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.

Genetic variants of transferrin in cystic fibrosis.

BACKGROUND: Genetic polymorphism of serum transferrin (Tf) was studied in order to differentiate between protein genetic variants and congenital disorders of glycosylation (CDG), further focusing on unusual findings. METHODS: Screening of Tf hypoglycosylation was carried out by isoelectric focusing with direct immunofixation and Coomassie blue staining in 100 healthy controls and a group of 1247 patients with various symptoms and diagnoses. RESULTS: Of the seven different genotypes detected, a significantly higher (p = 0.004) frequency of Tf C1C2 was found among 92 patients with cystic fibrosis; only the most severe DF508 mutation (in either homozygous or heterozygous form) was regularly present in the carriers of this Tf genotype, in contrast to those with the Tf C1C1 variant. CONCLUSIONS: Association of Tf C2 allele with various malfunctions has been noticed before, but is so far unresolved. This is the a report on increased frequency of Tf C1C2 genotype found in cystic fibrosis. Analysis of larger samples and independent confirmation of our results are needed.

Intracardiac thrombus--a rare complication of the steroid resistant nephrotic syndrome.

BACKGROUND: An intracardiac thrombus is extremely rare in children with the nephrotic syndrome (NS). OBJECTIVES: To present a case report of a child with steroid resistant NS and intracardiac thrombus. METHODS AND RESULTS: A 3.5-year-old boy with the first attack of steroid resistant NS was admitted to the hospital. A histological evaluation of the renal biopsy specimen revealed the minimal changes disease (MCD). There were no mutations in the podocin gene. The treatment with furosemide, albumin, prednisone, metylprednisolone, cyclophosphamide, enalapril and losartan was ineffective, as the intermittent oedema, proteinuria, hypoalbuminemia and hypercholesterolemia were still present. 8 weeks after the disease onset, the sinus tachycardia occurred and the echocardiography revealed a thrombus in the right ventricle, which had gradually proceeded to the pulmonary artery bifurcation. The thrombolysis with 40 mg of alteplase was initiated. Two hours after the alteplase application, the thrombus was not detectable. The mutational analysis of factors V, II and MFTHR genes were negative. The repeated echocardiography performed after 1 week, 2 and 6 months, respectively, revealed a normal cardiac function and morphology. The patient received prophylactic doses of fraxiparin for 3.5 months followed by warfarin. A remission of the nephrotic syndrome was achieved with high doses of cyclosporine A together with atorvastatin at 7 month after the disease onset. CONCLUSION: The thromboembolism as a result of the hypercoagulation status is a serious complication of the nephrotic syndrome. The intracardiac localisation of thrombus is extremely rare (Fig. 2, Ref. 10). Full Text (Free, PDF) www.bmj.sk.

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.

Genetic variants of transferrin in the diagnosis of protein hypoglycosylation.

Human transferrin (Tf) shows genetic polymorphisms, which may interfere in the screening of congenital disorders of glycosylation (CDG). Isoelectric focusing followed by direct immunofixation was used for Tf analysis in controls and several groups of patients. Equivocal results in one case have been recognized as a rare Tf CD variant. A higher incidence of some genetic variants has been reported in connection with certain diseases; of the seven Tf phenotypes detected in our set of samples, an apparently higher frequency of Tf C1C2 variant found in some groups of patients was not significant.

[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.