[Dynamics of platelet hemostasis indices in patients with cardioembolic stroke against the background of atrial fibrillation]. / Dinamika pokazatelei trombotsitarnogo gemostaza u patsientov s kardioembolicheskim insul'tom.

OBJECTIVE: To study the parameters of platelet hemostasis in patients with cardioembolic ischemic stroke on the background of atrial fibrillation and taking warfarin to assess the effectiveness of antiplatelet drugs in the prevention of recurrent ischemic strokes. MATERIAL AND METHODS: 93 patients with ischemic stroke on the background of atrial fibrillation were examined, of which the main group consisted of 43 patients who took warfarin and 50 patients from the reference group without warfarin. The study of the platelet link of hemostasis using inductors (adrenaline, ristomycin, arachidonic acid, collagen, ADP) in patients of both groups was carried out. In the group of patients taking warfarin there was a significant increase in platelet aggregation for adrenaline up to 57.15 [29.51; 62.61] (p=0.0315), spontaneous aggregation 2.46 [1.39; 6.75] (p=0.047), reduction of platelet aggregation for collagen 14.45 [4.80; 43.63] (p=0.008). In 35 patients of the study group (n=93), laboratory resistance to aspirin was also revealed in terms of platelet aggregation to arachidonic acid, which is a criterion for evaluating the effectiveness of preventive measures for recurrent ischemic strokes with antiplatelet drugs. CONCLUSION: The obtained data are additional risk factors for recurrent strokes. It is also recommended to study platelet aggregation for arachidonic acid to assess the effectiveness of antiplatelet drugs prophylaxis of recurrent ischemic strokes.

[A clinical and genetic analysis of risk factors for the development of acute and chronic cerebral ischemia]. / Kliniko-geneticheskii analiz faktorov riska razvitiia ostroi i khronicheskoi ishemii golovnogo mozga.

To study the association between polymorphic markers in the ACE, SERPINE1, FGB, F5, F7, F12, GP1BA, GPIIIa, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS2, HIFla, LTA, ALOX5AP genes and clinical characteristics of acute and chronic forms of circulatory disorders of the brain. MATERIAL AND METHODS: The analysis of polymorphic variants in ACE, FGB, F5, F7, F12, GP1BA, GPIIIa, SERPINE1, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS3, PDE4D, HIF1a, LTA, ALOX5AP in 81 patients with chronic cerebral ischemia (CCI) and 69 patients with ischemic stroke (IS), and their interrelation with clinical manifestations of disease were investigated. RESULTS AND CONCLUSION: The association between the T/T genotype of the PDE4D SNP 83C>T polymorphism and a rapid progression of hypertensive disease (GB) was revealed (OR=6.22, CI=1.86-20.79, p=0.0036) in the group of patients with CCI. The association of the allele D and the DD genotype of the ACE (I>D, rs1799752) with cardioembolic stroke (OR=2.67, 95% CI=1.23-5.8, p=0.02 and OR=7.14, 95% CI=1.72-29.69, p=0.0057) was found. When comparing subgroups of patients with different degrees of stenosis of brachiocephalic arteries (BCA), the association of the allele C and the TC genotype of the GP1BA (rs2243093, -5T/C) with BCA occlusion and expressed hemodynamically significant stenosis (>75%) was revealed (OR=3.39, 95% CI=1.12-10.25, p=0.03 and OR=4.44, 95% CI=1.27-15.54, p=0.023, respectively). Thus, polymorphic markers in PDE4D, ACE, GP1BA in combination with certain clinical characteristics are risk factors for the progression of CCI and development of IS.

[The state of microcirculation and platelet hemostasis in patients with ischemic stroke after systemic thrombolytic therapy]. / Sostoianie mikrotsirkuliatsii i trombotsitarnogo zvena gemostaza u patsientov s ishemicheskim insul'tom posle provedeniia sistemnoi tromboliticheskoi terapii.

AIM: The state of microcirculation and platelet hemostasis in patients with ischemic stroke after systemic thrombolytic therapy. MATERIAL AND METHODS: Forty-two patients after systemic thrombolytic therapy (TLT) (mean age 64.26 [60.58; 68.06]) and 47 patients without TLT (54.52 [47.48; 60.83]) were studied. The study of platelet hemostasis was conducted with the determination of platelet aggregation (AT) on adrenaline, ADP, ristomycin, spontaneous aggregation on days 1, 7 and 14. Studies of the state of microcirculation of cerebral vessels were carried out using the laser Doppler flowmetry (LDF). RESULTS AND CONCLUSION: Characteristics of changes in induced AT and parameters of the microcirculation system in patients after systemic TLT at 1, 7 and 14 days in comparison with the indices of patients without TLT were revealed that allowed to expand the understanding of pathological mechanisms of the microcirculatory bed, their connection with violations of central hemodynamics and to obtain additional markers of disease course and prognosis.

A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours.

BACKGROUND: Two strategies to interrogate the insulin growth factor 1 receptor (IGF-1R) pathway were investigated: vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation, angiogenesis, and stem cell propagation. METHODS: A phase I, multi-cohort dose escalation study was conducted in patients with advanced solid tumours. Patients received dalotuzumab (10 mg kg(-1)) and escalating doses of MK-2206 (90-200 mg) or escalating doses of dalotuzumab (7.5-10 mg kg(-1)) and MK-0752 (1800 mg) weekly. Upon maximum tolerated dose determination, patients with low-RAS signature, high-IGF1 expression ovarian cancer were randomised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus, whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752. RESULTS: A total of 47 patients were enrolled: 29 in part A (18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm) and 18 in part B (6 in each arm). Dose-limiting toxicities (DLTs) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction, maculopapular rash, and gastrointestinal inflammation. For dalotuzumab/MK-0752, DLTs included grade 3 dehydration, rash, and diarrhoea. Seven patients remained on study for >4 cycles. CONCLUSIONS: Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable. Further developments of prospectively validated predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed.

[The results of a joint project of the State Department of Ukraine on the Implementation of Punishments and UNAIDS to decrease the risk of the spread of HIV in the prisons of Ukraine]. / Rezul'taty sovmestnogo proekta gosudarstvennogo departmenta Ukrainy po voprosam ispolneniia nakazanii i IuNEIDS po snizheniiu riska rasprostraneniia VICh v mestakh lisheniia svobody Ukrainy.

During the period of 1987-1999 altogether 7,800 cases of HIV infection were detected among the prisoners of the penitentiary institutions of the Ukraine. In 1997 the penitentiary system of the Ukraine abolished the mandatory testing and isolation of HIV-positive persons. In April 1998 the realization of measures aimed at reducing the spread of HIV infection started in the penitentiary system. The main trends in the activities aimed at the realization of the Project were information and educational work among prisoners both during investigative detention and after conviction, as well as among the personnel of penitentiary institutions; availability of condoms and disinfectants; ensuring the possibilities of voluntary testing for HIV, as well as pre- and post-test counselling.

[HIV infection in the penitentiaries of Ukraine]. / VICh-infektsiia v mestakh lisheniia svobody Ukrainy.

In connection with a sharp increase of the number of HIV-infected persons in the Ukraine the natural growth of the number of such persons in penitentiary institutions was registered, starting from 1995 (455 persons in 1995, 2,937 persons in 1996, 2,779 persons in 1997 and 173 persons during 5 months of 1998). 83% of HIV infection persons were drug addicts introducing drugs intravenously. In 1997 the strategy of decreasing the risk of infection in penitentiary institutions was worked out in collaboration with UNAIDS experts: repressive and isolation measures were replaced with measures aimed at the "decrease of harm". Special attention is given to circumstances aggravating the epidemic situation in HIV infection, and particularly at the sharp growth of morbidity in tuberculosis and syphilis (10.6 and 10.3 times respectively in 1997 in comparison with 1993). In addition, in 1997 the number of person having drug addiction was noted to increase 2.3 times in comparison with 1993. The necessity of taking constant information and educational measures aimed at decreasing the risk of the spread of HIV infection is emphasized.