Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets with ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis.

BACKGROUND: There are no comparative studies of coated mesalazine. AIM: To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis. METHODS: A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission. RESULTS: Of 215 patients, 69% achieved clinical remission in both treatment groups (P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified. CONCLUSIONS: Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks.

A double-blind dose-escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis.

BACKGROUND: Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations. AIM: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups. METHODS: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g. RESULTS: The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients. CONCLUSIONS: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.

Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine.

BACKGROUND AND AIMS: Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. PATIENTS AND METHODS: In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. RESULTS: The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. CONCLUSIONS: The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.

[Peptic ulcer and Helicobacter pylori, diagnosis and therapy]. / Peptický vred a Helicobacter pylori, jak je diagnostikovat a lécit.

The diagnosis of peptic ulcer must be precise and based on both endoscopic examination (in the case of gastric ulcer to differentiate between benign or malign ulcers), and on bioptic examination. Peptic ulcer is pathogenetically associated with H. pylori. A small group of patients with duodenal ulcers and without H. pylori or without an other known cause (NSAID, etc.) is a poorly defined sub-group of patients. H. pylori has an important role in the pathogenesis of gastritis and bulbitis. Both states are involved in the pathogenesis of peptic ulcer. If H. pylori is eradicated, inflammatory changes of the gastric and duodenal mucosa recede and the recurrence of peptic ulcer decreases to a minimal size. For estimation of H. pylori, several invasive and non-invasive techniques are used. Among invasive methods most used in peptic ulcers, a combination of the rapid urease test and histology seems to be the most important. Among non-invasive methods, the breath tests are the most reliable. The treatment is focused on the eradication of H. pylori (no H. pylori is found one month or more after completed therapy). Of the eradication regimens, the triple therapy with proton pump inhibitors, claritromycin and metronidazole or amoxicillin are most effective. If this therapy fails, quadrutherapy (triple therapy combined with colloid bismuth subcitrate) may be successful. The precise diagnosis of peptic ulcer and H. pylori infection is a basic prerequisite for rational therapy of peptic ulcer disease and its relapses.

Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis.

BACKGROUND: Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non-pathogenic E. coli. METHODS: A total of 120 patients with inactive ulcerative colitis were included in a double-blind, double-dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse-free times and global assessment. RESULTS: The start and end scores of the CAI demonstrated no significant difference (P = 0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse-free time of 103 +/- 4 days for mesalazine and 106 +/- 5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported. CONCLUSIONS: From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.

[Helicobacter pylori eradication in patients with diseases of the stomach]. / Moznosti a význam eradikace Helicobacter pylori u osob s onemocnením zaludku.

The authors present a review of contemporary findings concerning treatment of gastroduodenal ulcers with a positive finding of Helicobacter pylori. Only combined anti-Helicobacter treatment leads to the eradication of Helicobacter pylori in 80-96% of the patients. Moreover it leads to gradual recovery from gastritis and bulbitis and thus prevents ulcer recurrence.

Gastric juice neopterin in Helicobacter pylori infection.

Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori, a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 +/- 15.6 vs. 2.1 +/- 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 +/- 12.0 vs. 11.1 +/- 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 +/- 3.2 vs. 1.3 +/- 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 +/- 4.6 vs 1.6 +/- 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.

[Thrombocytes as an indicator of activity in Crohn's disease treated with total parenteral and/or enteral nutrition]. / Trombocyty jako ukazatel aktivity u Crohnovy nemoci lécené úplnou parenterální a/nebo enterální výzivou.

UNLABELLED: Inflammatory bowel disease can be associated with increased platelet count. Aim of our study was focused on assessing thrombocyte count in evaluation of the activity in Crohn's disease (CD). The study included a total of 19 patients [6 men, 13 women (aged 18-57 years, mean 33, median 28]. All patients were malnourished in active stage of the disease on total parenteral and/or enteral nutrition (TP/EN). Thrombocytes were estimated at the beginning and after 3 weeks of TP/EN in venous blood sample using automatic analyser Coulter Counter JT3 (normal range: 130-380.10(9)/l). Serum prealbumin, transferrin, haptoglobin, alpha 1-orosomucoid and C-reactive protein were measured simultaneously. Thrombocytes count below 400.10(9)/l was found only in 1/19 at the beginning and in 7/19 patients in the end of the study. After 3 weeks of TP/EN a significant platelet count fall was found (mean +/- sd: 472 +/- 98 vs. 354 +/- 110, p < 0.01). A correlation was found between thrombocytes and serum prealbumin (r = -0.3871, p < 0.05), haptoglobin (r = 0.5247, p < 0.001), alpha 1-orosomucoid (r = 0.4857, p < 0.01) a C-reactive protein (r = 0.4354, p < 0.01). CONCLUSION: Thrombocyte count helped in the assessing of disease activity in CD on 3-week-TP/EN. Improvement of clinical status, increase of nutritional parameters and decrease of positive acute phase reactants were associated with a fall of platelet count in 15/19 patients.

[Helicobacter pylori in the etiology of ulcer disease and gastritis]. / Helicobacter pylori v etiologii vredové choroby a gastritidy.

Helicobacter pylori (Hp) is unequivocally the most frequent cause of antral gastritis and most probably participates in the majority of cases in the aetiology of gastritis affecting the body of the stomach. The close relationship between antral gastritis and duodenal ulceration is documented by the high incidence of Hp in these patients (90-100%). The problem of Hp negative cases of duodenal ulceration was not finally resolved yet. The absence of Hp in duodenal ulcer usually implies a different aetiology (NSAID, gastrinoma etc.). Hp is eliminated by a number of drugs (bismuth preparations, some antibiotics, metronidazole), however, eradication (Hp negativity after a month or longer following termination of treatment) is ensured so far only by a combination of several drugs. Less clear are the relations with gastric ulcers. The presence of Hp in the antral mucosa is substantially smaller, however, when the mucosa near the ulcer is examined it is also almost 100%. The relationship of antral gastritis and non-ulcer dyspepsia is not quite clear. Hp is found in about half the patients and its elimination (e.g. by bismuth preparations), has a favourable impact on inflammatory changes as well as on the patient's complaints. The regression of complaints is more permanent than after antacids which have only a favourable effect on complaints but not on Hp and the inflammation.

Immunoglobulin G subclasses in Crohn's disease with and without bowel resection.

Increased immunoglobulin G2 [IgG2] in Crohn's disease in contrast with increased IgG1 in ulcerative colitis was reported in literature data. The aim of our study has been focused on serum IgG subclasses in Crohn's disease with resected bowel (11 patients) and without previous surgery for Crohn's disease (12 patients). All patients were in active stage of the disease on total parenteral nutrition. Serum IgG subclasses were estimated by means of radial immunodiffusion. There was no significant differences between in IgG subclasses in Crohn's disease with and without bowel resection. IgG2 over 4.5 g/l was found only in 2/12 with resected bowel and 1/11 without previous surgery for Crohn's disease. Surprisingly, IgG1/IgG2 ratio below 1.5 was found only in 5/23 persons. In 3/23 patients IgG1 was over 10.5 g/l although there was no doubt about the diagnosis of Crohn's disease. IgG subclasses failed to help in confirmation of the diagnosis of Crohn's disease. Serum IgG subclasses alterations probably are not influenced by bowel resection and/or nutritional status.

[An unusual expression of cALL antigen on blast cells in a patient with acute myelomonocytic leukemia]. / Neobvyklá exprese cALL antigenu na blastických bunkach nemocného s akutní myelomonocytární leukémií.

The authors describe a case of myeloid leukemia of the myelomonocytic type (M4, FAB 1976) where blastic cells bear the lymphoblastic cALL sign. These cases of the so-called hybrid phenotype of acute leukemia are rare. The importance of the hybrid phenotype for the course and prognosis of the disease is not known.

[Plasmapheresis in the treatment of Crohn's disease]. / Plazmaferéza v lécbe Crohnovy choroby.

Crohn's disease is a disease with unknown etiology of which immunological mechanisms participate. As standard treatment is sometimes ineffective, in 15 patients therapeutic plasmapheresis was used. Before plasmapheresis and immediately after it some immunological parameters were assessed. In the serum a significant drop of all immunoglobulins of the basic classes was recorded: (P less than 0.05) and of circulating immunocomplexes (P less than 0.02). Marked clinical improvement was observed in three patients, which as compared with data in the literature, is somewhat less. The cause is in the author's opinion in the selection of patients (plasmapheresis is usually most successful in patients with marked activity of the disease and non-intestinal symptoms) even in case of less active plasma exchange. Despite this plasmapheresis can be recommended in patients with a poor response to common conservative treatment and in some of them we may expect a marked therapeutic effect with a favourable influence on the prognosis of the disease.

[Colicinogeny in nonspecific intestinal inflammations and colorectal cancer]. / Kolicinogenie u nespecifických strevních zánetu a kolorektální rakoviny.

Colicins are proteinaceous substances produced by Escherichia coli strains and related bacteria of Enterobacteriaceae family. They are considered to be an important factor in preserving the balance of the intestinal microflora. Their antibiotic action on susceptible bacteria is supplemented with cytotoxicity for several pro- and eukaryotic cells. The large bowel is a natural site of their action. Besides of enhancing oxidoreductive activity of leukocytes in vitro, colicins are also believed to influence inflammatory reaction in vivo. For these reasons, the first part of the present work was concerned with studying colicinogeny in nonspecific inflammatory bowel diseases (IBD). No significant difference has been found out in colicinogeny between a total of 93 IBD-related and 160 healthy controls. In testing leukocyte migration inhibition, colicins of autologous E. coli were used as antigens. The migration index out of normal range showed 36% patients with ulcerative colitis (5/14), 80% patients with Crohn's disease (12/15), and only one clinically healthy control subject (1/16; 6%). The obtained results are considered to be proof of cellular hypersensitivity of IBD patients to colicins of their own E. coli strains. In several colicins the antitumorous effect has been reported in both the in vitro and in vivo experimentation. The second part of this work was concerned with colicinogeny in colorectal cancer. Colicinogenic E. coli were evidenced in 42 subjects (40%) from 105 patients with colorectal carcinoma. Controls showed colicinogenic E. coli in 102/160 clinically healthy subjects (64%), and the difference was as significant as p less than 0.05. In colorectal cancer group, the subjects with proved colicinogeny showed lesser amounts of colicinogenic E. coli strains in contrast with non-colicinogenic ones. In colorectal cancer patients with colicinogenic E. coli strains, B and M colicins were of most frequent occurrence in them no antitumorous effect has been experimentally stated. If changes of colicinogeny were only either the manifestation or consequence of tumor disease, so both the presence or absence of colicinogenic E. coli would have been dependent of clinical patients's condition, stage of disease (in accord with Dukes) or correlated with the tumor markers. For these accounts, a total of 28 colorectal cancer patients underwent a colicinogenic study. However, no colicinogeny dependence was evidenced of either clinical condition or Dukes stage, showing no correlation with any of cancer markers investigated (carcinoembryonic antigen, CA 19-9, alfa-1-fetoprotein, alfa-1-orosomucoid, Cancer serum index, sialic acid, lysozyme).(ABSTRACT TRUNCATED AT 400 WORDS)

Specific cellular immune response in patients with Helicobacter pylori infection.

The leukocyte migration inhibition test was performed in 39 patients with Helicobacter pylori infection and in 38 patients without such infection. The culture of Helicobacter pylori was used as antigen. A highly significant inhibitory effect on leukocyte migration was found in patients with Helicobacter pylori infection. The results can be taken as proof of a systemic immune response to helicobacters at the cellular level in patients with Helicobacter pylori infection.

[Human immunodeficiency virus infection and the pathogenesis of AIDS]. / Infekce virem lidského imunodeficitu a patogeneze onemocnení AIDS.

The prerequisite of effective infection with the virus of human immunodeficiency (HIV) are the interaction between the CD4 complex of the susceptible cell and outer glycoproteins of the virus. The CD4 complex is found above all on the sub-population of helper inducer T lymphocytes and cells of the monocyto-macrophage line. These interactions are essential for the penetration of the virus into the cell and participate also in the fusion of infected and non-infected cells which is typical for HIV infection. The outer layer glycoproteins of HIV are immunogenic, however, the antibodies which are formed do not neutralize the virus. It is even probable that antibodies can under certain conditions facilitate the penetration of HIV into cells which have on their surface receptors for the Fc fragment of immunoglobulin, i.e. in the first place into cells of the monocyte-macrophage line. These cells play obviously a key role in HIV infection because they are resistant to the cytopathic action of the virus and during their numerous physiological functions serve above all as cells, presenting antigen to T lymphocytes and thus are repeatedly in close contact with other cellular elements of the immune system and may thus help to spread HIV in the organism.

[Excretion of phenol and p-cresol in the urine in fasting obese individuals and in persons treated with total enteral nutrition]. / Vylucování fenolu a p-krezolu mocí u hladovejících obézních a u osob lécených úplnou enterální výzivou.

In the literature it is maintained that phenol and p-cresol are produced in humans in the gut by bacteria from dietary protein. Both substances are absorbed from the small intestine and excreted in the urine. If the urinary output of phenol and p-cresol depends really on the dietary protein intake it should decline to zero values during fasting and correlate with the protein supply into the gut. The objective of the present work was therefore to investigate the urinary phenol and p-cresol excretion in fasting obese subjects (21 fasting subjects, 7 subjects with modified fasts--Nutramine R-350) and in subjects treated by complete enteral nutrition by a nasojejunal tube (8 patients with Crohn's disease, 8 with another disease of the gastrointestinal tract). Phenol and p-cresol in 24-hour urine specimens were assessed by gas chromatography in all four groups always on the 1st, 7th and 14th day. In fasting obese subjects the phenol and p-cresol values did not decline (the difference of values from the assumed zero value is significant z = 0.000055). There was no difference between patients with a complete and modified fast. The phenol and p-cresol values did not correlate mutually, nor with the protein intake, nitrogen balance and cumulated nitrogen balance. There are great individual differences in the urinary phenol and p-cresol excretion and it does not depend on the oral dietary protein intake, as hitherto assumed. It has most probably more complex causes and the decisive factor seems to be the metabolic activity of the intestinal bacterial microflora.

[Campylobacter pylori, its detection and association with common pathologic conditions of the gastro-duodenum]. / Campylobacter pylori, jeho prukaz a vztah k nekterým castým patologickým stavum gastroduodena.

The authors evaluate clinical experience based on a correlation between the clinical condition and the finding of Campylobacter pylori (CP) in a total of 1027 specimens of the gastric mucosa. They confirmed the high incidence of CP in patients with a fresh duodenal ulcer (g 7%) but also in the inactive stage of duodenal ulcer disease (97.8%) and in patients with a pyloric ulcer (94.4%). An analogous incidence of CP in patients with so-called isolated duodenitis (in the course of the disease no ulcer lesion was ever detected), i.e. in 95.5%, indicates the relationship of this condition with peptic ulcer disease. The authors indicate diagnostic possibilities as regards CP infection by cultivation, rapid urease tests and microscopic examination and they emphasize the practical value of urease tests. Based on their own experience the authors confirm the high eradication effect of bismuth preparations, in particular bismuth subsalicylate and colloid bismuth subcitrate.

[Acute phase proteins in acute myocardial infarct]. / Proteiny akutní fáze u akutního infarktu myokardu.

The authors investigated changes of proteins of the acute stage (transferrin, prealbumin, orosomucoid, alpha-1 antitrypsin) after the development of acute coronaries. Blood specimens were collected from 84 patients with the diagnosis of acute myocardial infarction (AMI) on the 1st, 3rd, 7th and 21st day of hospitalization. The authors observed a significant reduction of transferrin and prealbumin values on the third day after the development of AMI and a significant rise with a maximum on the 7th day in orosomucoid and alpha-1 antitrypsin (p less than 0.05). The assessed changes are consistent with data reported in the literature. When the patients were divided into groups with AMI type Q and AMI type non Q, the authors observed a significant rise of alpha-1 antitrypsin on the 7th day in group AMI type Q (p less than 0.01). In patients with AMI type non Q alpha-1 antitrypsin was within the normal range, while in group AMI type Q it was on the 3rd and 7th day beyond the normal range. In the remaining proteins of the acute stage no significant differences were found on comparison of the two groups.

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.