INTRODUCTION
Problem urgency
The syndrome of an angry intestine (SRK) is often meeting disease of organs of digestion. According to large-scale researches, to it suffers from 10 to 20 % of adults [35, 135, 139, 194, 219], women are ill more often, than men [66, 99, 145, 150, 173, 204].
Prevalence SRK among a pathology of organs of a gastroenteric tract (GASTROINTESTINAL TRACT) reaches 40-70 % [33, 217]. Frequency SRK at children remains not found out, but, according to different sources, among children of school age and teenagers frequency SRK reaches from 2-4 % [110, 193] to 22 % [74]. The parity of number of girls and young men makes 2-4:1 [77, 128]. According to data W. El-Matary, S Spray, V Sandhu (2004), at 36 % of children, suffering abdominal pains, it is diagnosed SRK [44, 74]. Real prevalence SRK at children considerably above as many of them cannot describe the painful sensations in details. Symptoms SRK not always reach that clinical level which defines necessity of the reference to the doctor. There are data, that only at 5 % of patients clinically demonstrative forms SRK [108] take place. Though SRK is not serious disease, it considerably reduces quality of a life and is bound to the big economic losses for a society [44, 166].
Last years in the literature there was a term postinfectious SRK if symptoms appear after the transferred acute intestinal infection [59]. According to a number of authors, at 7-33 % of the patients who have transferred intestinal infections during the period from 3-4 months till 6 years, picture SRK [115, 158, 192, 213, 222] develops.
At the heart of SRK there is no the certain pathophysiological defect explaining all available symptoms, that is, by the nature this functional disease. According to the Roman criteria III, all functional disorders are gastrointestinal tract characterised as variabelnye
Combinations of chronic and relapsing symptoms which cannot be explained structural and biochemical changes [78, 220].
The reasons of development SRK remain unknown persons. Abundantly clear, that the given pathology is not a simple consequence of the isolated impellent disorders of an intestine. The concept of "visceral hypersensitivity» thick and especially - a rectum is in details developed, but also this concept cannot explain to the full difficult enough and multistage mechanism of disturbances.
Special interest causes studying of relationships of cause and effect between disturbances of an intestinal microflora, changes in structure of intestinal contents, a degree of activity of local inflammatory process and functional disorders thin and a colon.
SRK throughout last 15 years it is intensively studied, but on - former remains insufficiently studied disease with not up to the end clear the pathophysiological mechanism which is difficultly giving in to treatment, that partly speaks absence of the exact diagnostic methods capable in short terms to establish the diagnosis. In children's practice these questions are even less studied, there are no exact representations about clinical types of implication SRK at children, data about a role of an inflammation and a microflora in disease development are inconsistent, effective medical approaches are not developed.
The work purpose
To estimate clinical value and interrelation of inflammatory, microbiological changes and visceral hypersensitivity at a syndrome of an angry intestine at children.
Research problems:
1. To study structure of a syndrome of an angry intestine at children.
2. To define major factors of risk of development of a syndrome of an angry intestine at children.
3. To estimate level of inflammatory activity in a mucosa of a colon according to morphology, to level kalprotektina in a feces and to level of proinflammatory cytokines in a colon mucosa (IL-8, IFN-y) at children with a syndrome of an angry intestine.
4. To estimate a condition of a microflora of an intestine according to feces crops on a dysbacteriosis and by results of the hydrogen respiratory test with a lactulose at children with a syndrome of an angry intestine.
5. To estimate volume-threshold sensitivity of a rectum as biological marker of a syndrome of an angry intestine.
6. To estimate dynamics of clinical symptoms, signs of inflammatory activity, volume-threshold sensitivity of a rectum and changes of an intestinal microbiocenosis against various schemes of treatment with including probiotikov, prebiotikov and a preparation correcting a motility of an intestine.
Scientific novelty of work
1. Structure SRK at children, taking into account clinical types of a current and communication with the transferred intestinal infection is shown.
2. For the first time the complex estimation of activity of inflammatory process in a mucosa of a colon according to endoscopic and morphological researches, to level fecal kalprotektina and proinflammatory cytokines (IL-8, IFN-y) At children with SRK is spent.
3. Connection of changes of an intestinal microbiocenosis with activity of inflammatory process in a mucosa of a colon and level of visceral sensitivity of a rectum at children with SRK is established.
4. It is spent opened randomizirovannoe platsebo-supervised research of efficiency of various schemes of therapy SRK with including
probiotikov, prebiotikov and a preparation influencing a motility of an intestine.
The practical importance
1. Clinical value of an inflammation in a mucosa of an intestine (JUICE) of weak degree in development of visceral hypersensitivity and clinical symptoms SRK is shown. Signs of a weak chronic inflammation, according to histological research, are found out practically in all patients with SRK, at an endoscopy - only in half of cases that confirms expediency of a capture bioptata and histological research even at visually not changed JUICE.
2. In connection with detection of disturbances of an intestinal microbiocenosis and a syndrome of superfluous bacteriemic growth at patients with SRK, the establishment of communication of these disturbances with signs of an inflammation and visceral hypersensitivity, develops optimum schemes of therapy SRK with including probiotikov (Enterolum, Lineks, Rela Lajf) in a combination with prebiotikom (Zakofalk) or trimebutinom (Trimedat).
Approbation and introduction of results in practice
On dissertation materials 7 printing works, including 3 publications in the magazines reviewed VAK are published. Results of research are reported at city scientifically-practical conferences of of St.-Petersburg «New aspects dieto - and pharmacotherapies at a pathology of organs of digestion at children» in 2011, 2012, 2013, at XIV International Slavjano-Baltic scientific forum «St.-Petersburg - Гастро-2012» in 2012 and at XV International Slavjano-Baltic scientific forum «St.-Petersburg - Гастро-2013» in 2013; in Moscow on XIX Gastroenterologichesky week in 2013.
The basic materials of dissertational work are entered into practice gastroenterologicheskogo units № 13 SPb GBUZ «the Nursery city
Hospital № 5 of N.F.Filatova »Ministry of Health of Russia and pediatric unit № 4 Clinics GBOU VPO SpbGpMu of Ministry of Health of Russia, in teaching on chair of gastroenterology FP and DPO GBOU VPO SPbGPMU Ministry of Health of Russia.
Volume and dissertation structure
The dissertation consists of following sections: introductions, the review of the literature, the description of a material and research methods, 4 heads of own researches, discussion of the received results, conclusions, practical references, the appendix, the list of the literature including 86 domestic and 137 foreign sources. Work is stated on 180 pages of the typewritten text, illustrated by 50 tables and 51 drawing.
The personal contribution of the author
The author personally participated in scheduling, working out of a computer database, the collecting and processing of the medical information, mathematical both statistical processing and the analysis of the received results. The author personally spent questionnaire of parents and children, survey of children, and also research of volume-threshold sensitivity of a rectum to all children who were under observation.
The substantive provisions which are taken out on protection
1. Clinical symptom-complex SRK in 97,5 % of cases is accompanied by signs of a weak chronic inflammation JUICE which proves to be true gistologicheski and characterised by slight increase of level fecal kalprotektina and proinflammatory cytokines (IL-8, IFN-y) in JUICE.
2. Degree of inflammatory changes does not depend on an aetiology and a clinical variant of current SRK, but correlates with level of rising of volume-threshold sensitivity of a rectum and changes of an intestinal microbiocenosis.
3. Signs of a syndrome of superfluous bacteriemic growth in a small bowel are found out in 85,1 % of children with SRK. They are accompanied by change fecal mikrobioty which is characterised by depression of an obligate microflora and presence UPF.
4. The greatest clinical efficiency therapy SRK with simultaneous appointment probiotikov (Enterolum, Rela Lajf, Lineks) and a preparation influencing a motility of an intestine (Trimedat) or a combination prebiotika (Zakofalk) and probiotikov (Enterolum, Rela Lajf, Lineks) differs. Effective elimination of clinical symptoms is accompanied by depression of volume-threshold sensitivity of a rectum, elimination disbioticheskih disturbances and parallel depression of signs of an inflammation in SOTK.
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