[Limb-shaking transitory ischaemic attack in a patient with subocclusion of the internal carotid artery]. / Tranzitornaia ishemicheskaia ataka «limb shaking¼ u bol'nogo s subokkliuziei vnutrennei sonnoi arterii.

Described in the article is a clinical case report concerning symptomatic subocclusion of the internal carotid artery in a male patient with a rare variant of recurrent limb-shaking transitory ischaemic attacks (LS-TIA). The patient presented with a three-month history of episodes of involuntary jerky movements in his left hand. These episodes occurred invariably on assuming a vertical position. The findings of duplex scanning revealed subocclusion of the right internal carotid artery. The patient was subjected to stenting with the use of the system of proximal cerebral protection. The postoperative period was complicated by the development of cerebral hyperperfusion syndrome the risk of which in patients with LS-TIA is known to be elevated. Via telephone interviewing carried out at 1, 6 and 12 months after the intervention, the patient confirmed that the episodes of hand shaking did not recur. This case report highlights the importance of accurately assessing the clinical findings while selecting patients for carotid revascularization, since such ischaemic episodes are strongly suggestive of a severe lesion of the contralateral carotid artery. Once subocclusion is revealed, it is optimal to perform stenting with the use of a system of proximal protection, as a safer and more effective method of surgical revascularization in such conditions.

[Retrograde type A aortic dissection after endovascular repair of the thoracic artery].

Retrograde type A aortic dissection is a severe and prognostically unfavourable complication of endovascular repair of the thoracic aorta. The aim of the present article is to describe a clinical case report concerning a hybrid operative intervention for retrograde type A aortic dissection in a patient having endured two-stage endovascular repair of the thoracic artery.

Theory of intercellular communication in the development of endothelial dysfunction.

Activation of intracellular signaling and blebbing of the plasma membrane lead to rafting and clustering of membrane receptors. Lymphocyte with high receptor density at the cell pole interacts with endothelial cells, which leads to their hyperactivation. In this case, lymphocyte getting a response from the endothelial cell can release membrane particles, which interact with endothelial receptors and penetrate through gaps between endothelial cells forming aseptic inflammation and causing atherogenesis. Endotheliocytes also contribute to generation of active membrane microparticles. Hyperactivation of endothelial cells and constant stimulation by the lymphocytes and microparticles trigger programmed cell death resulting in exfoliation of the endothelial cell. The endothelial defect is replaced by endothelial cells of the vascular wall (in case of mild endothelial dysfunction) or by progenitor endothelial cells (in case of severe dysfunction).

[Stabilization of cellular membranes as a target of vascular therapy].

We present data of the study of effect of trimetazidine MB on the state of cellular membranes assessed on lymphocytes as highly sensitive model of hypoxia and endothelial dysfunction. Detection of external cytoplasmatic membrane blebbing and registration of quantity of membrane released microparticles by the method of phase-contrast microscopy were carried out in groups of patients with hypertensive disease without and with ischemic heart disease (IHD). It was found that number of cells in the state of terminal blebbing statistically significantly decreased and number of cells with intact cytoplasmic membrane increased at the background of intake of trimetazidine in all groups of patients. With correlation coefficient 0.76 (p<0.05) between content of membrane microparticles and terminal blebbing lowering of content of membrane released microparticles was noted in peripheral blood of patients of all studied groups. The investigation conducted allows to make conclusion that stabilization of cellular membranes is one of spectra of trimetazidine actions underlying improvement of self feeling of patients with vascular pathology.

[Modulation of membrane blebbing and microparticle sheddimg as a target of cardiovascular prophylaxis].

Physicocemical and antigenic properties of peripheral blood lymphocytes and shed membrane microparticles were studied in patients with CHD and angina of effort and in those with hypertensive disease. The frequency of lymphocyte blebbing in CHD and angina patients was significantly higher than in those with HD (70.56, 52, 25.7% respectively). Incubation with rotenone and zymosan resulted in an increase of lymphocyte blebbing to 77.34 and 86.5% vs the initial level of 70.56% (p < 0.05). Patients of both groups had an increased number of membrane microparticles in peripheral blood (59.6 and 78.2 U/4 cm2 respectively). It is concluded that modulation of Imphocyte blebbing and microparticle shedding may be a promising target of cardiovascular prophylaxis.

Role of CD38 in cell-cell interactions under conditions of endothelial dysfunction.

We studied the role of receptor/ectoenzyme CD38 in the formation of endothelial damage and pathogenesis of endothelial dysfunction. CD38 was located in sites of protrusion of the outer cytoplasmic membrane. The majority of CD38+ accumulation sites coincided with the protrusion pole, while in some cells expression of CD38 was spread along the entire cell membrane surface or located on the pole opposite to the protrusion. We hypothesized that these states reflect the processes of rafting and clustering of the receptor, which are essential for cell-cell interactions in the pathogenesis of endothelial dysfunction.

Outcomes of conventional surgery and combined with endovascular intervention for acute thromboses of atherosclerotically arteries comparative study.

UNLABELLED: The study was aimed at early outcome retrospective analysis of conventional surgery (CS) for acute arterial obstruction (AAO) of lower limb arteries with atherosclerotic lesions and of simultaneous combined treatment (SCT) - endovascular intervention undertaken during open surgery. MATERIALS AND METHODS: 166 histories of patients with AAO and atherosclerotic lesions of lower limb arteries, treated during 1998-2005. Conventional surgical therapy was used in 72 cases and comprised open and indirect thrombectomy with endarterectomy and/or femoral arterioplasty if indicated. In 94 eases open surgery was combined with pre- or intraoperative angiography and endovascular balloon angioplasty. RESULTS: restoration of blood flow during primary intervention was achieved in 58.3% of patients after CS and in 72.3% of patients after SCT; the rate of amputations was 31.9% and 18.1%, respectively, mortality - 16.6% and 6.3%, respectively, favorable outcome at the discharge - 62.5% and 79.9%. CONCLUSION: endovascular angioplasty of atherosclerotic stenoses during open surgery for acute thromboses of lower limb arteries has distinct benefits over conventional surgical treatment.

[Esophagoplasty with the colon in flap patients with burn strictures of the esophagus]. / Plastika pishchevoda tolstoi kishkoi u bol'nykh s ozhogovymi strikturami pishchevoda.

Results of coloesophagoplasty in 366 patients with long burn strictures of the esophagus are presented. The lesion was total in 74 (21.2%) of them. Inefficacy of bougieurage was indication for plastic surgery in 133 (36.3%) patients, complete obliteration of esophagus--in 53 (14.5%). Left half of the colon was used in 296 (80.9%) cases, transverse colon--in 48 (13.1%), right half of the colon--in 22 (6.0%) cases. Retrosternal shunting esophagoplasty was performed in 247 (67.5%) patients. Complications were in 84 (34.0%), necrosis of the transplant--in 4 (1.6%) patients. Extirpation of the esophagus with posteriormediastinoplasty was performed in 16 (4.4%) patients, in 14 of them--transhiatally. Complications occurred in 7 patients coloesophagopharyngoplasty was carried out in 52 (14.2%) patients with combined stricture of the esophagus and the pharynx, in 23 of them--simultaneously. Complications were in 28 (53.8%) patients. Intrapleural of coloesophagoplasty was performed in 51 patients. General hospital lethality was 3.3%. Long-term results were studied in 259 patients. Good results of esophagoplasty were seen in 135 (52.1%) patients, satisfactory--in 65 (25.1%), unsatisfactory--in 59 (22.8%) patients. Dysfunction of the artificial esophagus was seen in 22.0% patients, 12.7% patients underwent repeated reconstructive surgeries.

Aromatase in skeletal muscle.

Aromatase gene expression and activity have been studied in human skeletal muscle. Using two separate rounds of RT-nested PCR, transcripts from the coding region of aromatase mRNA were detected in 32 of 34 samples. In terms of the non-coding exon I, PCR product for I.4 was detected in 13 cases (38%), I.3 in 10 cases (29%), P.II in 6 cases (18%) and I.1 was not detected in any case. No transcripts for any studied variants of exon I were detected in 18 samples (53%). Aromatase activity was assessed using two different methodologies: in 19 cases by definitive product isolation (DPI) and in 42 cases by tritium-release assay (TRA). Using both methods detectable activity was present in 52% of cases. Average values for the cases with detectable activity were 2.2 fmol/mg protein/h for DPI and 6.5 fmol/mg protein/h for TRA. In the cohort studied by TRA, a positive correlation of aromatase activity with age of the donor was observed (r=0.34, P=0.03). In six cases paired comparison of aromatase activity in muscle and associated fat tissue were performed by DPI. When expressed per milligram of protein the activity was always higher in fat. However, this difference disappeared when activity was based on the gram of wet tissue. Taking into account bulk in the body it is concluded that muscle can be an important source of estrogens in men and post-menopausal women and its contribution to the circulating pool of estrogens may be comparable to that of adipose tissue. The nature of mRNA transcripts in muscle suggests that estrogen formation may be controlled by glucocorticoid- as well as cAMP-dependent promoters of the aromatase gene.

Local uptake and synthesis of oestrone in normal and malignant postmenopausal breast tissues.

Uptake and local formation of oestrone (E1) were studied in vivo by a double isotopic technique in normal and malignant breast tissues from 24 postmenopausal women with breast cancer. Active uptake of radio-labelled E1 beyond plasma was found both in normal and malignant tissue, the effect being significantly greater in non-malignant compared with cancer tissue. The presence of local E1 formation was also demonstrated in most samples. Both uptake and synthesis positively correlated with total amount of radioactive E1 found in the tissues. Uptake appeared to make a greater contribution to E1 levels within the breast than in situ synthesis, although there were marked variations between specimens from different patients and the relative proportion of synthesis to uptake was higher in tumour compared with non-malignant tissue. These results demonstrate quantitative differences in the different compartments by which postmenopausal breasts obtain oestrogen and highlight variations between individual breasts. This may be important in optimising oestrogen deprivation therapy for postmenopausal patients with hormone-dependent cancers.

Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears.

PURPOSE: To clarify the role of lymphocytes as a possible source of estrogens. METHODS: In the present study, lymphocytes were isolated from 11 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. Simultaneously, using the latter procedure, mononuclears were separated from the blood of 15 female volunteers. RESULTS: Expression of the aromatase (CYP19) gene was readily demonstrated by standard RT-PCR in blood mononuclears cultivated in the presence of 10% fetal calf serum for 48 h. In the tumor-infiltrating lymphocytes (TIL) of breast cancer patients, CYP19 expression was discovered only with the aid of nested PCR. CONCLUSIONS: The data obtained suggest that aromatase gene expression is presented in TIL at a rather low level. Nevertheless, this can have some functional significance for the estrogen-dependent growth of breast cancer tissue.

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. / Neoad''iuvantnoe primenenie ingibitora aromatazy letrozola pri rake tela matki: éndokrinnye i klinicheskie éffekty.

Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.

[Aromatase (estrogen synthetase) gene expression in human leukocytes]. / Ekspressiia gena aromatazy (éstrogensintetazy) v leikotsitakh cheloveka.

Extragonadal aromatization plays an important role in many physiological and pathological conditions. It has been found that incubation of the peripheral blood mononuclears in the RPMI-1640 medium with 10% fetal calf serum during 48 hrs is able to induce the aromatase gene expression. The latter did not occur in 11 samples of mononuclears of the intra-tissue leukocyte infiltration which finding needs further investigation. The data obtained suggest that the possibility of the aromatase gene induction in leukocytes is associated with the cellular fraction capable of the substrate adhesion.

[Aromatase gene expression and its modifying factors in breast tumor tissue]. / Ekspressiia gena aromatazy i modifitsiruiushchie eë faktory v tkani opukholei molochnoi zhelezy.

Aromatase (CYP 19) gene expression was studied in 70 breast tumors. When RNA-dot-blot or rt-polymerase chain reaction were used expression frequency was 60.4 and 91.7%, respectively. An analysis of individual variants of non-coding exon of aromatase gene confirmed that, unlike normal mammary tissue, tumor switched from activation of exon I.4 ("sensitive" to glucocorticoids) to exons II ("sensitive" to cAMP) or I.3. This difference was relatively somewhat more pronounced in the Russian material. Direct correlation between aromatase enzymatic activity and expression of exons II and I.3 in tumor tissue appeared more significant than that of aromatase gene coding site. An evaluation of the expression of adenylate cyclase G-protein alpha-subunit genes established an inverse correlation between expression of Gi2a and exon I.3. Breast tumors with elevated basal aromatase activity were more sensitive to aromatase inhibitors (letrozole, 4-OHA) in vitro although no relationship between use of CYP19 (aromatase) 5' exon variant and in vitro inhibition of aromatase was detected. A correlation was observed between expression of aromatase gene and variants of its 5' exon, on the one hand, and age, tumor grade, steroid receptor presence and tumor lymphocytic infiltration, on the other. To summarize, local estrogen production in breast tumor tissue is regulated by a wide range of factors expression both aromatase gene influencing and its enzymatic activity, thus providing leverage on both.

[Distraction osteosynthesis in occlusive diseases of the limb arteries]. / Distraktsionnyi osteosintez pri okkliuziruiushchikh zabolevaniiakh arterii konechnostei.

The method of distraction osteosynthesis was used in 265 patients with arterial occlusions of the upper and lower limbs, which developed due to obliterative thromboangiitis and atherosclerosis. Surgical treatment of patients with distal type of occlusive disease of the arteries was followed by steady compensation of ischemic disturbances after bone chip formation and its dosage across transfer with formation of distraction regenerate transforming into mature osseous tissue. Favourable results of the treatment were observed in 236 patients (88.9%). They persisted during 3 years in 86% of patients. Analysis of outcomes after treatment demonstrated the best results in patients with grade II ischemia. Distraction osteosynthesis ensured protracted remission of the disease and elimination of its symptoms.

Ability of lymphocytes infiltrating breast-cancer tissue to convert androstenedione.

Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL.

[Correlation between tumor tissue aromatase, histological pattern and reproductive status in patients with breast cancer]. / Sviaz' aktivnosti aromatazy v opukholevoi tkani s kharakteristikoi zabolevaniia i pokazateliami reproduktivnogo statusa u bol'nykh rakom molochnoi zhelezy.

Aromatase levels were measured in tumor tissue vis-a-vis clinico-morphological patterns of tumor, menopausal status and sex hormone concentration in blood in 50 patients with breast tumors. The test was based on heavy water release from 1 beta-3H-androstenedione. Direct correlation was established between aromatase concentration, on the one hand, and tumor size, cell differentiation status and blood-testosterone on the other. The data point to the role of aromatase concentration in situ during breast tumor genesis, its dependence on hormonal environment of tumor and its presence in breast tumor cells.

[Aromatase activity and its gene expression in tumor tissue of smokers and non-smokers with breast cancer]. / Aktivnost' aromatazy i ékspressiia eë gena v opukholevoi tkani u kuriashchikh i nekuriashchikh bol'nykh rakom molochnoi zhelezy.

Tissue was sampled from 121 tumors of the breast. The activity of aromatase (estrogen synthetase) was assessed by radiobiochemical means in 61 cases; gene expression was evaluated with the aid of polymerase chain reaction in 14 and the same--by the dot-blot procedure in 46 patients. Inveterate smokers (15 years and more) made up 16.5%. The smokers revealed a distinct tendency towards aromatase activity decreasing in tumor tissue (chiefly in menopausal patients) as well as lower intensity of aromatase gene expression assessed in terms of polymerase chain reaction. Alongside with other evidence, our finding point to long-term-smoking-related sensitivity of intratissular estrogen synthesis being higher than in general circulation. It also demonstrated local aromatization inhibition in tumor tissue, the latter being a possible mechanism which causes tumor tissue hormone sensitivity to change in smokers and affects course of disease.

[Metabolism of the androgenic precursor androstenedione and effects of aromatase inhibitors in cultured blood lymphocytes]. / Metabolism androgennogo predshestvennika androstendiona i vliianie na nego ingibitorov aromatazy v kul'tiviruemykh limfotsitakh krovi.

Blood lymphocytes from 26 women were cultivated in RPMI-1640 for 72 hrs with or without dexamethasone, dbcAMP, and TPA. Androstenedione conversion was most often activated by the dbcAMP, then by Dex and TPA. Response to dbcAMP was most obvious in women under 50, whereas response to Dex--in women over 50. Aromatase inhibitor fadrosol displayed a tendency towards prevention of the activation of androstenedione conversion in cultivated lymphocytes. A possibility of aromatase gene induction in cultivated lymphocytes cannot be completely excluded and demands further investigation with the aid of molecular-genetic methods.