[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation]. / Razrabotka rannei diagnostiki bolezni Parkinsona i kompleksnyi ekonomicheskii analiz effekta ot ee vnedreniya.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility¼ analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood]. / Razrabotka rannei diagnostiki bolezni Parkinsona na osnove biomarkerov v vide premotornykh simptomov i izmenenii v krovi.

OBJECTIVE: To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control. MATERIAL AND METHODS: Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people. RESULTS: Among seven catecholamines and their metabolites detected in the blood, only the concentration of L-dioxiphenylalanine (L-DOPA) changed (decreased) in subjects at risk compared with the control. A decrease in the concentration of L-DOPA is considered as a manifestation (marker) of selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the concentration of seven of the twelve detected sphingomyelins in the blood of the subjects at risk increased. Given that a change in the metabolism of sphingomyelins is associated with processes such as apoptosis, autophagy, and synucleinopathy, an increase in their concentration in the blood of patients at risk is considered as a manifestation of systemic general degeneration of central and peripheral neurons. Finally, in the blood of subjects at risk, we found a trend towards a decrease in the concentration of urates, which are endogenous neuroprotectors. CONCLUSION: The changes in the level of L-DOPA, sphingmyelins and urates in the blood of subjects at risk may serve as diagnostic markers of PD at the prodromal stage.

Changes in the Metabolism of Sphingoid Bases in the Brain and Spinal Cord of Transgenic FUS(1-359) Mice, a Model of Amyotrophic Lateral Sclerosis.

The aim of this study was to evaluate changes in the content of sphingoid bases - sphingosine (SPH), sphinganine, and sphingosine-1-phosphate (SPH-1-P) - and in expression of genes encoding enzymes involved in their metabolism in the brain structures (hippocampus, cortex, and cerebellum) and spinal cord of transgenic FUS(1-359) mice. FUS(1-359) mice are characterized by motor impairments and can be used as a model of amyotrophic lateral sclerosis (ALS). Lipids from the mouse brain structures and spinal cord after 2, 3, and 4 months of disease development were analyzed by chromatography/mass spectrometry, while changes in the expression of the SPHK1, SPHK2, SGPP2, SGPL1, ASAH1, and ASAH2 genes were assayed using RNA sequencing. The levels of SPH and sphinganine (i.e., sphingoid bases with pronounced pro-apoptotic properties) were dramatically increased in the spinal cord at the terminal stage of the disease. The ratio of the anti-apoptotic SPH-1-P to SPH and sphinganine sharply reduced, indicating massive apoptosis of spinal cord cells. Significant changes in the content of SPH and SPH-1-P and in the expression of genes related to their metabolism were found at the terminal ALS stage in the spinal cord. Expression of the SGPL gene (SPH-1-P lyase) was strongly activated, while expression of the SGPP2 (SPH-1-P phosphatase) gene was reduced. Elucidation of mechanisms for the regulation of sphingolipid metabolism in ALS will help to identify molecular targets for the new-generation drugs.

[Transabdominal ultrasonic scanning in evaluation of liver parenchyma: new opportunities].

On suspicion of the diffusive liver lesions 117 patients have been performed a transabdominal ultrasound investigation with a visual estimate of the echogenicity of the structure of the liver's parenchyma in comparison with the echogenicity of the cortical substance of the kidney and with the determination of the homogeneity of the liver's structure on its different areas. For the purpose of the elevation of the self-descriptiveness and precision of diagnostics as well as for the reduction of the subjective estimation the authors carried out the evaluation of the structure of the liver's parenchyma and the cortical substance of the kidneys using the histography on the marked area. The elaboration of the efficient quantitative assessment of the changes of the liver's parenchyma allowed to relieve complications in differential diagnostics and to estimate the damage level of the organ's parenchyma objectively during the investigation.

[Study of gastroduodenal complex wealthy with help of transabdominal ultrasonography].

In the present work we report the results of gastroduodenal complex transabdominal sonography in grayscale mode with Doppler techniques in 237 patients. Sonographic criteria for normal and abnormal intensity of contents outflow from stomach to duodenum were defined, that can be applied in diagnostic algorithm for proximal gastrointestinal tract functional disorders.

[The function of gastric stump and duodenum after proximal gastric resection in patients with esophageal and gastric varicose veins dilatation].

The authors had developed the technique of proximal gastric resection with cardiac orifice plasty. 21 patients with esophageal and varicose veins dilatation were operated on using the technique. Follow-up period came from 2 to 23 years. Results of the operation allow proximal gastric resection with cardiac orifice plasty to be considered the effective way of prevention and treatment of gastric bleedings of portal hypertension aetiology.

[The clinical features and the structural and functional status of the liver in chronic viral hepatitis B concurrent with superinvasion opisthorchiasis].

Clinical manifestations of chronic viral hepatitis B (CVH-B) in replicative phase in patients with superinvasive opisthorchosis comprise the asthenic-vegetative syndrome, pain syndrome, dyspepsia (53.3% of cases) and hepatomegaly (46.7% of cases). Superinvasive opisthorchosis, when combined with CVH-B, stimulates the cytolysis of hepatocytes and the intensity of inflammation; it also shapes the fibrosis of the liver, which complicates the course of viral infection and its outcome.

[Choice of radical surgical method in patients with sutured perforated gastroduodenal ulcers].

Long-term results of suturing of perforated gastroduodenal ulcer in 364 patients were analyzed. Within 16 years after surgery recurrence of ulcer was seen in 215 (62.9%) patients. Radical elective surgeries were performed in 197 (54.1%) from 2 mos to 16 years after perforation of ulcer. Indications for radical surgery were determined on the basis of the disease duration, presence and nature of complications, level of acid-production, etc., and also data of endoscopic ultrasonography. In early postoperative period 1 (0.5%) patient died. Long-term results were followed from 2 mos to 11 years in 168 (85.3%) patients. Recovery of reservoir and motor-evacuation function of the operated stomach was demonstrated with special examinations. The mean gastrointestinal index (GIQLI) in long-term period was 124.6 after resection surgeries and 120 after organ-retaining surgeries.

[Surgical treatment of gastroesophageal reflux]. / Khirurgicheskoe lechenie refliuks-ezofagita.

One hundred and seventy-five patients with gastroesophageal reflux disease (GERD) were treated, 144 (82.2%) of them underwent surgery. In 106 (73.6%) patients laparotomy was used, in 38 (26.4%) -- laparoscopic surgeries. Transabdominal USE of the esophagus, stomach and duodenum, endoscopic ultrasonoraphy (EUS) of the esophagus were used for diagnosis of GERD in addition to standard tests. Based on EUS data, classification of severity of reflux-esophagitis was proposed. New method of laparoscopic creation of artificial lower esophageal sphincter (LES) with super thin (95, 45 mm) and super elastic filaments made of nikelid-titan alloy was developed in experiment and introduced into clinical practice. Thirty-four laparoscopic surgeries were performed, 26 (76.4%) of them -- with creation of artificial LES. In this group 94.4% of patients demonstrated excellent and good results in long-term period. Pressure in the area of LES in these patients increased by 70%, on the average, after surgery.

[Method of selective proximal vagotomy]. / Sposob selektivnoi proksimal'noi vagotomii.

A method of selective proximal vagotomy has been developed experimentally. It provides additional parasympathetic denervation of an acid-producing zone of the stomach by means of circular transsection of gastric and esophageal muscular membranes above and below cardial sphincter with forming of are flux esophageal-gastric valve. Clinical use of this method in 75 patients confirmed experimental data about a good function of the created valve and adequate decrease of acid production. This improved short and long-term results and reduced the time of temporary disability.

[Surgical treatment of complicated duodenal ulcer: experience and prospects]. / Khirurgicheskoe lechenie oslozhnennykh duodenal'nykh iazv: opyt i perspektiva.

The article discloses the results of the surgery of 696 patients with completed duodenal ulcers. The organ-preserving treatment was provided for 31.8% of patients, and stomach resection was performed on 68.2% of patients. Postoperative mortality was found to be 0.6% and was not related to the surgery nature. The postoperative term of hospital treatment made up 11.8 +/- 2.4 days. A complex hospital examination of patients during early and late postoperative periods showed that methods for treatment of complicated duodenal ulcers with the use of new surgical technologies allow choosing an optimum operation providing a high level of life quality.