17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression.

To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-ß deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.

[Special features of coronary artery involvement in women with rheumatoid arthritis].

Aim of the study was to assess the state of coronary arteries and to reveal peculiarities of their involvement in women with rheumatoid arthritis (RA). We examined 51 women: 30 patients with RA and 21 women of the control group. Average age of patients with RA was 49+/-7.4, of control subjects - 47+/-9 years. Examination of coronary arteries was performed by a 64-spiral computer tomography (LightSpeed VCT, GE). Coronary calcium was assessed using the SmartScore and calcium score by the Agatston scale. Different changes of coronary arteries were diagnosed in 44% of patients with RA and in 19% of subjects of the control group. Coronary atherosclerosis was detected in 34%, calcification of coronary arteries - in 27% of patients with RA. Average degree of coronary artery stenosis in patients with RA was 2.2 times greater than in the control group. In RA prevailed multiple involvement of coronary arteries with large number of atherosclerotic plaques. Hemodynamically significant stenoses were diagnosed only in patients with RA.

[Relationship between changes in brachiocephalic arteries and osteoporosis in women with rheumatoid arthritis].

This study included 50 women with rheumatoid arthritis (mean age of 50.6 +/- 6.4 years) examined by duplex scanning of brachiocephalic arteries and double-energy X-ray absorptiometry. 56% of patients had changes in brachiocephalic arteries, 62 % suffered osteoporosis and osteopenia. The inverse relationship between the thickness of the intima-media complex of brachiocephalic arteries and bone mineral density in the proximal part of the femur and lumbar spine was documented.

[On the polypathias in males].

The structure and prevalence of polypatias (i.e. three and more diseases in single person), their qualitative and quantitative characteristics were investigated on the basis of comprehensive population study of 1050 males aged from 18 and older in unorganized rural population. It is established that in the structure of chronic infectious diseases the share of persons with multinozoology constituted 65.3%? with binozoology--18% and with mononozoology--16.7%. The prevalence level of multinozoology among males constituted 604.7 per thousand? binozoology--166.8 per thousand and mononozoology--154.4 per thousand. The leading positions among multinozoologies are taken by the circulatory system diseases (428.0 per thousand), respiratory system diseases (400.4 per thousand) and digestive system diseases (368.9 per thousand). This fact proves the leading role of the diseases of those classes in the development of polypatias.

Progressive Multifocal Leukoencephalopathy Following Combined Rituximab-Based Immune-Chemotherapy for Post-transplant Lymphoproliferative Disorder in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), an opportunistic infection due to reactivation of JC virus. Post-transplant lymphoproliferative disorders (PTLDs) represent a common malignancy in this population, and antiCD20-therapy has become an established component of its treatment. CASE PRESENTATION: We describe the first case of a renal allograft transplant recipient with PTLD who received rituximab-based immune-chemotherapy and developed PML shortly thereafter. Despite early suspicion and diagnosis, the disease ran a relentlessly progressive course, and the patient succumbed to his illness shortly thereafter. CONCLUSION: PML should be strongly suspected whenever unusual neurologic symptoms appear in the context of immunosuppression. Clinicians and patients should be aware of the potential for PML after rituximab therapy.

[Diagnostic potential of the first ECG derivative in assessing the coronary artery status of patients with ischemic heart disease]. / Diagnosticheskie vozmozhnosti pervoi proizvodnoi EKG v otsenke sostoianiia koronarnykh arterii u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The results of the maximal rate of heart ventricle activation (HVA) determined according to the ECG readings and its first derivative were compared in 38 patients suffering from coronary disease (CD) with the coronarography data. 54 healthy men without the clinical and bicycle ergometry signs of CD were examined as control. In patients with angina pectoris, postinfarction cardiosclerosis and acute myocardial infarction, there was a significant decrease of HVA. As the rate of the degree of coronary artery stenosis increased, there was a progressive reduction of the rate of HVA.

[Impact of Bestim on the immunological status and clinical course of ulcer]. / Vliianie bestima na immunologicheskii status i klinicheskoe techenie bolezni.

Ulcer disease is accompanied by all immune responses with the development of secondary immune deficiency. This makes it necessary to include immunomodulators into the complex antiulcer treatment. The application of a new drug Bestim in the combined antiulcer treatment affects the immune state of the patients favourably. It decreases the inflammatory effect in the stomach and duodenal mucosa, it precipitate regress of clinical symptoms and scarring of the ulcer.

[Duplex scanning of brachiocephalic arteries and multislice spiral computed tomography of coronary arteries in the comprehensive evaluation of the arteries in women with rheumatoid arthritis].

Comprehensive examination was made in women (mean age 49.6 +/- 7.4 years) with rheumatoid arthritis diagnosed abnormalities of brachiocephalic and coronary arteries in 86% of cases. Duplex scanning of brachiocephalic arteries revealed changes in 82% of the women. 64-section spiral computed tomography established coronary artery abnormalities in 33% of cases. There were isolated changes in the brachiocephalic arteries in 50% of the patients, a concomitant lesion of the brachiocephalic and coronary arteries in 32%, and isolated changes in the coronary arteries in 4%. A direct correlation was found between the index of coronary artery calcification and the intima-media thickness of brachiocephalic arteries.

[Orbital lymphoma].

INTRODUCTION: Orbital lymphomas are neoplasms with increasing incidence in recent years in immunocompromised, as well as immunocompetent patients, which defines their social importance. AIM: To describe and analyze the experience of the University hospital "'Sv. Ivan Rilski" with the treatment of this pathology for the period 1997-2008. MATERIAL AND METHODS: Fourteen patients (8 females, 6 males - 13 primary orbital lymphomas, 1 systemic lymphoma). Mean age at diagnosis was 65.6 years (from 50 to 80 years). In 2/3 of the patients the lesion was localized in left eye, without a case with bilateral orbital involvement. Seven cases the diagnosis was made 6 months from the onset of symptoms, 5 cases - 1 year and 2 cases - more than one year. The most common clinical symptoms were exophthalmus (12 case), tumor or bulging mass of the eyelid - 8, diplopy - 6, decreased visual acuity - 5. Intraconal localization of the tumor was in 6 cases, extraconal - 2. intra-extraconal - 6. The diagnosis was made by neuro-ophthalmologist and precised with the aid of CT and MRI. All the patients were operated on with the following approaches - fronto-orbital - 9 cases, lateral - 3, anterior orbitotomy (without bone resection) - 2 cases. In six cases "'gross total" resection was achieved, in the rest of the cases the resection was partial. On histological examination, a high grade lymphoma was established in 2 cases with primary orbital lymphoma and one case with systemic lymphoma. All other cases were diagnosed as low-grade B-call small lymphocytic non-Hodgkin's lymphoma. Long-term survival (over 5 years) was observed in 4 cases with primary lymphoma, whereas the patient with systemic form of the disease died 10 months after the operation.