluten free diet on a metabolic control of diabetes has not been proved. It is necessary to assess (at least once per two years) actively and on regular basis endogenous myosin and/or tissue transglutaminase antibodies in patients with type I diabetes.

[Bacterial meningitis in neonates. Retrospective study 1977-1991]. / Bakteriální meningitida novorozence. Retrospektivní studie za období 1977-1991.

In 1977-1991 at the Paediatric Clinic in Hradec Králové 43 neonates with bacterial meningitis (BM) were hospitalized. In 31 (72%) risk factors for the development of perinatal infection were detected. The aetiological agent was proved in 40 neonates, most frequently E. coli (46.5%), Streptococcus agalactiae (16.2%), Proteus (11.6%). In the second half of the investigation period (1984-1991) there was a significantly higher ratio of G+ microorganisms, in particular Streptococcus agalactiae. In three neonates the diagnosis of BM was based on a positive cytological finding in cerebrospinal fluid. The total lethality was 60.4%. The lethality was not significantly influenced by early diagnosis and treatment (within 48 hours), correct selection of antibiotic before knowing the cultivation finding and sensitivity. The total incidence of BM during the investigation period in the Faculty Hospital in Hradec Králové was 0.51/1000, in mature neonates 0.36/1000 and 1.8/1000 in neonates with a low birth weight.

[The importance of clinical symptoms in the diagnosis of bacterial meningitis in neonates]. / Význam klinických príznaku pro diagnostiku bakteriální meningitidy novorozence.

In a group of 32 neonates with bacterial meningitis (BM) the authors investigated the frequency of clinical symptoms and compared it with the frequency in a control group of 27 neonates where BM was ruled out. The following were significantly more frequent in neonates with BM: elevated temperature (p < 0.01) and seizures (p < 0.05). In the control group impaired muscular tonus was significantly more frequent (p < 0.05). Temperature had the highest diagnostic sensitivity (93.7%), followed by seizures (62.5%); exanthema had the highest specificity (92.6%), followed by bulging (92%). Neither sensitivity nor specificity of any of the investigated clinical symptoms reached the required level of 96%.

[Hepatobiliary disorders in chronic nonspecific intestinal inflammation]. / Hepatobiliární postizení u chronických nespecifických strevních zánetu.

In 1977-1992 chronic inflammatory bowel disease was diagnosed in the gastroenterological department at the Clinic of Pediatrics in 31 children. Idiopathic proctocolitis was diagnosed in 16 children--mean age at the time of diagnosis was 13 years and 9 months. Fifteen children were treated for the diagnosis of Crohn's disease. Their mean age was 12 years and 9 months. During the investigation period all patients were examined regularly with special attention to hepatobiliary disease. Elevated aminotransferase values were observed in four children, three of these children have had permanent elevation of aminotransferase. Percutaneous liver biopsy revealed chronic persistent or active hepatitis. The authors investigated the course of the liver disease in relation to GIT disease. In the discussion they analyze the incidence, etiopathogenesis and type of liver lesions in inflammatory bowel disease with regard to the case-histories of their three patients.

Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease.

BACKGROUND AND AIM: Azathioprine (AZA) has a slow onset of action in treatment of pediatric inflammatory bowel disease (IBD). It is anticipated, that this delay correlates to the kinetics of 6-thioguanine nucleotides (6-TGN) accumulation. The aim of this study was to evaluate the time to steady state of 6-TGN concentration in red blood cells. METHODS: The inclusion criteria were: a) age 0-19 years b) IBD diagnosis c) AZA treatment initiation. High performance liquid chromatography was used for the 6-TGN analysis. Concentrations of metabolites were studied in weeks 0, 1, 2, 5, and 8 after beginning of treatment. RESULTS: The inclusion criteria were matched to 18 patients with IBD. The median time to steady state of 6-TGN was 55.3 days. The mean 6-TGN concentration at the steady state achieved 326 (SD 154) pmol/8.108 erythrocytes. High erythrocyte TPMT activity corresponds to the low steady state 6-TGN concentration and vice versa. This correlation reached statistical significance (p<0.01) for the dose expressed in mg per square meter of body surface area. CONCLUSION: The time to steady state of 6-TGN erythrocyte concentration is significantly shorter than would expected according to clinical observation describe earlier.

Immunological aspects of diagnosis of celiac sprue in children.

Serum anti-gluten (AGA) and anti-reticulin (ARA) antibodies were examined in children suffering from celiac sprue (CS); cellular hypersensitivity to gluten was tested and secretion of immunoglobulins and anti-gluten antibodies into the culture medium after 24-hour in vitro cultivation of jejunal mucosal biopsies was investigated with the aim to assess significance of these methods for CS diagnosis. Indirect immunofluorescence was used in ARA determination, ELISA method for AGA determination, cellular hypersensitivity was examined using the test of leucocyte migration inhibition (LMIT) with gluten. ARA were detected in 69% of children with untreated CS and in 28% of CS children who were on a gluten-free diet. ARA specificity was 100%. Statistically significant higher titres of IgG AGA and IgA AGA were proved in children with untreated CS as compared with the control group. IgA AGA were detected significantly more frequently than IgG AGA. No relationship between positive AGA and the degree of alteration of the jejunal mucosa was found. IgG AGA sensitivity in CS children with pathological findings on the jejunal mucosa was 52%, specificity being 95%. IgA AGA sensitivity was 82% with specificity 90%. After a parallel application of IgA AGA and ARA, sensitivity of the tests rose up to 95.5%, specificity being 90%. Examinations of ARA and AGA have a significant importance for laboratory tests used for screening children with pathological findings on the jejunal mucosa and for indication to jejunal biopsies. The above tests do not replace jejunal biopsy in CS diagnosis. They can be applied in monitoring children with CS during gluten challenge and in checking how the gluten-free diet is observed. Significantly higher stimulation of leucocyte migration in gluten environment was proved in children suffering from CS as compared with the control group. Stimulation of migration is supposed to indicate cellular hypersensitivity to the antigen used in CS children. After a 24-hour culturing of jejunal mucosal biopsies, significantly elevated concentrations of IgA immunoglobulin and IgG, IgA and IgM AGA were found in the culture medium as compared with those obtained from cultured jejunal mucosal biopsies of control group children. The test of leucocyte migration inhibition and in vitro culturing of jejunal mucosa are quite complex and exacting methods when used in routine practice. Their significance lies in the fact they enable us to study in vitro immunological reactions in children suffering from celiac sprue.

Increased levels of circulating ICAM-1, E-selectin, and IL-2 receptors in celiac disease.

Adhesive interactions between endothelium and circulating cells are crucial for the development of inflammatory reactions. We found significantly higher serum levels of soluble intracellular adhesion molecule-1 (sICAM-1, 492.5 +/- 22.1 ng/ml) in patients with active celiac disease (including IgA-deficient patients) than in patients on a gluten-free diet (335.7 +/- 20.0 ng/ml) (P < 0.001) and healthy controls (207.4 +/- 11.2 ng/ml) (P < 0.001). The concentration of soluble E-selectin in sera from celiac patients (37.2 +/- 3.4 ng/ml) was also higher (P < 0.001) than in sera from healthy controls (15.5 +/- 0.7 ng/ml) but, in contrast to sICAM-1, it remained high in the patients after treatment (30.2 +/- 2.7 ng/ml). Interestingly, the concentration of circulating soluble interleukin-2 receptors, molecules indicating lymphocyte activation, was only increased in sera from patients with active celiac disease (2943.0 +/- 214.1 pg/ml), and the level in sera from treated patients and healthy controls was comparable (1936 +/- 349 and 1416 +/- 111.7 pg/ml). The elevated serum level of soluble cell adhesion molecules could be used as a supplementary, noninvasive procedure for monitoring intestinal immune reactions.