LECTURES AND REVIEWS
The aim of review. To present the standard and alternative therapeutic modes used at treatment of autoimmune hepatitis (AIH).
Original positions. Autoimmune hepatitis is a chronic inflammatory disease of the liver of the unknown etiology, accompanied by elevation of serum transaminase level, hypergammaglobulinemia and circulation of the fixed spectrum of autoantibodies in the blood. In most of the cases disease can be treated by combination of prednisolon and azathioprin. However, according to current data, 20% of the patients remain resistant to these agents or have low tolerability, 10 % have to discontinue treatment due to development of serious side effects. Budesonide is a synthetic glucocorticosteroid which is characterized by rapid metabolism in the liver, having no systemic action. Results of some studies on efficacy and safety of application of budesonide at patients with AIH at various stages of disease are published in the world literature. In the review the data on epidemiology, clinical, diagnostics and main therapeutic strategy at autoimmune hepatitis are covered.
Conclusion. Now the combination of prednisolon and azathioprin serves as the classical mode for AIH treatment. Results of original studies demonstrated, that budesonide can be a drug of the 1-st line in patients who received no previous treatment. So, considerably less frequency of side effects development, than at intake of prednisolon and azathioprin combination is observed. However application of budesonide for treatment of liver cirrhosis patients is related to quite high risk of development steroid-related side effects and lower frequency of remission induction.
The aim of review – to present up-to-date data on application of proton pump inhibitors (PPI) e.g. esomeprazole for treatment and prophylaxes of gastropathies, induced by intake of nonsteroid anti-inflammatory drugs (NSAIDs).
Original positions. PPI serve as drugs for treatment and prophylaxis of NSAIDs-induced gastropathies. Recently carried out controlled studies showed clinical efficacy of esomeprazole in conducting patients with NSAID -gastropathies. The drug in a dose of 20 and 40 mg is significantly faster and resulted in healing of stomach ulcer at higher number of patients in comparison to ranitidine in a dose of 300 mg for 8 wks of treatment. Esomeprazole (20 and 40 mg) appeared effective for prophylaxis of erosions and ulcers at long-term intake of NSAID and-or aspirin in placebo- controlled investigations. Dyspepsia which was not related to erosiveulcerative lesions of upper regions of gastro-intestinal tract (GIT), was successfully stopped by prescription of esomeprazole in the same dose to the 4-th week of treatment, and the maintaining course for 6 months promoted the relapse of pain and epigastric discomfort on a background of ongoing intake of NSAID.
Conclusion. Esomeprazole can be utilized at whole spectrum of undesirable effects of NSAID and aspirin on the upper regions of GIT both for treatment and prevention.
ORIGINAL ARTICLES
Aim of investigation. To determine new pathogenic mechanisms of peptic ulcer of the duodenum (PUD) associated to Helicobacter pylori, basing on features of diffuse endocrine system (DES) and processes of cellular homeostasis of stomach mucosa (SM) epithelial cells, to improve quality of PUD remission achievement.
Material and methods. Overall 115 patients were investigated: 100 – with PUD associated with H. pylori infection and 15 – generally healthy persons. Patients with PUD were separated into two peer groups: in the first group eradication H. pylori under traditional 7-day’s algorithm with application of omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid was carried out, in the second group melaxen (melatonin) 3 mg per day was added to the traditional mode of eradication. Then the first group continued to receive omeprazole, the second – omeprazole in combination to melaxen up to complete healing of ulcerative defect. Both groups of patients with PUD were investigated dynamicly, prior onset of treatment and after six weeks under the common program including clinical methods of investigation, gastroduodenoscopy (GDS), general morphological, immunohistochemical studies and histiobacterioscopy. The GDS-control was carried out in two, with four and six weeks. The group of generally healthy persons was investigated once by similar procedure.
Results. The relapse of PUD is associates with hyperplasia of epithelial cells of the stomach, immunopositive to nitric oxide synthase, endothelin-1, melatonin, and with subsequent increase in number of epithelial cells, immunopositive to Ki-67, and increase of apoptotic activity. Eradication of H. pylori in patients with PUD reduces proliferation of epithelial cells of the SM and in the greater degree – their apoptotic activity that promotes healing of ulcerative defect. Introduction to the algorithm of eradication treatment of melaxen significantly increases the rate of elimination H. pylori, reduces terms of healing of duodenal ulcers. At application of melaxen and omeprazole in PUD maintenance treatment parameters of DES and cellular homeostasis of epithelial cells of the SM recovered in significantly greater degree, than at single omeprazole treatment.
Conclusions. Addition of melaxen in the algorithm of eradication treatment increases rate of H. pylori elimination, reduces terms ulcer healing, improves parameters of DES and epithelial cells homeostasis of the SM.
Aim of investigation. To study clinical efficacy of highly selective M-cholineblocker hyoscine butylbromide (buscopan) in patients with chronic pancreatitis (CP), to estimate its effect on myoelectric activity, рН of the upper regions of gastro-intestinal tract (GIT), and also on dynamics of quality of life of the patients.
Material and methods. The study group included 54 patients with CP, of them 40 (74,1%) had primary pancreatitis and 14 (25,9%) – biliary pancreatitis. Besides traditional methods of investigation electrogastrointestinography, transendoscopic topical express pH-metry with positioning of potential electrodes in the esophagus, body, antral region of the stomach and duodenum were carried out. Quality of life of patients estimated by SF-36 questionnaire.
Results. Application of hyoscine butylbromide within complex treatment of CP (basic group) allows to achieve significant increase of activity and improvement of state of health of patients (by visual-analog scale) along relief of abdominal pain and dyspeptic symptoms. On a background of remission achievement in group of the patients receiving hyoscine butylbromide, in comparison to control group quality of life by such scales as PF, BP, GH, MH significantly increased, while in comparison group – only by ВР scale. In basic group statistically significant decrease of the stomach, duodenum and jejunum tone was marked that provided increase of functional volume of the stomach and jejunum.
Conclusions. Hyoscine butylbromide has physiological influence on secretory function of GIT and is capable to eliminate selectively motor disorders of its upper regions – duodenum and jejunum that determines rate of CP remission achievement. Ability of this drug to reduce effictively acid production and positively influence scores of quality of life of patients defines good prospects of its application in complex treatment of chronic pancreatitis of mild and average severity.
Aim of investigation. To reveal clinical features of acute drug-induced hepatites (ADH) at inpatients. To estimate change of basic clinical characteristics of ADH for the period of 1966–2005.
Materials and methods. Acute hepatites developed as a result of indeliberate drug poisoning were studied. Overall 211ADH patients without precious selection (for the period of 1984–2005) made a basic group. Data of 103 patients with ADH treated in 1966–1979 for comparison purpose were utilised as additional group. Investigation was carried out by the standard clinical, laboratory and instrumental methods. In particular, visualization of liver by radionuclide scintigraphy in 1966–1979 was done for 43 (41,7%) patients, and in 1984–2005 – with the help of US and CT – for 193 (91,4%).
Results. In the basic group ADH was caused by antibacterial (32,1%) and cardio-vascular pharmaceuticals (20,2%) most often. Proving of etiology was associated with greatest complexities at patients with combined drug and viral and especially drug-induced and alcoholic acute hepatites. In the spectrum of ADH mild (163 patients – 79,9%) and nonicteric (145 person – 74%) forms prevailed. Cases without apparent disorders of general state, but with liver enzyme elevation (AST, ALT, GGT, AP) were assessed as mild forms. Moderate and severe course of disease was observed at 56,5 % of patients with icteric and at 4,2 % with nonicteric ADH. All 4 cases of coma and single lethal outcome developed at patients with icteric forms. Lingering course of acute hepatitis is revealed in the majority of patients (87,5 %) with immune intrahepatic cholestatic disease. In main group in comparison to additional group the percentage of cholestatic forms decreased 1,6 times, moderate and severe forms – in 1,5 times, lethal outcomes – in 5,8 times.
Conclusions. Most nonicteric forms were frequently observed, but icteric, especially cholestatic, ADH forms were more severe. In 1984–2005 in comparison with 1966–1979 the proportion of moderate and severe, and also cholestatic forms and lethal outcomes decreased. The favourable changes of course and outcomes of ADH were related to improvement of diagnostics of liver diseases prior to application of hepatotoxic drugs, decrease of use of agents with potent hepatotoxic action (ftorotanum, paracetamol, phenothiazines), and also with rapid cessation of hepatotoxic drugs at development of ADH.
Aim of investigation. To compare a level of apoptosis of peripheral blood leukocytes at chronic hepatites (CH) B, C and autoimmune overlap syndrome (AOS) of autoimmune hepatitis and primary biliary cirrhosis.
Material and methods. To study level of apoptosis and pattern of DNA of peripheral blood leukocytes 54 patients with CH have been investigated. In 12 person CHB was diagnosed, in 22 – CHC, in 20 – AOS. The control group consisted of 20 healthy volunteers without symptoms of liver disease and with negative markers of HBV-and HCV-infections. In patients with CH and healthy persons quantity of lymphocytes and granulocytes of peripheral blood in apoptosis state immediately after extraction and after 24-hour incubation in culture medium by cytoflowmetry method, in patients with AOS – only spontaneous apoptosis of total leukocytic fraction was determined.
Results. At CH patients apoptosis of both lymphocytes and granulocytes was significantly higher in comparison to control immediately after extraction, as well as after 24-hour incubation. The number of leukocytes of peripheral blood in a state of spontaneous apoptosis in patients with AOS was also significantly higher in comparison to scores of control group (9,9±0,8 and 4,2±0,1, p< 0,05). Comparison of average levels of spontaneous apoptosis of total fraction of leukocytes showed absence of significant differences between CHB and AOS and CHC and AOS groups (p> 0,05).
Conclusions. The level of apoptosis of peripheral blood leukocytes at investigated patients significantly exceeds the level of apoptosis of these cells at healthy persons. In peripheral blood of patients with CH there are not only leukocytes at a state of apoptosis, but also apoptosis-committed cells, that is manifested by mononuclear and polymorphonuclear leukocytes apoptosis enhancement after 24-hour incubation in culture medium. Significant differences between a level of apoptosis of leukocytes of peripheral blood in patients with CHB, CHC and AOS were absent, that indicates a role of apoptosis as the unified mechanism of cell damage.
Aim of investigation. To study potentials of noninvasive methods application for assessment of liver fibrosis at screening diagnosis of patients with diffuse liver diseases.
Material and methods. Overall 188 HCV RNApositive patients and 61 HBV DNA-positive were investigated. The stage of disease in all patients was verified by morphological study with assessment of histological activity index (HAI) and stage of fibrosis (F). These data were compared to data of non-invasive evaluation of liver fibrosis – i.e. results of biochemical tests (de Ritis coefficients, APRI), ultrasound investigation with Doppler ultrasonography, videodensitometry, elastometry (EM) by FibroScan device («EchoSens», France).
Results. Significant differences in scores of liver tissue elasticity in relation to stage of fibrosis (F0, F1, F2, F3, F4) – р<0,001 were revealed at HCV-infection and р><0,05 at HBV-infection. EM sensitivity and specificity ranged from 0,8 to 0,99 (area under the ROC-curve). Canonical discriminant analysis with drawing of territorial map, that allow to define fibrosis stage as mild, moderate or severe, using data of ultrasound investigation, was carried out. Conclusions. Application of non-invasive methods of evaluation of fibrosis is reasonable at primary investigation of HCV RNA-and HBV DNA-positive patients. Today high diagnostic accuracy allows to consider elastometry as a method of choice in diagnostics of liver fibrosis in diffuse liver diseases. ><0,001 were revealed at HCV-infection and р< 0,05 at HBV-infection. EM sensitivity and specificity ranged from 0,8 to 0,99 (area under the ROC-curve). Canonical discriminant analysis with drawing of territorial map, that allow to define fibrosis stage as mild, moderate or severe, using data of ultrasound investigation, was carried out.
Conclusions. Application of non-invasive methods of evaluation of fibrosis is reasonable at primary investigation of HCV RNA-and HBV DNA-positive patients. Today high diagnostic accuracy allows to consider elastometry as a method of choice in diagnostics of liver fibrosis in diffuse liver diseases.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
The aim of the publication. To discuss physiological mechanisms of absorption in a gastro-intestinal tract.
Original positions. Mechanisms of transport of nutrients and other substances across mucosa of the gut are analyzed. Mechanisms of coupled transport of glucose, aminoacids and sodium – models of common transporter (that seems to be improbable) and common canal are considered. Two-channel model of sodium and glucose transport looks the most probable.
Conclusion. The comprehension of mechanisms Na+-dependent absorption of glucose and aminoacids allows to prove scientifically, first, application of a well known drug for relief of secretory diarrhea, second, forms a basis for development of pharmaceuticals, capable to be absorbed efficiently through Na+- dependent transporters for aminoacids, third, promotes search of strategies increasing rate of absorption of medicines. Registration of spectrums of Na+-dependent absorption of nutrients in the small intestine is a key to comprehension of malabsorption role in development of several diseases.
NEWS OF COLOPROCTOLOGY
Aim of investigation. Assessment of algorithm of physiological methods of investigation to reveal basic pathogenic mechanisms of the functional incompetence of anal pulp sphincter.
Material and methods. Original study is based on data of the functional studies of 125 patients without organic changes of muscular structures of rectum obturator apparatus (ROA), investigated in SSC of coloproctology within 2001–2008. Interferential and segmentary electromyography (EMG), anorectal manometry, sphincterometry, profilometry, study of reservoir function of the rectum were applied.
Results. Basic types of ROA disorders at the functional failure of anal sphincter include: 1) decrease of contractile capacity of muscles of external sphincter and its refectory regulation at the background of decrease of tension of internal sphincter which can be combined to disorder of its reflex activity, 2) isolated disorder of the functional state of internal sphincter, 3) disorder of reservoir function of the rectum.
Conclusions. In pathogenesis of the functional failure disorder of anal component of continence prevails (76,0% of cases) over disorders of intestinal component (24,0%). The algorithm of the functional studies of obturator apparatus includes: EMG, profilometry, anorectal manometry, study of reservoir function of the rectum.
EXCHANG OF EXPERIENCE
The aim of clinical case presentation. To demonstrate a rare case of the low colic obstruction, masking clinical manifestations of gastroparesis.
The main contents. Gastroparesis – is a motor disorder with delayed emptying of the stomach in absence of mechanical obstruction. Causes of gastroparesis include diabetes mellitus and other metabolic disorders (hypothyroidism, hypokalemia, hypercalcemia), effects of drugs (cholinoblockers, opioids, L-dopa, estrogens, progesteron), effect of nicotine, neurologic disorders, intestinal pseudo-obstruction, etc. The example of one of the rare causes of gastroparesis and disorder of evacuation of the stomach is presented: low colic obstruction developed on a background of adenocarcinoma of large intestine that was characterized by untypical clinical pattern with predominance of gastroparesis manifestations.
Conclusion. Transabdominal ultrasound investigation of abdominal cavity is an adequate method of diagnostics of both gastroparesis, and its rare cause – low colic obstruction caused by malignant tumor in rectosigmoid region of the large intestine.
The aim of presentation of clinical case – to show endoscopically and histologically proved Barret’s esophagus, at the patient after gastrectomy without previous history of gastroesophageal reflux disease.
Features of clinical case. The male patient, 59 years old, 7 years ago underwent gastrectomy for adenocarcinoma of the stomach. Symptoms of bile reflux became dominating, and erosive esophagitis was revealed at esophagogastroduodenoscopy (EGDS) on regular basis. Barret’s esophagus, that was confirmed at present admission to hospital, was suspected at 2008 during EGDS and histological investigation of esophagus. A bitter taste in a mouth, eructation of bile and retrosternal burning essentially decreased at prescription of ursodeoxycholic acid (UDCA), erosions in the esophagus were revealed no more.
Conclusion. The plan of the further management of patient with Barret’s esophagus after gastrectomy is based on a endoscopic control with biopsy of esophageal mucosa and long-term intake of UDCA, along with alginates and antacid drugs.
INFORMATION
The aim of review. To reflect in brief the contents of reports presented at the 16th United European Gastroenterology Week devoted to irritable bowel syndrome (IBS) problem.
Original positions. The submitted reports prove that etiology and pathogenesis of IBS continue to remain insufficiently clear. The IBS is not, apparently, only «functional» disease, and develops with certain microbiologic, immunologic, and sometimes — with morphological changes of intestinal mucosa. Meta-analysis confirmed efficacy of spasmolytics, antidepressants and psychotherapeutic methods at treatment of IBS.
Conclusion. Pathophysiological and clinical aspects of IBS require continuation of scientific investigations.
Ye.V. Komarova – Chronic constipation at children: medical and social issues (The theses for PhD degree).
A.A. Repin – Characteristic of lipid metabolism disorders and treatment options at the latent form of celiac sprue (The theses for MD degree).
I.D. Uspenskaya – Clinical and pathogenic role of the body defense system disorders at diseases with malabsorbtion syndrome in children (The theses for PhD degree).
Ye.V. Motuzova – Comparative evaluation of clinical and pharmacoeconomical efficacy of treatment of non erosive reflux disease by proton pump inhibitors (The theses for MD degree).
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