Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe--a Hungarian nationwide observational study.

BACKGROUND: Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. METHODS: During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6) at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. RESULTS: Three hundred and sixty three patients (183 women and 180 men) were treated with IFX since 2000. Mean age was 33.5 +/- 11.2 years and the mean duration of disease was 6.7 +/- 6.1 years. The population included 114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26 patients (7.2%) with steroid dependent CD. Overall response rate was 86.2% (313/363). A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99) and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596). Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections (4.4%), and 3 malignancies (0.8%). CONCLUSION: IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

[Neutropenia and sepsis in hematologic patients]. / Neutropenia és szepszis a hematológiai osztályon: a Kaposi Mór Oktató Kórház tapasztalatai.

INTRODUCTION: The neutropenic patient's infections are challenging problems for modern medicine. The increasing number of iatrogenic neutropenia, the invasive procedures and the growing resistance to antibiotics and antimycotics make the treatment of sepsis difficult. The aim of this study was to analyse the frequency and mortality of neutropenic infections in hematologic patients. METHODS AND RESULTS: In the department of the authors 146 patients with sepsis were diagnosed out of 2173 treated patients in 24 months (67/1000 patients). 78 of them were neutropenic (absolute neutrophil count below 0,5 G/I) and 63 were severe neutropenic (absolute neutrophil count below 0,1 G/I). Sepsis occurred on the 10-11th day of neutropenia. 45% of positive hemoculture were caused by Gram positive bacteria, 30% by Gram negative bacteria, 10% by fungi and 15% were polymicrobic infections. The overall mortality was 36%, but in the severe neutropenic group it was about 60%. CONCLUSIONS: These results show that despite of the use of new, broad spectrum of antibiotics and antimycotics in neutropenic patients with sepsis, it is difficult to treat these patients.

Crohn's disease is associated with polymorphism of CARD15/NOD2 gene in a Hungarian population.

Crohn's disease (CD) is commonly classified as an immune-mediated disorder, but genetic and environmental factors seem to be important in its pathogenesis. Mutations within the CARD15/NOD2 gene have been associated with CD in the Caucasian population. The aim of our work was to investigate the allele frequency and clinical impact of the three common mutations in Hungarian CD patients and healthy controls. Seventy-four CD patients and 107 controls were examined. The genotyping of the three common CARD15/NOD2 mutations (Arg702Trp, Gly908Arg, and Leu1007fsinsC) was carried out by restriction fragment length polymorphism (RFLP) and amplification refractory mutation system (ARMS) techniques. The demographic and clinical parameters were correlated with chi(2) analysis. The overall prevalence of CARD15/NOD2 mutations in the Hungarian CD patients (33.78%) was significantly higher than in healthy control individuals (16.23%) (P < 0.025). The allele frequency of the Gly908Arg mutation did not differ, but the Arg702Trp and Leu1007fsinsC mutation were more common in CD patients than in controls. The onset of CD occurs about three years earlier in CARD15/NOD2 carriers. Carriage of the Arg702Trp and Leu1007fsinsC allele within the CARD15/NOD2 gene is associated with CD. These data are in line with similar findings showing a role of the CARD15/NOD2 protein in the etiopathogenesis of CD. The genotyping of these mutations might be used to identify high-risk patients.

Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary.

AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers. METHODS: The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used. RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer. CONCLUSION: Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

Protective effect of lactulose on dextran sulfate sodium-induced colonic inflammation in rats.

Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS), and histology were examined. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. These results demonstrated the protective effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora.

Hemochromatosis (HFE) gene mutations and hepatitis C virus infection as risk factors for porphyria cutanea tarda in Hungarian patients.

AIM: It is not clear whether the mutations in hemochromatosis (HFE) gene and hepatitis C virus (HCV) infection act independently in the pathogenesis of porphyria cutanea tarda (PCT). The prevalence of both risk factors varies greatly in different parts of the world. PCT patients from Hungary were evaluated to assess both factors. METHODS: The prevalence of C282Y and H63D mutations in the HFE gene was determined in 50 PCT patients and compared with the reported control frequencies. Furthermore, the presence of HCV infection was determined and related to the patients' HFE gene status. RESULTS: The C282Y mutation was found in 8/50 cases (three homozygotes and five heterozygotes), with an 11% allele frequency (vs. 3.8% control) (P<0.05). Seventeen patients were heterozygous, one was homozygous for the H63D mutation, allele frequency 19%, which did not differ significantly from the reported control prevalence of 12.3%. Twenty-two patients (44%) were HCV-RNA positive; six out of them were heterozygous for H63D mutation, one only for the C282Y mutation and one was compound heterozygous for both mutations. CONCLUSION: HCV infection and HFE C282Y mutation may probably be independent predisposing factors for development of PCT in Hungarian patients.

[Experiences in the invasive treatment of acute coronary syndrome]. / Tapasztalataink az akut coronaria-szindróma invazív kezelésével.

INTRODUCTION: Primer percutaneous coronary intervention is a very powerful tool in the treatment of acute coronary syndrome. The aim of the authors was to work out and analyse the methods of making the upto-date percutaneous coronary intervention available for patients living far from the Heart Institute. PATIENT AND INTERVENTIONS: Between 1st January 2000 and 31st October 2002, 221 patients with acute coronary syndrome were sent to intensive treatment from Kaposvár to the Heart Institute in Pécs partly by helicopter. The average age of patients was 54 years. 103 of them with acute myocardial infarction and 118 others with unstable angina were catheterised. Revascularization was achieved in 133 cases, and coronary operation in 63 cases. Primary intensive therapy was applied on 34 patients with infarction. RESULTS: No lethal complications arose during transport or operation. Mortality rate coming from cardial complications was only 4% during the first two years. These results are based on well organised cooperation between the Department of Internal Medicine Kaposvár and Heart Institute Pécs. CONCLUSION: Given suitable logistic background and adequate indication the risk of transporting patients can be taken. The percutaneous coronary intervention proved to be successful.

Effect of retinoic acid treatment on cytogenetic remission of chronic myeloid leukaemia.

The cytogenetic responses during the first chronic phase of 11 patients with chronic myeloid leukaemia (CML) treated with all-trans retinoic acid (ATRA) + interferon (IFN) were compared with those of 9 other CML patients treated with IFN alone. Metaphase and interphase cytogenetics and a semi-quantitative polymerase chain reaction were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + IFN group were withdrawn, one of them because of IFN intolerance, and the other because of non-compliance. Of the 9 remaining ATRA + IFN-treated patients 6 exhibited major cytogenetic responses, 3 of which were complete. Of the 9 patients treated with IFN alone, only 2 showed major cytogenetic responses. No severe adverse effects were observed. The preliminary results suggest that the ATRA + IFN combination may be superior in achieving cytogenetic remission in the first chronic phase of CML.

[New methods for the diagnosis of acute pulmonary embolism]. / Az akut pulmonalis embolia diagnosztikájának újabb lehetöségei.

INTRODUCTION: Pulmonary embolism is a high mortality cardiovascular disease, which is difficult to diagnose even today. AIM AND METHOD: In this study the symptoms and the results of diagnostic methods were analysed in 81 patients with acute pulmonary embolism, admitted during a one-year period to Kaposi Mór County Hospital. The patient records were examined with special emphasis on the diagnostic value of novel methods such as D-dimer assay and chest computed tomography scanning along with the routine techniques used in the management of pulmonary embolism. RESULTS: In all patients ECG, in 88% of the cases chest X-ray, in 57% blood gas analysis and in 53% D-dimer assay results were evaluated. 14.8% of the patients died during hospitalisation. The following diagnostic imaging procedures were undertaken: in 80.2% of the cases lung scan, in 59.3% echocardiography and in 8.7% of the cases spiral computed tomography scan were prepared. In 12.3% of all cases thrombolysis proved necessary. The results were compared with data from International Cooperative Pulmonary Embolism Registry Study, which analyses 2454 patient cases. CONCLUSION: It is foreseen that the increasing use of echocardiography, lower limb ultrasound and highly informative spiral computed tomography scanning as an additional means in pulmonary embolism diagnostics may in some cases spare the use of pulmonary scintigraphy.

[Prevalence of Leiden mutation in various gastrointestinal disorders]. / A Leiden-mutáció prevalenciája a különbözó gastrointestinalis kórképekben.

Molecular biological examinations have been carried out by the authors from 1995 in patients with different haemostasis, very recently these types of the studies were done in patients with different gastrointestinal (Helicobacter pylori-induced gastritis, hepatitis C infection, ileitis terminalis, ulcerative colitis, colon polyposis and adenocarcinoma in polyps) disorders. AIM, PATIENTS, METHOD: The Leiden mutation was detected by polymerase chain reaction (PCR) in 1354 healthy persons and patients with different GI disorders. RESULTS: The results of Leiden prevalence in patients with different gastrointestinal disorders were compared to those obtained in patients with venous thrombosis and familiar thrombophilia. The authors indicated that the prevalence of heterozygous Leiden positive persons was 5.9% in healthy (n = 87) and blood donors (n = 600). The prevalence of heterozygous Leiden mutation was 27% in patents who under went venous thrombosis (n = 300; P < 0.001), 38% in patients with familial thrombophilia (n = 116; P < 0.001). The prevalence of Leiden mutation was 0 in patients with Helicobacter pylori-induced gastritis (n = 24), 8% in hepatitis C infections (n = 75), 14.28% in Crohn's disease, (n = 49; P < 0.01), 27.5% in ulcerative colitis (n = 35; P < 0.001), 44% in colon polyposis (n = 59; P < 0.001) and 55% in situ adenocarcinomas (in polyposis) (n = 9; P < 0.001). CONCLUSION: The presented results suggest that the Leiden mutation is involved in patients with different inflammatory bowel disease, colon polyposis, as one of the suggested genetic factors.