Serum Citrulline and Ornithine: Potential Markers of Coeliac Disease Activity.

INTRODUCTION: To date, there is not generally accepted and universal indicator of activity, and functional integrity of the small intestine in patients with coeliac disease. The aim of our study was to investigate whether serum concentrations of the non-essential amino acids citrulline and ornithine might have this function. METHODS: We examined serum citrulline and ornithine concentrations in a subgroup of patients with proven coeliac disease and healthy controls (blood donors). RESULTS: A total of 94 patients with coeliac disease (29 men, mean age 53 ± 18 years; 65 women, mean age 44 ± 14 years) and 35 healthy controls (blood donors) in whom coeliac disease was serologically excluded (10 men, mean age 51 ± 14 years; 25 women, mean age 46 ± 12 years) were included in the study. Significantly lower concentrations of serum ornithine were found in patients with coeliac disease (mean 65 ± 3 µmol/L; median 63 µmol/L, IQR 34 µmol/L, p < 0.001). No statistically nor clinically significant differences were found in the citrulline concentrations between the study and control group. CONCLUSIONS: Serum ornithine (but not citrulline) may be useful for assessing the functional status of the small intestine in uncomplicated coeliac disease. Further studies involving more detailed analysis of dietary and metabolic changes in patients will be needed to reach definitive conclusions.

The Effect of Lactobacillus casei on Experimental Porcine Inflammatory Bowel Disease Induced by Dextran Sodium Sulphate.

BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.

The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-O-desmethyldonepezil, and Gastric Myoelectric Activity in Experimental Pigs.

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.

Peutz-Jeghers syndrome.

PURPOSE OF REVIEW: Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients. RECENT FINDINGS: A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence. SUMMARY: Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs.

BACKGROUND: Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). METHODS: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). RESULTS: Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 µV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 µV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 µV^2; p<0.001), lasting till 120 min. (p<0.001). CONCLUSIONS: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

Familial adenomatous polyposis: complex patient management.

Familial adenomatous polyposis (FAP) is a hereditary disease characterized by presence of numerous colorectal adenomas. It often exposes its carrier to absolute risk of colorectal cancer, but also to other extracolonic tumours (especially to duodenal cancer and desmoid). Screening and surveillance of FAP patients leads to reduction of colorectal cancer incidence and mortality. Colonoscopy/lower endoscopy and esophagogastroduodenoscopy (including use of side-viewing endoscope) are the principal examinations. Colectomy is the standard therapeutic procedure, but endoscopic therapy plays relevant role both in upper and lower gastrointestinal tract. Recent international guidelines and some new tools for severity classification enable effectively reduce the mortality related to this disease by individualized patient management. Key words: colorectal cancer - familial adenomatous polyposis.

The prevalence and sociodemographic determinants of uninvestigated dyspepsia in the Czech Republic: a multicentre prospective study accomplished 10 years after the first study from the same geographical areas.

OBJECTIVE: The epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of the current multicenter prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. PARTICIPANTS AND METHODS: A total of 38 147 individuals comprised the general population for a random two-step selection process. A total of 1836 participants (863 males and 973 females; aged 5-98 years) took part in the questionnaire-based study. Helicobacter pylori status was investigated in all participants by means of C-urea breath test. RESULTS: The overall prevalence of dyspepsia was 2.6% among children and adolescents aged 5-17 years and 16.0% among adults aged 18-98 years. We did not detect any statistically significant sex differences in the prevalence of total dyspepsia or its subtypes. Overall, 2.4% of H. pylori-negative children and adolescents aged less than 18 years reported dyspepsia, and 16.8% of H. pylori-negative adults reported it. Among H. pylori-positive children and adolescents and adults, dyspepsia was present in 8.3 and 15.8%, respectively. Type A dyspepsia (as the only long-lasting symptom) was statistically significantly associated with H. pylori status among children and adolescents. Among adults aged 18 years or older, we noted a lower prevalence of dyspepsia in adults with elementary education compared with university education. Current use of antibiotics was associated with an increased prevalence of dyspepsia in adults. CONCLUSION: Despite the substantial decrease of H. pylori infection in the Czech Republic over the past 10 years, the prevalence and sociodemographic determinants of uninvestigated dyspepsia did not change significantly.

The Importance of Wireless Capsule Endoscopy for Research into the Intestin al Absorption Window of 5-Aminosalicylic Acid in Experimental Pigs.

BACKGROUND: Absorption windows in particular segments of the small intestine can contribute to the development of orally administered drug formulations and can limit the bioavailability of released compounds. OBJECTIVE: The aim of this study was to evaluate use of wireless capsule enteroscopy regarding the disintegration kinetic process of tablets in the small intestine and its comparison with the levels of the model drug (5- aminosalicylic acid; 5-ASA), and its majority metabolite (N-acetyl-5-aminosalicylic acid; N-acetyl-5-ASA) in blood plasma. METHODS: Tablets were endoscopically introduced into the duodenum and their disintegration was monitored using wireless capsule enteroscopy in anaesthetised pigs. In parallel, blood plasma time profiles of the model drug (5-ASA) released from tablets and its metabolite (N-acetyl-5-ASA) were detected. RESULTS: The disintegration of tablets was evident in the proximal jejunum (until the 90-minute mark) and culminated at the 3rd hour. The maximum plasmatic concentration of 5-ASA was reached at the 3rd hour and in the case of its metabolite (N-acetyl-5-ASA) at the 4th hour. CONCLUSION: The study demonstrated the advantage of combination of wireless capsule enteroscopy and bioanalytical determination of pharmacokinetic parameters in an animal experiment to localise the disintegration site of solid dosage form and following kinetics of intestinal absorption of the released active agent.

Treatment of Multifocal Multisystem BRAF Positive Langerhans Cell Histiocytosis with Cladribine, Surgery and Allogenic Stem Cell Transplantation.

Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a very rare cause of sellar expansion. The clinical presentation can be heterogeneous, from a single bone lesion to potentially fatal, widespread disease. We describe the difficulties with the diagnosis and treatment of LCH as well as successful treatment with cladribine chemotherapy and allogeneic stem cell transplantation.

Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy.

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

Wireless Capsule Enteroscopy in Healthy Volunteers.

INTRODUCTION: The aim of our prospective study was to define endoscopy appearance of the small bowel in healthy volunteers. METHOD: Forty-two healthy volunteers underwent wireless capsule endoscopy, clinical investigation, laboratory tests, and completed a health-status questionnaire. All subjects were available for a 36-month clinical follow-up. RESULTS: Eleven subjects (26%) had fully normal endoscopy findings. Remaining 31 persons (74%), being asymptomatic, with normal laboratory results, had some minor findings at wireless capsule endoscopy. Most of those heterogeneous findings were detected in the small intestine (27/31; 87%), like erosions and/or multiple red spots, diminutive polyps and tiny vascular lesions. During a 36-month clinical follow-up, all these 42 healthy volunteers remained asymptomatic, with fully normal laboratory control. CONCLUSIONS: Significant part of healthy subjects had abnormal findings at wireless capsule endoscopy. These findings had no clinical relevance, as all these persons remained fully asymptomatic during a 36-month follow-up. Such an endoscopic appearance would be previously evaluated as "pathological". This is a principal report alerting that all findings of any control group of wireless capsule endoscopic studies must be evaluated with caution.

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis.

The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10-20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. TRIAL REGISTRATION NUMBER: DRKS00004940.

Buried bumper syndrome: A complication of percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is a widely used method of nutrition delivery for patients with long-term insufficiency of oral intake. The PEG complication rate varies from 0.4% to 22.5% of cases, with minor complications being three times more frequent. Buried bumper syndrome (BBS) is a severe complication of this method, in which the internal fixation device migrates alongside the tract of the stoma outside the stomach. Excessive compression of tissue between the external and internal fixation device of the gastrostomy tube is considered the main etiological factor leading to BBS. Incidence of BBS is estimated at around 1% (0.3%-2.4%). Inability to insert, loss of patency and leakage around the PEG tube are considered to be a typical symptomatic triad. Gastroscopy is indicated in all cases in which BBS is suspected. The depth of disc migration in relation to the lamina muscularis propria of the stomach is critical for further therapy and can be estimated by endoscopic or transabdominal ultrasound. BBS can be complicated by gastrointestinal bleeding, perforation, peritonitis, intra-abdominal and abdominal wall abscesses, or phlegmon, and these complications can lead to fatal outcomes. The most important preventive measure is adequate positioning of the external bolster. A conservative approach should be applied only in patients with high operative risk and dismal prognosis. Choice of the method of release is based on the type of the PEG set and depth of disc migration. A disc retained inside the stomach and completely covered by the overgrowing tissue can be released using some type of endoscopic dissection technique (needle knife, argon plasma coagulation, or papillotome through the cannula). Proper patient selection and dissection of the overgrowing tissue are the major determinants for successful endoscopic therapy. A disc localized out of the stomach (lamina muscularis propria) should be treated by a surgeon.

Unroofing Technique as an Option for the Endoscopic Treatment of Giant Gastrointestinal Lipomas.

Gastrointestinal lipomas are usually asymptomatic, detected incidentally. However, they can cause severe symptoms such as obstruction, invagination, and bleeding. The transsection of an infarcted or large lipoma by needle sphincterotome (needle knife) and/or snare polypectomy of the upper part of the tumour is an option for the endoscopy treatment of giant infarcted lipomas. Cutting a top of lipoma (unroofing technique) allowed flow out of adipose tissue from the lipoma.

Oesophageal Manometry in Experimental Pigs: Methods and Initial Experience.

The aim of this study project was to prepare our own method of porcine oesophageal manometry. Ten mature experimental pigs entered the study. Conventional water-perfused system was decided for manometry. Porcine resting and relaxed pressures of the lower oesophageal sphincter are fully comparable with healthy human subjects. Evocable swallowing is doable and oesophageal peristalsis is quantifiable. Basic manometric parameters were different in male and female animals. Oesophageal manometry in experimental pigs is feasible. Porcine oesophageal manometry will be usable for preclinical studies in future.

Impact of tacrine and 7-methoxytacrine on gastric myoelectrical activity assessed using electrogastrography in experimental pigs.

OBJECTIVES: Tacrine was the first acetylcholinesterase inhibitor approved for therapy of Alzheimer's disease. It has currently been withdrawn in some countries mostly due to the risk of hepatotoxicity and might be replaced by its derivate 7-methoxytacrine (7-MEOTA). The aim of this study was to assess the impact of these two compounds on gastric myoelectrical activity by means of surface cutaneous electrogastrography (EGG). METHODS: Twelve pigs (Sus scrofa f. domestica, weighing 30-35 kg) entered the study. A single dose of tacrine (200 mg i.m., n=6) or 7-MEOTA (200 mg i.m., n=6) was administrated. All EGG recordings were performed under general anaesthesia in the morning after 24 hours of fasting. Basal (30 minutes) and study recordings (150 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Results were expressed as dominant frequency of gastric slow waves, power analysis (areas of amplitudes) and power ratio assessment (ratio of the areas of amplitudes after and before study drug administration). RESULTS: Tacrine decreased EGG dominant frequency 10 minutes after its administration (from basal 3.1±0.6 to 2.8±0.6 cycles per minute; p=0.014). Tacrine induced a non-significant 60-minute increase of the power (with maximal value 493±533 µV2 at 20 minutes) and power ratio (with maximal value 2.04±3.4 at 10 minutes). Tacrine caused substantial gastric arrhythmia. 7-MEOTA did not influence dominant frequency of gastric slow waves significantly. 7-MEOTA caused a short-term late increase of the power ratio at 60 minutes (6.3±11.2; p=0.003). Blood cholinesterase activity did not correlate with any EGG parameter either after tacrine or 7-MEOTA at any time. CONCLUSIONS: Tacrine and 7-MEOTA have different impacts on EGG. Tacrine decreased dominant frequency and induced long-lasting gastric arrhythmia. 7-MEOTA caused a short-term late increase of the EGG power in experimental pigs.

[Epidemiology of dyspepsia]. / Epidemiologie dyspepsie.

Epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of our current multi-centre prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. A total of 22 centres entered the study. A total of 1,836 subjects (aged 5-98 years) were enrolled. The overall prevalence of dyspepsia was 12 %; namely 3.5 % in subjects aged 5-24 years, 18 % among 25-64-year-old persons and 15 % in subjects 65 years. Despite the substantial decrease of Helicobacter pylori infection in the Czech Republic over the past 10 years, the prevalence and basic socio-demographic determinants of uninvestigated dyspepsia did not change significantly.

Blood pressure and stature in Helicobacter pylori positive and negative persons.

To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1818 subjects (aged 5-98 years) took part in the study, randomly selected out of 38147 subjects. H. pylori infection was investigated by means of a 13C-urea breath test. Data on height, weight, systolic and diastolic blood pressure and heart rate were collected at the clinics of general practitioners. The overall prevalence of H. pylori infection was 30.4% (402/1321) in adults (≥ 18 year-old) and 5.2% (26/497) in children and adolescents (≤ 17 year-old). Once adjusted for age and gender, only a difference in body mass index remained statistically significant with H. pylori positive adults showing an increase of 0.6 kg/m(2) in body mass index. Once adjusted for age and gender, we found a difference in height between H. pylori positive and H. pylori negative children and adolescents. On further adjustment for place of residence, this difference became statistically significant, with H. pylori positive children and adolescents being on average 3.5 cm shorter. H. pylori positive adults were significantly older compared to H. pylori negative subjects. Once adjusted for age and gender, H. pylori infection had no impact on body weight, body mass index and vital signs either in adults or children and adolescents. Chronic H. pylori infection appeared to be associated with short stature in children. H. pylori infection did not influence blood pressure, body weight and body mass index either in adults or children and adolescents.

Cronkhite-Canada syndrome: review of the literature.

Cronkhite-Canada syndrome is a rare disease characterised by diffuse polyposis of the gastrointestinal tract, diarrhoea, weight loss, abdominal pain, cutaneous hyperpigmentation, dystrophic changes of fingernails, and alopecia. The etiology is probably autoimmune and diagnosis is based on history, physical examination, endoscopic findings of gastrointestinal polyposis, and histology. The disease is very rare; about 450 cases have been described in the literature so far. We present a review of the literature with our own picture documentation of this rare condition.