Diagnostic technique for undifferentiated connective tissue dysplasia in females with personal history of miscarriage

FIELD: medicine.

SUBSTANCE: invention concerns diagnosing undifferentiated connective tissue dysplasia (UCTD) in females with a personal history of miscarriage. The technique involves determining the fibrinolytic activity in an endometrial biopsy sample. If the value is less than 23.55 mm2, undifferentiated connective tissue dysplasia is diagnosed.

EFFECT: invention provides the high diagnostic accuracy and enables diagnosing UCTD in the females with the personal history of early miscarriage.

2 tbl, 2 ex


The invention relates to medicine, namely to obstetrics and gynecology.

Women define fibrinolytic activity (FA) in endometrial biopsy method fibrin plates, and when the indicators F below 23,55 mm2diagnosed undifferentiated connective tissue dysplasia (NDCT) with efficiency of 92.6% (Method, based on fibrin plates (the determination of the activity of plasmin and plasminogen activator) by T. Astrup, S. Mullertz, 1952).

The problem of loss of pregnancy continues to maintain its relevance and priority in modern obstetrics. This is due primarily to the fact that the loss of a pregnancy is one of the main components of reproductive loss [N. To. Tetruashvili, A. A. Agadzhanova. The screening program and pregestational preparation of patients with habitual miscarriage (clinical lecture). - 2012. - №6. - S. 87-91; Sidelnikov Century Meters Miscarriage - a modern view on the problem // ROS. Vestn. akush.-gynecol. - 2007. No. 2. - S. 62-64]. So, from 15 to 25% of all reported pregnancies spontaneously abort, with 5-20% recurrent miscarriage (PPF), and 80% pregnancies terminate up to 12 weeks [D. Y. hayrapetov. Etiological factors of habitual miscarriage // Obstetrics and Gynecology. - 2011. No. 8. - S. 102-106; Baimuradov S. M. Pathogenesis, rincipa diagnostics, prevention and treatment of the syndrome of fetal loss due to acquired and genetic defects of hemostasis: dis. ... Prof. the honey. Sciences. - M., 2007. - 286 S.].

The causes of pregnancy loss, are extremely varied and include anatomical abnormalities, hormonal disorders, genetic/chromosomal defects, the pathology of hemostasis, Islamically failure, uterine cancer, congenital malformations, intrauterine synechia, endocrine and infectious disorders [B. I. Medvedev, E. E. Voropaeva, E. L. Kazachkov, E. A. Kazachkov. Extragenital diseases and social status of women with spontaneous abortion // Obstetrics and Gynecology. - 2012. - №4, 2. - S. 97-102; Tetruashvili N. To. Early pregnancy loss (immunological aspects, ways of prevention and treatment): dis. ... Prof. the honey. Sciences. - M., 2008. - 247 S.; Ivaschenko, I. E., Bespalova O. N., Tarasenko O. A., Swede N.Y. The genetic basis of susceptibility to obstetric and gynecological pathology / Molecular medicine. - 2007. No. 3. - S. 19-26; N. In. Dolgushin. Immunological aspects of the development of placental insufficiency and miscarriage in patients with chronic viral infections // Obstetrics and Gynecology. - 2008. No. 4. - S. 16-19]. Despite the fact that modern diagnostic capabilities allow with great accuracy to verify Ave is in the office of pregnancy loss, it is not always possible to achieve the desired result. Thus, the loss of a pregnancy in the early stages occupies an important place in the structure of the obstetric-gynecologic pathology, and continues to remain at a fairly high level [Sidelnikov Century Meters Miscarriage - modern look // Dr. Roux. - 2009. No. 6-1. - S. 42-46], which makes it necessary to search for new possible causes that affect the course of pregnancy in the early stages, and methods of early diagnosis. One of the reasons for the development of pregnancy loss is the disruption of the formation of connective tissue in the human body in the form of undifferentiated connective tissue dysplasia and, in particular, in the sex organs [Caurina T. I. Hereditary collagenoses. - SPb.: Nevsky dialect, 2000. - 272 S.; zemtsovsky E. C. dysplastic phenotypes. Dysplastic heart: analytical absor. - SPB.6 Olga, 2007. - 80 S.]. It is shown that the presence of undifferentiated connective tissue dysplasia in women is the main reason for the formation of the isthmic-cervical insufficiency in the late first and early second trimester of pregnancy, the formation of placental insufficiency, disorders of angiogenesis in the myometrium [Gurbanova S. R. the Role of undifferentiated connective tissue dysplasia in the pathogenesis of isthmic-cervical insufficiency // proceedings of the IX Sarossy the ski scientific. forum "Mother and Child". - M., 2007. - S. 121; Gazazian M., Characteristics of pregnancy and delivery in patients with connective tissue dysplasia. - 2007; L. M. Komissarov, A. N. Karachaevo, M. I. Kesava. During pregnancy and childbirth with connective tissue dysplasia // Obstetrics and gynecology. - 2012. No. 3. - S. 4-8; Starostin T. A., Lipman A. D., A. A. Y. Diagnostic value of blood flow in the uterine arteries and small arteries of the cervix with isthmic-cervical nedostatocnosti // Akush. and gin. - 1998. No. 2. - S. 15-17; Caurina T. I., Gorbunov Century. N. Connective tissue dysplasia. - SPb., 2009; D. Daskalakis, Papantoniou N, Mesogitis S, Antsaklis A. Management of cervical insufficiency and submissive fetal membranes // Obstet. Gynecol. - 2006. - Vol.107, No. 2. - P. 221-226]. At the same time during pregnancy to actively influence the formation of connective tissue is not possible. This makes it necessary to actively involve in the scheme pregravid and preconceptually preparations preparations ramblinrosie the formation of connective tissue, which are widely used in cardiology, pulmonology, internal medicine, Pediatrics [makatsariya A. D., Yudaeva HP Management of pregnancy and delivery in patients with mesenchymal dysplasia (syndrome, Marfan's syndrome, Ehlers-Dunloe, Rendu-Osler). M, 2005; Grachev, O. N. Connective tissue dysplasia prevention of gestational complications / Matters. gin., akush. and perinatal. - 010. No. 3. - S. 25-29; zemtsovsky E. C. Diagnosis and treatment of connective tissue dysplasia / Medical Bulletin. - 2006. №11 (354); Klimanov A. C., Tkachev O. N., Wertkin A. L. connective tissue Dysplasia and pregnancy (review) // Ter. Arch. - 2004. No. 11. - S. 80-83]. However, diagnosis of the presence NDCT represents certain difficulties due to the need of a large volume of research: the diagnosis is established by a combination of phenotypic characteristics that require costly, long period of examination and attraction of specialists of different profiles. In addition, until now, have not developed a unified classification, allowing vysokomehanizirovannoe to diagnose the presence of undifferentiated connective tissue dysplasia.

The main methods of diagnosis of undifferentiated connective tissue dysplasia are clinical when the diagnosis is established by a combination of phenotypic traits, such as asthenic body type, no stretch marks on the abdominal wall in women with a history of childbirth, violation of refraction at the age of 45, muscular hypotonia and low rates manometry, a tendency to easy bruising, bleeding in the postpartum period, vascular dysfunction, cardiac rhythm and conduction, EPI is ant, hypertelorism eyes, blue sclera, accrete lobe, the nasal septum, liver spots, anomaly bite anomaly teeth, scoliosis, kyphosis, kyphoscoliosis, flatfoot 2-3 degrees, elastosis of the skin, hypermodernity joints, prone to sprains, allergies and colds, varicose veins, hemorrhoids, biliary dyskinesia, a violation of the evacuation function of the gastrointestinal tract, the threat of premature birth at term 32-35 weeks of gestation, preterm delivery, fast rapid delivery history with hypotonic hemorrhage in the 3rd period of confinement or without genital prolapse, hernia, diverticula, dolichosigmoid, abnormalities in the platelet hemostasis. On the basis of these characteristics suggested several diagnostic protocols for verification of the diagnosis of undifferentiated connective tissue dysplasia (S. K. Yevtushenko, 2002; T. Y. Smolenova, 2003; T. I. Kaurinui, 2006; L. N. Fomin, 2000; So Milkowski-Dimitrova and A. Kartasheva, 1985). These methods are not sufficiently accurate due to the lack of standardization of the evaluation of detected features. Thus, the same patient may be attributed not only to different degrees of severity of undifferentiated connective tissue dysplasia, but not the diagnosis of undifferentiated connective tissue dysplasia which may be rejected. In addition, the classification So Milkowski-Dimitrova and A. Kartasheva (1985) limits us a number of secondary characteristics.

The main disadvantage of these methods of diagnosis NDCT is:

1) the inaccuracy of diagnosis,

2) lack of standardization in the objectification detected symptoms,

3) the large number of studies.

The proposed method for the diagnosis of NDCT, based on the determination of FA in biopsies of the endometrium, will eliminate the disadvantages of the above methods.

The solution of this problem is achieved by the fact that in women with recurrent pregnancy loss pregnancy history is taken PayPal endometrial biopsy on 23-26 day of the menstrual cycle. Preparing the sample - weight of 3 mg is Further defined fibrinolytic activity by the method of fibrin plates. The principle of the method is to visually check the degree of dissolution of fibrin clot prepared in the form of thin plates, put the investigated sample. If the latter (plasma, serum, tissue extract, serous fluid, etc.) has fibrinolytic activity, it creates around itself a zone of lysis, the area of which is proportional to this activity.

The progress of the operation.

I - preparation of a standard fibrin plates. In chemical glass gently mixing the season (avoid foam formation!) 9 ml of a solution of fibrinogen and 0.2 ml of thrombin. The mixture is immediately poured into a Petri dish with an inner diameter of 10 cm Light tilting the Cup to achieve a uniform distribution of liquid on its plane, after which the Cup is placed on a horizontal surface until complete coagulation of fibrinogen.

II - application of the material on record. The sample weight of 3 mg is applied parallel to the surface of the cold plate. Petri dishes are placed in a thermostat (37°° C) for 20 hours. After a specified period of time measured two mutually perpendicular diameters of each zone of lysis and calculated the areas of these zones.

III - evaluation of results. The size of the zone of lysis is directly proportional to the magnitude of the fibrinolytic activity of the investigated samples. And when indicators FA endometrium less than 23.5 mm2receives a diagnosis NDCT. In this way the surveyed 68 women. Of them women without NDCT - 25 women, their average FA was 61,0±4.8 mm2with fluctuations in individual performance from 23,55 to 94.2 mm2(PL.2), women with NDCT - 43 women, the average FA of 14.5±1.0 mm2with fluctuations in individual performance from 7,06 to 28.3 mm2(PL.1). Moreover, in the group of women with NDCT indicators FA endometrium was in the performance of the group of women without NDCT only are 11.62% of cases.

Thus, the claimed method surveyed 68 size is n, of them positive result was achieved in 63 patients, which is of 92.6% and allows the accuracy to diagnose NDCT in women with miscarriage in the early stages in history.

Previously fibrinolytic activity, the method fibrin plates were determined in the urine (Mingaleev E. I., 2006) for optimization of the method of local hemostasis.

The novelty of the proposed method lies in the fact that the first set of indicators fibrinolytic activity in the endometrium, and this index is first used to diagnose the presence of NDCT in women with pregnancy loss in the early stages in history.

Distinctive features of the process are: established diagnostic criteria for fibrinolytic activity of the endometrium in the range below 23,55 mm2.

The technical result of the provided method is that the tissue sample is determined fibrinolytic activity and when it is less 23,55 mm2diagnosed with undifferentiated connective tissue dysplasia.

Clinical examples

Example No. 1. The patient Polina I. I., 37 years old, IB No. 881. Diagnosis: habitual miscarriage mixed Genesis. The patient was examined at the level of FA endometrium. Was the result - 9,42 mm2. When using classification So Milkowski-Dimitrova and A. Kartasheva(1985) and L. N. Fomin (2000) the patient has NDCT of the third degree. When using classification T. Y. Smolenova (2003) the patient has NDCT second severity. The diagnosis was confirmed (Table.1).

Example No. 2. Ivanova, E. S., 23 years old, IB No. 1017. Diagnosis: habitual miscarriage mixed Genesis. The patient was examined at the level of fibrinolytic activity of the endometrium. Was the result - 78.5 mm2. When assessing phenotypic signs of the patient was not identified NDCT none of the presented classificati: So Milkowski-Dimitrova and A. Kartasheva (1985), L. N. Fomin (2000), T. Y. Smolenova (2003) (Table.2).

Table 1
Data fibrinolytic activity of the endometrium in women without undifferentiated connective tissue dysplasia with the loss of a pregnancy in the early stages in history
F. ActingIBDiagnosisFibrinolytic activity
1. G-VA T. C.957Habitual miscarriage mixed Genesis12,56 mm2
2. W-VA A. G.826Habitual miscarriage mixed Genesis9,42 mm2
3. And O. G.1393Habitual miscarriage mixed Genesis12,56 mm2
4. Islands E. C.244Habitual miscarriage mixed Genesis15.7 mm2
5. S-VA N.N.143Habitual miscarriage mixed Genesis19,62 mm2
6. E-VA N.N.208Habitual miscarriage mixed Genesis15.7 mm2
7. B-UK N. In.237Habitual miscarriage mixed Genesisof 28.26 mm2
8. X-WA O. I.216Habitual miscarriage mixed Genesis,42 mm 2
9. F-VA E. Y.336Habitual miscarriage mixed Genesis12,56 mm2
10. With-Kaya L. C.336Habitual miscarriage mixed Genesis15.7 mm2
11. Peninsula E. K.359Habitual miscarriage mixed Genesisof 28.26 mm2
12. X-WA So N.769Habitual miscarriage mixed Genesis9,42 mm2
13. G-VA T. C.436Habitual miscarriage mixed Genesis9,42 mm2
14. M-VA A. C.373Habitual miscarriage mixed Genesis23,55 mm2
15. G-VA E. C.495Habitual miscarriage mixing the spent Genesis 23,55 mm2
16. H-VA M. I.580Habitual miscarriage mixed Genesis9,42 mm2
17. M-Kai E. A.611Habitual miscarriage mixed Genesisof 28.26 mm2
18. B-VA, M. P.868Habitual miscarriage mixed Genesis9,42 mm2
19. C-ha T. N.816Habitual miscarriage mixed Genesis12,56 mm2
20. K-VA A. Y.874Habitual miscarriage mixed Genesis15.7 mm2
21. P-VA.999Habitual miscarriage mixed Genesis7,06 mm2
22. With-I. N.918The usual is evansiana pregnancy mixed Genesis 15.7 mm2
23. M-VA A. N.998Habitual miscarriage mixed Genesis7,06 mm2
24. P.-E. C.881Habitual miscarriage mixed Genesis9,42 mm2
25. C-VA E. C.923Habitual miscarriage mixed Genesis23,55 mm2
26. S-VA L. A.517Habitual miscarriage mixed Genesis12,56 mm2
27. R-VA N. A.146Habitual miscarriage mixed Genesis15.7 mm2
28. In-VA A. C.1048Habitual miscarriage mixed Genesis7,06 mm2
29. W-A. B.241The usual n is the pregnancy mixed Genesis 9,42 mm2
30. U-VA P. F.339Habitual miscarriage mixed Genesis12,56 mm2
31. B-VA N. And383Habitual miscarriage mixed Genesis9,42 mm2
32. E-O. R.368Habitual miscarriage mixed Genesis23,55 mm
33. W-VA S. C.438Habitual miscarriage mixed Genesis7,065 mm2
34. S-VA M. A.490Habitual miscarriage mixed Genesis23,55 mm2
35. K-on A. C.469Habitual miscarriage mixed Genesisof 28.26 mm2
36. H-VA L N.577Familiar Nevins the of pregnancy mixed Genesis 9,42 mm2
37. P-Ko A. C.AMB.Habitual miscarriage mixed Genesis12,56 mm2
38. W-WA M N.AMB.Habitual miscarriage mixed Genesis15.7 mm2
39. F-VA S. C.AMB.Habitual miscarriage mixed Genesis15.7 mm2
40. O-to N.In.875Habitual miscarriage mixed Genesis12,56 mm2
41. B-BA, N.909Habitual miscarriage mixed Genesis7,06 mm2
42. G-VA O. C.884Habitual miscarriage mixed Genesis9,42 mm2
43. P-1097Habitually the miscarriage mixed Genesis 9,42 mm2

Table 2
Data fibrinolytic activity of the endometrium in women with undifferentiated connective tissue dysplasia with the loss of a pregnancy in the early stages in history
F. ActingIBDiagnosisFibrinolytic activity
1. C-VA E. M.1495Habitual miscarriage mixed Genesis78.5 mm2
2. T-VA S. C.1209Habitual miscarriage mixed Genesis56,52 mm2
3. G-VA M. S.230Habitual miscarriage mixed Genesisof 28.26 mm2
4. K-VA K. E.205Habitual miscarriage mixed Genesis50,24 mm2
5. K-VA I. C.226Habitual miscarriage mixed Genesis23.5 mm2
6. C-WA Y. Y.401Habitual miscarriage mixed Genesis23.5 mm2
7. Peninsula A. A.389Habitual miscarriage mixed Genesis23.5 mm2
8. H-E. A.531Habitual miscarriage mixed Genesis32,97 mm2
9. Peninsula A. A.437Habitual miscarriage mixed Genesis77,71 mm2
10. H-e O. C.514Habitual miscarriage mixed Genesis50,24 mm2
11. And-VA M. H.436Habitual miscarriage mixed Genesis12. K-VA I. M.585Habitual miscarriage mixed Genesisof 28.26 mm2
13. B-C. S.554Habitual miscarriage mixed Genesis78.5 mm2
14. L-VA N. In.540Habitual miscarriage mixed Genesis63,58 mm2
15. S-VA N.And.568Habitual miscarriage mixed Genesis56,52 mm2
16. S-VA N.A.709Habitual miscarriage mixed Genesis70,65 mm2
17. K-VA O. N.581Habitual miscarriage mixed Genesis63,58 mm2
18. C-VA S. A.578Habitual miscarriage of beremend the STI mixed Genesis a 94.2 mm2
19. S-VA E. C.1498Habitual miscarriage mixed Genesisa 94.2 mm2
20. K-VA C. N.763Habitual miscarriage mixed Genesis78.5 mm2
21. D-VA A. S.760Habitual miscarriage mixed Genesisa 94.2 mm2
22. K-VA L. N.764Habitual miscarriage mixed Genesisa 94.2 mm2
23. H-VA E. A.804Habitual miscarriage mixed Genesis78.5 mm2
24. And society E. S.1017Habitual miscarriage mixed Genesis78.5 mm2
25 .K-on E. I.1151Habitually the miscarriage mixed Genesis 56,52 mm2

Method for the diagnosis of undifferentiated connective tissue dysplasia in women with pregnancy loss early in history by examining biopsies of the endometrium, characterized in that the tissue sample is determined fibrinolytic activity and when it is less 23,55 mm2diagnosed with undifferentiated connective tissue dysplasia.


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7 dwg, 1 ex, 6 tbl

FIELD: clinical medicine, pulmonology.

SUBSTANCE: one should carry out complex estimation of interleukin-1β) concentration in blood, saliva, bronchoalveolar liquid. Moreover, one should detect distribution coefficient (DC) for IL-1β as the ratio of IL-1β blood content to IL-1β salivary content. At increased IL-1β blood content by 10 times and more, by 2 times in saliva, unchanged level of bronchoalveolar IL-1β, at DC for IL-1β being above 1.0 one should predict bronchial obstruction. The method enables to conduct diagnostics of the above-mentioned disease at its earlier stages.

EFFECT: higher efficiency of prediction.

2 tbl

FIELD: medicine, diagnostics.

SUBSTANCE: the present innovation deals with genetic trials, with diagnostic field of oncological diseases due to analyzing DNA by altered status of gene methylation that take part in intracellular regulation of division, differentiating, apoptosis and detoxication processes. One should measure the status of methylation in three genes: p16, E-cadherine and GSTP1 in any human biological samples taken out of blood plasma, urine, lymph nodes, tumor tissue, inter-tissue liquid, ascitic liquid, blood cells and buccal epithelium and other; one should analyze DNA in which modified genes of tumor origin or their components are present that contain defective genes, moreover, analysis should be performed due to extracting and purifying DNA out of biological samples followed by bisulfite treatment of this DNA for modifying unprotected cytosine foundations at keeping 5-methyl cytosine being a protected cytosine foundation followed by PCR assay of bisulfite-treated and bisulfite-untreated genes under investigation and at detecting alterations obtained according to electrophoretic result of PCR amplificates, due to detecting the difference in the number and electrophoretic mobility of corresponding fractions at comparing with control methylated and unmethylated samples containing normal and hypermethylated forms of genes one should diagnose oncological diseases. The method provides higher reliability in detecting tumors, detection of remained tumor cells after operation.

EFFECT: higher efficiency of therapy.

1 cl, 3 dwg, 4 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: one should carry out diagnostic studying, moreover, on the 5th -6th d against the onset of exacerbation in case of gastric and duodenal ulcerous disease one should detect the content serotonin, histamine and acetylcholine in blood, then during 2-3 wk one should conduct medicinal therapy to detect serotonin, histamine and acetylcholine level in blood again and at serotonin content being by 2-3 times above the norm, histamine - by 1.15-1.4 times above the norm and acetylcholine - by 20-45% being below the norm one should predict the flow of gastric and duodenal ulcerous disease as a non-scarring ulcer.

EFFECT: higher accuracy of prediction.

3 ex

FIELD: medicine.

SUBSTANCE: method involves taking blood from ulnar vein (systemic blood circulation) and from large vein of the injured extremity proximal with respect to lesion focus (regional blood circulation). Spontaneous NST-test value is determined and difference is calculated in systemic and regional blood circulation as regional-to-systemic difference. The difference value is used for predicting clinical course of pyo-inflammatory disease in extremities.

EFFECT: high accuracy of diagnosis.

4 cl, 2 tbl

FIELD: medicine, gastroenterology.

SUBSTANCE: one should introduce biologically active substance, moreover, in patient's blood serum one should detect the content of acetyl choline and choline esterase activity followed by 2-h-long intragastric pH-metry at loading with biologically active substance as warm 40-45%-honey water solution at 35-40 C, and at increased content of acetyl choline being above 1.0 mM/l, choline esterase being above 0.5 mM/l/30 min and pH level being 6.0-6.9 it is possible to consider apitherapy to be useful for treating ulcerous duodenal disease.

EFFECT: higher efficiency and accuracy of detection.

3 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: it has been suggested a new method to detect pharmacological sensitivity to preparations as acidosuppressors. After the intake of the preparation a patient should undergo fibrogastroduodenoscopy 3 h later, then, through endoscopic catheter one should introduce 0.3%-Congo red solution intragastrically and the test is considered to be positive at keeping red color that indicates good sensitivity to the given preparation, and in case of dark-blue or black color the test is considered to be negative that indicates resistance to this preparation. The suggested innovation widens the number of diagnostic techniques of mentioned indication.

EFFECT: higher efficiency of diagnostics.

2 ex