Diagnostics of Fabry disease in arrhythmology practice: a case report

Heart failure in Fabry disease (FD) is unfavorable prognostic manifestation and cause of death. Given that the disease is rare in clinical practice, the low awareness of physicians about this pathology leads to its late diagnosis and the lack of pathogenetic therapy.Aim. To present a clinical picture of the cardiovascular phenotype in FD in order to increase the awareness of doctors about this disease.Material and methods. In this clinical case, an asymptomatic FD course up to 46 years of age and mani festation in the form of arrhythmia were observed. According to echo car dio graphy, severe left ventricular hypertrophy (myocardial mass index, 214 g/m2) without signs of left ventricular (LV) outflow tract obstruction and left atrial (LA) dilatation were revealed (LA volume index — 47 ml/m2). Right ventricular (RV) and LV systolic function was assessed using two-dimensional speckletracking strain echocardiography. Latent subclinical RV and LV systolic dysfunction was established.Results.  Tandem mass spectrometry revealed a sharp decrease in alphagalactosidase activity of 0,03 umol/L/h (norm range, 0,80-15,00 umol/L/h), as well as an in creased Lyso-GB3 concentration of 95,18 ng/ml (normal range, 0,05-3,0 ng/ ml). A molecular genetic study of blood samples was carried out. By direct automatic sequencing of the GLA gene, a variant of the c.1229 C>T nucleotide sequence was identified, leading to the replacement of p.Thr4101le in the hemizygous state.Conclusion. This case shows the possibility and expediency of diagnosing FD in cardiology practice in patients with LV myocardial hypertrophy of unclear etiology, while atypical variants can be diagnosed only by molecular genetic testing

Опыт успешного применения плазменных потоков при лечении обширной постинъекционной флегмоны у больной наркоманией

The usage of home-made narcotic in RF, the main variant of which is intravenous administration, has increased greatly for the last ten years. According to such poor statistics a number of patients with pyoinflammatory complications after injections is increasing as well. The results of group of patients with complex treatment are significantly improving while using additional physical methods in management of wound, and here plasma technology has a special place. The described case shows a successful usage of plasma flows from different sources in dissection and stimulation in difficult clinical situations.Употребление кустарно приготовленных наркотиков в РФ, основным способом введения которых является внутривенный, за последнее десятилетие увеличилось в несколько раз. В соответствии с этими неутешительными данными растет и число больных с постинъекционными гнойно-воспалительными осложнениями. Результаты комплексного лечения приведенной группы пациентов значительно улучшаются при использовании дополнительных физических методов обработки ран, среди которых особое место занимает плазменная технология. Представленный случай демонстрирует успешное использование плазменных потоков из различных источников в режимах диссекции и стимуляции в сложной клинической ситуации

MUSCULOSKELETAL SYSTEM IN THE ENDOGENOUS HYPERCORTISOLISM

The authors review the current literature data on the pathogenesis, clinical manifestations and treatment of glucocorticoid induced osteoporosis in patients with endogenous hypercortisolism. High levels of glucocorticoids lead to bone loss, bone quality deterioration and low traumatic fractures as a consequence of reduced bone formation. In addition to this, muscle weakness and sex steroids hormone abnormalities increase the risk of falls and fractures. The new available data on possible mechanisms of these changes including the involvement of RANKL/RANK/OPG, Wnt-betacatenin signaling pathway and pathogenesis of myopathy are discussed. This review also outlines the practical recommendation and new questions that should be evaluated in future research

DINAMIKA MINERAL'NOY PLOTNOSTI KOSTI, MARKEROV KOSTNOGO OBMENA I KAChESTVA ZhIZNI PATsIENTOV S ENDOGENNYM GIPERKORTITsIZMOM POSLE DOSTIZhENIYa REMISSII ENDOGENNOGO GIPERKORTITsIZMA

This study estimates the recovery of bone mineral density (BMD), markers of bone remodeling and quality of life in patients with endogenous Cushing’s syndrome (CS) after 12 months of achieving remission. Materials and methods: 21 patients with CS were prospectively evaluated at active stage of the disease and after being in a full remission (substitutional therapy with hydrocortisone or normal 24 hours urinary free cortisol (24h UFC) and late-night cortisol) during 12 months.A thoracic and lumbar X-ray was performed to reveal vertebral fractures. Bone mineral density (BMD) was measured by DXA ((Prodigy, Lunar, GE, USA). The level of 24h UFC was measured on a VitrosECi. Late-night serum cortisol and markers of bone remodeling were assayed by ECLIA Cobas e601 Roche. Patients fulfilled EQ-5D, ECOS-16 questionnaires and performed "up-and-go ”, "tandem ” and "chair-rising ” tests. Results: Among enrolled patients 17 (80%) were females and 4 (20%) - males; median of age (Q25-Q75) - 41 (33-49) years old; in 10 cases (48%) low traumatic fractures were diagnosed: 7 patients suffered from vertebral fractures; in 3 cases - ribs fractures. After the achieving remission no new fractures were registered and significant improvement in Z-score was reviled at all regions: L1-L4 -1,8 [-2,6; -0.5] at active stage vs -1,2 [-2,2; -0.5] after 12 months of remission (p=0.05); Neck Z-score -0,9 [-1,7; - 0,8] vs -0,7 [-1,6; -0,3], (p=0,003). The level of both bone metabolism markers increased: osteocalcin from 8,2 (6,912,0) to 22,7 (12,1-36,5) ng/ml (p=0,01) and CTx from 0,35 (0,22-0,63) to 0,7(0,28-1,05) ng/ml (p=0,01); whereas 24hUFC decreased from 1449 (926,4-2371) nmol/24h to 66,4(54,2-76,4) nmol/24h (p=0,01). The quality of life significantly improved at all dimensions if measured by ECOS-16. According to the EQ-5D patients suffered less from pain 1,35 (0,49) vs 1,12 (0,34), (p=0,04) and reported the improvement in their health (visual analogue scale) from 49 (18,9) to 68 (10,9), (p=0,004), but did not differ in others dimensions. Although 100% of patients admitted the improvement in their functional ability, the difference in functional tests did not reach statistical significance. Conclusions: Achieving the remission of CS improves BMD and quality of life in patients with CS. However, longer time is needed for full recovery, including the functional performance

PROCESS FOR MANUFACTURING ALUMOMAGNESIAN SPINEL

FIELD: inorganic chemistry. SUBSTANCE: magnesium chloride solution is mixed together with solution containing basic aluminum chloride, Al2(OH)4,35Cl1,65, with their concentration being at least 2.5 and 1.25 M, respectively. The alkaline nature of basic aluminum chloride solution used in the combined solution promotes the hydrolysis of magnesium chloride and makes use of neutralizing agent unnecessary. The hydrolysis of magnesium chloride assists in aluminum hydroxyl-ion association which is one of the stages of solid phase transfer. This allows spinel crystallization to conduct at reduced temperatures. The resulting precipitated product is evaporated at temperatures of 600 to 1100 C. EFFECT: high purity and yield of the end product. 1 tbl.Использование: при изготовлении изделий, стойких в химически агрессивных средах, в области высоких температур, до 2100С. Сущность изобретения: для смежения берут растворы хлорида магния и основного хлорида алюминия состава Al2(OH)4,35Cl1,65, концентрацией не менее 2,5 М и 1,25 М соответственно. Использование раствора основного хлорида алюминия, имеющего щелочную среду, обусловливает интенсификацию процессов гидролиза хлорида магния в смешанном растворе и исключает необходимость использования нейтрализующего агента. Гидролиз хлорида магния способствует ионной ассоциации гидроксоионов алюминия, которая является одной из стадий образования твердой фазы, что обеспечивает возможность кристаллизации шпинели при пониженных температурах. Прополку осадка ведут при 600 - 1100С. Обеспечивается, практически, 100% использование алюминия и магния, снижается количество неутилизируемых отходов, а также повышается чистота получаемого продукта. 1 табл

LOW-TRAUMATIC FRACTURES IN PATIENTS WITH ENDOGENOUS HYPERCORTISOLISM. PREDICTORS AND RISK FACTORS, THE IMPACT ON QUALITY OF LIFE

The objective of this study was to investigate the prevalence of low traumatic fractures, the factors influencing fractures in endogenous Cushing’s syndrome (CS) of various etiologies and their contributions into functional abilities and quality of life in patients with CS. Materials and methods: the retrospective data of patients, who had received treatment due to endogenous CS, (2001-2011), was evaluated. All enrolled patients underwent standard spinal radiographs in lateral positions of the vertebrae Th4-L4. Recent low traumatic non-vertebral fractures were recorded in the medical cards. Bone mineral density (BMD) was measured by DXA GE Lunar Prodigy. Serum samples on octeocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), latenight cortisol in serum were assayed by electrochemiluminescence (ECLIA). 24h urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether). Functional assessment was performed using «chair rising», «up and go» and «tandem» tests. Universal pain assessment tool (verbal descriptor scale, Wong-Baker facial grimace scale, activity tolerance scale), EQ-5D and ECOS-16 questionnaires were given to patients and they self-reported their conditions. Results: Among 215 patients, 178 were females and 37 males, median age 35 (Q25-Q75 27-48); 88patients (40,9%) had low traumatic fractures, including vertebral fractures in 76 cases (in 60 cases multiple vertebral fractures) and non-vertebral fractures in 27 cases (17 patients had rib fractures, 3 -fractures of metatarsal bones, 2 fractures of radius, 2 fractures of tibia and fibula, 1 humerus, 1 breastbone; 1 hip fracture). Patients with fractures had higher 24hUFC, late-night cortisol in serum, lower OC, Total Hip BMD, but did not differ in age, BMI, CTx or etiology of CS. After applying the logistic regression analysis (adjusted for sex, age, BMI, BMD, OC), the main predictor of fractures was late-night serum cortisol level (p=0,001). Patients with late-night serum cortisol higher than 597 nmol/l were more likely to have low traumatic fractures (Odds ratio 2,86 (95%CI 1,55-5,28) p=0,001). Patients with fractures suffered from more pain and reported worse functional abilities. They had slightly worse results in «tandem» test, but did not differ in other functional tests, which assessed mainly muscle power. Conclusions: Patients with CS have very high risk of low traumatic fractures. The severity of hypercortisolemia is the best predictor of low traumatic fractures in patients with CS. Patients with fractures sufferedfrom more severe pain and because of this they restricted their daily activity even more than patients with CS without fractures. Consequently, patients with higher levels of late-night serum cortisol need earlier preventive treatment for osteoporosis

RELAPSE PREVENTION AND IMPROVEMENT OF RESULTS OF COMPLEX ARRHYTHMIAS’ SURGICAL CORRECTION IN CARDIAC PATIENTS

Aim: To examine results of surgical intervention in cardiac surgery patients with atrial fibrillation after a loading pre-operative dose of amiodarone.Material and methods: The study included 49 cardiac patients with atrial fibrillation who underwent a surgery during a 14 months’ period in 2013–2014. Group 1 (n = 23) received preoperative amiodarone saturation at a dose 0.6–1.0 g daily with a maintenance dose 0.4 g daily in early postoperative period and at a dose 0.2 g daily up to 6 months after surgery. Group 2 (control, n = 26) was on a postoperative maintenance dose of amiodarone 0.6–1.0 g daily.Results: Stable sinus rhythm after left atrial Maze IV procedure was established in 44/49 of patients (90%). Atrial fibrillation relapsed in 1 patient from group 1 and in 4 patients from group 2. All 5 patients with recurrence of persistent atrial fibrillation had a long-term persistent arrhythmic history of more than 3 years, and echocardiography revealed left atrial dilatation of more than 6 cm.Conclusion: The use of saturating doses of amiodarone before surgery improves outcomes of left atrial Maze IV procedure (up to 95%), compared to those in the control group where amiodarone was used postoperatively (up to 85%)

SURGICAL TREATMENT OF COMPLEX ARRHYTHMIAS IN PATIENTS WITH NON-ISCHEMIC MITRAL INSUFFICIENCY

Aim: To analyze and improve efficacy of surgical treatment of patients with non-ischemic mitral insufficiency and atrial fibrillation.Materials and methods: The study included 64 patients with degenerative mitral insufficiency complicated by atrial fibrillation who had surgical interventions from 2011 to 2014. Surgical treatment consisted of surgical correction of mitral regurgitation: mitral valve reconstruction (group 1, n = 133) and mechanical prosthesis (group 2, n = 31), as well as left atrium Maze IV procedure in “box lesion” modification with the use of AtriCure bipolar destructor in both groups.Results: No postoperative deaths were registered. After surgery, all patients showed a decrease in all cardiac cavities’ sizes and of pulmonary hypertension, an improvement in left ventricular systolic function assessed by transthoracic echocardiography. During follow-up of up to 14 months’ duration, sinus rhythm was maintained in 56 (86%) of patients, whereas 9 patients had recurrent atrial fibrillation resistant to medications and electrical cardioversion. Patients, who had undergone valve preserving correction of mitral insufficiency and left atrium Maze IV procedure, had the best results as to contractility of left ventricle (7.86%), reduction of cardiac cavities’ size (end-diastolic dimension – 11.05%, end-systolic dimension – 15.15%, right atrium – 15.19%), especially that of left atrium (19.03%), reduction of pulmonary hypertension (27.75%) and significant improvement in quality of life (7 points) assessed by Minnesota Living with Heart Failure Questionnaire.Conclusion: Plastic correction of mitral insufficiency with atrial fibrillation combined with Maze IV procedure gives the highest improvement of left ventricular contractility and diminishing of cavities compared to mitral valve replacement with mechanical prosthesis in combination with Maze IV procedure

SERUM CONCENTRATIONS OF PROTEIN REGULATORS OSTEOBLASTOGENESIS AND OSTEOCLASTOGENESIS IN PATIENTS WITH ENDOGENOUS HYPERCORTICISM

Purpose. Endogenous Cushing’s syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of Wnt/ß-catenin signaling pathway (sclerostin, Dickkopf1 (Dkkl), secretedfrizzled-related protein 1 (SFRP1)) along with osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-beta ligand (RANKL) in patients with CS as compared to healthy individuals. Materials and methods. Forty patients with clinically and biochemically evident CS and 40 sex, age and body-mass index matched healthy individuals provided fasting serum samples (8:00-10:00AM) for measurement of sclerostin, SFRP1 and Dkkl, RANKL., OPG along with bone turnover markers. Serum samples on RANKL., OPG., Dkkl, SFRP1, sclerostin were frozen and then concurrently measured by an enzyme immunoassay (ELISA) using commercially available reagents. Serum samples on osteocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), cortisol in serum and saliva were assayed by electrochemiluminescence (ECLIA) Cobas e601 Roche. Urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether) on a Vitros ECi. All participants were questioned regarding any recent low traumatic fractures. Patients with CS underwent standard spinal radiographs in anterior-posterior and lateral positions of the vertebrae Th4-L4 (Axiom Icons R200 "Siemens"). Results. Patents with CS (30 (26-40) years old with 24hUFC 2575 (1184-4228) nmol/l (Me (Q25-Q75)) had suppressed OC and normal CTx levels as compared to healthy subjects. A significant correlation, which we observed between OC and CTx (po=0.724 (p<0.001)) among the healthy volunteers, weakened to a non-significant level (po - 0.285 (p=0.083)) when analyzing patients with CS only. 24hUFC correlated with OC po = - 0.464 p=0.003, but not with CTx po= 0.245 (p=0.132) in patients with CS. Patients with CS had higher sclerostin levels versus healthy control subjects (p=0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper-limits of the healthy control individuals. Sclerostin levels higher than 662 pg/ml were four times more frequent in patients with CS as compared to healthy subjects (OR=4,19, 95% CI 1,44-12,22), p=0,006. Dkk1, SFRP1 did not differ from the control group. Patients with CS had a significantly lower level of RANKL (0.083 (0.075 0.093) pmol/L) as compared to healthy subjects (0.106 (0.089 0.131) pmol/L) p<0.001. Conversely, no difference was found between the OPG level in patients with CS (6.65 (4.92-7.66) pmol/L) and healthy individuals (5.77 (5.00-6.40) pmol/L), p=0.14. RANKL was lower (p=0.02) and OPG was higher (p=0.04) in patients with CS and low traumatic fractures (n=19) versus patients without fractures (n=21). Conclusions. Patients with CS have higher sclerostin level as compared to healthy subjects. Hypercotisolism prevents the normal physiological suppression of sclerostin rather than raising its absolute level. Of all the tested proteins (sclerostin, Dkk1, SFRP1, RANKL., OPG) only sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with endogenous CS