Vol 72, No 2 (2017)

INTERNAL DISEASES: CURRENT ISSUES
INTESTINAL MECHANISMS OF ENTEROHEPATIC CIRCULATION DISTURBANCE OF BILE ACIDS IN CHOLELITHIASIS
Vakhrushev Y.M., Lukashevich A.P., Gorbunov A.Y., Penkina I.A.
Abstract

Background: Cholelithiasis is one of the most common diseases of the digestive system which affects all segments of the population and preserves a stable growth of incidence rates. In recent years the development of cholelithiasis is associated with impaired enterohepatic circulation (EHC) of bile acids (BA). The small intestine (SI) plays an important part in EHC of BA because 80‒90% of BA are absorbed into the blood after deconjugation by bacteria in the SI. However, in spite of a number of works dealing with the problem of EHC of BA at the intestinal level, the problem is far from being solved.

Aims: To assess the association between the level of bile acids in the blood and bile of patients with cholelithiasis and disturbance of resorbing function of the small intestine as well as changes in the condition of the intestinal microbiota.

Materials and methods: Non-randomized controlled trial. The study group included patients aged 18‒74 with lithogenic stage of cholelithiasis. The diagnosis was based on clinical data and the results of ultrasound examination of the gallbladder. Bile acids in the blood and bile were determined by mass spectrometry using the apparatus AmazonX (Bruker Daltonik GmbH, Bremen, Germany). Biochemical examination of bile was conducted. Absorption in the small intestine was studied by functional glucose tolerance test. Condition of the intestinal microbiota was assessed by the hydrogen breath test with lactulose using the apparatus LaktofaH2 (AMA, St. Petersburg). Stool culture was performed in selective media.

Results: 115 patients aged 18 to 74 with prestone stage of cholelithiasis and 25 healthy people, comparable in age and sex, were examined. In patients with prestone stage of cholelithiasis biochemical examination of bile revealed increased cholesterol and decreased bile acids and bile acids-cholesterol ratio in B and C bile. The level of bile acids in the blood was reduced in comparison with the control group; it was associated in particular with a significant reduction in chenodeoxycholic, deoxycholic and glycodeoxycholic acids. Resorption in the small intestine was increased in patients with cholelithiasis compared with the control group (blood glucose increase within 30 minutes after the glucose load was 3.13±0.17 and 2.32±0.11 mmol/l respectively; p<0.05). In the majority of patients small intestinal bacterial overgrowth (SIBO), mainly (75% of patients) associated with ileocecal insufficiency, and dysbiosis in the large intestine were established (88 and 100% of patients respectively).

Conclusions: The small intestine is an important component in disturbance of enterohepatic circulation of bile acids. Significant changes in deconjugation of bile acids occur due to SIBO in the distal ileum and dysbiosis in the large intestine, thus disturbings the proportion of fractions of bile acids in the blood and bile.

Annals of the Russian academy of medical sciences. 2017;72(2):105-111
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INFECTIOUS DISEASES: CURRENT ISSUES
NATURAL RESERVOIR OF FILOVIRUSES AND TYPES OF ASSOCIATED EPIDEMIC OUTBREAKS IN AFRICA
Shchelkanov M.Y., Magassouba N., Dedkov V.G., Shipulin G.A., Galkina I.V., Popova A.Y., Maleev V.V.
Abstract

Family Filoviridae includes a set of etiological agents of human hemorrhagic fevers distributed in Africa: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SUDV), Bundibugyo ebolavirus (BDBV), Taï Forest ebolavirus (TAFV), Marburg marburgvirus (MMARV). Historiography and recent taxonomical structure of Filoviridae family are considered in the review. The discussed data of laboratory and ecological-virological field researches demonstrate the presence of a natural reservoir of filoviruses among fruit-bats (Chiroptera, Megachiroptera) which carry filovirus infection without clinical signs but allocate viruses with urine, saliva, excrements, and sperm, as well as contain viruses in blood and internals. The potential hosts of filoviruses are various mammal species including the higher primacies (Anthropoidea) and the humans (Homo sapiens sapiens). A brief comparison of anatomic and morphologic features of fruit bats and bats (Chiroptera, Microchiroptera) belonging to another suborder of chiropterans is presented. The description of the basic characteristics of the four types of epidemic outbreaks linked with Filoviridae-associated fevers — speleological (from Ancient Greek σπήλαιον — cave), forest, rural, and urban are given; their possible transformation directions are considered as well.

Annals of the Russian academy of medical sciences. 2017;72(2):112-119
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CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUES
ASSOCIATION OF ENOS GENE POLYMORPHISMS AS A RISK FACTOR OF CORONARY IN-STENT RESTENOSIS
Ogorodova L.M., Rukin K.Y., Vintizenko S.I., Petrova I.V.
Abstract

Background: In recent years more attention is paid to the methods of interventional treatment of coronary artery disease. However, despite the numerous clinical studies the problem of stent restenosis after interventional procedures remains an important one. The studies of the molecular mechanisms of restenosis of coronary arteries and findings for new genetically determined predictors of restenosis after stenting become vital and essential. The NO-synthase influence on the development of endothelial dysfunction is practically assured, but the studies on the NOS genes' polymorphism effect on the incidence rate of in-stent restenosis are isolated and based on a limited number of clinical observations. The determined facts demonstrate the relevance of the conducted study, the results of which formed a new understanding of the role of NO-synthase genes in the predisposition to hyper-proliferative stents in patients with coronary artery disease. Aims: Set association between the eNOS gene polymorphisms and the risk of restenosis in patients with coronary artery disease hospitalized for coronary restenosis.

Materials and methods: We examined 484 patients with the verified diagnosis of the ischemic heart disease who underwent treatment at the unit of atherosclerosis and chronic coronary heart disease of «Cardiology Research Institute». Stenting of coronary arteries was performed in 210 people. The group of a restenosis enrolled 60 patients and the group without restenosis — 150. Genotyping was performed by non-enzymatic technique for isolation of genomic DNA from the venous blood of the surveyed, NOS genes' polymorphisms were detected by polymerase chain reaction (PCR).

Results: The established development of in-stent restenosis was associated with the following eNOS gene polymorphisms: VNTR ― in homozygotes for the minor allele (genotype aa) and heterozygotes (genotype ab); 894G/T ― in heterozygotes (the GT genotype) and homozygotes (TT genotype).

Conclusions: VNTR and 894G/T polymorphisms of eNOS gene are associated with risk for restenosis and can serve as additional markers for risk of restenosis after coronary stenting.

Annals of the Russian academy of medical sciences. 2017;72(2):120-125
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HEALTH CARE MANAGEMENT: CURRENT ISSUES
AUTOMATED DOCUMENT MANAGEMENT SYSTEM OF PHARMACEUTICAL MANUFACTURER’S QUALITY MANAGEMENT SYSTEM IN ACCORDANCE WITH REQUIREMENTS OF GMP
Pyatigorskaya N.V., Beregovykh V.V., Aladysheva Z.I., Belyaev V.V., Meshkovskii A.P., Pyatigorskii A.M.
Abstract

Drugs must be produced in compliance with good manufacturing practice rules approved by an authorized federal agency. Pharmaceutical Quality System is a global requirement for development and production processes for pharmaceutical products. The article describes a variant of automated document management system of pharmaceutical manufacturer’s quality management system in accordance with current requirements of GMP. The peculiarity of the proposed system is the focuses on pharmaceutical production taking into account the characteristics and requirements for the pharmaceutical products production. All documents which are supposed to be used within the system are grouped into the four blocks: normative legal acts, core manufacturer standards according to GMP, regulatory documents, and register documents.

Annals of the Russian academy of medical sciences. 2017;72(2):126-133
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PEDIATRICS: CURRENT ISSUES
SEXUAL DIMORPHISM OF HEIGHT-WEIGHT INDICES AND BODY COMPOSITION IN RUSSIAN CHILDREN AND ADOLESCENTS AGED 5–18 YEARS: THE RESULTS OF MASS POPULATION SCREENING
Starodubov V.I., Melnikov A.A., Rudnev S.G.
Abstract

Background: Population screening in Health Centers (HCs) represents the only data source of mass anthropometric and body composition in Russia. Previously, an overview of the physical development and body composition of the population according to HCs’ data along with centile reference tables were published while a detailed analysis of sexual dimorphism was not carried out.

Aims: The analysis of sexual dimorphism of height-weight indices and body composition data in modern Russian children and adolescents aged 5–18 years according to HCs data, as well as comparison of the dynamics of age-related changes in anthropometric data with the WHO growth references.

Materials and methods: Non-clinical cross-sectional observational study was conducted using bioimpedance and related anthropometric HCs’ data over the period 2010–2012. The data was obtained according to Russian Health Ministry letter no. 14-1/10/2-3200 dated Oct. 24, 2012. The study sample included 268 153 subjects, 140 769 boys and 127 384 girls. Intergroup differences were evaluated with the Mann-Whitney test. The distributions of Ht, Wt, and BMI for age and sex were matched with the WHO reference data using LMS-transformation with the parameters from the WHO expanded tables with the subsequent calculation of 95% confidence intervals for median z-scores.

Results: Availability of double crossing of growth curves in boys and girls for Ht and Wt during puberty is shown with a narrower double crossing interval for Wt as compared to conventional data. The relative annual growth rates for Ht and Wt were higher in females up to the age of 12 years, and in males older 12. Throughout the age range, median values of BMI in boys and girls were similar (with the differences in the range of 1 kg/m2); median values of FFM were significantly higher in males, and of BF and %BF in females. In most age groups, the median values of Ht and Wt in Russian children and adolescents were higher as compared to WHO reference data (with the maximal difference z=+0.74 for Wt in 10 years-old boys). The similar pattern was detected for BMI in boys aged 5–17 and girls aged 6–14.

Conclusions: The narrower interval of double-crossing of growth curves for Wt may indicate adverse environmental effects associated with overnutrition and reduced physical activity which leads to elevated fatness in boys. Taking into account mass character of data, relatively broad coverage of regions, and the observed differences with the WHO growth references, the use of Health Centers’ data is advisable for the elaboration of the national standard of physical development in children and adolescents.

Annals of the Russian academy of medical sciences. 2017;72(2):134-142
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STOMATOLOGY: CURRENT ISSUES
A COMPARATIVE EXAMINATION OF QUANTITATIVE AND SPECIFIC STRUCTURE OF YEAST FUNGI OF THE CANDIDA GENUS CONSIDERING PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS OF VARYING SEVERITY
Volchenkova G.V., Kiryushenkova S.V., Nikolaev A.I., Shashmurina V.R., Devlikanova L.I.
Abstract

Background: Periodontitis is a major reason of tooth loss in people of middle and older age groups that requires more attention of researchers to the problems of etiology, pathogenesis, diagnosis, and therapy of the disease. Currently, the interaction of the microbial content of dental plaque and local tissue response is considered to be the main reason for the development of inflammatory periodontal diseases. At the same time, Russian and foreign researchers mark a high frequency of so-called torpid or resistant to antimicrobial therapy forms of periodontitis.

Aim: To study the specific and quantitative composition of a fungi of the Candida genus in the contents of periodontal pockets of patients with varying severity of chronic generalized periodontitis.

Materials and methods: A non-randomized non-controlled retrospective research was conducted. We studied the main clinical and radiological indicators of periodontal status and its contamination with fungi of the Candida genus in people with mild, moderate, or severe chronic periodontitis.

Results: Research participants enrolled in four groups: 1–3 groups included patients with chronic generalized light, medium and heavy periodontitis; group 4 included twenty-five subjects with no signs of periodontal disease. Among the examined patients from the control group, the frequency allocation of Candida from the contents of the gingival sulcus was 9.09%, patients with periodontal pathology of periodontal pockets ― 64.91%. High contamination with fungal flora (more than 6.0 CFU / mL) was observed in all patients with chronic periodontitis. Total allocated 40 strains of Candida with a predominance of Candida albicans.

Conclusions: The results of microbiological research confirmed an increase of contamination of periodontal with fungi of the Candida genus in patients with periodontitis if compared with healthy people. The degree of the contamination with fungi of the Candida genus decreased with increasing severity of periodontitis. It can be assumed that the presence of Candida fungi in the periodontal pocket can be considered as a possible component of the etiology of chronic periodontitis and as a factor aggravating it.

Annals of the Russian academy of medical sciences. 2017;72(2):143-148
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TRAUMATOLOGY: CURRENT ISSUES
MULTICENTER ANALYSIS OF THE RESULTS OF APPLICATION OF DIRECT LATERAL INTERBODY FUSION (DLIF) AND TRANSCUTANEOUS TRANSPEDICULAR FIXATION IN PATIENTS WITH DEGENERATIVE DISC DISEASES OF THE LUMBAR SPINE
Byvaltsev V.A., Kalinin A.A., Akshulakov S.K., Krivoshein A.E., Kerimbayev T.T., Stepanov I.A.
Abstract

Background: The technique of lateral lumbar interbody fusion for the surgical treatment of patients with degenerative diseases of the lumbar spine was developed in the early 2000s. But at the same time in modern literature there is no uniform approach to the use this technique, clinical outcomes and radiological findings are contradictory.

Aims: to conduct a multicenter analysis of clinical outcomes and instrumental data of direct lateral interbody fusion (DLIF) approach combined with transcutaneous pedicle fixation in patients with single-level degenerative disc diseases of the lumbar spine.

Materials and methods: The study included 103 patients (63 men and 40 women, mean age 45.8±9.7 years) who underwent surgery followed by DLIF transcutaneous pedicle fixation. The surgery was performed at neurosurgical and vertebrological departments in Irkutsk (Russia), Omsk (Russia), and Astana (Kazakhstan). Dynamic observation and comprehensive clinical and instrumental evaluation of the treatment results were carried out for an 18-month period after surgery.

Results: After the simultaneous decompressive-stabilizing intervention, in all patients we detected a decrease in the severity of pain syndrome on VAS — from 6.9±1.6 to 1.7±1.2 cm (p<0.001), and improved quality of life index (Oswestry) — from 21.3±6.8 to 12.3±4.4% (p<0.001). The instrumental methods of examination determined the effective indirect decompression: an increase in the size of interbody gap in the middle of its department compared with the preoperative value from 8.6±3.1 to 15.7±4.2 mm (p<0.001) and an increase in the area of the intervertebral foramen (on the left with an average of 98.7±32.3 and 156.8±45.1 mm2, p<0.001; on the right —99.7±37.3 to 153.4±38.7 mm2, p<0.001). We also registered the restoration of both the segmental (from 10.2±3.8 to 13.6±6.7°, p<0.001) and regional (from 32.8±5.9 to 48.2±7.3°, р<0.001) lumbar lordosis. Complete interbody fusion was diagnosed in 87 (86.4%) patients. Complications were observed in 8.7% of cases. 

Conclusions: DLIF technique combined with transcutaneous transpedicular stabilization has high clinical efficacy confirmed by significant reduction in the severity of pain according to VAS. The studied approach improves the quality of life of patients by Oswestry index and reveals a low number of postoperative complications. The described simultaneous minimally invasive method of surgical treatment in patients with degenerative disc diseases allows to restore the sagittal profile of the lumbar spine and implement an effective stabilization of the operated vertebral-motor segments with a high degree of formation of interbody bone block.

Annals of the Russian academy of medical sciences. 2017;72(2):149-158
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TO THE MEMORY OF
A FEW WORDS ABOUT THE TEACHER. IN MEMORY OF THE EXCELLENT TEACHER AND SCIENTIST M.R. SAPIN
Nikolenko V.N., Kudryashova V.A., Makarova V.D., Rizaeva N.A., Oganesyan M.V.
Abstract

M.R. Sapin (1925–2015) was a professor at I.M. Sechenov First Moscow State Medical University, honorary academician of Russian academy of medical sciences (1988), and an outstanding representative of the Moscow anatomical school of the middle of XX – early XXI century. From the very beginning of his medical training, Mikhail Romanovich got interested in anatomy, especially in angiology and lymphology, and later concentrated on its studying. The author of more than 30 text books and guidelines for schools, universities, and colleges, Mikhail Romanovich was the doctoral and thesis advisor of 51 Ph.D. and approximately 70 MD dissertations. M.R. Sapin made a significant contribution to the development of anatomical education providing the departments with a various range of dry and wet specimens. His stunning and effective work as a tutor was highly appreciated by his students and colleagues, Russian and foreign anatomists. M.R. Sapin was the leader of the Laboratory of Functional Anatomy since 1972, president of the International Association of Morphologists (1992–2006), chairman of the expert commission of Higher Attestation Commission (1959–1994), etc. A man of a great willpower, M.R. Sapin faced a lot of obstacles in his life and research work but overcame that all successfully. The article presents the most important facts of anatomist’s career and lifetime.

Annals of the Russian academy of medical sciences. 2017;72(2):164-166
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