Vol 73, No 1 (2018)


Clinical and Anamnestic, Immunological, Echographic, and Hysteroscopic Features of Chronic Endometritis Associated with Impaired Reproductive Function

Ishenko A.I., Unanyan A.L., Kogan E.A., Demura T.A., Kossovich J.M.


Background: The widespread prevalence of infertility, the low effectiveness of assisted reproductive technologies (ART), and the high incidence of chronic endometritis (CE) in infertile women determine the relevance of the considered problem. The aim of the study was to determine the clinical and anamnestic, laboratory, and instrumental features of CE associated with infertility and unsuccessful IVF cycles in women of reproductive age. 

Materials and methods: The study enrollred 150 women of reproductive age with morphologically established CE (main group, n=120) and without CE (control group, n=30). A subgroup I of the main group included 64 patients with infertility and IVF failures, a subgroup II – 56 fertile women. In addition to anamnesis collection and identification of CE clinical features, all patients underwent infectious screening, immunological and immunohistochemical analysis, ultrasound examination of pelvic organs with dopplerometry, and office hysteroscopy. A comparative analysis of the data obtained from subgroups of the main group was conducted. 

Results: Histological study of endometrial pipelle-biopsy specimens on the 7−10th day of the cycle revealed CE in all patients of the main group. We found prevalence of mean duration of CE in the subgroup I relative to subgroup II ― 5.5±0.06 years and 2.4±0.07 years, respectively (p<0.001). Infectious screening showed that 58 (90.6%) patients of the I subgroup had sterile endometrial seeding which was 16.9 times higher than in subgroup II (p<0.0001). Immunological analysis determined the presence of AEAT in all patients of the subgroup I, 43 of which (67.2%) were above 265 U/ml, while 51 (91.1%) of subgroup II had no AEAT (p<0.001). Immunohistochemical analysis of the endometrium on the 18th−24th day of the cycle established high expression of CD16 , CD20 , CD56 , and HLA-DRII in 58 (90.6%) patients of the subgroup I, whereas in 54 patients (96.4%) of II subgroup high expression of CD16 and CD20 with low amount of CD56- and HLA-DRII-positive cells was registered (p<0.001). We determined prognostically significant clinical and anamnestic risk factors predisposing to the development of infertility in patients with CE (p<0,05). We revealed certain echographic, dopplerometric, and hysteroscopic criteria of CE demonstrating the critical disruption of endometrial receptivity in infertile women. 

Conclusion: Most patients (90.6%) with infertility had autoimmune component of CE characterized by prolonged (more than 5 years) course, high serum level of AEAT, sterile endometrial crops, and high expression of inflammation markers CD16 , CD20 , CD56 and HLA-DRII .

Annals of the Russian academy of medical sciences. 2018;73(1):5-15
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Outcome Analysis of the Flow Diversion with Pipeline Embolization Device for the Surgical Treatment of Unruptured Large and Giant Paraclinoid Carotid Aneurysms

Byvaltsev V.A., Makhambetov Y.T., Stepanov I.A., Kaliyev A.B., Akshulakov A.K.


Background: Both the high frequency of recurrence of large or giant paraclinoid aneurysms (PA) of the internal carotid artery and the occurrence of intra- and postoperative complications, leading to unsatisfactory results of surgical treatment of this group of patients, make the stated problem urgent. Flow-diverter embolization devices are actively used in many large international neurosurgical centers for the treatment of cerebral aneurysms of different morphology, size, and localization. Currently, there are very few reports on the effectiveness of the use of flow diverting stents in the surgical treatment of large and giant PA of the internal carotid artery. The results of these studies are controversial and largely contradictory. 

Aim: Outcome analysis of the use of Pipeline embolization device (PED) for the surgical treatment of large and giant carotid PA. Methods: The study enrolled 37 patients (25 women, 12 men; mean age 51.7±10.7 years) who were divided into those treated with the PED alone versus those treated with the PED and concurrent coil embolization. The average follow-up period was 19.7±3.8 months. 

Results: In 56.7% of cases, PA caused the development of an insignificant neurological deficit (Modified Rankin Scale 1−2). In 18.9% of patients, PA provoked a gross neurologic deficit (MRS 3−5). 24.3% of patients with PA did not have any clinical-neurological manifestations. After the surgery, neurologic status improved in 32.4% of patients, remained the same — in 45.9% of cases, and the degree of neurologic deficit increased in 21.6%. PED procedure was performed in 70.2% of patients. In 29.7% of cases, the dislocation of large or giant PA of the internal carotid artery from the systemic blood stream was performed using PED and concurrent coil embolization. At the indicated period of patient observation, complete occlusion of large and giant carotid PA was achieved in 75.6% of cases, almost complete and partial occlusion — in 24.3%. The incidence of thromboembolic and hemorrhagic complications was 10.8% and 8.1%, respectively. Mortality rate among patients was 2.7%. 

Conclusions: The use of PED is an effective method for occluding large or giant PA of the internal carotid artery. Nevertheless, this method of endovascular treatment of PA is associated with a high complication incidence.

Annals of the Russian academy of medical sciences. 2018;73(1):16-22
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Evaluation of antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture

At'kova E.L., Krahoveckij N.N., Yartsev V.D., Subbot A.M., Gabashvili A.N., Rein D.A., Nesterova T.V.


Background: One of the main reasons of failure in surgical treatment of primary acquired nasolacrimal duct obstruction is excessive postoperative scarring of the dacryostomy. Despite the variety of procedures designed to prevent this, conflicting evidence of their efficacy and safety provide incentive for further research of antifibrotic therapeutics for adjunctive use in dacryocystorhinostomy.

Aims: To evaluate the antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture.

Materials and methods: Human nasal mucosal fibroblast cell cultures were established using samples obtained from 3 consecutive patients undergoing endonasal endoscopic dacryocystorhinostomy. Cell viability following treatment with pirfenidone was evaluated using MTS-assay. Induced inhibition of cell proliferation and migration was determined using scratch wound assay.

Results: In this study pirfenidone exhibited a significant dose-dependent inhibiting effect on fibroblast proliferation with insignificant cell toxicity. Cell viability following 48 hours of incubation with various pirfenidone concentrations did not drop below 80%. The recovery of the fibroblast monolayer assessed after 24 hours of incubation was 84.88 and 8.26% in the control group, at a drug concentration of 0.15 mg/ml. Cell proliferation and migration was severely inhibited in cell culture specimens treated with pirfenidone compared to controls. The difference between groups was statistically significant (p=0,001).

Conclusions: In our study pirfenidone demonstrated a pronounced antifibrotic effect. It is unlikely that inhibition of proliferation and migration of human nasal mucosal fibroblasts is mediated by cell toxicity of this medication as it was evaluated as low. Nonetheless an in vitro analysis is insufficient to judge pirfenidone’s efficacy and safety in preventing cicatrix formation following dacrycystorhinostomy. 

Annals of the Russian academy of medical sciences. 2018;73(1):23-29
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Multifocal Intraocular Lenses Clinical Assessment. Patient Selection for Multifocal Intraocular Correction

Morozova T.A., Kerimov T.Z.


There are some multufocal intraocular corrections particular qualities compared to monofocal correction. Therefore, the patient’s careful selection, detail preoperative diagnosis, accurate intraocular lens power calculation are necessary to get the optimal clinical results. There are some disadvantages in the postoperative period, such as the contrast sensitivities reduction, dysphotopsia, neuroadaptation. In addition multifocal IOLs are expensive. The clinical studies include evaluating of visual acuity for different distances, defocus curve, spectacle independence, contrast sensitivity, aberrometry data. Additionally, complications after multifocal IOLs implantation and the reasons of explantation are analyzed. This review includes 36 articles (34 clinical studies and 2 meta-analysis) of the following aspects of multifocal intraocular correction: contrast sensitivity, aberrometry analysis, pupil influence on the visual outcomes, postoperative complications, analysis of explantation reasons, preoperative patient’s selection for multifocal correction.
Annals of the Russian academy of medical sciences. 2018;73(1):30-39
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Autologous Plasma Enriched with Platelet Lysate for the Treatment of Idiopathic Age-Related Macular Degeneration: A Prospective Study

Lykov A.P., Poveshchenk O.V., Surovtseva M.A., Stanishevskaya O.M., Chernykh D.V., Arben’eva N.S., Bratko V.I.


Background: Plasma enriched in growth factors is widely used in medical practice. However, the clinical efficacy of its application in the treatment of age-related retinal integrity violations is investigated insufficiently. 

Aims: The aim of the study was to evaluate the clinical efficacy of autologous plasma enriched with platelet lysate for treating age-related macular degeneration. 

Materials and methods: A three-port subtotal transconjunctival vitrectomy was performed and administration of the autologous plasma enriched with platelet lysate was indicated. Autologous plasma enriched with platelet lysate was received from the peripheral blood. We assessed visual acuity, intraocular pressure; conducted optical coherent tomography examination of the eye on the side of the pathological process. 

Results: The study demonstrated that the combination of a standard 3-port transconjunctival subtotal vitrectomy followed by tamponade of the gap using the autologous plasma enriched with platelet lysate with the injections of the autologous plasma enriched with platelet lysate in the area of pterygopalatine fossa on the side of the operated eyes statistically significantly promoted recovery of the visual acuity in the early postoperative period (15 days) and late period (90 days) if compared with patients who received only surgical treatment (p≤0.05). Use of the autologous plasma enriched with platelet lysate in the treatment increased the closing rate of the tearing of the retina in the macular region up to 62,5%, while only surgical treatment leads to the closure of the defect of the retina in 37.5% of cases. The study showed that autologous plasma enriched with platelet lysate contains cytokines, growth factors, and nitric oxide which are involved in the regeneration/reparation of the retina. 

Conclusions: Additional administration of the autologous plasma enriched with platelet lysate in the scheme of treatment patients with age-related macular degeneration is accelerating the closure of retinal tears of the eye and improves visual acuity.

Annals of the Russian academy of medical sciences. 2018;73(1):40-48
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Food Allergy in Children with Inherited Epidermolysis Bullosa. The Results of the Observational Study

Makarova S.G., Namazova-Baranova L.S., Murashkin N.N., Vishneva E.A., Epishev R.V., Chumbadze T.R., Kogevnikova O.V., Snovskaya M.A., Ereshko O.A., Balabekova F.G., Yasakov D.S.


Background: Inherited epidermolysis bullosa (EB) refers to a group of rare inherited disorders characterized by severe damage of skin and in most patients — the gastrointestinal mucosa, what leads to a violation of skin and mucosal barrier properties in relation to allergens. However, the issues of food sensitization and food allergy in this category of patients have not been studied, and the study of this problem is important.

Aim: To evaluate the clinical manifestations of food allergy (FA) and IgE-response to food proteins in children with EB.

Methods: 82 patients with EB aged from 2 months to 16 years were entered this open non-randomized observational prospective study, including 20 patients with simple form of EB and 62 patients with dystrophic form of EB. We analyzed allergic history and clinical manifestations of the FA in all the patients. Every patient in this study underwent of determination of the concentration of total serum IgE and specific serum IgE to the most important food allergens, as well as to mixtures of household allergens in some cases (UniCAP System, Phadia AB). 

Results: Skin lesion in patients with EB masks allergic skin manifestations, causing a hypodiagnosis of the FA in this category of patients, which in turn leads to erroneous organization of nutritional support. FA (clinical manifestations) was identified in 20.7% of children with EB (in 10% of cases with simple form of EB and in 24.2% — in patients with dystrophic form of EB). Products containing cow’s milk protein, cereals, and eggs were identified as etiologic factors of FA in most cases. In the group of children with comorbidity FA and EB high and very high levels of total IgE (>1000 kUA / l) were detected most frequently. The main cause-significant allergens are cow’s milk proteins, cereals, eggs. 

Conclusions: Comorbidity with FA is high in patients with dystrophic form of EB. The main cause-significant allergens are cow’s milk proteins, cereals, eggs.

Annals of the Russian academy of medical sciences. 2018;73(1):49-58
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Experimental study of the antibacterial activity of the lytic Staphylococcus aureus bacteriophage ph20 and lytic Pseudomonas aeruginosa bacteriophage ph57 during modelling of its impregnation into poly(methylmetacrylate) orthopedic implants (bone cement)

Samokhin A.G., Kozlova J.N., Korneev D.V., Taranov O.S., Fedorov E.A., Pavlov V.V., Morozova V.V., Tikunova N.V.


Background: The problem of bacterial colonization of implants used in medical practice continues to be relevant regardless of the material of the implant. Particular attention deserves polymeric implants, which are prepared ex tempore from polymethyl methacrylate, for example - duting orthopedic surgical interventions (so-called "bone cement"). The protection of such implants by antibiotic impregnation is subjected to multiple criticisms, therefore, as an alternative to antibiotics, lytic bacteriophages with a number of unique advantages can be used - however, no experimental studies have been published on the possibility of impregnating bacteriophages into polymethyl methacrylate and their antibacterial activity assessment under such conditions.

Aims: to evaluate the possibility of physical placement of bacteriophages in polymethylmethacrylate and to characterize the lytic antibacterial effect of two different strains of bacteriophages when impregnated into polymer carrier ex tempore during the polymerization process in in vitro model.

Materials and methods:  First stage - Atomic force microscopy (AFM) of polymethyl methacrylate samples for medical purposes was used to determine the presence and size of caverns in polymethyl methacrylate after completion of its polymerization at various reaction  temperatures (+6…+25°C and +18…+50°C).

The second stage was performed in vitro and included an impregnation of two different bacteriophage strains (phage ph20 active against S. aureus and ph57 active against Ps. aeruginosa) into polymethyl methacrylate during the polymerization process, followed by determination of their antibacterial activity.

Results: ACM showed the possibility of bacteriophages placement in the cavities of polymethyl methacrylate - the median of the section and the depth of cavities on the outer surface of the polymer sample polymerized at +18…+50°C were 100.0 and 40.0 nm, respectively, and on the surface of the transverse cleavage of the sample - 120.0 and 100.0 nm, respectively, which statistically did not differ from the geometric dimensions of the caverns of the sample polymerized at a temperature of +6…+25°C.

The study of antibacterial activity showed that the ph20 bacteriophage impregnated in polymethyl methacrylate at +6…+25°C lost its effective titer within the first six days after the start of the experiment, while the phage ph57 retained an effective titer for at least 13 days.

Conclusion: the study confirmed the possibility of bacteriophages impregnation into medical grade polymethyl methacrylate, maintaining the effective titer of the bacteriophage during phage emission into the external environment, which opens the way for the possible application of this method of bacteriophage delivery in clinical practice. It is also assumed that certain bacteriophages are susceptible to aggressive influences from the chemical components of "bone cement" and / or polymerization reaction products, which requires strict selection of bacteriophage strains that could be suitable for this method of delivery.
Annals of the Russian academy of medical sciences. 2018;73(1):59-68
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Dmitry A. Zhdanov ― the Founder of the Functional Anatomy of the Lymphatic System (to the 110th Birth Anniversary)

Nikolenko V.N., Kudryashova V.A., Oganesyan M.V., Rizaeva N.A., Zakirov F.H.


D.A. Zhdanov is the eminent member of Russian anatomy school, member of the USSR Academy of Medical Sciences, great lymphologist, talented master and wise mentor whose 110th jubilee is held this year. Having introduced completely new way of teaching and learning anatomy, Zhdanov expanded knowledge of functions and structure of lymphatic system, presented new information unknown before and determined direction of further studies for his disciples. Being the founder of functional anatomy of the lymphatic system, D.A. Zhdanov brought up a lot of scientists of morphology who developed the aspects he had noticed. The article reveals main directions of Zhdanov’s occupation and activity (studying the lymphatic system, mentorship and tutorship); major findings and methods which he used in his researche works; his interesting and many-sided personality. The article also describes works of D.A. Zhdanov in other scientific areas such as history of medicine and art, analyzes his international scientific work and role in formation of the Russian anatomy school, presents some biographical data, description of researches and recollections of colleagues.

Annals of the Russian academy of medical sciences. 2018;73(1):69-73
pages 69-73 views

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