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4. Kullo I., Cooper L. Early identification of cardiovascular risk using genomics and proteomics//Nat. Rev. Cardiol. - 2010. - 7(6). 309-317.
5. Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol. - 2005; -25:39-42.
6. Meng Q Yue J., Shang M. et al. Correlation of GLUT9 Polymorphisms With Gout Risk//Medicine. - 2015. 94. (44). 1-7.
7. Min L. Association of the polymorphisms of SLC2A9 gene with primary gout and uric acid levels in Chinese Han population. North Sichuan Medical College. - 2009;60:3446.
8. Stark K, Reinhard W, Neureuther K, et al. Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study. PLoS ONE. - 2008;3: e1948.
9. Swerdlow D., Holmes M., Harrison S. et al. The genetics of coronary heart disease//Br.Med. Bull. - 2012. 102. (1). 59-77.
10. Vitart V, Rudan I, Hayward C, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. - 2008;40:437-442.
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-138-142
Fayzullaeva Dilfuza, Specialized republican research and practicemedical
center of phthisiology and pneumonology of Health of the Republic of Uzbekistankandidat of medical sciences Tillyashaykhov Mirzagolib, Specialized republican research and practicemedical center of phthisiology and pneumonology of Health of the Republic of Uzbekistandoctor of medical sciences
Khakimovh Mirazim, Specialized republican research and practicemedical center of phthisiology and pneumonology of Health of the Republic of Uzbekistan kandidat of medical sciences
E-mail: saodat.us@mail.ru
Differential diagnostics of peripheral lymph node tuberculosis in hiv-infected patients
Abstract: Biopsy is more informative to diagnose the lymph node tuberculosis. Pathomorphological pattern features ofthe lymph node tuberculosis in HIV-infected patients areprincipally specified during the active period ofthe lymph node inflammatory process. Three stages are classified as per changes in lymph node tissues as follow:
— low-active period — primarily by granulomatous and productive changes.
— active period — productive and necrotic changes.
— progressive period — purulence and fistula occurrence.
As the immune system deteriorates, the progressive period intensifies in combination with otheropportunistic infections. Keywords: peripheral lymph node, tuberculosis lymphadenopathy, HIV-infected patients.
Against deterioration of the TB epidemiological situation, the increase in the incidence of extrapulmonary tuberculosis is reported, including peripheral lymph node TB. In case of extrapul-monarytuberculosis, peripherallymph node lesion ranks almost the first all over the world [4; 3; 5]. Tuberculosis lymphadenopathy is known to be specific among other lymph node diseases. Its clinical pattern is diverse, unstable and has no pathognomonic signs. Various diseases of non-specific origin are often confused with TL [1]. As per statistic data by the Tuberculosis Research Institute of Russia, the results ofhistological studies of the active extrapulmonary tuberculosis structure conventionally reveal the lymph node involvement which makes 44.5% [1; 9].
In the current context of high incidence in lymphadenopathy of different etiology, the TL diagnostics remains the challenging and immediate problem in phthisiology [10; 11; 6; 7; 8].Normally, the publications on TL diagnostics and differential diagnostics are
limited. All these circumstances were motivating to perform this study.
Purpose of study: To improve the procedure for comprehensive diagnostics and differential diagnostics of the tuberculous lymphadenopathy.
Study material and methods. The study is based on the review of medical records of patients with lymphadenopathy who underwent examinations and treatment at the clinics of the Specialized Republican Research and Practice Medical Center of Phthisiology and Pneumonology ofthe Ministry of Health of Uzbekistan from 2013 to 2015. We examined 150 subjects with lymph node diseases and relevant imitating processes. Patients were examined by a single method that included medical history data collection, clinical method (including the local status description as per the standard plan), radiological method (chest X-ray, lymph node sonography and computed tomography), laboratory tests (clinical analysis), bacteriological methods
(examination of sputum, urine, lymph node tissues excised and/or fistula discharge to identify Mycobacterium tuberculosis, tuberculin testing using the Mantoux test with 2TE PPD-L.
Needle biopsy was performed by the standard practice. Several drugs were prepared. After fixing with ethanol for 20-30 minutes, they were stained with azure-eosin (Giemsa stained). In case of purulent biopsy specimens, the smears were stained by the Ziehl-Nielsen and, in some particular cases, they were Gram stained for further bacteriological examination. These methods allowed to significantly expand the scope of diagnostic information and create the most favorable environment for timely diagnostics of the Peripheral Lymph Node Tuberculosis (PLNTB) and, thus, early TB management.
Based on comprehensive clinical, laboratory, sonographic and morphological studies of 150 subjects with peripheral lymphade-nopathy as related to tuberculosis, 99 patients (66.0%) were TL diagnosed, 51 patients (34.0%) were diagnosed with other lymph node diseases.Resulting from these types of studies, the subjects were ranged as follows: the peripheral lymph node tuberculosis is diagnosed in 99 (66.0%) subjects, non-specific lymphadenitis was diagnosed in 34 (22.7%) subjects, lymphogranulomatosis — in 10 (6.7%) subjects, tumor deposits — in 4 (2.7%), neck cysts — in 2 (1.3%), festered atheroma — in 1 (0.7%) subject. A wide variety of conditions, including tumor and systemic diseases mistakenly diagnosed as the TL indicates the difficulty of the differential diagnosis to identify them. This is proved through the periods these patients
were observed in clinics and PDD for correct diagnosis. Of the 99 patients who were initially wrongly diagnosed with the TL, the observation period at the TB Dispensary and polyclinics in half of them (56 persons) upon the pathology identification to establishment of the true disease was more than 6 months, of which in 18 patients it was 2-6 years. Only in 25 patients the correct diagnosis was made within first three months since the date of disease identification.
99 patients with TL were classified into two groups: Group 1-59 subjects without concurrent pathology and Group 2-40 subjects with concomitant diseases (tuberculosis at other sites, patients with HIV infection, diabetes milletus, viral hepatitis, and etc.).
Table 1 shows classification of subjects by age. As it is seen based on the tabulated data, younger and middle-aged people prevailed among the subjects (74.1%). In patients under 20 years, TL Group 1 patients were almost 5 times more in number than Group 2 patients (83.3% and 16.7%, respectively, P <0.01). Also, in patients aged 21 to 30, the incidence of one group of patients was 3.1 times more frequent than TL Group 2 (75.7% and 24.3%, respectively, P <0.01). This is somewhat different when the first and second groups of TL patients are compared among elderly and senile aged patients. Thus, the incidence of Group 2 patients increased 2.5 and 4 times (71.4% and 28.6%, 80.0 and 20.0, respectively, at P>0.2, P <0.02). Thus, TL patients without comorbidities are more often reported among younerg patients and on the contrary, TL patients with concomitant diseases are more often observed among elderly and senile aged patients.
Table 1. - Classification of TL patients by age, n(%)
Age Group of TL patients Total
Group 1 Group 2
Aged 20 and younger 10 (83,3±10,7) 2 (16,7±10.7)* 12 (12,5±3,3)
Aged 21-30 28 (75,7±7,0) 9 (24,3±7,0)* 37 (37,4±4,8)
Aged 31-40 14 (58,3±10,0) 10 (41,7±10,0) 24 (24,2±4,3)
Aged 41-50 4 (28,6±12,0) 10 (71,4±12,0)* 14 (14,1±3,4)
Aged 51-60 2 (28,6±17,0) 5 (71,4±17,0) 7 (7,1±2,5)
Aged 60 and older 1 (20,0±17,8) 4 (80,0±17,8)* 5 (5,1±2,2)
Total 59 40 99 (100,0)
Note: * — statistical significance ^<0.02; Р<0.01) between Groups 1 and 2.
In TL patients, of all peripheral lymph node groups, the neck group (67.7%) is the most affected, of which in 45.5% patients, the tubercular process was localized in the anterior cervical region and in 22.2% — in the back of the neck region (see Flowchart 1).
4,00%
9,10%
11,10?
The combined involvement of cervical lymph nodes with axillary lymph nodes was reported in 9.1% of cases. The submandibular lymphadenitis (11.1%) ranks the second and the axillary lymphadenitis ranks the third (8.1%). The tuberculosis of inguinal lymph nodes was reported in only four (4.0%) patients.
67,70%
cervical STLbmajti llary associated axillary ; i ligni nal
Figure 1. Incidence of lympth node groups Flowchart 1
The groups of TL patients with concomitant diseases tended to develop conglomerates of lymph nodes (62.5%). In patients without concomitant diseases, the conglomerates were normally formed by the second month of observations. In this case, the destructive process with abscess (32.3%) and fistula (25.3%) development was developed in affected lymph nodes.
The statistical analysis of study results was conducted using the IBM compatible PC based on the Microsoft Excel software package for statistic computation.
Thus, the proposed modern methods to diagnose the peripheral lymph node tuberculosis allow identifying a range of new trends, both for diagnostics and for the integrated management of the peripheral lymph node tuberculosis.
Results and discussions.The clinical pattern of the tuberculous lymphadenitis developed differently. As per our observations, the development of TL with scarce symptoms was reported in 88.9% patients (88 of 99) was gradual and sometimes unsymptomatic for the patient. In this case, dense and elastic lymph nodes not more than 2-3 in number are initially palpable in the appropriate section of the lesions sized 2-3 cm, painless, which slowly grow in size often reaching large sizes. In 11.1% patients the acute onset of the disease is reported that was accompanied with the abrupt soreness of affected lymph nodes. Significant differences were observed between the tested groups depending on the disease localization signs.
So, in case of tuberculous lymphadenitis, fluctuation was observed in 32.3% cases, the skin redness was reported in 41.4%, in 56.6% cases the nodes sized 3 cm or larger, in 38.4% patients the node conglomerates were reported, and in 25,3% — the fistula was reported. The PPD test showed that the tuberculin sensitivity in most TL patients (54.5%) were of hyperergic nature; in 30.3%cases, they were of normerergic nature; negative reaction to tuberculin was seen in 15.2% patients.
In case of local TL in most patients (54%%), the peripheral blood values were within the normal range, and only in 6.1% patients abnormal values were reported to prove on the leukocytosis with the slight shift of segmented rod neutrophils.
In 68.7% patients the increaed level of ESR was noted and anemia — in 65.5%. The urinalysis revealed the protein, isolated eryth-rocytes and leukocytes in the urine samples. An increase in ALT and AST was insignificant. All these data may be referred to para-specific signs typical for primary tuberculosis.
As per data by M. V. Chulochnikova (2005), when analysing affected lymph nodes in TL patients, the Mycobacterium tuberculosis (MBT) was identified by bacteriological analysis in 22.8%.As the result of our observations, the significant decrease in MBT detection (in percentage) in TL patients was obtained. These studies showed that the MBT detection by the method of regular smear is possible only in 6.1% cases and in 11.1% cases — by the MGIT
method. As per our studies, the cultured pathological material of lymph nodes significantly revealed TL forms. Most often (54.5%), the MBT was isolated in case of abscess and fistula stage of tuberculous lymphadenitis. During the PLNTB bacteriological diagnosis, given the specificity of the pathological material, additional methods (Lowenstein-Jensenliquid mediuminoculation, MGITmethod, HAIN test, PCR) should be used in addition to conventional methods of Mycobacterium tuberculosis detection.
The review of histological preparations in 68 cases of tuberculous lymphadenitis showed that pathologic pattern features at TL are primarily determined by the phase of inflammatory activity in the lymph node.
Based on morphological traits, we have identified three groups of patients with the pathological process in different phases of activity: Group 1 (29 patients; 29.3%) primarily showed granulomatous-productive changes in lymph nodes (inactive phase), Group 2 (13 patients; 13.1%) — productive-necrotic (active phase of the process), Group 3 (57 patients; 57.6%) — mostly necrotic lesions with insignificant involvement of the lymph node with slight granulomatous changes, purulence and fistula formation (progressive phase).
Differences were observed in activity groups by the nature of the disease onset and course. Thus, in TL progressive phase (Group 3) the abruptonset was more frequent with severe intoxication and frequent melt of lymph nodes. At the same time, asymptomatic onset was often reported in the inactive and active (productive-nectrotic) phases when the only disease manifestation was enlarged lymph nodes discovered accidentally. Patients of Group 3 were often disturbed with intoxication symptoms, of which were the general fatigue, increased body temperature were most frequent.
TL diagnostics remains the immediate problem in phtysiatry. According to our data, of 99 patients who initially wrongly diagnosed with TL, about half of them (56 persons) was observed at the TB Dispensary and the clinic for over 6 months within the period from the pathology detection and the real disease establishment, of whom 18 patients were observed for 2-6 years. This is to say about the inadequate level of TL diagnostics and the need to develop a single medical algorithm for differential diagnosis of TL andperiph-eral lymphadenopathy of other etiology.
The difficulty of diagnostics relates to inadequate efficiency of the existing research methods. Bacteriological methods are limited in significance due to paucibacillary with extrapulmonary tuberculosis and higher likeliness to detect MBT in obvious destructive forms of the disease. So, according to our study, MBT was detected only in 17.2% patients with progressive phase of TL, and not at all detected during inactive phase of the disease.
Therefore, the morphological study is the method of choice. The process of tuberculous lymphadenitis diagnostics should include the sequence of steps as the range of diagnostic and therapeutic actions.
Table 2. - classification of tl patients by the disease stage, n(%)
TL stage Number of patients Group 1 Group 2
Proliferative 29 (29,3) 25 (86,2±6,4)* 4 (13,8±6.4)*
Caseous 13 (13,1) 8 (61,5±13,4)* 5 (38,5±13,4)*
Abscessed 32 (32,3) 16 (50.0±8.8)* 16 (50,0±8,8)*
Fistulose 25 (25,3) 10 (40.0±9,7)* 15 (60,0±9,7)*
Total 99 59 40
Note: * — statistical significance (P<0.001) between Groups 1 and 2. In the TL proliferative stage, the patients with concomitant conditions were 4.2 times less than patients without co-morbidities (13.8 and 86.2%, respectively, P <0.001).And, on the contrary, in the TL fistulose stage, patients with co-morbidities were 1.5 times more
than patients without co-morbidities (60.0 and 40.0%, respectively, P>0.2). In the TL caseous stage, no statistical significance was revealed between patients with and without concomitant conditions (38.5% and 61.5%, respectively, P>0.2). Also, in the TL abscessed stage, no
statistical significance was revealed in patients with and without concomitant conditions (50.0% and 50.0%, respectively, P>0.1).
Based on results of own researches, as well as literature data, we propose the algorithm of the physician action to perform the TL differential diagnostics that may be useful for doctors of general health care and TB facilities to early diagnose the tuberculosis lymphadenitis (Scheme 1).
Of high significance to improve the PLNTB differential diagnosis based on pathogenesis study was the evolutionary and patho-
genetic classification developed at the St. Petersburg Research Institute of Tuberculosis (N. A. Brazhenko 2013) which isolates 4 stages of the disease: 1) initial, proliferative; 2) caseous; 3) abscess; 4) fistula (ulcer). As per this classification, given the clinical data of the process and nature of morphologic changes in lymph nodes,29 patients (29.3%) were detected in their proliferative stage, 13 (13.1%) -in caseous, 32 (32.3%) — abscessed, 25 (25.3%) — fistulose stage of TL (see Table 2.) In other words, the majority ofpatients (57.6%) experienced abscessed and fistulose stages of TL.
Figure 2. Algorithm of TL
Conclusion
In the current conditions, the tuberculous lymphadenopathy differs in torpidity, scarcity of clinical signs and blood parameter changes. In 40.4% patients, the peripheral lymph node tuberculosis develops in association with other diseases (pulmonary tuberculosis, HIV Hepatitis C, Hepatitis B, abdominal tuberculosis). In more than half of cases, several groups of lymph nodes (56.6%) are affected, the process is most often detected at the advanced abscessed stage (32.3%) and the fistulose stage — (25.3%). From the lymph node, the Mycobacterium tuberculosis was isolated only in 17.2% cases. At the specialized in-patient hospital, the tuberculosis lymph-
differential diagnostics
adenopathy was detected in 99 (66.0%) patients, non-specific lymphadenitis — in 34 (22.7%), lymphogranulomatosis — in 10 (6.7%), tumor metastasis — in 4 (2.7%), neck cysts — in 2 (1.3%), festered atheroma — in 1 (0.7%) patient with the lymphadenopathy. The histological pattern ofremoved lymph nodes was reviewed and made it possible to distinguish three phases oftuberculous lymphadenitis activity: inactive phase in 29 (29.3%) patients (predominantly granulomatous-productive changes in the lymph nodes), active in 13 (13.1%) patients (productive-necrotic changes) and the progressive phase in 57 (57.6%) patients (predominantly necrotic lesions with minimal lymph node granulomatous changes, purulence and fistula formation.
References:
1. Azhmukhanbetov K. A., Nemova L. A., Beskova A. I., Bagramova B. B. Tuberculosis of peripheral lymph nodes in the Central Kazakh-stan//Collection of scientific works P (XII) Congress of TB specialists. - Saratov, - 1994. - P. 193.
2. Azhmukhanbetov K. A. Peculiarities of peripheral lymph nodes tuberculosis against deteriorating epidemiological situation//Medicine and Ecology. - 1996. - №.1. - P. 64-67.
3. Batyrov F. A., Khomenko V. A., Shmakova L. N. Epidemiology of extrapulmonary tuberculosis//Tuberculosis problems. - 2003. -№ 8. - P. 49-50.
4. Garbuz A. E. Current status of the extrapulmonary tuberculosis problem//Tuberculosis problems. - 1998. - No 2. - P. 32-34.
5. Kulchavenya E. V. Tuberculosis of extrapulmonary locations in the Western Siberia//Tuberculosis and lung diseases. - 2003. - № 4. -P. 13-15.
6. Savina T. A. Non-specific lymphadenopathy in the clinical practice of peripheral lymph node tuberculosis//Tuberculosis as the object ofscientific research. Works collection. SPb., - 1994. - T. 1. - P. 166-170.
7. Savina T. A. Lymphadenopathy of different etiology in the clinical practice of peripheral lymph node tuberculosis: Abstract of dissertation Candidate of Medical Science SPb., - 1997. - 25 p.
8. Savina T. A. Challenges to diagnose tuberculous lymphadenopathy and nonspecific lymphadenopathy//Extrapulmonary tuberculosis -the challenge of the health sphere. Works collection.All-Russian scientific and practical conference. - SPb., - 1997. - P. 47.
9. Solovyova I. P., Fligel D. M. Extrapulmonary tuberculosis by autopsy examination materials//IV (XIV) Congress of Scientific and Medical Association of Phthisiologists. - Moscow - Yoshkar-Ola, - 1999. - P. 192-193.
10. Talantov V. A., Butkarev I. N. Differential diagnosis and comprehensive management of peripheral lymph node tuberculosis: Guidelines, L., - 1983. - P. 23.
11. Titarenko O. T., Dyakova M. E., Chuzhova N. M., etc. Criteria to diagnose the tuberculosis of peripheral lymph nodes using adenosine desaminase//Guidelines - № 99/152. - SPb., - 2000. - 17 p.
12. Chulochnikova M. A. Clinical and morphological characteristics of the peripheral lymph node tuberculosis in different phases of activity: Abstract of dissertation of the Candidate of Medical Science - Moscow, - 2005. - P. 26.
DOI: http://dx.doi.org/10.20534/ESR-16-9.10-142-144
Khodjaeva Nodira Vakhidovna, Republican Specialized Scientific and Practical Medical Center of Endocrinology under the Ministry of Health of the Republic of Uzbekistan,
external degree candidate.
E-mail: nadira202@mail.ru Khaidarova Feruza Alimovna, MD, Republican Specialized Scientific and Practical Medical Center of Endocrinology under the Ministry of Health of the Republic of Uzbekistan,
therapeutic work director.
E-mail:alimovna@mail.ru
Estradiol-progesterone correlation as a marker of severity of premenstrual syndrome
Abstrct: The level of estradiol in the luteal phase of menstrual cycle was significantly higher in women with severe course of PMS compared to patients from other groups. During PMS, a correlation relation between the level of estradiol (r=0,87; P<0,0001), estradiol-progesterone correlation (r=0,81; P<0,0001) and degree of severity of PMS in the luteal phase of menstrual cycle was observed.
Keywords: premenstrual syndrome, estradiol, progesterone, correlation estradiol/progesterone.
Premenstrual syndrome (PMS) is a complicated complex of In some researches, the formation of PMS is related to the ac-
symptoms cyclically appearing in women in luteal phase of menstru- tivity of neuro-active metabolites of progesterone, including those, al cycle and is characterized by various neuro-psychotic, vegeto-vas- which are produced spontaneously in the CNS [2; 3; 9]. Also, it is cular and metabolic-endocrine disorders, which reduce professional noted that women with clearly expressed deficit of progesterone in and household working capacity and level of social adaptation. luteal phase of the cycle showed no disposition to PMS. PMS is not
There are numerous theories about pathogenesis of PMS. One observed during anovulatory cycles, when relative hyperestrogen-of the key theories is the hormonal theory of PMS, according to ism is developed. The authors reckon that PMS can be the result of which, the disease is determined by the disruption of the correla- disruption of the balance of estrogens and progesterone [1]. tion of estrogens and progesterone during luteal phase of menstrual Goal of research: to study estradiol-progesterone correlation in
cycle [3; 5]. Estrogens affect the receptors in the limbic system of the women with PMS depending on the degree of disease severity. brain, which determines the appearance of a range of symptoms in Materials and methods: 129 women aged 18 to 40 with com-
the phsyco-emotional sphere [1; 5]. plaints about somatic and/or psycho-emotional symptoms appear-
