Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.

BACKGROUND: Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. AIM: To compare the therapeutic efficacy, tolerability and safety, and patient's preference of budesonide foam vs. budesonide enema. METHODS: Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) were eligible for this double-blind, double-dummy, randomized, multicentre study. They received 2 mg/25 mL budesonide foam and placebo enema (n = 265), or 2 mg/100 mL budesonide enema and placebo foam (n = 268) for 4 weeks. Primary endpoint was clinical remission (clinical activity index < or = 4) at the final/withdrawal visit (per protocol). RESULTS: A total of 541 patients were randomized--533 were evaluable for intention-to-treat analysis and 449 for per protocol analysis. Clinical remission rates (per protocol) were 60% for budesonide foam and 66% for budesonide enema (P = 0.02362 for non-inferiority of foam vs. enema within a predefined non-inferiority margin of 15%). Both formulations were safe and no drug-related serious adverse events were observed. Because of better tolerability and easier application most patients preferred foam (84%). CONCLUSION: Budesonide foam is as effective as budesonide enema in the treatment of active ulcerative proctitis or proctosigmoiditis. Both budesonide formulations are safe, and most patients prefer foam.

Management of reflux disease in clinical praxis in hungary.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a chronic condition that affects a large proportion of the population. The majority of patients are treated in the primary care but effective management of the disease still remains a challenge for specialists as well. A recent survey - based on the case of a typical GERD patient - conducted in Germany indicated that mainly specialists adhered to the guidelines. AIM: The purpose of this study was to conduct a survey among specialists and primary care physician members of the Hungarian Society of Gastroenterology about the practical management of GERD using the same questionnaire as in the German study. METHODS: A questionnaire based on the case of a typical patient with GERD was sent out to a total of 1090 members of the society. The questions concerned general measures for avoiding reflux symptoms (dietary and life-style modifications), diagnosis of GERD and the type of treatment. Answers were compared with those in the German study. RESULTS: A total of 421 questionnaires were evaluated (38 %), which had been returned by 174 general practitioners (GP), 173 gastroenterologists (GE), 41 paediatricians, and 33 surgeons. Only 9 % (38/421) of the responders think that there is no necessity to carry out specific diagnostic approaches before starting any treatment. In 91 % of the cases (25 % always and 66 % only if symptoms persist) doctors carry out specific diagnostic tests (75 % endoscopy, 13 % 24 hours pH-metry, and 12 % X-ray). 47 % of responders start drug treatment at once while 35 % start medications only after getting the results of the requested examinations. 18 % of Hungarian doctors do start with a non-medical therapy. Almost all responders feel that it is important to advise a reduction of weight and a cessation of smoking for GERD patients. Altering specific dietary and life-style habits was considered useful by more than 85 % of our responders. Hungarian physicians were more concerned about different alcoholic drinks and spicy, fatty or bloating meals and less about sweets than their German counterparts. More than 85 % of GPs administer some kind of drug therapy as first choice. Over 65 % of GPs are using the step-down approach with proton pump inhibitors as the initial strategy and 78 %, 76 %, and 81 % of GEs, paediatricians, and surgeons, respectively, do the same. Almost one-third of GPs and paediatricians are willing to continue therapy and almost two-thirds of GPs will reduce the dose of current medical therapy if the GERD patient is responding well to the initial therapy. CONCLUSIONS: Irrespective of the country, specialists are adhering more strictly to the guidelines on the diagnosis and treatment of GERD than general practitioners. The majority of responders, however, ask for endoscopy prior to initiation of any medication and use the step-down approach. Despite the lack of scientific evidence, reduction of weight, cessation of smoking, dietary and life-style modifications are still part of the treatment of GERD in both Germany and Hungary.

Proton pump inhibitor co-therapy normalizes the increased cell turnover of the gastric mucosa both in NSAID and selective COX-2 users.

Proton pump inhibitor (PPI) co-therapy is considered the best strategy in preventing gastrointestinal complications during non-steroidal anti-inflammatory drug (NSAID) treatment, but there is limited information available on its effect on gastric mucosal cell kinetics. To evaluate the effect of PPI co-therapy on gastric mucosa we investigated epithelial cell proliferation, apoptosis, epithelial growth factor receptor (EGFR) and p53 expression in patients on chronic non-selective NSAID or cyclooxygenase-2 selective inhibitor (COX-2) treatment. Gastric biopsies of the antrum were taken from 10-10 patients on chronic NSAID and COX-2, therapy prior and after 6 months PPI co-therapy, and 10 controls without any treatment. Cell proliferation, apoptosis, EGFR and p53 expression were measured by immunohistochemistry. At least 600 glandular epithel cells were encountered and results were expressed as % of total cells counted. We found increased cell proliferation in patients on chronic COX-2 but not on NSAID therapy. Patients on either NSAID or COX-2 therapy had an increased p53 and decreased EGFR expression. PPI therapy reversed not only the increased cell proliferation and p53 expression, but also the suppressed EGFR expression when administered as co-therapy. The fewer gastrointestinal side effects observed during chronic COX-2 therapy may partially be the result of the higher cell proliferation. This effect is not mediated by the EGFR pathway. PPI co-therapy normalizes the disturbed cell kinetics irrespective of NSAID treatment used.

COX-2-selective inhibitors (COXIBs): gastrointestinal safety.

COX-2 selective inhibitors (coxibs) have been developed with the primary aim to reduce/avoid gastrointestinal (GI) toxicity observed during conventional (non-selective) non-steroidal anti-inflammatory (NSAID) therapy. Coxibs have clearly and convincingly been shown to be superior to conventional NSAIDs with significantly less GI side effects. When hard endpoints such as perforation, obstruction, and serious bleeding considered, coxibs reduce the risk by approximately 50 percent. Although selective COX-2 inhibition seems not to be enough for complete elimination of GI toxicity, coxibs posses no more GI toxicity than placebo in prospective clinical studies and further increase in COX-2 selectivity does not reduce GI toxicity. For the initial aim developed, thus coxibs fulfilled their promise and will soon replace conventional NSAIDs.

[Gastrointestinal side effects of non-steroidal anti-inflammatory drugs in high-risk patients--role of selective cyclooxygenase inhibitors]. / A nem szteroid gyulladásgátlók emésztórendszeri mellékhatásai fokozott kockázatú betegekben--a specifikus ciklooxigenázgátlók szerepe.

Non-steroidal anti-inflammatory drugs (NSAID) are the most widely used drugs in the world. Gastrointestinal (GI) side effects of NSAID have a significant economical impact (3-4% clinical GI event, and 1.5% serious/life threatening GI event/year). Selective cyclooxigenase-2 inhibitors (coxibs) are equally effective as non-selective NSAID with about 50% reduction of serious/life threatening GI events. Serious GI events are significantly less in high-risk patients (history of peptic ulcer disease, age over 65 years, treatment with anticoagulants), therefore the use of coxibs is cost-effective in these population. Most of patients with long-term NSAID therapy also require co-therapy with acid suppression or prostaglandin analogue, but coxibs may replace both. The treatment with coxibs in long-term NSAID users thus is cheaper then non-selective NSAID + co-therapy. Patients with GI adverse events during coxib therapy require co-therapy with acid suppression or prostaglandin analogue.

Effect of Helicobacter pylori infection and eradication on gastric epithelial cell proliferation and apoptosis.

OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.

Determination of Helicobacter pylori cagA, vacA genotypes with real-time PCR melting curve analysis.

OBJECTIVES: genotypes of Helicobacter pylori are the focus of interest because they play a prominent role in mucosal injury. The purpose of this study was to determine cagA and vacA genotypes of H. pylori using real-time polymerase chain reaction (PCR) method with a double strain DNA binding SYBR Green I.dye, and to compare this with those of two immunohistochemical methods. METHODS: forty-three paraffin-embedded biopsy tissue samples were examined by histology, epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) immunohistochemistry and melting curve analysis of real-time PCR. RESULTS: the presence of cagA gene was associated with a significantly higher frequency of gastritis (P=0.003) than that of vacA gene with intestinal metaplasia (P=0.045). Significant difference was found between the presence of cagA gene and EGFR expression in intestinal metaplasia cases in comparison with cagA negative samples (P=0.0418). Statistically significant difference was detected between increased cell proliferation and the presence of gastritis. CONCLUSIONS: this method seems to be suitable for H. pylori genotype determination. Sensitivity, speed and simplicity are key areas in the development of PCR assays for H. pylori. Results supported the notion that infection with cagA positive H. pylori strain causes more augmentated cell proliferation in the stomach mucosa.

[Determination of cagA, vacA genotypes of Helicobacter pylori with real-time PCR-method]. / Helicobacter pylori cagA, vacA genotípusának meghatározása real-time PCR módszerrel.

Presence of cagA gene of Helicobacter pylori (H. pylori) increases proliferation of stomach mucosa and it is an index of raised virulence of the bacteria. The vacA gene of H. pylori induces a serious inflammation of stomach. The purpose of this study was to determine cagA and vacA genotypes of H. pylori using real-time polymerase chain reaction (PCR) method with the double strain DNA-(dsDNA) binding SYBR Green I. dye. Results were compared with those of two immunohistochemical methods. 43 patients' paraffin embedded biopsy tissue samples were examined by histology, epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) immunohistochemistry and melting curve analysis of real-time PCR using LightCycler instrument. Results of histology and real-time PCR from gastric biopsies correlated in 57% of cag acases and in 58% of vac cases. Significant difference was detected between normal and gastritis cases in the presence of cagA gene (p = 0.003) and between normal epithelial and intestinal metaplasia cases in the presence of vacA gene (p = 0.045) by investigation of association of histology and genotype of bacterium. Statistically significant difference (p = 0.02) was found between increased cell proliferation and the presence of gastritis. Significant correlation was found between the presence of cagA gene and EGFR expression in intestinal metaplasia cases (p = 0.0418). Results underlie the statistics that infection with cagA positive H. pylori strain increases the cell proliferation on the stomach mucosa and raises the chance of development of intestinal metaplasia. Infection with vacA positive H. pylori inhibits the signal-transduction pathway of EGFR, which influences mechanisms of mucosa repair. The role of EGFR and H. pylori infection is yet unclear in intestinal metaplasia and cancer. The authors' method seem to be suitable for determination of genotypes of H. pylori.

[Comparison of various methods in the detection of Helicobacter pylori infection]. / A Helicobacter pylori-fertózést kimutató eljárások összehasonlítása.

There are several possible methods to detect H. pylori in the gastric mucosa. The aim of our prospective study was to evaluate the diagnostic value of these tests and to define their place in the clinical practice. 109 (45 male, 64 female) patients who underwent upper GI endoscopy were included. Before endoscopy, whole blood was collected for serological test and 13C-UBT (13C-urea breath test) was performed. During endoscopy, multiple biopsies were collected from the antrum and corpus for the examination of H. pylori status by histology and rapid urease test. Patients with positive histology and a positive result of any other examinations, or--in case of negative histology--with two positive results of the remaining examinations were considered to be H. pylori-positive. 50 patients (46%) proved to be H. pylori-positive. Sensitivity and specificity, respectively, were as follows [in brackets: negative predictive value (NPV) and positive predictive value (PPV), respectively]: histology, 98% and 92% (98% and 91%); 13C-UBT, 93% and 98% (94% and 98%); rapid urease test, 83% and 100% (86% and 100%); serological examination, 86% and 74% (88% and 70%). The sensitivity and the clinical role of the methods used for the detection of H, pylori infection is different. Histology is the most reliable method if endoscopy in performed. The positive result of the rapid urease test is also of good diagnostic value. The 13C-UBT is the method of choice if no endoscopy is performed and the clarification of H. pylori status is necessary. This method can be useful to control the success of bacterium eradication as well. The serological examination provides instant result, therefore this method is proposed for screening and epidemiological studies.

[Detection of aneuploidy from gastrointestinal biopsy samples]. / Aneuploidia meghatározása emésztórendszeri endoszkópos biopsziás mintákból.

Aim of the present work was the development of a mechanic cell separation protocol for gastrointestinal biopsy analysis. Evaluation of the technique was performed on selected group of patients who underwent routine endoscopy. Routine gastrointestinal biopsies were obtained after informed consent. 23 gastric (6 healthy, 14 gastritis, 3 adenocarcinoma) and 15 colon samples (5 healthy, 7 colitis ulcerosa, 3 adenocarcinoma) were evaluated. The mechanic disruption of the biopsies was performed by Medimachine (DAKO, Denmark), a commercially available system using a 30 microns miner and a 30 microns mesh. The cell solution was centrifuged for 5 minutes by 250 g. The cells were fixed in paraformaldehide and stained by propidium iodide. The flow cytometry analysis was performed on a BD FacStar Plus flow cytometer. The DNA data were evaluated using the Winlist software. All of the preparations were appropriate for flow cytometric analysis. The coefficient of variation of the DNA histograms (n = 7) (CV mean +/- SD. 6.45% +/- 1.21) were acceptable for analysis. In the gastric biopsy samples aneuploidy was determined only in malignant cases. In four of the seven colitis ulcerosa samples and in one of the three adenocarcinoma aneploidy was found. The histologically healthy specimen were all diploid. Mechanic cell separation and disaggregation is a useful method for preparing fresh biopsy specimen for flow cytometry.

Quantitative DNA and morphometric analysis of gastroscopic brush smears by TV image analysis.

OBJECTIVES: To determine quantitative nuclear morpho-and densitometric classifiers and classification techniques for analysis of gastric, Feulgen-stained brush smears. DESIGN: TV image analysis-based quantitative DNA and morphometric analysis of gastric brush smears in a prospective study. PATIENTS AND METHODS: Ninety-eight (11 normal, 77 gastritis (17 with intestinal metaplasia) and 10 adenocarcinoma) Feulgen-Schiff-stained gastric brush smears were analysed by TV image analysis. The classification of the smears was based on parallel histological examination. For standards, DNA content of lymphocyte cell cultures was determined by the image and by flow cytometry. From every nucleus, six morphometric (surface, layers, minimum diameter, maximum diameter, perimeter and form factor) and six densitometric (integrated optical density (IOD), average density, sigma density, minimum and maximum density and density range) parameters were simultaneously determined. The smear parameters (object cells CV, DNA index, 2c deviation index, 5c exceeding rate, G1 -S-G2 ratio) were analysed together with the mean and SD values of the nuclear parameters by discriminant analysis and back-propagation neural networks. RESULT: The normal smears were all diploid and their S + G2 ratio was 15.24+/-7.75% (mean +/- SD). The gastritis smears were all diploid with a proliferation fraction of 20.89+/-6.75%. The tumours were aneuploid in eight of the ten cases with 5c exceeding rate > 6.23%, the S + G2 fraction ratio was 34.72+/-10.12%. The mean nuclear surface area was 46+/-20, 58+/-20 and 74+/-22 microm2 in normal, gastritis and malignant groups, respectively. Significant differences (P<0.05) were found in nuclear surface, minimum and maximum diameter, and perimeter parameters. Using linear discriminant analysis, 100% of the non-malignant cases and 70% of the tumour cases were correctly classified. Using 30 non-malignant and five malignant cases as a training set, the neural networks classified 95% of the remaining cases correctly. The DNA index increased significantly (P<0.05) in Helicobacter pylori-positive cases compared to the negative ones. In gastritis with intestinal metaplasia, the proliferation ratio decreased significantly (P<0.05). CONCLUSIONS: The image analysis is a useful tool for quantitative gastric cytology. The combination of nuclear morphometric parameters and neural network classifiers with multivariate quantitative DNA analysis is suggested for gastric brush smear quantitative cytology analysis.

Development of a speech-based dialogue system for report dictation and machine control in the endoscopic laboratory.

BACKGROUND AND STUDY AIMS: Reporting and machine control based on speech technology can enhance work efficiency in the gastrointestinal endoscopy laboratory. MATERIALS AND METHODS: The status and activation of endoscopy laboratory equipment were described as a multivariate parameter and function system. Speech recognition, text evaluation and action definition engines were installed. Special programs were developed for the grammatical analysis of command sentences, and a rule-based expert system for the definition of machine answers. A speech backup engine provides feedback to the user. Techniques were applied based on the "Hidden Markov" model of discrete word, user-independent speech recognition and on phoneme-based speech synthesis. Speech samples were collected from three male low-tone investigators. RESULTS: The dictation module and machine control modules were incorporated in a personal computer (PC) simulation program. Altogether 100 unidentified patient records were analyzed. The sentences were grouped according to keywords, which indicate the main topics of a gastrointestinal endoscopy report. They were: "endoscope", "esophagus", "cardia", "fundus", "corpus", "antrum", "pylorus", "bulbus", and "postbulbar section", in addition to the major pathological findings: "erosion", "ulceration", and "malignancy". "Biopsy" and "diagnosis" were also included. We implemented wireless speech communication control commands for equipment including an endoscopy unit, video, monitor, printer, and PC. The recognition rate was 95%. CONCLUSIONS: Speech technology may soon become an integrated part of our daily routine in the endoscopy laboratory. A central speech and laboratory computer could be the most efficient alternative to having separate speech recognition units in all items of equipment.

Evidence of in vivo peroxynitrite formation in patients with colorectal carcinoma, higher plasma nitrate/nitrite levels, and lower protection against oxygen free radicals.

Endogenously formed nitrogen and oxygen free radicals are believed to be involved in human cancer etiology. Plasma nitrate/nitrite originates from endogenous nitric oxide production in fasting humans, decrease in superoxide scavenger activity (SSA), and free sulfhydryl groups (SH) reflects the amount of superoxide anion generated, and nitrotyrosine is believed to be formed by the interaction of tyrosine and peroxynitrite in vivo. The aim of the current study was to measure plasma nitrate/ nitrite, SSA, and SH in 69 patients (mean age +/- standard deviation, 66 +/- 11 years) with colorectal carcinoma. Nitrotyrosine was measured from both the plasma and tumor tissues in 32 patients. All patients had adenocarcinoma of the colon or rectum. Twenty-five patients were classified as stage B according to Dukes classification as modified by Astler-Coller, 13 were classified as stage C, and 31 patients were classified as stage D. To determine whether the changes are specific for colorectal cancer, 20 patients with active inflammatory bowel disease (IBD; mean age, 52 +/- 18 years) and 30 healthy volunteers, who served as control subjects (mean age, 48 +/- 11 years), were studied. Plasma nitrate/nitrite was measured by the modified Griess method, SSA was measured by an electron/spin resonance spin trapping method, free SH was measured by Ellman's method, and the presence of nitrotyrosine in the plasma and tumor tissue was detected by high performance liquid chromatography (HPLC) using C- 18-derivatized silica (5 microm) column (C18S, Crestpaque, New York, NY, USA) and at a wavelength of 274 nm. Patients with colorectal carcinoma and with active IBD had a significantly higher plasma nitrate/ nitrite level (51.2 +/- 26.2 microm and 56.0 +/- 14.6 microm versus. 29.6 +/- 6.3 microm; p < 0.01), and a lower SSA level (39 +/- 11.5 U/g protein and 52.0 +/- 18.9 U/g protein versus. 88 +/- 25.1 U/g protein; p < 0.05) and SH level (7.7 +/- 3.89 microm protein and 6.4

Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry.

BACKGROUND: [corrected] Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium. METHODS: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58+/-15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n = 10), chronic gastritis without IM (n = 24), chronic gastritis with IM (n = 20), and gastric carcinoma (n = 16). Thirty-three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho- and densitometric parameters of each nuclei and 6 additional parameters of each smear. RESULTS: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3+/-13.05% prior to the eradication and it decreased to 55.8+/-23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in GL phase (r = -0.415) and S phase (r = 0.385), Integrated Optical Density mean (r = 0.598), density maximum (r'= 0.608), surface (r = 0.670), layers (r = 0.638), diameter minimum (r = 0.619), diameter maximum (r = 0.730) and perimeter (r = 0.501), respectively (p < 0.05). CONCLUSIONS: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.

[Effect of Helicobacter pylori infection and eradication on proliferative kinetics of the gastric mucosa]. / A helicobacter pylori-fertózés és az eradikáció hatása a gyomornyálkahártya proliferációjának kinetikájára.

Helicobacter pylori infection is associated with an increased cell proliferation activity, however the exact mechanisms have not been elucidated. Our aim was to study the effect of Helicobacter pylori infection on normal gastric epithelia, gastritis, intestinal metaplasia and carcinoma by the expression of proliferating cell nuclear antigen and nucleolus organizer regions. Antral biopsies were taken from 121 patients (61 women, 60 men; mean age 58.5 y.). Sections were scored for normal epithelia (n = 15), gastritis without intestinal metaplasia (n = 74), gastritis with intestinal metaplasia (n = 24) and gastric carcinoma (n = 8). 52 patients had H. pylori positive gastritis, and success of eradication therapy was controlled in 34 cases. To characterize cell proliferation immunohistochemistry (PCNA) and histochemistry methods (AgNOR) were used. Results of PCNA and AgNOR significantly correlated except of that in the intestinal metaplasia group. PCNA LI and AgNOR counts were not significant higher in H. pylori positive compared to the H. pylori negative gastritis. Presence of H. pylori caused higher proliferation rate in intestinal metaplasia group measured by PCNA. In the group of intestinal metaplasia the proliferation activity decreased to the activity of the normal epithelia after the successful eradication, but remained high if eradication therapy was failed. Our results suggest, that H. pylori infection plays only as a co-factor in gastric carcinogenesis. Results were controversial in the intestinal metaplasia group, that can be explained by the heterogeneity of the bacteria.

MSC, a new benzoquinone-containing natural product with antimetastatic effect.

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) has been invented by Hungarian chemists under the trade name of AVEMAR. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes in mice. The same treatment shortens the survival time of skin grafts in a co-isogenic mouse skin transplantation model, pointing to the immune-reconstructive effect of MSC. A highly significant antimetastatic effect of MSC has been observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic effect of MSC--besides the immune-reconstitution--may also be due to its cell adhesion inhibitory, cell proliferation inhibitory, apoptosis enhancing, and antioxidant characteristics, also observed in our in vitro experiments. It is even more noteworthy that combined treatment with MSC and one of the following antineoplastic agents (5-FU and DTIC)--both in wide use in every day clinical practice--exhibited a significantly enhanced antimetastatic effect in appropriate metastasis models (established from C38 mouse colon carcinoma and B16 mouse melanoma respectively) as compared to the effect elicited by any component of these therapeutic compositions (MSC + 5-FU and MSC + DTIC) administered alone. The results show that the fermented wheat germ extract (MSC) has more than an additive effect and synergistically enhanced the metastasis inhibitory effect of both antineoplastic agents studied till now. It is also worthy of mention that the synchronous treatment with MSC profoundly decreased the toxic side effects of the applied antineoplastic agents (decreased weight loss etc). Based on the biological effects of MSC--shown to be non-toxic by subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immune-deficiency.

[A new benzoquinone-containing antimetastatic product]. / Egy új, szubsztituált benzokinon tartalmú antimetasztatikus készítmény.

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) was invented by Hungarian chemists under the trade--name of AVEMAR. The following biological effects of this product were observed. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes of mice. The same treatment shortens the survival time of skin grafts in co-isogenic mouse skin transplantation model, which points to immune-reconstructive effect of MSC. Highly significant anti-metastatic effect of MSC was observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic activity of MSC--besides the immune reconstitution--may also due to the cell-adhesion inhibitory, cell proliferation inhibitory, apoptosis-enhancing and antioxidant effects, which were also observed in our in vitro experiments. Based on the biological effects of MSC--which is non-toxic, according to subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immunedeprivation.

Octreotide in the prevention of pancreatic injury associated with endoscopic cholangiopancreatography.

BACKGROUND: Data on whether long-acting somatostatin analogue octreotide causes or prevents pancreatic injury following endoscopic retrograde cholangiopancreatography (ERCP) are controversial. AIM: This multicentre, prospective trial studied the effect of octreotide on pancreatic injury in a large unselected group of patients after ERCP and endoscopic sphincterotomy. METHODS: The study was carried out in a prospective random manner on 2102 patients in 11 endoscopic centres. Patients in the study received 0.1 mg octreotide acetate and those in the control group received isotonic sodium chloride, subcutaneously before and 45 min after ERCP. Pancreatic injury was assessed by clinical symptoms such as pain, fever and abdominal tenderness. Serum amylase and blood sugar were determined prior to, and 6 and 24 h after the endoscopic procedure. RESULTS: Data from 599 patients in the study group and 600 in the control group were included in the final evaluation. When all the patients were considered, octreotide did not induce pancreatic injury as assessed by clinical symptoms, and diminished the increase of serum amylase levels following ERCP. However, when subgroups of patients were studied, the frequency of increased amylase levels decreased significantly in patients with chronic obstructive pancreatitis and in patients who underwent endoscopic sphincterotomy (P < 0.01). The peak serum glucose level was higher in the treated group when compared to the controls. CONCLUSION: The prophylactic use of long-acting somatostatin does not alter the frequency of post-ERCP pancreatic injury, but it may diminish the rate of increased serum amylase levels in patients with chronic obstructive pancreatitis and also in those with an endoscopic sphincterotomy.