A method for predicting the growth of uterine leiomyoma

 

(57) Abstract:

The invention relates to medicine, namely to gynecology, and can be used to predict the growth of fibroids. The essence of the invention lies in the fact that in the peripheral blood to determine the relative content of CD38+ lymphocytes and their values equal to or greater 23%, forecast the rapid growth of fibroids in the course of the year. The technical result is the creation of accurate, sensitive and specific method for predicting rapid growth of fibroids. table 1.

The invention relates to medicine, namely to gynecology, and can be used to predict the growth of uterine fibroids.

The urgency of the invention is determined by a high incidence of leiomyoma (uterine fibroids) in women older than 30 years (15-17%). Up to 80% of all cases occur in women of reproductive age [4]. In 50% of patients with rapid growth of uterine fibroids, which is an indication for surgery. Radical intervention with removal of the uterus leads to the loss of reproductive and menstrual function. Development of reliable criteria for predicting the growth of uterine fibroids will allow the physician to choose optimum non-invasive diagnostic morphological type of uterine fibroids by conducting color Doppler mapping (DDC), namely, that sarcoma myomatous node unlike other forms has intense neovascularization with Central and peripheral, chaotic arrangement of vessels, low resistance to blood flow, which contributes to the rapid growth of fibroids [2].

The disadvantages of the method:

1) the method is based on the differential diagnosis of sarcoma of the uterus, whereas the frequency of malignancy uterine fibroids is not more than 0.8% [6];

2) the method is non-specific, because the nature of intratumoral blood flow in sarcomas and proliferating the fibroids are identical;

3) this method does not allow to predict the growth of fibroids;

4) there are no data on the accuracy of the method.

The closest technical solution to the claimed method is a method for predicting the growth of uterine fibroids, namely, that in the tissues of myomatous nodes, obtained by the method of transcervical needle biopsy, immunohistochemical method is proposed to determine the density and intensity of staining of receptors for progesterone, and the increase of these parameters predicted growth of fibroids in the past 12 months [9].

This method was chosen as the closest analogue. About the prigotovlenii slices, nonuniform intensity of staining fabrics, features microscopy [1];

2) high invasiveness and trauma;

3) high complexity;

4) the authors do not indicate the accuracy, sensitivity and specificity of the method.

These drawbacks are proposed to be eliminated in the present method.

The claimed technical result is achieved by the fact that in the peripheral blood of women with fibroids determine the relative amount of CD38+ lymphocytes and the values of this index, equal to 23% or more, forecast the rapid growth of fibroids with an accuracy of 75.8% during the year.

The novelty of the proposed method lies in the fact that for the first time proposed to predict the rate of growth of fibroids in the determination of the relative content of CD38+ lymphocytes in the peripheral blood.

Previously the content of CD38+ lymphocytes was determined in peripheral blood sickly and persons, while there was an increase in the number of lymphocytes bearing on its surface the molecule [5]. In the acute phase neurogenesis form of mumps infection in patients was also characterized by a high content CD38+ lymphocytes in the peripheral blood [3]. To predict the rate is acetami at different stages of their development. First CD38 molecule appears on immature cells, then in the process of maturation and differentiation of cells it stops expressionate, but again appears on the surface of lymphocytes at very late stages of activation [7]. We assume that the high content of CD38+ lymphocytes in women with fibroids is associated with an increase in the peripheral blood pool of immature cells that can result from violations of the processes of differentiation of immune cells and to serve as one of the factors that promote tissue growth.

The method is performed by a standard method as follows:

1 ml of blood from the cubital vein taken in a test tube containing 25 IU heparin, add 1 ml of Medium 199 and padlayat 1 ml ficollverographine density 1,078. The cellular fraction of lymphocytes receive the standard method of high-speed centrifugation at 1500 rpm for 20 minutes [1]. Lymphocytes collected at the interphase Environment 199 - finalversion and washed 2 times with Medium 199 by centrifugation at 1500 rpm for 10 minutes [8].

Further in accordance with the instructions of the company-developer of monoclonal antibodies (Med-Biospectra, , Moscow, Russia, registration number 29/240/70700/2013-01 from 14.0.6.01) 100 μl of cells at a concentration of 1x10The use of the proposed method with high accuracy (75.8 per cent) to predict the rate of growth of fibroids in the course of the year.

Distinctive features of the process are: a prognostic parameter of the relative content of CD38+ lymphocytes in the peripheral blood, with quantitative values, which is 23% and is projected rapid growth of fibroids.

The essence of the proposed method is illustrated by the following examples.

Example 1. Patient A., aged 40. Observed in female consultations on uterine myoma of the small sizes (8 weeks) for 5 years. Complains of profuse prolonged menstruation, weakness. History 2 timely delivery, 2 med. abortion without complications, Navy for 6 years, removed 5 years ago. Contraception currently barrier methods.

At vaginal examination: cervix without defects mucosa, uterus enlarged to 8 weeks ber is dry.

According to the ultrasonic scanning (CCS): the body of the uterus with a rough surface, non-uniform patterns, sizes 768477 mm On the front wall intermuscular node 20 mm, on the back wall and the bottom 17 mm M-echo 10 mm Right ovary - 3729 mm, left ovary - 3026 mm, normal structure.

Blood test: b - 104 g/l, erythrocytes - 3,34 m/l, color index - 0,81, leukocytes - 6.4 g/l, eosinophils - 2, segmented neutrophils - 63, monocytes - 3, lymphocyte - 32, ESR - 16 mm/h

Clinical diagnosis: mimusica-podbroshena uterine fibroids, hyperprolinemia, anemia 1 degree.

According to immunological examination by the present method the indicator of the relative content of CD38+ lymphocytes in peripheral blood was 11.5%, which is lower than the proposed option (23%).

Conclusion: predicted no growth of fibroids in the course of the year.

When you re-inspection after 1 year gynecological status of the patient is the same (confirmed by ultrasound).

Example 2. Patient L., 41. Turned in the antenatal clinic with complaints of heavy menstruation. History 1 timely delivery, 3 medical abortion without complications, Navy 5 years removed 1 year ago.

During examination: cervix without defects mucous, body matanya CCS: the body of the uterus heterogeneous structure, size 584464 mm At the rear intermuscular node 16 mm M-echo 8 mm Right ovary - 3618 mm Left ovary - 3311 mm. Both ovaries normal structure.

Blood test: b - 114 g/l, erythrocytes - 3.8 t/l, colour index - 0.9, leucocytes - 5 g/l, stab neutrophils - 2, segmented neutrophils - 66, monocytes - 5, lymphocytes - 27, ESR - 10 mm/h

Clinical diagnosis: intermuscular uterine fibroids, hyperprolinemia.

The examination by the present method showed that the content of CD38+ lymphocytes in peripheral blood was 38%, which is higher than the proposed option (23%).

Conclusion: the projected rapid growth of the tumor within 1 year.

Patient registered, recommended gynecologist examination 1 time in 3 months, control of hemoglobin before and after the menstrual period, ultrasound.

Turning after 1 year, the patient complained of weakness, profuse menstruation, lower abdominal pain, frequent urination.

During examination: cervix without defects mucosa. The body of the uterus for up to 12 weeks of pregnancy, with a rough surface, dense, mobile, painless. The appendages are not defined.

The ultrasound results: the body of the uterus 9467124 mm, with several mimusica-podbroshennye nodes, the most settled and normal ovarian structure.

Blood test: Hb - 99 g/L.

Clinical diagnosis: mimusica-podbroshena uterine fibroids, rapid growth, hyperprolinemia, anemia 1 degree, dysuric phenomena.

The patient is directed to the gynecological examination in the hospital for surgical treatment. Thus, the forecast rapid growth of fibroids present method was confirmed.

Example 3. Patient S., 43 years. Observed in female consultations on uterine myoma of the small sizes (8 weeks) for 3 years. Complains of profuse prolonged menstruation, weakness. History 2 timely delivery 3, honey. abortion without complications, Navy for 6 years, removed 3 years ago. Contraception currently barrier methods.

At vaginal examination: cervix without defects mucosa, uterus increased to 7 weeks of pregnancy, with a rough surface, firm, mobile, painless, appendages are not defined, arches free.

According to CCS: the body of the uterus with a rough surface, non-uniform patterns, sizes 766477 mm On the front wall intermuscular node 25 mm M-echo 7 mm Right ovary - 3628 mm, left ovary - 3329 mm, normal structure.

Blood test: b - 108 g/l, erythrocytes - 3.2 t/l, color pakiety - 3, lymphocytes - 41, ESR - 6 mm/h

Clinical diagnosis: intermuscular uterine fibroids, hyperprolinemia, anemia 1 degree.

According to immunological examination by the present method the indicator of the relative content of CD38+ lymphocytes in the peripheral blood of 23.5%.

Conclusion: projected growth of fibroids in the course of the year.

When referring a patient 1 year after the complaints are the same. During examination: cervix without defects mucosa, uterus enlarged to 12 weeks of pregnancy, with a rough surface, firm, mobile, painless, appendages are not defined.

Data ultrasound: uterus size 11074117 mm inhomogeneous structure with multiple mimusica-podbroshennye nodes. Most - on the front wall 64 mm and 48 mm at the rear - 55 mm M-echo - 9 mm Right ovary - 3830 mm, left ovary - 3527 mm, normal structure.

In the analysis of blood Hb - 95 g/L.

Clinical diagnosis: mimusica-podbroshena uterine fibroids, rapid growth, hyperprolinemia, anemia 1 degree.

The patient is directed in gynecological hospital for surgical treatment. Thus, the forecast rapid growth of fibroids present method was confirmed.

The specified method on the basis of gynecological is adavani shown in the table. Monitoring of patients was carried out within 1 year. In all cases women histological examination confirmed the diagnosis of leiomyoma uterus”.

The advantages of the proposed method:

1) high accuracy of 75.8%, sensitivity 71%, specificity 81%;

2) atraumatically way;

3) a survey of women possible in the outpatient setting, does not require the participation of numerous staff and does not lead to temporary incapacity women;

4) forecast wealthy during the year.

Bibliography

1. Immunological methods (edited by H. of Primes).// M.: Mir, - 1979, - 518 S.

2. Kapustin, I. N., Sidorov I. S. the Value of color Doppler mapping in the assessment of the type of fibroids.// The Russian Bulletin of the obstetrician-gynecologist. - 2001, No. 1, - n-27-32.

3. Kashuba, E. A., Hanipova L. C., Drozdova, So, Malyshkin, A. A., Chebyshev E. C., A. L., Immunology acute mumps infection //Sat. 47 Congress RAACI "Modern problems of Allergology, immunology and immunopharmacology".// - M, - 2001, - S. 70.

4. Sidorov I. S., A. Karaulov Century, Kurashvili Y. B. To the question of the pathogenesis of false growth of fibroids in women of reproductive who Argunova, A., Beresnev, L. A., Petrov S. A. General immunological characteristics of the groups sickly and in remission in the indigenous and alien population of the Tyumen region.// Russia Journal of Immunology, - 199, - v.4, - Supplement 1, p.191.

6. Tikhomirov A. L., Lubnin D. M. the Role of microvascular changes in the mechanism of uterine bleeding in patients with leiomyoma uterus.// AG-info. - 2000, No. 1, - n-5-7.

7. The Yarylo A. A. fundamentals of immunology./M: Medicine - 1999, - 608 S.

8. Boyum A. Isolation of mononuclear cell fnd granulocytes from human blood and bone marrow// Scand. J. Clin. Lab. Invest. - 1968, - v.21, No. 97, p.77.

9. Ichimura T., Kawamura N., Ito F., Shibata, S., Minakuchi K, Tsujimura, A., N. Umesaki, Ogita S. Correlation between the growth of uterine leiomyomata and estrigen and progesterone receptors in needle biopsy speciments // Fertil. Steril. - 1998, - v.70, p.967-971.

A method for predicting the growth of uterine leiomyoma by examining peripheral blood, characterized in that to determine the relative content of CD38+ lymphocytes and their values equal to or greater 23%, forecast the rapid growth of fibroids in the course of the year.

 

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SUBSTANCE: in lacrimal liquid one should detect the content of interleukin 8 (IL-8) and that of interleukin 1 beta (IL-1β) to calculate prognostic coefficient (PC) due to dividing the first value by the second one by the following formula: At PC value being below 10.0 one should predict favorable disease flow, and at PC value being above 10.0 - unfavorable flow.

EFFECT: higher accuracy of prediction.

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