Vol 83, No 2 (2011)


Biological treatment of gastrointestinal diseases

Lazebnik L.B., Lazebnik L.B.


Biological methods are widely used in the treatment of intestinal inflammation (II). The TNFalpha inhibitor infliximab can quickly correct recurrence, provide long-term remission and reduce hormone need in many patients with hormone-resistant and hormone-dependent forms of Crohn's disease (CD) and ulcerative colitis (UC). However, almost half of II patients fail anticytokine therapy. Some clinical trials of biological medicines were stopped because of toxicity and complications. One of promising approaches to II treatment is now transplantation of mesenchymal stromal cells (MSC). The trial with participation of 85 CD and UC patients demonstrates that intravenous injection of allogenic MSC significantly prolongs duration of remission, reduces recurrence risk and is indicated for patients with hormone-resistent, hormone-dependent forms of II. Cell therapy can be also used in combined treatment of other gastrointestinal diseases, hepatic cirrhosis, in particular. A clinical trial is initiated of efficacy of transplantation of bone marrow autologous cells CD133+ for stimulation of regeneration of the liver in its extensive resection and cirrhosis. The future of this method depends on the results of controlled, randomized clinical trials.
Terapevticheskii arkhiv. 2011;83(2):5-8
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Fundoplication as prophylaxis of reflux-esophagitis in patients with varicose esophageal veins

Vasnev O.S., Yanova O.B., Kovyazina I.O., Vasnev O.S., Yanova O.B., Kovyazina I.O.


Aim. To investigate the condition of esophageal mucosa (EM) before and after surgical and endoscopic treatment of varicose esophageal veins (VEV). Material and methods. EM was examined in 100 patients (64 males and 36 females aged 33-74 years, mean age 52.8±5.7 years) with hepatic cirrhosis (HC). Of them, 80 patients have undergone endoscopic ligation of the esophageal veins, 20 patients - surgical disconnection of the azigoportal blood flow according to the original method with additional fundoplication. All the patients had intrahepatic portal hypertension caused by HC of different etiology. Results. Before operation, 70% patients had inflammation-induced alterations of the EM of different severity. Endoscopic ligation of the esophageal veins did not change the rate of EM inflammation detection. In operated patients reflux-esophagitis was detected significantly less frequently. Conclusion. The above results show efficacy of fundoplication as a method of esophagitis prevention. Esophagitis is one of VEV hemorrhage risk factors. Fundoplication is not easy to make and is not indicated for all HC patients, especially in urgent situations. However, in case of decision to operate for prevention of VEV hemorrhage, it is advisable to conduct fundoplication.
Terapevticheskii arkhiv. 2011;83(2):9-12
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Treatment of disbacteriosis of gastroduodenal mucous microflora in its inflammation and erosion

Chernin V.V., Chervinets V.M., Bondarenko V.M., Bazlov S.N., Chernin V.V., Chervinets V.M., Bondarenko V.M., Bazlov S.N.


Aim. To propose pharmacotherapy of disbacteriosis of gastroduodenal mucous microflora in gastroduodenal inflammation, erosion and ulcer. Material and methods. The study enrolled 30 healthy volunteers, 130 ulcer patients and 36 patients with chronic gastritis (27% of the latter had chronic duodenitis). In addition to general clinical examination, fibrogastroduodenoscopy, we made histological and microbiological examinations of biopsy specimens of the mucosa from different parts of the stomach and duodenum, determined sensitivity of the microflora to antibacterial drugs. Results. We found that recurrent ulcer, chronic gastritis and duodenitis are accompanied with overgrowth of pathogenic microflora in gastric and duodenal mucosa. Conclusion. We developed an effective method of the treatment of gastroduodenal mucosa microflora disbacteriosis in gastroduodenal inflammation, erosion and ulcer including antibacterial, antifungal drugs and probiotics.
Terapevticheskii arkhiv. 2011;83(2):12-16
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Population association features of interleukine gene polymorphism in khakases with gastroduodenal diseases

Ageeva E.S., Shtygasheva O.V., Ryazantseva N.V., Ageeva E.S., Shtygasheva O.V., Ryazantseva N.V.


Aim. To investigate association of polymorphisms of IL-1 genes and antagonist of IL-2 receptor (IL1Ra). Material and methods. Patients with chronic gastritis and ulcer were examined using the method of restriction analysis. Results. It was found that CCIL1beta and R4/R4IL1Ra are most prevalent allel variants in khakas population. Conclusion. It is expedient to define population risk and protective genotypes of development of ulcer associated with Helicobacter pylori in khakases.
Terapevticheskii arkhiv. 2011;83(2):16-19
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Functional condition of the stomach,pancreas, liver, ulcer and gall-bladder in celiac disease

Krums L.M., Sabel'nikova E.A., Parfenov A.I., Krums L.M., Sabelnikova E.A., Parfenov A.I.


Aim. To study condition of the stomach, gall-bladder, pancreas, liver in celiac disease (CD) and contribution of their dysfunction to clinical presentation of CD symptoms. Material and methods. A total of 215 CD patients entered the study (191 females and 24 males) aged under 20 years (n = 100), 20 to 50 (n = 74) and over 50 years (n = 41). The control group consisted of 25 healthy volunteers. Acid-forming function of the stomach, blood serum gastrin level were studied. Bile for biochemical test was obtained at duodenal intubation using 40 ml of 40% glucose solution or 25% magnesium solution as food stimulators, and intravenous injection of cholecystokininpancreosimin. Cholic acid was assayed in bile portions B and C. Two-channel probe was used to obtain duodenal content before meal and after intravenous injection of pancreosimin for tripsin, amylase and lipase assay. Clinical and biochemical blood tests were made as well as puncture biopsy of the liver with histological study of biopsy material. Results. CD patients were found to have high basal and stimulated acid-forming function, high gastrin concentration in the blood. The morphological examination detected lymphocytic gastritis. There were an inert type of pancreatic enzyme secretion, gall-bladder hypokinesia or atony. Gall-bladder contracted only after intravenous injection of cholecystokinin. Changes in the liver were characterized by hypertransaminasemia, steatohepatitis. Conclusion. Changes in the stomach in patients with new-onset CD promote formation of ulcer. Decline in excretory pancreatic function, slow enzyme secretion, marked hypokinesia of the gall-bladder, hyperenzymemia and steatohepatitis as manifestations of hepatic pathology result in dramatic disorder of digestion and absorption of food substances.
Terapevticheskii arkhiv. 2011;83(2):20-24
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Different characteristics of quality of life in celiac disease patients

Moiseenko E.E., Osipenko M.F., Ageeva T.A., Krotov S.A., Burbik N.N., Moiseenko E.E., Osipenko M.F., Ageeva T.A., Krotov S.A., Burbik N.N.


Aim. To study quality of life (QoL) in patients with celiac disease (CD) in the course of treatment with aglutenic diet (AD). Material and methods. Modern algorithm of glutenic enteropathy diagnosis (enzyme immunoassay, histological examination of the biopsy of distal duodenum mucosa) was used in 650 patients with different gastrointestinal symptoms. QoL was assessed in the course of AD treatment of CD with application of universal standard questionnaire MOS SF-36. Results. CD was diagnosed in 56 (8.6%) patients. Classic CD was diagnosed in 44 (78.6%) patients, atypical CD - in 12 (21.4%). Significant lowering of QoL characteristic "psychological health" was observed in CD patients under 30 and over 50 and "physical health" in 30-50-year-old CD patients. Women had low points on "mental health" scale. After 3 AD months QoL worsened by all the scales, but after 12 months QoL significantly improved. Conclusion. QoL in patients with classic CD is associated with gender and age. First, AD deteriorates QoL, but 1-year diet therapy improves QoL.
Terapevticheskii arkhiv. 2011;83(2):25-28
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The role of immune system in development of structural changes in colonic mucosa in diverticulosis

Levchenko S.V., Gudkova R.B., Potapova V.B., Parfenov A.I., Rogozina V.A., Lazebnik L.B., Levchenko S.V., Gudkova R.B., Potapova V.B., Parfenov A.I., Rogozina V.A., Lazebnik L.B.


Aim. To determine the role of immune response with production of auto- and heterologous antibodies (Ab) in development of the pathological process and in structural changes in colon mucosa (CM) in diverticulosis (Dv). Material and methods. Of 219 Dv patients, 39 were newly diagnosed with x-ray-detected signs of previous inflammation (group 1), 180 had earlier detected Dv which was confirmed and endoscopic examination detected inflammation (group 2). The comparison group consisted of 25 patients with irritable colon syndrome. The immune status was assessed by concentration of immunoglobulins (Ig), auto- and heterologous Ab. Antibodies to catalytic cytoplasmic antigens to proteinase-3, myeloperoxidase, bactericide protein BPI, tissue transglutaminase (tTG) and antiglycanic Ab were detected with solid-phase enzyme immunoassay. Results. IgA and IgG levels in group 2 were significantly higher than in group 1 and in the controls. Elevation of both IgA and IgG levels reflects activation of B-cell immunity. Group 2 patients had a higher level of Ab to endogenic peptides Saccharomyces cerevisiae (ASCA) of class IgG and IgA than group 1 and controls. The level of Ab to tissue molecules was elevated: antibodies to tTG IgG were detected in both groups - in group 2 twice more often than in group 1, while Ab to BPI - in 27% cases in group 1 and in 97% - in group 2. IgG Ab to antigens associated with phagocytic cells were detected in group 2, while Ab in group 1 were positive in single cases. Conclusion. Activation of immune response with a high concentration of IgA and IgG, Ab to tissue antigens (BPI, tTG) and IgGAb to catalytic antigens is characteristic of chronic course of Dv. Morphological changes in CM reflect different severity of inflammation-dystrophic process.
Terapevticheskii arkhiv. 2011;83(2):29-33
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Diagnosis and treatment of intrahepatic cholestasis in chronic diseases of the liver

Golovanova E.V., Petrakov A.V., Golovanova E.V., Petrakov A.V.


Aim. To improve diagnosis of intrahepatic cholestasis (IHC) basing on clinicobiochemical picture in chronic hepatic diseases (CHD) of different etiology with cholestasis and to develop a differential approach to treatment. Material and methods. We examined 875 CHD patients with IHC with evaluation of the levels of the enzymes, biliary acids (BA), lipids, characteristics of hemostasis and phosphocalcium metabolism in blood. We also studied correlations and changes of the above parameters in IHC of different etiology. A comparative analysis of efficacy of mono- and combined treatment of CHD patients with IHC was made. Results. We revealed correlations between the levels of the enzymes, bilirubin, lipids and BA concentration in blood serum; unfavourable prognostic value of aggravating cholemia; no correlations between content of serum BA, duration of IHC and intensity of skin itching (SI). We propose to establish "the degree of IHC severity" with 4 degrees of this severity. Characteristics of impairment of hemostasis and phosphocalcium metabolism in IHC of different etiology depending on the degree of IHC severity are presented. Efficacy and universality of combined treatment with ursodeoxicholic acid and ademetionin in moderate and severe IHC of different etiology are shown. Conclusion. Introduction of the definition "the degree of IHC severity" allowed us to classify IHC by severity. This enables adequate assessment of the patient's condition, prognosis the risk of complications and their severity, a differential approach to treatment and, finally, improvement of the disease outcome prognosis.
Terapevticheskii arkhiv. 2011;83(2):33-39
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Comparative characteristics of porphirine metabolism in chronic viral diseases of the liver

Krivosheev A.B., Kondratova M.A., Krivosheev B.N., Morozov D.V., Danilenko D.B., Krivosheev A.B., Kondratova M.A., Krivosheev B.N., Morozov D.V., Danilenko D.B.


Aim. To study porphirin metabolism in chronic viral infections of the liver. Material and methods. The examination of 101 patients with hepatic viral infections diagnosed chronic HCV-infection in 30 patients, chronic HBV infection in 25 patients and combined infection in 6 patients. Patients with chronic alcohol intoxication were not included in the trial. Urinary uroporphirin and coproporphirin (CP), fecal protoporphirin and CP were estimated. Total porphirines were calculated. Results. 29 patients with chronic viral hepatitis had no porphirin disbolism. The latter (elevation of porphirine fractions in the urine and/or feces) was detected in 11 (84.6%) of 13 patients with hepatic cirrhosis (HC). Biochemical syndromes of elevated fecal porphirines, secondary coproporphirinuria, chronic latent hepatic porphiria were developing. The above disorders progressed with aggravation of the disease severity. In manifest late skin porphiria chronic HCV infection was detected in 19 (32.2%) of 59 patients. Conclusion. In non-alcoholic patients with chronic diffuse diseases of the liver of viral etiology non-specific disturbances of porphirine metabolism develop at the stage of arising HC and are registered more frequently in the presence of chronic HBV-infection. Frequent combination of chronic HCV-infection with manifest late skin porphiria suggests a trigger role of HCV initiating specific disbolism of porphirines in this disease.
Terapevticheskii arkhiv. 2011;83(2):40-47
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Spontaneous bacterial peritonitis and systemic inflammatory reaction in hepatic cirrhosis patients

Vinnitskaya E.V., Lazebnik L.B., Osipov G.A., Drozdov V.N., Vinnitskaya E.V., Lazebnik L.B., Osipov G.A., Drozdov V.N.


Aim. To develop criteria of early diagnosis of spontaneous bacterial peritonitis (SBP) in hepatic cirrhosis (HC). Material and methods. Clinical symptoms of SBP including systemic inflammatory reaction were analysed in 286 patients. The count of polymorphonuclear neutrophils (PNL) in ascitic liquid (AL), microbiological study of the blood and AL were made. Ultrasound investigation assessed acoustic homogeneity of AL. Blood serum (BS) and AL were tested for cytokines content: interleukine-1beta, TNF-alpha, interleukine-4, transforming growth factor beta, C-reactive protein. Gas chromatography - mass spectrometry (GC-MC) estimated quantity and quality of chemical components - markers of potential infectious agents of AL. Results. Three groups of patients were identified: group A (a classic SBP) consisted of 23 patients with clinical symptoms of SBP and PNL content > 0.25109/l; group B (control) consisted of 19 patients free of SBP symptoms and PNL content < 0.25109/l; group C (patients at risk) - 18 patients with SBP symptoms and PNL content < 0.25109/l. Cultural test of AL was negative in all the groups. Symptoms of SIR occurred equally often in groups A and C. CRP in AL was higher (23.8±4.3 g/l) in group A than in group B (p < 0.05). CRP concentration (8.6±2.1 g/l) was higher in group C than in group B (p < 0.05). Changes in cytokine composition were similar in groups A and C. The number of chemical bacterial markers was higher in groups A and C (p < 0.005). Conclusion. Patients of group C with SIR, elevated CRP, changed cytokine status, high content of chemical markers of AL infection by GC-MC are at high risk of SBP. Such patients need adequate and early antibacterial therapy.
Terapevticheskii arkhiv. 2011;83(2):47-52
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An IL-6 level in the serum and urine in estimation of cryoglobulinemic vasculitis activity in patients with chronic hepatitis C associated with renal damage

Korotchaeva Y.V., Kozlovskaya L.V., Gordovskaya N.B., Speranskiy A.I., Korotchaeva Y.V., Kozlovskaya L.V., Gordovskaya N.B., Speransky A.I.


Aim. To estimate serum and urine IL-6 levels and to study its role in diagnosis of nephritis activity in patients with cryoglobulinemic glomerulonephritis (CGN) associated with chronic hepatitis C (CHC). Material and methods. Enzyme immunoassay was used to assay IL-6 in blood serum of 124 patients having different stages of CHC. IL-6 was also estimated in the urine of 57 patients with CHC systemic manifestations including renal damage. Results. Abnormal serum IL-6 level was seen in 36% CHC patients. Patients with elevated level of IL-6 in the serum vs patients with normal IL-6 level had cryoglobulinemia (CGE) (56% vs 26%, p < 0.01) and related systemic manifestations including cryoglobulinemic glomerulonephritis (30% vs 9%, p < 0.01). Most of (90%) patients with CHC-associated CGN had urinary IL-6 excretion correlating with severity of renal damage: the highest urinary level of IL-6 was seen in development of acute nephritic and nephritic syndromes (from 83.5 to 250 pg/ml). It did not correlate with IL-6 in the serum and proteinuria. This is evidence that IL-6 in the urine had a local origin (intrarenal), reflecting activity of immune inflammation in the kidney. Conclusion. Control of IL-6 levels in the blood serum and urine of patients suffering from CHC with cryoglobulinemic syndrome and renal damage can be used for monitoring of the disease activity.
Terapevticheskii arkhiv. 2011;83(2):52-56
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Stages of chronic pancreatitis development

Vinokurova L.V., Trubitsyna I.E., Tkachenko E.V., Vinokurova L.V., Trubitsina I.E., Tkachenko E.V.


Aim. To ascertain correlations between pancreatic secretion disturbances and stage and complications of chronic pancreatitis (CP). Material and methods. The examination covered 81 CP patients (32 females, 49 males, mean age 55.9±1.8 years). Alcohol pancreatitis (AP) was diagnosed in 52 of them, biliary pancreatitis - in 29, complicated pancreatitis - in 25 patients. The control group consisted of 22 patients without symptoms of gastrointestinal disease. Results. By the results of clinical, device, laboratory and morphological tests we recognize 3 variants of CP course. Variant A: duration under 5 years, distinct pain syndrome, pancreatic fecal elastase (E-1) level insignificantly decreased, elevated blood levels of acetylcholine (Ac), serotonin (5-NT), cholecystokinin (CCK), secretin is subnormal. Pancreatic tissue is inflamed and swollen. Variant B: duration 5-10 years, E-1 under 100 mcg/g, moderate pain syndrome, prevalence of 5-NT as a stimulator of pancreatic secretory activity. CCK is high and secretin is low. Further progress of fibrous changes by ultrasound investigation, abdominal CT leads to calcinosis in pancreatic tissue. Variant C: duration 10 years and longer, weak pain syndrome, further rise of 5-NT concentration, decompensation of regulatory mechanisms of secretory pancreatic activity, CCK is high, secretin is subnormal. Conclusion. Changes in correlations between neuromediators and hormones in CP reflect adaptation aimed at retension of secretory pancreatic activity in significant fibrous changes of pancreatic tissue.
Terapevticheskii arkhiv. 2011;83(2):57-61
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Comparative investigation of quality of life and clinical pancreatic index in patients with chronic pancreatitis

Umnova L.M., Orlikov G.A., Voytsekhovskaya Y.G., Voltnere V.K., Ostrovskis E.K., Voytsekhovskiy V.V., Umnova L.M., Orlikov G.A., Voitsekhovskaya Y.G., Voltnere V.K., Ostrovskis E.K., Voitsekhovsky V.V.


Aim. To compare efficacy of using EORTC QLQ-C30 and clinic pancreatic index (CPI) in assessment of severity and treatment efficacy of chronic pancreatitis (CP). Material and methods. The CPI is proposed which is an integrated quantitative index based on formalization of CP symptoms (number of operations for CP complications, efficacy of outpatient treatment, number of treatment courses in hospital, body mass loss, pain intensity, degree of steatorea, number of daily defecations, other dispeptic complaints, glucose tolerance). Quality of life (QoL) estimated with EORTC QLQ-C30 was compared with CPI in 22 patients before and 1 month after start of treatment of CP with enzyme medicine in combination with proton pump inhibitor and, on demand, analgetic from the group of nonsteroid anti-inflammatory drugs. Results. A significant negative correlation was observed between QoL and health estimation by the patient according to EORTC QLQ-C30 and total CPI before treatment. At the end of the study this correlation was absent. It was found that both EORTC QLQ-C30 and CPI differed significantly before and after the study. When the indices of both EORTC QLQ-C30 and CPI before and after the study were pooled in groups, strong negative correlations were revealed between total CPI and such EORTC QLQ-C30 parameters as physical, role, cognitive and social function, with patient's assessment of QoL and symptoms severity by EORTC QLQ-C30. Conclusion. EORTC QLQ-C30 and CPI are similar in reflection of CP severity. CPI is more sensitive than EORTC QLQ-C30 method of assessment of CP treatment efficacy.
Terapevticheskii arkhiv. 2011;83(2):61-63
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Infection agents and irritable colon syndrome

Uspenskiy Y.P., Zakharenko S.M., Fominykh Y.A., Uspensky Y.P., Zakharenko S.M., Fominykh Y.A.


The discussion concerns onset and pathogenesis of functional intestinal diseases. Current data are presented on association of functional intestinal diseases with different infectious agents with illustration on the model of postinfectious irritable colon syndrome (ICS). ICS-like conditions in patients who had previously intestinal infections are considered.
Terapevticheskii arkhiv. 2011;83(2):64-67
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Metabolic correctors based on siccine acid as pathogenic therapy in chronic virus hepatitis

Stel'makh V.V., Radchenko V.G., Kozlov V.K., Stelmakh V.V., Radchenko V.G., Kozlov V.K.


Chronic viral hepatitides (CVH) run with long-term activation of the system of mononuclear phagocytes associated with hyperproduction of active oxygen forms. This can be considered as risk factors of antioxidant insufficiency which determines the course of the disease. Now, antioxidant, cytoprotective medicines are more and more actively used in hepatology. The results are reviewed of many Russian clinical trials of efficacy of metabolic correctors based on siccine acid (reamberin, remaxol) as pathogenetic treatment in CVH. Metabolic correctors in combined treatment of CVH improve basic clinicolaboratory indices, raise efficacy of basic therapy, correct insufficiency of antioxidant defense. The results of the studies confirm advantage of antihypoxic medication over standard infusion therapy for treatment of CVH patients.
Terapevticheskii arkhiv. 2011;83(2):67-71
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Diabetes mellitus and functional and structural changes in the gastroduodenal tract: a clinical and epidemiological study (a review and the authors' data)

Tsimmerman Y.S., Zinnatullin M.R., Tsimmerman Y.S., Zinnatullin M.R.


The paper presents the currently available data on the prevalence of diabetes mellitus (DM), its complications, including functional and structural changes in the gastrointestinal tract (GIT). A range of unsolved problems associated with the frequency, pattern and mechanisms of gastric functional and structural disorders in DM; the cause-and-effect relationship between DM and upper GIT pathology; and the role of Helicobacter pylori in the development of gastroduodenal mucosal changes in the presence of DM are described. The authors give the results of their own studies on 2 groups of patients with DM: 1) 463 patients treated for GIT pathology in a specialized gastroenterology unit; 2) 1500 patients were followed up by a polyclinic endocrinologist. The study has shown that the number of diabetic patients with GIT dysfunction complaints constantly increases. Ulcerative erosive lesions were detected in 36.6% of the inpatients with DM and only in 1.9 and 3.2% of the outpatients with Types 1 and 2, respectively; moreover, the patients with Type 2 DM more frequently complained of epigastralgia than those with Type 1 DM.
Terapevticheskii arkhiv. 2011;83(2):71-75
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The X congress of the Russian Gastroenterological Society

Bordin D.S., Bordin D.S.
Terapevticheskii arkhiv. 2011;83(2):75-79
pages 75-79 views

Leonid Borisovich Lazebnik (the 70th anniversary of birth)

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Terapevticheskii arkhiv. 2011;83(2):79-80
pages 79-80 views

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