[Epstein-Barr virus genome positive lymphoepithelioma-like carcinoma of the stomach]. / A gyomor Epstein-Barr-vírusgenom pozitív lymphoepitheliomaszerú carcinomája.

EBV is associated with a high number of tumours and non-tumourous conditions. The rare lymphoepithelioma like carcinoma of the stomach,--just as similar tumours of foregut origin (thymus, lung, salivary gland)--are frequently EBV genom positive with the expression of only a few genes (EBV nuclear antigen 1, EBV encoded ribonucleoproteins/EBER/, latency I). On the basis of the clinicopathological analysis of two cases and literature data the authors point out the male predominance and the relatively favourable prognosis of the patients, furthermore the frequent cardial-subcardial localization of these tumours. Since the frequent non-lymphoepithelioma like stomach tumours,--adenocarcinomas,--show EBV genom positivity in about 1% of the cases, it is concluded that the characteristic lymphoepithelioma like histological pattern is not a sine qua non condition of EBV genom positivity. It may also be assumed, that the CD8 and TIA 1 cytotoxic lymphocytes are not virus but tumour cell specific, however not efficient, perhaps not activated. The low level of apoptotic tumour cells supports this assumption. In one of the cases a double tumour, a genom positive lymphoepithelioma like carcinoma and a genom negative adenocarcinoma, adjacent to each other was seen which speaks in favour of common carcinogenetic factors and shows that microscopic neighbourhood is not a necessary condition in viral association. The origin of the possible oncogenic effect of EBV in the absence of the transforming gene products latent membrane protein 1 and EBNA 2 in genom positive stomach carcinomas is uncertain. The significance of the presence in both cases of CD 5+ tumour cells is not clear, the study of further cases is indicated.

[Changes in the treatment of choledocholithiasis]. / A choledocholithiasis kezelésének megváltozása.

UNLABELLED: The therapeutic approaches to gallstone disease and bile duct stone changed dramatically in the last decade by spreading of endoscopic and laparoscopic methods. The authors have reviewed the most frequent curing methods of bile duct stone recently. They examined patients treated for gallstone and common bile duct stone in Surgical Department and Gastroenterological Department of their hospital. Retrospective study was performed to evaluate the issue of treatment for gallstone disease in addition to common bile duct stone (CBDS) and papillary stenosis in the last six years from 1993 to 1998, in the era of laparoscopic cholecystectomy (LC). There was formed a control group from similar patients of these two departments, between 1986-1991, in the six-year period before the laparoscopic era. The postoperative complications and perioperative mortality were analysed in present period compared with the outcome of control group. RESULTS: 734 patients were treated by sequential endoscopic laparoscopic approach or open operation between 1993-1998: 632 endoscopic sphincterotomy (EST), from which 236 LC followed the preoperative EST, 102 open choledochotomy were performed. Overall complications were 4.4% and mortality was 0.9% (EST plus LC plus open operations.) The control group made up of 534 patients underwent a treatment of choledocholithiasis: 196 EST and 338 open choledochotomy were achieved. Complications were 10.6% and mortality was 1.9%. The authors statistically evaluate the retrospective results. They conclude that there is a significant difference in the complications rate between the two groups, but the decrease of mortality is not significant. The mean hospital stay is 6.5 days in the recent group and this value was 13.4 days in the control group. Saving of hospital cost is 62,100 Ft for one patients. The authors think that this sequential approach results in a safer and more effective treatment of cholecysto-choledocholithiasis than the former period's.

Efficacy of nizatidine, clarithromycin and bismuth subcitrate therapy for Helicobacter pylori eradication in duodenal ulcer patients--a preliminary report.

The triple combination of nizatidine, clarithromycin, and bismuth subcitrate resulted in an ulcer healing rate of 98% and an H. pylori eradication rate of 90%. Corresponding 'intention-to-treat' figures were 92% and 84%, respectively. These results suggest that further studies, shorter in duration, using lower dosages, and possibly testing other combinations with a double-blind methodology, are required.

[Bouveret syndrome diagnosed by endoscopy]. / Endoscopos vizsgálat során felismert Bouveret-syndroma.

The case of a 74 years old woman suffered from a gallstone disease for 5 years is reported. In the background of the upper abdominal pain and vomiting, which necessitated her hospitalization, a large-size gallstone penetrated into the duodenal bulb and obstructed pyloric channel was found by endoscopic examination. The upper duodenal ileus was verified during the operation, gastroduodenotomy and cholecystectomy were performed, and the 7 x 4 cm size gallstone was removed. After a complications free period the asymptomatic patient went home. Our above reported case is a preoperatively, endoscopically diagnozed Bouveret's syndrome.

Treatment of duodenal ulcers by antacid (Al-Mg-hydroxy-carbonate). A controlled, randomized, prospective, multicentre clinical trial.

TISACID (a new, modern Hungarian Al-containing antacid) with a high acid-neutralizing capacity (greater than 26.8 mmol/g) also enhances gastric mucosal defense mechanisms (prostaglandin-dependent gastroprotection). A simple-blind, prospective, randomized, parallel multicentre clinical trial has been performed on both the clinical efficacy and possible side effects of TISACID monotherapy (Al-Mg-hydroxy-carbonate) on informed patients suffering from active duodenal ulcers. The study groups were as follows: Group "A": 3 g/day of TISACID (acid-neutralizing capacity = 78 mmol, n = 85), Group "B": 6 g/day of TISACID (acid-neutralizing capacity = 156 mmol, n = 88), Group "C": 12 g/day of TISACID (acid-neutralizing capacity = 312 mmol, n = 68), Group "D": (as control): (1.0 g/day cimetidine (HISTODIL, RGH, Budapest, n = 91). The total number of patients: 332. It was found that: 1. The new Hungarian antacid compound (both tablet and suspension) can essentially accelerate the healing rate of duodenal ulcers. 2. The cumulative healing rate of ulcers and the decrease of complaints can be achieved equally by relatively low doses of TISACID monotherapy and cimetidine alone. 3. There were no differences between the clinical potency and side-effects of TISACID tablet and suspension.

A controlled multicentre therapeutic trial to determine the efficacy of a novel antacid (AI-Mg-hydroxy-carbonate) in duodenal ulcer.

Tisacid (a new, modern Hungarian AI-containing antacid) with a high acid-neutralizing capacity (greater than 26.8 mmol/g) also enhances gastric mucosal defense mechanisms (prostaglandin-dependent gastroprotection). A simple-blind, prospective, randomized, parallel multicentre clinical trial has been performed on both the clinical efficacy and possible side-effects of Tisacid monotherapy (AI-Mg-hydroxy-carbonate) on informed patients suffering from active duodenal ulcers. The four study groups were as follows: Group A: 3 g/day of Tisacid (acid-neutralizing capacity = 78 mmol, n = 85), Group B: 6 g/day of Tisacid (acid-neutralizing capacity = 156 mmol, n = 88), Group C: 12 g/day of Tisacid (acid-neutralizing capacity = 312 mmol, n = 68), Group D (as control): 1.0 g/day cimetidine (n = 91). The total number of patients was 332. It was found that the new Hungarian antacid compound (both tablet and suspension) can essentially accelerate the healing rate of duodenal ulcers; the cumulative healing rate of ulcers and the decrease of complaints can be achieved equally by relatively low doses of Tisacid monotherapy and cimetidine alone; and there were no essential differences between the clinical potency and side-effects of Tisacid tablets or the suspension.

Human tolerability and pharmacodynamic study of Tisacid tablet in duodenal ulcer patients. A prospective, randomized, self-controlled clinicopharmacological study.

A randomized, prospective, crossing-over clinico-pharmacological study was conducted on the tolerability by humans, of TISACID (Al-Mg-hydroxy-carbonate), a new antacid of up-to-date composition produced in Hungary. Even a relatively high dose of the preparation is tolerated by the human organism. During a 6-week continuous treatment neither subjective nor objective side-effects were observed. The tablet is immediately decomposed in the gastric juice, a considerable portion of it will permanently stick to the mucosa of the stomach and duodenum. Depending on the dose, it rapidly and permanently reduces the acidity of the gastric content and increases serum gastrin concentration only moderately and for a short time. Administered together with cimetidine, it promotes healing of duodenal ulcer and the cessation of complaints. It does not increase the aluminium and magnesium concentrations of the plasma not even on prolonged administration, and clinical symptoms and laboratory changes characterizing the phosphate depletion syndrome do not develop either. Based on the results, authors consider Tisacid a beneficial preparation as regards both effectivity and tolerability.

Cimetidine and placebo-cimetidine in the treatment of patients with chronic gastric ulcer (a multiclinical randomized double-blind comparative study).

The efficacy of a 4-week cimetidine treatment was examined by a double-blind randomized study in 37 outpatients with endoscopically verified chronic gastric ulcer. The patients received a daily dose of 3 times 1 tablet and, at night before going to bed 2 more tablet, thus a total amount of 1 g cimetidine, or cimetidine-placebo, but in case of complaints they could take in addition a mixed alkaline powder. Patients not recovering in response to a 4-week treatment, were then administered daily 5 tablets of cimetidine up to their complete recovery. Endoscopic, laboratory and clinical examinations were carried out every other week. As a result of a 4-week treatment, 56% of the cimetidine group recovered. The difference was not significant (P less than 0.2). The size of the ulcer and the intensity of the complaints were reduced significantly in both groups. The decrease in the size of the ulcer was significantly greater in the first two weeks of cimetidine treatment than in the cimetidine-placebo group (P less than 0.05). This favourable dynamics of ulcer healing was not felt in the second two weeks of treatment, and after four weeks there was no difference in the size of the residual ulcer to between the two groups. Cimetidine seemed to be a suitable drug for treating chronic gastric ulcer, since its healing rate proved to be better than that of placebo, the gain in weight also was favourable and there were no side-effects.

Molecular biochemistry and pharmacology of peptic ulcer treatment. A review.

The membrane-bound ATP-dependent energy systems (ATP-membrane ATPase-ADP and ATP-adenylate cyclase-cAMP) play an essential role in the physiological regulation of the gastrointestinal mucosa and its damage in rat and man. A good, physiologically, hormonally and pharmacologically well controlled and regulated feedback system exists between the two energy systems. The significant increase of ATP transformation into ADP or cAMP represents a causative metabolic background of the development of gastric, duodenal and jejunal ulcer (damage) in man and rat. The ulcer preventive effects of vitamin A, beta-carotene, atropine, cimetidine, prostacyclin I2, and surgical vagotomy were studied in connection with their effects on the membrane-bound ATP-dependent energy systems of the gastric, duodenal and jejunal mucosa in man and rat. Atropine and cimetidine were applied in cytoprotective and antisecretory doses, and the tissue levels of ATP, ADP, AMP, cAMP and lactate were measured. The results indicated that the disturbed equilibrium between the two energy supply systems can be modified (normalized) by drugs and surgical vagotomy; the drug effect depends on the actual biochemism of the gastroduodenal mucosa; the values of affinities (pD2) and intrinsic activities (alpha) of the different drugs differ in relation to membrane-bound ATP-splitting enzymes; the changes in the membrane-bound ATP-dependent energy systems of the damaged rat gastric mucosa, produced by vitamin A and beta-carotene, depend on their cytoprotective doses which are connected with their cytoprotective effects; the biochemical changes induced by drugs (given in cytoprotective and anti-secretory doses) differ only quantitatively but not qualitatively; the drug effects on the membrane-located ATP-splitting enzymes (membrane ATPase and adenylate cyclase) in human gastric, duodenal and jejunal mucosa are similar to those in rats, but their affinities (pD2) and also their intrinsic activities (alpha) differ to the enzyme systems.

Biochemical background of the development of gastric mucosal damage in pylorus-ligated plus aspirin-treated rats.

Gastric mucosal damage was produced in rats after pyloric ligation by intragastric administration of 200 mg/kg aspirin diluted in 2 ml 150 mmol/l HCl. The animals in the control group received 2 ml saline solution, or submitted to pyloric ligation only. The animals were killed 4 h after the pyloric ligation, when the number and severity of gastric lesions (ulcers), and the gastric fundic mucosal level of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) and lactate, were noted and measured. The adenylate pool (ATP + ADP + AMP) and the energy charge (ATP + 0.5ADP). (ATP + ADP + AMP)-1 were calculated. It was found that: the gastric H+ output decreased significantly in the pylorus-ligated plus aspirin-treated animals; the number and severity of gastric lesions increased significantly in the pylorus-ligated aspirin-treated animals; the extent of ATP transformation into the ADP decreased significantly in the pylorus-ligated aspirin-treated animals; the extent of ATP transformation into the cAMP decreased significantly during the aspirin treatment; the values of adenylate pool and of "energy charge" remained unchanged in the different groups of animals. It is concluded that: the decreased H+ output in the pylorus-ligated plus aspirin-treated group can be obtained by the decreased extent of ATP transformation into the ADP by membrane ATPase, and the biochemical changes in the gastric mucosa indicate a decreased energy turnover.

Effect of atropine and cimetidine combinations on pentagastrin stimulated maximal gastric acid secretion in man.

Recently it has been reported that anticholinergics were able to increase the inhibitory effect on gastric secretion of specific histamine H2-receptor antagonists. The aim of the present study was to determine the degree of increased inhibition of gastric acid secretion and also to introduce an exact method for measuring the gastric acid output. Maximal gastric acid secretion provoked by continuous pentagastrin infusion 3.4-4.0 micrograms X kg-1 h-1) was dose-dependently inhibited by intravenous (i.v.) atropine (0.002; 0.003; 0.004 mg X kg-1) and cimetidine (1.0; 1.5; 2.0 mg X kg-1). A potentiated synergism was observed on the simultaneous administration of atropine and cimetidine, suggesting the good effect of a low dose combination of atropine and cimetidine in the therapy of peptic ulcer.

Comparison of inhibitory effects of atropine, cimetidine, and atropine plus cimetidine on the indomethacin-provoked gastric mucosal erosions in rats.

20 mg/kg-1 indomethacin suspended in 1% carboxymethyl-cellulose solution was given subcutaneously into rats to provoke gastric mucosal erosions during 5 h. Dose-dependent inhibitions of indomethacin erosions were observed following different doses of atropine (0.025; 0.2; 1.0 mg/kg-1) and cimetidine (2.5; 10; 50 mg/kg-1) administered intraperitoneally (25%; 38%; 81% and 0%; 42%; 89% respectively). More pronounced inhibitory effects have been obtained with the combinations of both drugs (51%; 68%; 92%). In particular there was a remarkable potentiated synergism in the lowest doses of atropine and cimetidine (51%, against 0% and 25%). These results provide further evidence of synergism of histamine H2-receptor blockers and anticholinergics, which combinations would be useful, for example, in peptic ulcer therapy.

The interrelationships between the lipid peroxidation, superoxide dismutase activity, development of gastric H+ secretion and gastric mucosal damage produced by intragastric administration of aspirin in pylorus-ligated rats.

Gastric mucosal damage of pylorus-ligated rats was induced by the intragastric administration of aspirin at 200 mg/kg at the time of ligation. The animals were sacrificed at 0, 1, 2, 3, and 4 h after the treatment. The gastric lesions (ulcers) were counted and their severities were calculated, and the volume of gastric secretion and the H+ output were measured. The extent of lipid peroxidation was assessed by measuring the malondialdehyde (MDA) in the gastric mucosa, simultaneously with measurement of the activity of superoxide dismutase (SOD). It was found in these pylorus-ligated rats that: the number of visible gastric lesions was significantly higher 1 h after aspirin administration than at other times; the severity of gastric lesions increased significantly at the 3rd and 4th hour after administration of aspirin; the volume of gastric secretory responses increased gradually after administration of aspirin and to a higher extent than the H+ output; the H+ output was significantly less after aspirin administration than that after pylorus ligation only; the gastric mucosal SOD activity significantly increased 1 h after administration of aspirin, decreasing significantly and gradually thereafter; the tissue level of MDA remained unchanged 1 h after aspirin administration, decreasing significantly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence of the gastric cytoprotective effects of vitamin A, atropine and cimetidine on the development of gastric mucosal damage produced by administration of indomethacin in healthy subjects.

Certain compounds such as prostaglandins, atropine, cimetidine and carotenes are able to prevent the development of gastric mucosal damage produced in experimental animals or in man by intragastric administration of necrotizing agents such as indomethacin without significantly inhibiting gastric acid secretion. The clinical background of this gastric cytoprotection and its importance for man is not yet known, although the beneficial effects of these compounds have been demonstrated in human therapy. In the present study, carried out in 66 healthy human subjects, it was found that vitamin A at a dose of 100,000 IU i.m., atropine at 0.125 mg i.m., and cimetidine at 12.5 mg i.m., which doses do not inhibit the gastric basal secretion nor the maximal secretory response to pentagastrin stimulation, each prevented the gastric microbleeding produced by the oral application of indomethacin. It is concluded that this gastric cytoprotection, characteristic of prostaglandins but extending to atropine, cimetidine and vitamin A, holds good in man as well as experimental animals. Thus the potential clinical significance of gastric cytoprotection induced by these compounds may be considerable.

Cytoprotective effect of free radical scavengers against mucosal damage produced by different antirheumatic drugs.

Following 200 mg aspirin, 20 mg indomethacin or 100 mg diclofenac, gastric mucosal damage was evoked after five hours in rats. By administering vitamin A, vitamin E, MTDQ (6,6-methylenebis-2,2,4-trimethyl-1,2-dihydroquinoline), vitamin C, lipoic acid and penicillamine intragastrically at the time of the application of the damaging agent, the authors studied the beneficial effect of these free-radical scavengers upon the mucosal lesions. Vitamin C and penicillamine exerted no significant protective effect. Among the other drugs, the most effective were the lipid-soluble ones: vitamin A, vitamin E and MTDQ. The authors hypothesized that the gastric damage may be connected with the degradation of the polyunsaturated fatty acid components of the cellular membranes and thus the lipid-soluble free radical scavengers were able to offer protection.

Some aspects of the critical evaluation of peptic ulcer therapy in patients.

The disease peptic ulcer in patients does not present a uniform clinical entity. Hence, the therapeutic approaches to peptic ulcers are significantly different. Independently from the therapeutically given drugs, some common problems can be found in the methods of critical evaluation of the peptic ulcer therapy in patients. This paper deals with goals, the possible ways to evaluate critically the efficacy of peptic ulcer therapy and the problems in patients in relation to both evaluation of clinical pharmacology and as well as to everyday medical practice.

Interrelationships between the membrane-bound ATP-dependent energy systems of the gastric mucosa and the gastric cytoprotective effect of beta-carotene on the development of gastric mucosal damage produced by 0.6 M HCl in rats.

The effects of different doses (0.01-0.1-1.0-10.0/mg/kg-1) of beta-carotene were studied on gastric secretory responses of 4 hr pylorus-ligated rats: development of gastric mucosal damage (as assessed by number and severity of lesions) produced by intragastric administration of 0.6 M HCl; tissue level of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenylate pool (ATP + ADP + AMP), ratio of ATP X ADP-1, "energy charge" (ATP + 0.5 ADP X X (ATP + ADP + AMP)-1) (during the development of gastric mucosal damage by 0.6 M HCl and of gastric cytoprotection by beta-carotene. It was found that beta-carotene did not decrease the gastric secretory responses of 4 hr pylorus-ligated rats; The development of gastric mucosal damage could be decreased dose-dependently by the administration of beta-carotene; the ATP transformation could be decreased by beta-carotene; the tissue levels of cAMP and AMP could be increased significantly and dose-dependently by beta-carotene; the ratio of ATP X ADP-1 could be increased significantly and dose-dependently by beta-carotene; the values of adenylate pool and "energy charge" remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative dynamic study of the effectiveness of gastric cytoprotection by vitamin A, De-Nol, sucralfate and ulcer healing by pirenzepine in patients with chronic gastric ulcer (a multiclinical and randomized study).

The gastric cytoprotective effects of vitamin A, De-Nol and sucralfate were compared with the effectiveness of pirenzepine in healing ulcer in patients with chronic gastric ulcer. A total of 100 patients was randomized into different groups: the patients were treated with antacids, vitamin A (3 X 50.000 IU), De-Nol liquid (4 X 5 ml), sucralfate (4 X 1 g) or pirenzepine (3 X 50 mg). The treatment was continued for 4 weeks. At the beginning, 2 and 4 weeks after starting treatment the patients were subjected to endoscopy and the size of the ulcer was measured planimetrically. The ulcer-healing effect of De-Nol liquid was significantly better than that of the antacids (p less than 0.01). Ulcer size was reduced significantly in all groups (p less than 0.01), however, at the end of the study the gastric ulcers were smallest in the De-Nol treated group (p less than 0.001). The dynamics of ulcer healing in the second week was most favourable in the patients receiving vitamin A (p less than 0.01). The present data point to the cytoprotective effects of De-Nol liquid, vitamin A and sucralfate and to their ability of healing chronic gastric ulcers.