Aberrant methylation of placental development genes in chorionic villi of spontaneous abortions with trisomy 16.

In humans, aneuploidy is incompatible with the birth of healthy children and mainly leads to the death of embryos in the early stages of development in the first trimester of pregnancy. Trisomy 16 is the most common aneuploidy among spontaneous abortions of the first trimester of pregnancy. However, the mechanisms leading to the death of embryos with trisomy 16 remain insufficiently investigated. One of these potential mechanisms is abnormal placental development, including aberrant remodeling of spiral arteries. Spiral artery remodeling involves the migration of trophoblast cells into the maternal spiral arteries, replacing their endothelium and remodeling to ensure a stable embryonic nutrition and oxygen supply. This is a complex process which depends on many factors from both the embryo and the mother. We analyzed the methylation level of seven genes (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C, and TICAM2) involved in placental development in the chorionic villi of spontaneous abortions with trisomy 16 (n = 14), compared with spontaneous abortions with a normal karyotype (n = 31) and the control group of induced abortions (n = 10). To obtain sequencing libraries, targeted amplification of individual gene regions using designed oligonucleotide primers for bisulfite-converted DNA was used. The analysis was carried out using targeted bisulfite massive parallel sequencing. In the group of spontaneous abortions with trisomy 16, the level of methylation of the PRDM1 and PSG2 genes was significantly increased compared to induced abortions (p = 0.0004 and p = 0.0015, respectively). In the group of spontaneous abortions, there was no increase in the level of methylation of the PRDM1 and PSG2 genes, but the level of methylation of the ADORA2B gene was significantly increased compared to the induced abortions (p = 0.032). The results obtained indicate the potential mechanisms of the pathogenetic effect of trisomy 16 on the placental development with the participation of the studied genes.

Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy.

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p <0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 - R = -0.59, YWHAB - R = -0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 - R = -0.46, YWHAB - R = -0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.

Biomechanical evaluation of stand-alone interbody fusion cages in the cervical spine.

STUDY DESIGN: An in vitro biomechanical investigation of the immediate stability in cervical reconstruction. OBJECTIVES: The purpose of this study was to compare the segmental stability afforded by the interbody fusion cage, the anterior locking plate, and the "gold standard" autograft. SUMMARY OF BACKGROUND DATA: Recently, interbody fusion cage devices have been developed and used for cervical reconstruction, but to the authors' knowledge no studies have investigated the biomechanical properties of the stand-alone interbody cage device in the cervical spine. METHODS: Using six human cervical specimens, nondestructive biomechanical testing were performed, including axial rotation (+/-1.5 Nm, 50 N preload), flexion/extension (+/-1.5 Nm) and lateral bending (+/-1.5 Nm) loading modes. After C4-C5 discectomy, each specimen was reconstructed in the following order: RABEA cage (cage), tricortical bone graft (autograft), cervical spine locking plate system (plate). Unconstrained three-dimensional segmental range of motion at C4-C5 and above and below were evaluated. RESULTS: In flexion/extension, the plate demonstrated significantly lower range of motion than did the cage and the autograft (P < 0.005), and the cage showed a significantly higher range of motion than did the intact spine (P < 0.05). Under axial rotation, the plate indicated a significantly lower range of motion than did all other groups (P < 0.05). No significant differences were indicated in lateral bending. Adjacent to C4-C5, an increased range of motion was observed. CONCLUSIONS: The increased motion adjacent to C4-C5 may provide an argument for acceleration of disc degeneration. From the biomechanical point of view, this study suggests that the cervical interbody fusion cage should be supplemented with additional external or internal supports to prevent excessive motion in flexion-extension.

[Clinico-radiographic evaluation of the state of the spine in stomach and duodenal diseases]. / Kliniko-rentgenologicheskaia otsenka sostoianiia pozvonochnika pri zabolevaniiakh zheludka i dvenadtsatiperstnoi kishki.

Data are given on the condition of the thoracic spine of 465 patients with certain gastric and duodenal diseases. Degenerative-dystrophic lesions (spondylosis deformans and intervertebral osteochondrosis) of the thoracic spine together with osteoarthritis deformans of the costovertebral and costotransverse articulations lead to neurodystrophy of the gastric and duodenal mucosa through chronic stimulation by osteophytes of the thoracic sympathetic ganglia. Disorders of gastric and duodenal motor activity are also important. The attendant reflux gastritis is stipulated by reflux of the intestinal contents into the gastric lumen. Condition of the stomach and duodenum can be improved by relieving changes in the spine.

[Spinal osteomyelitis]. / Osteomielit pozvonochnika.

The paper covers questions of etiology, pathogenesis, clinical and radiographic appearance and diagnosis of spinal osteomyelitis. Principles of conservative and surgical treatment are outlined. It is noted that pain in the spine associated with elevated body temperature and alterations in blood count may be suggestive of setting up inflammation (with occasional destruction) in the vertebra and adjacent structures.

[Etiology, pathogenesis and treatment of pancreatitis]. / Etiologiia, patogenez i lechenie pankreatita.

Data are given on the specific features of the diagnosis and treatment of more than 2000 pancreatitis patients. In 388 of them the clinical signs of affection of the spine were verified by X-ray: intervertebral osteochondrosis and osteoarthrosis of the costovertebral articulations. The appropriate correction of changes in the spine promotes more rapid improvement of the state of the pancreas.

[Outpatient surgical treatment of chronic venous insufficiency of the lower extremities]. / Khirurgicheskoe lechenie bol'nykh khronicheskoi venoznoi nedostatochnost'iu nizhnikh konechnostei v poliklinike.

The results are analyzed for 30 surgical interventions on the legs for chronic venous insufficiency. Feasibility is considered of surgical correction of the function of the deep vein valvular apparatus, of retrograde circulation arrest by obturation of posterior tibial veins in varicosity and postthrombotic diseases.

[Ultrasonic methods of diagnosis of late complications after reconstructive surgery of the aorta and major arteries of the lower limbs]. / Ul'trazvukovye metody diagnostiki pozdnikh oslozhnenii posle rekonstruktivnykh operatsii na aorte i magistral'nykh arteriiakh nizhnikh konechnostei.

Long-standing results were studied in 587 patients who sustained reconstructive vascular surgeries when aged under 16 years (the average age was 6 years and 4 months). Out of them 141 patients faced the necessity of repeated surgeries: in 115 (81.6%) patients the extremity function was preserved, in 19 (13.5%) a repeated amputation was performed, 7 patients (4.9%) expired. All those operated on had been actively followed up with the use of periodical instrumental investigation which included dopplerography and ultrasonic angiography. High significance of ultrasonic technique was proved as the use of it permitted one to detect late complications on the early stages of their development and perform surgical corrections before the development of life-threatening complications. Therefore repeated preventive surgeries were performed in 53 patients, 52 of them were a success. Repeated amputations were performed in 1 patient. All those operated on survived.

[Effect of intravascular laser irradiation of the blood on blood cells in pancreatitis]. / Vliianie vnutrisosudistogo oblucheniia krovi lazernym svetom na kletki krovi pri pankreatite.

Inpatient examinations included 17 patients with necrosis of the pancreas (4 patients had hemorrhagic and 14 fat necrosis): synthetic lymphocyte activity was studied by the luminescent method and the erythrocyte content of adenyl nucleotides by thin-layer chromatography in the toxic phase of pancreatitis. Synthetic lymphocyte activity was found to be decreased and the ATP pool of erythrocytes exhausted in the toxic phase of pancreatitis. Intravascular laser irradiation of the blood caused recovery of lymphocyte activity and increase in the ATP content in erythrocytes.

[Computerized tomography in the diagnosis of degenerative-dystrophic lesions of the spine and herniated intervertebral disk]. / Kompiuternaia tomografiia v diagnostike degenerativno-distroficheskikh porazhenii pozvonochnika--gryzhi mezpozvonkovogo diska.

Computed tomography (CT) examination was performed in 711 patients with various degenerative and dystrophic processes in the spine. The most numerous group (485 patients) included those with a posterior discal hernia associated in 54.3% of cases with other degenerative and dystrophic alterations in the vertebral column. The hernias were paramedial in 336 and central in 147 patients. In 98.4% of cases the lumbosacral portion was involved. The CT diagnosis was verified at surgery in 103 patients (21.3%) providing evidence for setting up the principal CT criteria of the hernia: deformity of the disk posterior margin in the form of its local prolapse, deformity of the epidural fat, presence of a soft tissue component, dislocation and deformity of the dural sac. It is established that CT is a safe and highly informative diagnostic procedure in discal hernias.

[Tietze's syndrome]. / Sindrom Tittse.

The results of treatment of 14 patients (11 males and 3 females) with Tietze's syndrome are discussed. The patient's ages ranged from 22 to 56 years. Most of them were engaged in heavy physical work. The correct diagnosis was established before admission only in 9 patients. The complaints and clinical symptomatology were of the same type almost in all of the patients: pain and swelling in the region of the II-IV costal cartilages at the sternum or along the whole cartilaginous part of the ribs, in some cases pain was referred to the upper part of the shoulder girdle. Clinical and X-ray methods of examination failed to make recognition of the disease easier. The diagnosis was established on basis of scrupulous investigation of the complaints, the history of the disease, and the local clinical manifestations. Most patients were subjected to nonoperative treatment, 2 patients were treated by operation--resection of the hypertrophied cartilage. Local application of hydrocortisone and kenalog produced good results. Pain disappeared completely in 7, was relieved significantly in 5, and was not relieved at all in 2 patients.

[Characteristics of blood flow in the vertebral arteries in scalenus anticus syndrome]. / Osobennosti krovotoka po pozvonochnym arteriiam pri skalenus-sindrome.

The authors studied hemodynamics in the vertebral arteries in 62 patients with the scalenus-anticus syndrome by means of radioconstrast angiography and ultrasonic angiography which produced a colour image of the vessels with calculation of the diameter and the linear and volume blood flow rate. The results of the study showed that in constriction of the subclavian artery to 60% of its diameter in the typical place, the volume blood flow rate in the vertebral arteries remained normal (184 +/- 6.9 ml/min) but reduced 1.5-2 times during the functional test. Adequate surgical correction restored normal hemodynamics, control ultrasonic angiography recorded increase of the volume blood flow rate in the vertebral values to normal values. Ultrasonic angiography provides authentic information on the character of affection of the subclavian artery in the scalenus-anticus syndrome and makes it possible to appraise the hemodynamic significance of affection of the vertebral arteries. Besides, the method allows objective evaluation of the efficacy of treatment and quantitative characteristics of hemodynamics.

[Evaluation of the results of the treatment of pseudarthroses of the forearm bones based on the analysis of the data of radionuclide studies]. / Otsenka rezul'tatov lecheniia lozhnykh sustavov kostei predplech'ia, osnovannaia na analize dannykh radionuklidnykh issledovanii.

The work is based on the analysis of the results of radionuclide examination and treatment of 14 patients with ununited tractures and pseudoarthroses of the forearm bones. Treatment was accomplished by means of external fixation apparatuses which in comparison with intramedullary and epiosseous osteosynthesis provide a better stability of the site of bone injury and create ortimal biomechanical conditions for consolidation of ununited fractures and pseudoarthroses of the forearm bones. Radionuclide examination was conducted before the treatment to determine the initial activity of reparative regeneration in the zone of the pseudoarthrosis and the adjacent healthy regions, 2-3 weeks after perosseous osteosynthesis when the bone fragments were reduced and the compression or distraction regimen was established, and before removal of the apparatus when consolidation of the pseudoarthrosis was demonstrated radiologically. This made it possible to control the activity of reparative regeneration during treatment and to introduce corrections, if necessary. The radionuclide method is preferable to the radiological method in the intermediate stages of treatment not only because of the lesser exposure of the patient to radiation but because of the higner informativeness.

[The potentials of computed tomography in the treatment of cysts and inflammatory diseases of the internal organs]. / Vozmozhnosti komp'iuternoi tomografii v lechenii kist i vospalitel'nykh zabolevanii vnutrennikh organov.

Computed tomography (CT) is used more and more often recently in the treatment of some surgical diseases of the internal organs. The subject of discussion in this work are the results of treatment of cysts and pyoinflammatory diseases of the internal organs. The work was conducted on CT IV generation "QUAD 1" of the CMS firm (England). Needles measuring 14-18d in diameter (Charrière scale) were used for aspiration. A total of 23 therapeutic interventions were performed in 19 patients with exudative pleurisy (1 patient), pleuritis (4), pulmonary abscesses (1), abscesses of the liver (1), abscesses of the subhepatic and subdiaphragmatic spaces (2), cysts of the liver (1) and kidneys (1 patient). Among the interventions 21 were aspirations and 2 drainage of the abscess. A mechanical syringe is used lately for more effective evacuation of the contents. The removed contents, ranging in volume from 10.0 to 600.0 ml, was subjected to cytological, biochemical, and bacteriological analysis. A single puncture is sufficient, as a rule, for aspiration of the cyst contents, one-stage aspiration from cysts of both kidneys may be conducted (as was the case in two of our patients). 96% alcohol was used as the sclerosing agent. In cases of small abscesses aspiration may be repeated for removal of the contents, irrigation of the cavity, and administration of antibiotics. In abscesses measuring more than 10 cm drainage is advisable. Control CT examination is conducted once a week. The condition of the cavity is appraised by combining CT with its contrast study. The immediate results were good and satisfactory in 17 (94.7%) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of femoral neck fractures using carbon implants]. / Lechenie perelomov bedrennoi kosti s pomoshch'iu uglerodnykh implantatov.

The article generalizes the experience in the use of endoprostheses of carbon materials in fractures of the femoral neck in elderly individuals. Twenty-seven cases are discussed, the average age of the patients was 76 years. Owing to the possibility of forming from carbon materials a device which meets the functional demands of the organs and tissues, such widely encountered complications in endoprosthesis as stretching of the implant's pedicle and destruction of the device were avoided.

[Osteomyelitis of the sacrum]. / Osteomielit kresttsa.

The authors had 11 patients of different age with osteomyelitis of the sacrum; 9 were males and 2 females. The process was unilateral in most (9) of them. The duration of the disease was approximately 4 months. Before admission to the clinic 8 patients were treated for a long time and unsuccessfully by other specialists. From their experience the authors describe the characteristic complaints, signs, and clinical picture of the disease. They suggest that modern methods of examination (scintigraphy of the skeletal bones, computerized tomography) should be used more frequently. These methods ensure earlier and more reliable detection of destruction of the sacrum and leakage of pus. The 11 patients were operated on. One patient died on the 11th postoperative day from thromboembolism of the pulmonary artery. The disease did not recur in any of the patients who recovered.

[Invasive interventions with computerized tomography guidance]. / Invazivnye vmeshatelstva pod kontrolem kompíuternoi tomografii.

Invasive interventions (diagnostic and therapeutic) were conducted on 125 patients. Fifty-six has diseases of the lungs, 16 of the mediastinum, 4 of the pleura, 17 of the liver, 2 of the pancreas, one of the spleen, 15 of the kidneys, 7 of the retroperineal space, two of the soft tissues, and 5 patients had diseases of the skeletal bones. Biopsy was combined with aspiration of the renal cyst content in 7 cases. The diagnostic value of biopsy under control of CT was 86% (106 cases); negative and pseudonegative results were recorded in 18 (14%) patients. The efficacy of biopsy is determined by such factors as the size of the lesion and the depth of its localization in the involved organ, the character of the pathological process and the region of its localization, the site from which the material is collected, and the needles used. Among 7 patients with therapeutic interventions, 5 had good and 2 had satisfactory immediate results. Complications were revealed in 4 (3.3%) patients, pneumothorax was encountered most frequently.

[Diagnosis of cancer of the thyroid gland]. / Diagnostika raka shchitovidnoi zhelezy.

The clinical diagnosis of carcinoma of the thyroid gland (CTG) is a difficult and responsible problem. The importance of cytologic and histologic methods of examination has grown, they determine the therapeutic tactics and the volume of the operative intervention. Clinical examination and operations were carried out on 484 patients with various diseases of the thyroid. The examination included inspection of the thyroid gland, radioisotope scanning, radiological examination of the neck, mediastinum and lungs, ultrasonic study, and aspiration biopsy with further cytologic study of the material. Among the patients treated by surgery 58 (11.9%), 39 females and 19 males (2:1), were found to have CTG. Intraoperative emergency cytologic and histologic study was conducted in 30 patients. Differentiated CTG was revealed in all cases. Among the patients who were operated on 5 died from CTG in a 10-year follow-up period. The importance of aspiration biopsy, under conditions of an outpatient clinic in particular, is emphasized. The results of operative treatment of differentiated CTG show that early diagnosis and appropriate surgical intervention are conducive to a favourable prognosis in relation to the patients survival period.

[Primary controlled endolymphatic antibiotic therapy in traumatology and orthopedics]. / Priamaia upravlennaia éndolimfaticheskaia antibiotikoterapiia v travmatologii i ortopedii.

The work analyses 55 cases of traumatic osteomyelitis of the leg bones, open fractures of the leg bones, and medial fractures of the femoral neck. Patients with medial fractures of the neck of the femur were treated by endoprosthesis after Mur-Kaplan. Endolymphatic antibiotic therapy was included in the complex of therapeutic measures in each group of patients. This method allowed suppuration of the postoperative wounds to be avoided and promoted in this manner rehabilitation of the patients.

[Prophylaxis of purulent complications in operations on large joints by endolymphatic infusion of drugs]. / Profilaktika gnoinykh osloznenii pri operatsiiakh na krupnykh sustavakh s pomoshch'iu éndolimfaticheskogo vvedeniia lekarstvennykh veshchestv.

2 groups of patients operated on knee joints for traumatic injuries were examined. In the study group endolymphatic drug therapy was carried out in postoperative period, in control group of patients conventional way of intramuscular administration of preparations was used. During the treatment, plasmatic cells, macrophages and tissue basophiles in synovial liquor were studied as well as synthesis of nucleic acids (DNA and RNA) in plasmatic cells. It was shown that immune homeostasis of synovial liquor in postoperative period normalized faster in endolymphatic administration. The studies of tissue basophiles have shown that inflammatory process in the knee joint is completed faster when endolymphatic route of drug administration was used. Clinical results evidence of higher effectiveness of endolymphatic therapy in comparison with conventional method of treatment in postoperative period. In the former case the inflammatory process was completed by the 5th day, in the latter--by the 7th-9th day. The endolymphatic therapy in all the patients resulted in healing of operation wounds by primary intention. In the group of patients treated by standard methods, suppuration of the wound was detected in 6 from 27 patients and postoperative synovitis in 7-9 days was observed in 6 patients.