Vol 29, No 1 (2021)

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the disease’s clinical course, the phenylalanine blood level, and the patient’s genotype.

Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the disease’s clinical course, and the patient’s genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two «severe» mutations (residual activity of phenylalanine hydroxylase <10%). The second group (n=12) had one «severe» and one «mild» mutation (the residual activity of the enzyme >10%).

Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federation’s average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11G>A (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the
mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the disease’s clinical course, and the patient’s genotype revealed a reliably higher content of amino acid in the first group on retest (32.1±1.7 mg/% vs. 17.7±1.5 mg/% in the second group, р<0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р<0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group.

Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the disease’s clinical portrait, the phenylalanine blood level, and the patient’s PAH genotype was revealed.

Aim. To evaluate the potential utility of fibrin matrices containing 10, 20, and 25 mg/ml of fibrinogen (fibrin-10, fibrin-20, and fibrin-30, respectively) in vascular tissue engineering (VTE).

Materials and Methods. Fibrinogen was isolated using the method of ethanol cryoprecipitation and polymerized using a solution of thrombin and CaCl₂. The fibrin structure was studied in a scanning electron microscope, and the physical and mechanical properties of the material were tested on a Zwick/Roell test machine. The metabolic activity of endothelial cells (EC) on the fibrin surface was evaluated by the MTT assay, and the viability of fibroblasts in the thickness of fibrin and possibility for migration by in fluorescent and light microscopy. Percent of fibrin shrinkage was determined from the difference in the sample volumes before and after removal of moisture.

Results. The fiber diameter did not differ among all fibrin samples, but the pore diameter in fibrin-30 was smaller than those in fibrin-10 and fibrin-20. A possibility for migration of fibroblasts into the depth of the fibrin matrix and preservation of 97-100% viability of cells at a depth 5 mm was confirmed. The metabolic activity of EC on the surface of fibrin-20 and fibrin-30 exceeded that on collagen, fibronectin, and fibrin-10. All fibrin samples shrank in volume to 95.5-99.5%, and the highest shrinkage was seen in fibrin-10. The physical and mechanical properties of fibrin were inferior to those of human A. mammaria by a factor of 10.

Conclusion. Fibrin with fibrinogen concentrations of 20 and 30 mg/ml maintains a high metabolic and proliferative activity of EC on the surface and also a high viability of fibroblasts in the matrix. Its availability, ease of preparation, and a number of other favorable properties make fibrin a promising material for VTE. However, the problem of insufficient strength requires further investigations.

Aim. This study aimed to investigate the mechanisms of autonomic regulation and  autonomic support in focal frontal and temporal lobe epilepsy.

Materials and Methods. Thirty-six individuals were examined (19 men and 17 women; mean age 33.7±1.4 years) in the control group (without history of epileptic seizures) and 68  patients (32 men and 36 women, 34.1±1.5 years) with focal epilepsy (36 patients with frontal lobe epilepsy, of which 32 had temporal lobe epilepsy). Physiological parameters of heart rate  variability and of skin sympathetic evoked potentials were evaluated.

Results. Predomination of sympathetic influences in both groups of patients was found.  According to the analysis of skin sympathetic evoked potentials, a high activity of the  suprasegmental autonomic centers was determined in patients with epilepsy. Based on the results of the correlation analysis, the initial state in patients with temporal lobe epilepsy was  characterized by greater intrasystemic tension that reflects the high level of physiological  costs. The logit regression analysis model makes it possible to distribute patients with focal  epilepsy into groups with different disease courses on the basis of the parameters of the autonomic support of the activity.

Conclusion. In patients with focal epilepsy, predomination of sympathetic influences was  observed, as well as greater activity of the suprasegmental centers of the autonomic regulation. Intrasystemic ratios of autonomic regulation parameters demonstrate an increase in the intrasystemic tension and a limitation of functional reserves in patients with temporal lobe epilepsy. A complex of parameters of autonomic support allows, based on the logit regression analysis, to distribute patients into groups with different courses of focal epilepsy.

During surgical endarterectomy, carotid cross clamping is needed for arteriotomy and plaque removal. Carotid cross clamping reduces the blood flow to the circle of Willis, and some patients show intolerance to the temporary occlusion of the internal carotid artery (ICA).

Aim. This study demonstrates locoregional anesthesia’s safety in patients with carotid cross clamping intolerance (CCI) and the risk factors that predict this condition.

Materials and Methods. All patients who underwent surgical carotid endarterectomy between January 2019 and December 2020 (n=53, 29 were male, age (median with range) – 78 (56-90) years) were identified in a retrospective review. The indication for surgical treatment was made for a stenosed ICA of 70-99% or in the case of symptomatic stenosis.

Surgical technique. An incision is made at the front edge of the sternocleidomastoid muscle. The common carotid artery (CCA) is identified and isolated from the surrounding tissues with sharp dissection and continued toward the bifurcation. Next, the internal and external carotid arteries can be isolated. Heparin (5000 U) is administrated intravenously, and the systolic arterial pressure is increased and kept over 160 mm Hg. In the next step, the cross clamping tolerance test is performed for 60 s. During clamping, the patient is neurologically meticulously observed. In the case of CCI, the operation proceeds with the insertion of a temporary shunt. The arteriotomy is started in the CCA and continues to the ICA. The plaque is completely removed, and the arteriotomy incision is covered with a patch. Before completing the suture, the clamps are partially removed to flush out the debris using the blood flow. Now, the external and common artery can be released. Finally, the clamp of the ICA can be removed.

Results. Eight patients had cross clamping tolerance test intolerance. In all these cases, the surgical procedure was continued with a shunt. The further operation course remained uncomplicated. The in-hospital mortality was nil, and a transient ischemic attack occurred in only one case.
Coronary artery disease (CAD) [odds ratio (OR) 12.65, 95% confidence interval (CI) 1.43-112.50], a history of cerebrovascular events [OR 10.50, 95% CI 1.83-60.30], and contralateral stenosis of 70% or more [OR 26.66, 95% CI 2.29-304.37] presented a significant association with the CCI and the need to shunt. The remaining factors showed no significant association with intolerance.

Conclusions. Regional anesthesia is a safe method for identifying patients with CCI and safely performing the surgical procedure. Contralateral stenosis of the ICA and a history of cerebrovascular events are significant factors to predict CCI.

Aim. This study aimed to investigate potential use of radiofrequency obliteration (RFO) of angiomatous tissues in patients with venous malformations.

Materials and Methods. A single-center study retrospectively involved 42 clinical cases [57.1% of men (n=24), aged 18-44 years; 42.8% of women (n=18) aged 18-56 years] of venous angiodysplasia, with a total of 46 interventions using RFO. Clinical manifestations of the disease were primarily characterized by pain syndrome (71.4%), cosmetic defect (100%), and edema syndrome (95.2%).

Results. Clinical improvement was possibly achieved with the reduction of the intensity of manifestations of angiomatous processes in 37 patients (88.1%). Stable and partial obliterations of caverns in the zone of exposure to radiofrequency were recorded in 37 (88.0%) and 5 (12.0%) patients, respectively. In caverns with small diameter, obliteration was achieved in 100% of the cases. Postoperative complications included bleeding (2.4%), burns in the zone of electrode introduction (2.4%), lymphorrhea (2.4%), and hypesthesia (2.4%). With this, according to the results of duplex scanning performed on control visits, no significant disease progression was observed. In the same patient, several complications could occur. All complications regressed within a month and required no treatment in hospital conditions.

Conclusion. RFO showed advantage as a minimally invasive treatment method of venous angiodysplasias. Results suggest that RFO can be recommended for use in patients with >1 cm depth of lesion with caverns of medium and large diameter as an independent treatment method and in combination with standard resection methods.

Aim. This study aimed to compare the effectiveness of conservative treatment methods, namely, estriol-containing cream and non-hormonal drug, in girls with labial adhesion (LA) in the clinical and diagnostic center of N.V. Dmitrieva Regional Children’s Clinical Hospital.

Materials and Methods. A retrospective analysis of pediatric clinical cases of labial adhesion (n=300) was carried out in N.V. Dmitrieva Regional Children’s Clinical Hospital in the period from 2016 to 2018. The study included 150 girls diagnosed with labial adhesion who were treated with estriol-containing cream (study group) and 150 girls with the same diagnosis (control group) who were treated with a non-hormonal gel containing onion extract 10 g, heparin 5000 IU, and allantoin. The age of the participants ranged from 4 months to 2 years and 2 months. Informed consent was obtained from the girls’ parents for the examination of the child, use of estriol-containing drug or a drug of non-hormonal composition, and processing of personal data. Recovery was considered the absence of recurrent synechiae for 2 years, improvement as not more than one recurrence not earlier than 6 months after the previous treatment, and no effect as two or more recurrences earlier than 6 months.

Results. In the main group, recovery, improvement, and no effect were achieved in 108 (72%), 39 (26%), and 3 (2%) girls, respectively. In the control group, recovery, improvement, and no effect was achieved in 30 (20%), 75 (50%), and 45 (30%) girls, respectively.

Conclusion. The results revealed the effectiveness and safety of using estriol-containing drugs in young girls diagnosed with labial adhesion.

Tracheobronchial injuries as a consequence of chest blunt trauma are rare. Blunt traumas of the cervical part of the trachea are a rarer pathology presenting a serious diagnostic problem for a clinician. Traumas of the larynx and the trachea account for 40 to 80% of lethality. The trachea’s cervical part is vulnerable despite that it is covered with the neck muscles, spine, clavicles, and mandible. In cut/stab wounds, the trachea’s cervical part is often damaged together with the adjacent structures. In blunt trauma, under a direct action of a traumatizing agent, the mobile
trachea displaces toward the spine, accompanied by damage to the tracheal cartilages, its membranous part, and the soft surrounding tissues with preservation of the integrity of the skin.

Tracheal ruptures along the distance up to 1 cm from the cricoid cartilage account for not more than 4% of all tracheal ruptures. A complete tracheal rupture and its abruption from the larynx are extremely rare pathology. Because of severe respiratory disorders, most victims die at the site where their injury occurred.

This article presents a clinical case of the successful treatment of patient Z., 41 years of age, with complete tracheal abruption from the larynx. The cause of tracheal damage was blunt neck trauma in a traffic accident. A peculiarity of this clinical case was that the victim arrived at a specialized thoracic surgery unit with a functioning tracheostomy two days after the trauma.

Conclusion. Tracheal trauma is a potentially fatal condition. Therefore, early diagnosis of tracheobronchial damage is essential since it permits timely surgical intervention and diminished risk of lethal outcome. When dealing with patients with trauma of the head, neck, and chest with non-corresponding clinical data and the absence of effective recommended standard therapeutic measures, a clinician should become alert and exclude the tracheal and bronchial damage.

X-ray computed tomography and fibrotracheobronchoscopy are strongly recommended as reliable methods to diagnose tracheobronchial damages. In a surgical intervention, it is necessary to perform the primary suture on the trachea, avoid preventive tracheostomy, and delay interventions associated with poorer prognosis and a high complication rate.

Chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) coexistence in the same patient has been rarely reported, more frequently due to treatment with chemotherapeutic agents. Blood parameter changes in cancer patients may be interpreted as disease progression or iatrogenic effects related to aggressive treatment, leading to delayed diagnosis. In our article, we call attention to the possibility of AML development in CLL patients and its diagnostic challenge.

Systemic inflammation makes a significant contribution to the pathogenesis of atherosclerosis and has been the subject of numerous studies. Works aiming to analyze the mechanisms of atherosclerosis development often include experiments on animals. A primary task of such research is the characterization, justification, and selection of an adequate model.

Aim. To evaluate the peculiarities of lipid metabolism and systemic inflammation in chronic obstructive pulmonary disease (COPD) in the development of atherosclerosis in animal models.

Materials and Methods. Analyses of cross-links between species-specific peculiarities of lipid metabolism and the immune response, as well as a bioinformatic analysis of differences in Toll-like receptor 4 (TLR4) in mice, rats, and rabbits in comparison with its human homolog, were carried out. A search for and analysis of the amino acid sequences of human, mouse, rat, and rabbit TLR4 was performed in the International database GenBank of National Center of Biotechnical Information and in The Universal Protein Resource (UniProt) database. Multiple alignments of the TLR4 amino acid sequences were implemented in the Clustal Omega program, version 1.2.4. Reconstruction and visualization of molecular phylogenetic trees were performed using the MEGA7 program according to the Neighbor-Joining and Maximum Parsimony methods.

Results. Species-specific differences of the peculiarities of lipid metabolism and the innate immune response in humans, mice, and rabbits were shown that must be taken into account in analyses of study results.

Conclusion.Disorders in lipid metabolism and systemic inflammation mediated by the innate immune system participating in the pathogenesis of atherosclerosis in COPD possess species-specific differences that should be taken into account in analyses of study results.

This article contains a literature review of the results of experimental and clinical studies of the influence of physical exercise on the clinical course of bronchial asthma (BA) and presents the pathophysiological mechanisms of this influence. A high prevalence of sedentary lifestyle among patients with BA, its cause, and consequences are considered. Some studies have shown that patients with BA more rarely perform physical activity, and their physical exercises are less intensive and/or take shorter time. Effects of different variants of physical exercise on patients with BA are also discussed. Regular aerobic and mixed exercises of moderate intensity reliably lead to an improvement of the quality of life, reduction of exacerbations, use of inhalators «on demand», nocturnal symptoms, and sleep; to a reduction of the hyperresponsiveness of the bronchi, eosinophil count in the sputum, levels of interleukin-6, and monocyte chemotactic factor-1; and to an increase in the level of interleukin-10. SOCS-JAK-STAT plays a role in the mechanism underlying the influence of aerobic exercises on inflammation, remodeling, and hyperresponsiveness of the airways by decreasing the expression of Th2 cytokines, chemokines, adhesion molecules, growth factors, NF-kB, and P2X7 receptors by the epithelium of the airways and by an increase in interleukin-10 level.

Conclusion. Data available in the literature are obtained on small cohorts of foreign patients. Clinical data devoted to the influence of aerobic exercises on control of BA and parameters of the respiratory functions are contradictory. Further investigations are required in this field.

This letter to the editor continues the discussion about the similarities and differences between secondary psychosis and schizophrenia, which was initiated by the authors of the article «Substance-induced psychosis and schizophrenia: the interaction point» (Fedotov I.A., Quattrone D., Shustov D.I. Substance-induced psychosis and schizophrenia: the interaction point. I.P. Pavlov Russian Medical Biological Herald. 2020;28(4):593-604. doi:10.238 88/PAVLOVJ2020284593-604).