Studies on the regulation of transient lower esophageal sphincter relaxations (TLESRs) by acid in the esophagus and stomach.

Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal reflux, but the regulation of TLESR by stimuli in the esophagus is incompletely understood. We have recently reported that acid infusion in the esophagus substantially (by 75%) increased the number of meal-induced TLESR in healthy subjects. We concluded that the TLESR reflex triggered by gastric distention with meal was enhanced by the stimulation of esophageal nerves by acid. However, the possibilities that the acid infused into the esophagus acts after passing though lower esophageal sphincter in stomach to enhance TLESR, or that the acid directly initiates TLESR from the esophagus were not addressed. Here, we evaluated the effect of acid infusion into the proximal stomach on meal-induced TLESR (study 1) and the ability of acid infusion into the esophagus to initiate TLESR without prior meal (study 2). We analyzed TLESRs by using high-resolution manometry in healthy subjects in paired randomized studies. In study 1, we found that acid infusion into the proximal stomach did not affect TLESRs induced by standard meal. The number of meal-induced TLESRs following the acid infusion into the proximal stomach was similar to the number of meal-induced TLESRs following the control infusion. In study 2, we found that acid infusion into the esophagus without prior meal did not initiate TLESRs. We conclude that the increase in the meal-induced TLESRs by acid in the esophagus demonstrated in our previous study is not attributable to the action of acid in the stomach or to direct initiation of TLESR from the esophagus by acid. Our studies are consistent with the concept that the stimuli in the esophagus can influence TLESRs. The enhancement of TLESR by acid in the esophagus may contribute to pathogenesis of gastroesophageal reflux in some patients.

[Neuroendocrine tumours of the upper gastrointestinal tract, characteristics and comparison of localization diagnostics]. / Neuroendokrinné nádory horného tráviaceho traktu, charakteristika a porovnanie efektivity lokalizacnej diagnostiky.

In daily clinical practice it's important to think of neuroendocrine tumors, since their prevalence for the past 5 years exceeded even the common occurrences of stomach, esophageal and pancreatic cancers. Patients diagnosed early and accurately with NET, have a greater chance for complete cure. The diagnostic tools over the past century were significantly inefficient in diagnosing NET i.e. (40% of tumors were not localized after USG, CT, MRI, AG investigations). Until the past 2 decades that major turnover in diagnostic methods has been achieved. In particular, the introduction of the somatostatine receptor scintigrafy (SRS) and endoscopic ultrasonography (EUS) have increased sensitivity of localization diagnostics up to 90%. Our work is to test the success of the localization diagnostics in 22 patients with surgically and histologically confirmed NET ofthe pancreas and duodenum. These patients fulfilled jointly SRS, CT and/or MRI, but also classic USG and EUS. From our comparison, clearly endoscopic USG is the most efficient tool with 90% sensitivity.

Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough.

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.

[Gastroduodenal complications associated with non-steroidal anti-inflammatory drugs in Slovak Republic: results of one-year prospective study]. / Podiel gastroduodenálnych komplikácií vo vzt'ahu k liecbe nesteroidovými antiflogistikami v Slovenskei republike: rocná prospektívna stúdia.

The aim of the one-year prospective study was to estimate the prevalence of non-steroidal anti-inflammatory drugs using in patients with symptomatic gastroduodenal ulcers, the upper gastrointestinal bleeding and perforation (PUB--perforation, ulcer, bleeding). Among of 326 patients with PUB, prevalence of non-steroidal anti-inflammatory drugs using was 60%. In the group of 194 patients with non-steroidal antiinflammatory drugs induced PUB, 49% patients took aspirin, 38% non-aspirin non-steroidal anti-inflammatory drugs and 13% their combination. Low dosing aspirin (daily dosis < or =200 mg) was associated with PUB in 21% of patients. Age higher than 60 years and women had statisticaly signiticant higher prevalence of non-steroidal anti-inflammatory drugs induced PUB.

Association between systemic lupus erythematosus and insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene.

OBJECTIVE: ACE takes part in the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin-II and inactivating bradykinin. ACE gene insertion/deletion polymorphism is associated with the level of circulating enzymes--subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards impaired vascular function and structure. Patients with systemic lupus erythematosus (SLE) suffer from differentially expressed vascular pathology. We attempted to determine whether the type of ACE polymorphism could contribute to this pathology. METHODS: 101 SLE patients fulfilling the ACR criteria were investigated. The I/D polymorphism was ascertained by PCR, followed by electrophoresis of the amplified fragments and UV visualization. RESULTS: The frequency of the D allele was higher in the SLE group (0.623) than in the controls (0.520) (chi 2 test, p < 0.025). The distribution of the ACE genotype in SLE group was different from that in the control group (p < 0.05). An association between the DD genotype and visceral damage (p < 0.006) was observed. CONCLUSION: Our results suggest that in the multifactorially determined vascular pathology of SLE, changes associated with I/D polymorphism could influence vessel wall inflammation (monocyte adhesion and activation with cytokine release, T-lymphocyte metabolism), a tendency towards vascular impairment (neointimal proliferation, vasospasm, platelet activation, myocyte proliferation) and lead to the subsequent ischemia. The ACE gene could serve as the visceral damage indicator in SLE.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus.

OBJECTIVE: Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred not only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively signalling molecule CTLA-4 is involved in establishing and maintaining of peripheral T cell tolerance, which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses. We tested if there was an association between CTLA-4 and SLE, a disease with B and T cell hyperreactivity and impaired peripheral T cell tolerance. METHODS: Using the polymerase chain reaction--restriction fragment length polymorphism method with Bbv I digestion, we assessed an exon 1 transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls. RESULTS: The distribution of CTLA-4 exon 1 genotypes in the SLE group was significantly different from that in the controls (chi 2 = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homozygotes vs 53.9% of the controls. The frequency of the G allele was significantly higher in SLE patients (35.8%) than in controls (25.7%; chi 2 = 4.142, p = 0.042). CONCLUSION: Our results indicate that the non-MHC linked CTLA-4 gene could confer susceptibility in SLE, as it does in various other autoimmune diseases (Hashimoto thyroiditis, Graves' disease, IDDM).

[Treatment and prevention of gastrointestinal complications caused by non-steroidal antiphlogistic agents]. / Liecba a prevencia gastrointestinálnych komplikácií vyvolaných nesteroidovými antiflogistikami.

The aim of our study is to give a survey of the most efficient methods for treatment and prevention of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse in cases when antiphlogistic treatment cannot be discontinued due to active and progressive joint disease. Analysis of published studies shows that, the proton pump inhibitors (omeprazole) are the most efficient agents in treatment of gastric and duodenal ulcers induced by NSAIDs. The analysis shows a reliable effect of prostaglandin analogues (misoprostol) as well. Prostaglandin analogues (misoprostol) proved the most effective in treatment of gastric erosions. Prophylaxis of adverse gastrointestinal mucosal abnormalities can be primary or secondary. Secondary prevention is intended for patients with gastrointestinal symptoms or those treated for mucosal defects (ulcer, erosions). The standard prevention using H2-antagonists or sucralphate does not provide sufficient protection against NSAID in these patients, but omeprazole reduces the chance of a peptic lesion relapse. Primary prevention is intended for patients with a higher risk of gastrointestinal complications (age above 60, history of peptic ulcer, a higher dose of NSAID, simultaneous treatment with glucocorticoids or anticoagulants). Diclofenac with misoprostol and nabumetone reduce the incidence of gastroduodenal ulcers and their complications in short-term as well long-term studies. Meloxicam reduces the incidence of gastroduodenal mucosal abnormalities is short-term studies. Nimesulide is associated with a lower incidence of adverse gastrointestinal events, but the fact is that, reliable data on gastroduodenal ulcer incidence reduction or their complications are not available.

[Famotidine in the treatment of gastropathy induced by non-steroidal antirheumatic agents]. / Famotidín v liecbe gastropatie vyvolanej nesteroidnými antireumatikami.

In an open clinical endoscopically controlled study in 30 consecutive patients with rheumatic diseases complicated by the ulcerative and erosive form of gastroduodenopathy induced by non-steroidal antiinflammatory drugs and oesophagitis, after four weeks treatment with oral famotidine (one dose of 40 mg/day) confirmed a significant improvement of the mean oesophageal (0.67 +/- 1.06 vs. 0.03 +/- 0.18, p rrr 0.01) gastric 2.10 +/- 1.49 vs. 0.63 +/- 0.85, p rrr 0.001) and duodenal mucosal score (1.80 +/- 1.52 vs. 0.43 +/- 0.82, p rrr 0.001). After four weeks treatment 71% lesions (5/7) in the oesophagus were cured, 77% gastric lesions (10/13) and 75% duodenal lesions (9/12). Treatment with non-steroid antirheumatics proceeded.

[Treatment of MALT lymphoma of the digestive tract]. / Lécba lymfomu MALTu trávicího traktu.

Mucosa-associated lymphoid tissue (MALT) is an autonomous part of the immune system with a specific function, histological structure and circulation of cells. As a result of malignant transformation of this tissue maltomas develop, peripheral extranodal non-Hodgkin lymphomas of B-origin more than two-thirds of which are found in the digestive system. The authors investigated in a retrospective study the effectiveness of different types of treatment of maltomas of the digestive tract with a low and high grade of malignity in 16 patients. It appears that splenectomy is not necessary in these patients and that the effectiveness of primary chemotherapy with a view of inducing complete remission of the disease is comparable with surgical treatment and subsequent adjuvant treatment without deterioration of the patient s life by mutilating surgery. An integral part of treatment of gastric maltomas is eradication of infection caused by Helicobacter pylori.

[Diagnosis of the Zollinger-Ellison syndrome. I: Significance of anamnestic, clinical and laboratory examinations]. / Diagnostika Zollingerovho-Ellisonovho syndrómu I.: význam anamnestických, klinických a laboratórnych vysetrení.

The authors describe the diagnostic algorithm of Zollinger-Ellison's syndrome which proved useful in the diagnosis of 73 patients with a confirmed diagnosis. They evaluate the diagnostic validity of anamnestic and clinical data, of different examination methods and compare them with experience assembled abroad. For the diagnosis of sporadic gastrinomas the onset of the disease after the age of 40 years is important, the development of serious peptic complications (haemorrhage F-70%, M-59%, perforation M-54%, F-47%) and the presence of watery diarrhoea (41%). As to laboratory parameters they rely on high BAO values (96% > 15 mmol H+/hour and 100% > 5 mmol H+ after gastric resection. Less important is the examination of basal serum gastrin (almost 30% patients have normal or liminal values of BSG--empirically set at 100-150 pg. ml-1). The authors draw attention to the fact that patients with ZES after gastric resections may have BSG values lower than 100 pg/ml (12%). A positive secretin test has a higher validity (rise of SG by 150-200 pg. ml-1 above basal values) positive in 82.2% patients, liminally positive in 11% and negative in 6.3% patients. An even higher diagnostic value was possessed by a BAO/MAO index higher than 0.6 which was positive in 93.4% patients. At present it is not used as pentagastrin is not available. Every year they diagnose 4-6 new cases of ZES which with regard to the number of inhabitants (5 million) places Slovakia along with Denmark and Sweden among the countries with the highest detection rate (0.8-1.2 ZES cases/1 million per year).

[Liver biopsy in Slovakia]. / Biopsie pecene na Slovensku.

INTRODUCTION: Liver biopsy is the most specific diagnostic modality in hepatology, but information about its application in Slovakia is rather obscure. METHODS: The authors performed a correspondence study with the aim to find out how many biopsy examinations has been done in Slovakia in 2001, for which indications, what kind of techniques have been applied and which small or great complications were encountered. RESULTS: It was established that in the year 2001, 400 biopsies for diffuse liver diseases were performed. There were 296 percutaneous biopsies, 82 laparoscopic biopsies and 22 trans-jugular biopsies forming the survey. Acute viral hepatitis was the most frequent indication, whereas non-alcohol steatohepatitis was a rare indication in spite of the high prevalence. The frequency of great complications was 0.00025%. No death associated with this procedure was reported. CONCLUSION: Liver biopsy has been done in Slovakia in indications, ways and with the frequency of complications, which were comparable with data from literature.

Acid infusion into the esophagus increases the number of meal-induced transient lower esophageal sphincter relaxations (TLESRs) in healthy volunteers.

BACKGROUND: Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal reflux (GER) but the regulation of TLESR by stimuli in the esophagus is incompletely understood. If stimuli in the esophagus can influence TLESR, then such regulation may perpetuate or limit GER. We addressed the hypothesis that acid in the esophagus enhances TLESRs. METHODS: We evaluated the effect of acid infusion into the distal esophagus on TLESRs evoked by a standard meal in a paired randomized study in healthy subjects. TLESRs were evaluated by using high resolution manometry (HRM). KEY RESULTS: We found that acid in the esophagus enhanced meal-induced TLESRs. Compared to control infusion the number of TLESRs (median [interquartile range]) was increased during 2 h following the acid infusion (11 [9-14] vs 17 [12.5-20], p < 0.01). The average duration of individual TLESRs was not affected. The time-course analysis revealed that a robust increase in TLESRs occurred already in the first hour when the number of TLESRs nearly doubled (6 [5.5-7.5] vs 11 [7.5-12.5], p < 0.05). In contrast to the enhancement of TLESRs, the number of swallows was not changed. CONCLUSIONS & INFERENCES: The acid infusion into the esophagus increases the number of meal-induced TLESRs in healthy subjects. Our results provide evidence for the concept that the stimuli in the esophagus can influence TLESRs. The regulation of TLESR by stimuli in the esophagus may contribute to pathogenesis of GER in some patients.