Polymorphism of the IL-1ß, TNF, IL-1RA and IL-4 Cytokine Genes Significantly Increases the Risk of Preterm Birth.

Preterm birth is not only medical, but also a social problem. The global goal of medicine is prevention of preterm labor and identification of risk factors leading to preterm birth. The objective of our study was to find the association between polymorphic markers in the cytokine IL-1ß, TNF-α, IL-1Ra, and IL-4 genes and development of preterm labor. The prospective study was conducted in 108 pregnant women with the risk of preterm birth. The main group consisted of 66 women whose pregnancy ended with preterm delivery despite the ongoing therapy. The comparison group included 42 women with the full-term delivery. The dominant T allele of the cytokine IL-1ß gene polymorphism rs1143634 (3953C→T) was 7.6 times more common in women with preterm delivery vs. the comparison group (36.4 and 4.8%, respectively; RR, 1.802; 95% CI, 1.420-2.288; p < 0.05); its homozygous form was detected only in women with preterm delivery at the very early gestation age (less than 26 weeks). The dominant proinflammatory allele 2R of the IL-1 receptor antagonist gene (IL-1Ra) was 1.5 times more common in women with preterm delivery than in the comparison group (63.6 and 42.8%, respectively; RR, 1.400; 95% CI, 1.009-1.943; p < 0.05), which makes the 2R allele the risk factor for preterm birth. The 2R/2R and 2R/4R genotypes led to a very early and early preterm delivery, respectively. The combination of three or four proinflammatory genotypes was detected only in women with a very early preterm delivery, which confirms that the combination of several proinflammatory genotypes is an extremely unfavorable factor for the full-term pregnancy. Identification of genetic polymorphisms in the interleukin genes at the periconceptional stage will help to prevent the risk of preterm delivery, which will reduce the incidence of preterm births, as well as perinatal morbidity and mortality.

Genetic Aspects of Preeclampsia: The Role of Polymorphisms in the Genes of the Renin-Angiotensin System.

Preeclampsia (PE) is a severe complication that develops in 10% pregnant women. It is the leading cause of maternal and perinatal morbidity and mortality worldwide. The goal of this study was to reveal the frequency of polymorphisms in the angiotensin-converting enzyme gene (ACE I/D) and type 1 angiotensin II receptor gene (AGTR1 A1166C) in pregnant women with severe early- and late-onset PE. A retrospective case-control study of 55 pregnant women with PE (main group) and 30 patients with uncomplicated pregnancy (control group) was conducted. In the main group, we considered two subgroups - early-onset PE (20 patients) and late-onset PE (36 patients). The I/D polymorphism of the ACE gene is associated with the risk of developing PE. The presence of the D allele increases the risk of severe PE. In case of DD genotype, the probability of early-onset PE is 5 times higher than that of the late-onset PE. The analyzed data confirm the involvement of renin-angiotensin system in the PE development. We conclude that the ACE gene polymorphism is a genetic predictor of the early-onset severe PE. Studying the polymorphic loci of the ACE gene makes it possible to use them for the individualized prognosis of the development and course of PE in patients.

[Placental insufficiency in pregnancy with gestosis: pathogenesis, diagnosis, evaluation, and obstetric care strategy].

Pathogenesis of placental insufficiency during pregnancy with gestosis was investigated by high-tech methods including ultrasonography, dopplerometry, echocardiography, and measurement of placental and endothelial growth factors. Their utility for the evaluation of the severity of placental insufficiency was demonstrated. Diagnostic criteria for compensated and uncompensated placental insufficiency were proposed along with an algorithm for the examination of pregnant women with gestosis and obstetric strategies at different severity of this disorder. Also, criteria for prolongation of pregnancy with uncompensated placental insufficiency, indications for planned and emergency delivery by cesarean section were developed. The importance of differential approach to the choice of obstetric strategy to reduce perinatal and maternal morbidity and mortality in case of gestosis and placental insufficiency is emphasized.

[The pathogenesis, early diagnosis, and pharmacocorrection of fetal condition disturbances in high risk pregnancy].

A longitudinal retrospective study of 803 women and a prospective study of 739 women were carried out. A complex system of the examination of women with a high placental insufficiency risk, starting from the first trimester, was developed; the appropriateness of the application of new technologies of placental system and fetal examination were substantiated. The authors offer optimal regimens of pharmacocorrection of fetal condition disturbances and the activation of compensatory and adaptive reactions of the fetoplacental complex in placental insufficiency of various origins. The optimal obstetric tactics, the possibilities of therapy and pregnancy prolongation, and indications to operative delivery were defined on the basis of the features of placental dysfunction pathogenesis and a thorough analysis of the features of placental insufficiency in women with a high risk of perinatal complications.

[Clinical significance of examinations of hemodynamics of mother and fetus in physiological and complicated pregnancy]. / Klinicheskoe znachenie issledovaniia gemodinamiki materi i ploda pri fiziologicheskoi i oslozhnennoi beremennosti.

Summarized in the paper is the experience of defining the clinical significance of examination of hemodynamics of mother and fetus in physiological and complicated pregnancy. The normative parameters of blood circulation in the vessels of mother and their central hemodynamics are described. An interrelation between the changes of central hemodynamics of mother and fetus are shown in the development of gestosis and placental insufficiency. The orientation, succession and changes of blood circulation in the arteries and venous vessels of fetus are demonstrated in chromosomal anomalies, congenital malformation, premature pregnancy, gestosis, fetoplacental insufficiency and postmaturity. It was proven as prognostically valuable to study the parameters of blood circulation of mother and fetus not only in diagnostically complicated pregnancy but also in evaluating the therapy efficiency, as well as in choosing a method and time for delivery and in prognosticating a perinatal outcome.

[Impaired maternal and fetal hemodynamics in the pathogenesis of gestosis]. / Narushenie materinskoi i plodovoi gemodinamiki v patogeneze gestoza.1

The study was undertaken to examine the specific features of maternal and fetal hemodynamics in the pathogenesis of gestosis and to develop differential approaches to obstetric policy. For this, a total of 345 pregnant women at risk for gestosis were examined. This condition was prevented using aspirin and trental in 60 women. The findings suggest that hypokinetic central hemodynamics with increased total peripheral vascular resistance and with impaired blood flow in the uterine and spiral arteries are a valid predictor of gestosis. Changes in maternal hemodynamics are revealed just in the late first to early second trimester of gestation. The use of aspirin and trental in patients with hypokinetic central hemodynamics and impaired blood flow in the uterine and spiral arteries reduced the incidence of gestosis by 2.5 times, delayed intrauterine fetal development by 3 times.

[Pathogenesis of systemic hemodynamic disorders and choice of optimal obstetrical strategy in pregnant patients with gestosis]. / Patogenez sistemnykh narushenii gemodinamiki i vybor optimal'noi akusherskoi taktiki u beremennykh s gestozom.

A total of 810 pregnant women were examined in order to elucidate the pathogenesis of hemodynamic disorders in gestosis. The main group consisted of 460 patients with gestosis of different severity and the control group included 150 women with uneventful pregnancy. Central and regional hemodynamics in normal pregnancy were studied in detail by modern diagnostic methods (echocardiography and dopplerometry) and the relationship between the detected shifts and the function of the utero-placento-fetal circulation was shown. The predominant type of central hemodynamics in gestosis is the hypokinetic. Disorders in renal and cerebral circulation contribute to the pathogenesis of severe gestosis. Pathogenetic variants of hemodynamics shifts in gestosis are analyzed and recommendations on the follow-up of pregnancy are offered. Indications for preterm delivery in the interests of the mother and fetus are defined.

[A permanent magnetic field in the combined treatment of acute endometritis after an artificial abortion]. / Postoiannoe magnitnoe pole v kompleksnom lechenii ostrogo éndometrita posle iskusstvennogo aborta.

117 patients with acute endometritis after induced abortion were examined using markers of wound process phases and treated according to the original method. This consists in combination of constant magnetic field with other modalities. Application of the constant magnetic field produced a significant clinical response and reduced the hospital stay through positive effect on healing of the endometrial wound.

[Central and regional hemodynamics during the physiological course of pregnancy and the systemic circulatory disorders in gestoses]. / Stanovlenie tsentral'noi i regionarnoi gemodinamiki pri fiziologicheskom techenii beremennosti i sistemnykh narushenii krovoobrashcheniia pri gestozakh.

Ninety-one patients with physiological pregnancy and gestosis were studied. This included examinations of maternal central hemodynamics and Doppler study of blood flow in the system of carotids, renal artery and its branches, uterine and umbilical arteries. The volumetric maternal central hemodynamic parameters were found to increase concurrently with a reduction in peripheral vascular resistance during physiological pregnancy, which is associated with the emergence and development of a fetoplacental complex. In gestosis, there are decreases in the volumetric maternal central hemodynamic parameters and increases in peripheral vascular resistance in all the vessels under study. Clear diagnostic criteria for predicting and diagnosing gestotic complications, such as preeclampsia and eclampsia, and fetoplacental failure in time have been defined. A contribution of echocardiographic and Doppler studies is shown in the evaluation of the severity of gestosis and the efficiency of the therapy used.

[Tubal pregnancy: the experience of early rehabilitative treatment]. / Trubnaia beremennost': opyt rannego vosstanovitel'nogo lecheniia.

The surgical treatment for tubal pregnancy including laparoscopy and antibacterial therapy were combined in 30 females with early start (on postoperative day 1) of rehabilitation: psychotherapy, diet, therapeutic exercise, low-frequency magnetotherapy. Hysterosalpingography and dynamic dopplerography assessed the effect as good.

[The interferon inducer neovir (kamedon) in the combined treatment of chronic inflammatory diseases of the adnexa uteri of chlamydial etiology (a clinical electron-microscopic study)]. / Induktor interferona--neovir (kamedon) v kompleksnom lechenii khronicheskikh vospalitel'nykh zabolevanii pridatkov matki khlamidiinoi étiologii (kliniko-élektronnomikroskopicheskoe issledovanie).

One of the major factors of nonspecific immunity i.e. the state of the host interferon system was studied with a purpose of its correction in the treatment of inflammatory diseases of the uterine appendages of the chlamydial etiology. In all the female patients with chronic inflammatory diseases of the uterine appendages of the chlamydial etiology there was observed a disorder in the function of the interferon system link: a decrease in the concentration of blood serum interferon and a lower capacity of the blood cells to produce alpha- and gamma-interferons. The findings were used as a theoretical ground for the inclusion of neovir, an inductor of alpha-interferon to the treatment of such patients. After the completion of the treatment course with the use of neovir the index of the serum interferon proved to be higher than the normal by 2.4 log2IU and the indices of alpha- and gamma-interferons were lower than the normal only by 0.1 and 1.3 log2IU respectively. Therefore, the mechanism of the neovir action included activation of the function of the interferon endogenic system. The morphometrical analysis of the number of the cytoplasmic granules of the polymorphonuclear leukocytes in the peripheral blood before, during and after the therapy with neovir and pefloxacin showed that neovir not only promoted restoration of the digestion function of the neutrophilic leukocytes but also markedly activated it which provided a success of the phagocytic attack.

[The clinical importance of the dopplerometric study of the blood flow in the normal iliac, uterine and ovarian arteries, in myoma and in endometriosis interna of the corpus uteri]. / Klinicheskoe znachenie dopplerometricheskogo issledovaniia krovotoka v podvzdoshnykh, matochnykh i iaichnikovykh arteriiakh v norme, pri miome i vnutrennem éndometrioze tela matki.

Dopplerometric investigation of pelvic arteries was carried out in 30 women without gynecologic diseases, in 51 patients with internal endometriosis, and 48 ones with uterine myomas. Internal endometriosis of the uterus was found to be characterized by specific qualitative changes in spectral curves of bloodstream velocity in the internal iliac and uterine arteries. Moreover, progressive changes in spectral curves related to dissemination of endometrioid heterotopias were revealed. In patients with uterine myomas combined with internal endometriosis disorders of peripheral circulation typical of endometriosis predominated.

[Myometrectomy--a method of choice for the therapy of adenomyosis patients in the reproductive period]. / Miometréktomiia--metod vybora terapii bol'nykh adenomiozom v reproduktivnom periode.

Seventy-six patients with adenomyosis were examined using computer-aided hysterosalpingography and transvaginal ultrasonic scanning in the "pseudocolor" mode. Organ-sparing operation, myometrectomy (removal of the involved myometrium with preservation of the uterus) was performed in 8 patients aged 18 to 34. In the postoperative period, conservative therapy was administered. Fifty percent of patients became pregnant within a year after the operation.

[Role of immune disorders in the pathogenesis of suppurative inflammatory diseases of the adnexa uteri]. / Rol' immunnykh narushenii v patogeneze gnoinykh vospalitel'nykh zabolevanii pridatkov matki.

Clinical and immunological studies were carried out in 60 patients with tubal pyoinflammatory diseases and in 20 healthy controls of a reproductive age. The immunity status was studied using IKO monoclonal antibodies to differentiation antigens of peripheral blood mononuclears. An acute purulent process was found to be characterized by an adaptive increase in the count of mononuclears carrying the markers of B lymphocytes (CD22, IgM mu-chain), of activated cells (CD38, HLA-D(r)), and of the total number of positive correlations between immunocompetent cells. A persistent course of tubal inflammation is connected with hyperproduction of antibodies and immune complexes, increased expression of HLA-Dr antigens in combination with congenital or acquired insufficiency of T-helper/inductors and suppressors/cytotoxic T-cells. An important factor in the development of a chronic suppurative process is triggering of immunocomplex mechanisms associated with fixation of IgG, IgM, and the complement in the walls of small vessels in the uterine tubes, with a high level of circulating immune complexes, and appearance of plasma cells containing IgG and IgM in the tissues of uterine tubes.

[Endometrial and ovarian morphology in internal uterine endometriosis]. / Morfologicheskie aspekty éndometriia i iaichnikov pri vnutrennem éndometrioze matki.

The ovaries and endometrium were examined in 66 patients with internal uterine endometriosis with various degrees of the process dissemination. A high incidence of combinations of uterine endometriosis with hyperplastic processes in the ovaries was revealed (72.7%) and a relatively low incidence of uterine body mucosa involvement (31.7%). The degree of endometriosis dissemination in the myometrium and the incidence of ovarian hyperplasia were in direct proportion. The authors emphasize the usefulness of morphologic studies of the ovaries in patients with internal uterine endometriosis.

[Current concepts in observation and treatment of patients with internal endometriosis of the uterus]. / Sovremennye kontseptsii sistemy obsledovaniia i lecheniia bol'nykh vnutrennim éndometriozom matki.

The paper outlines the issues of improving and systematizing clinical instrumental diagnostic and therapeutical techniques for internal endometriosis. The results of examining 220 patients with internal endometriosis, out of whom 116 were further operated on, have been prospectively and retrospectively studies. Based on the histological findings of the gross specimens intraoperatively removed, the authors analyzed the predictive value of clinical and instrumental diagnostic criteria, including those of transvaginal echography, Doppler echometry of the arteries supplying the uterus, those of hysteroscopy and the computer hysterosalping graphic technique developed by them. The ovarian morphological and receptor apparatuses were studied in internal endometriosis. The examination and treatment system for patients with internal endometriosis is presented in the paper.

[Uterine-placental-fetal blood flow and fetal cardiac activity during the ginipral treatment of premature labor]. / Sostoianie matochno-platsentarno-plodovogo krovotoka i serdechnoi deiatel'nosti ploda pri lechenii ginipralom prezhdevremennykh rodov.

Effects of intravenous and oral hinipral on the uteroplacentofetal blood flow and fetal heart work were studied in tocolytic therapy of preterm labor in 27 pregnant women at terms 25-35 weeks. Intravenous infusions of hinipral resulted in a significant reduction of the systolic-diastolic ratio in the umbilical artery, with the blood flow in the uterine arteries persisting stable, and in a significant reduction of the fetal heart rate and increase of fetal heart rhythm variability, as evidenced by cardiotocogram. In oral tocolysis the reduction of the umbilical artery was related to the pregnancy term; fetal heart rate and heart rhythm variability were within the normal range over the course of the investigation. The results evidence no negative effects of the drug on the uteroplacentofetal blood flow and fetal cardiovascular system both in oral and parenteral forms of tocolysis.

[The clinico-diagnostic importance of evaluating the blood flow in the mother-placenta-fetus system in EPH gestosis]. / Kliniko-diagnosticheskoe znachenie otsenki krovotoka v sisteme mat'--platsenta--plod pri OPG-gestoze.

A dynamic dopplerometry of the blood flow in the mother-placenta-fetus system, carried out in 79 women with EPH gestosis, revealed a direct correlation between uteroplacental and fetoplacental blood flow disturbances and gestosis, hypertension, edematous syndrome, and proteinuria severity. Comprehensive assessment of the blood flow in both uterine arteries and umbilical artery are preferable. When third-degree circulatory disturbances are revealed in the mother-placenta-fetus system, cesarean section is recommended. Comprehensive dopplerometric assessment of uterine and umbilical arteries blood flow may be regarded as an objective indicator of gestosis severity, whatever its clinical manifestations.