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We present a Cadence toolkit library written in VerilogA for simulation of electro-optical systems. We have identified and described a set of fundamental photonic components at the physical level such that characteristics of composite devices (e.g. ring modulators) are created organically - by simple instantiation of fundamental primitives. Both the amplitude and phase of optical signals as well as optical-electrical interactions are simulated. We show that the results match other simulations and analytic solutions that have previously been compared to theory for both simple devices, such as ring resonators, and more complicated devices and systems such as single-sideband modulators, WDM links and Pound Drever Hall Locking loops. We also illustrate the capability of such toolkit for co-simulation with electronic circuits, which is a key enabler of the electro-optic system development and verification.

Introduction: The aim of this study was to assess the frequency and features of metabolic syndrome (MetS) in myotonic dystrophy type 1 (DM1)., Methods: We studied 66 DM1 patients (50% men, aged 41.9 ± 10.5 years, disease duration of 19.3 ± 8.6 years). New worldwide consensus criteria for MetS from 2009 were used., Results: Components of MetS were present at the following frequencies: hypertriglyceridemia 67%; low HDL cholesterol 35%; hypertension 18%; central obesity 14%; and hyperglycemia 9%. MetS was present in 11 (17%) patients. The presence of MetS was not associated with patients' gender, age, disease severity, disease duration, or CTG repeat length (P > 0.05). Patients with MetS had significantly lower total SF-36 scores as a measure of quality of life in comparison to patients without MetS (P < 0.05)., Conclusion: Although certain components of MetS were very frequent in patients with DM1, only 17% met the criteria for MetS., (© 2014 Wiley Periodicals, Inc.)

Herein we report the modulation of the properties of mesoporous silica nanoparticles (NPs) via various synthetic approaches. Three types of elaborations were compared, one in aqueous media at 25 °C, and the other two at 80 °C in water or in a water-ethanol mixture. For all these methods, an alkoxysilylated two-photon photosensitizer (2PS) was co-condensed with tetraethylorthosilicate (TEOS) in the presence of cetyltrimethylammonium bromide (CTAB), leading to five two-photon-sensitive mesoporous silica (M2PS) NPs. The M2PS NP porous structure could be tuned from radial to worm-like and MCM-41 types of organization. Besides, the 2PS precursor spatial dispersion was found to be highly dependent on both the 2PS initial concentration and the elaboration process. As a result, two-photon properties were modulated by the choice of the synthesis, the best results being found in aqueous media at 25 or 80 °C. Finally, the M2PS NPs were used for in vitro two-photon imaging of cancer cells.

Background and Purpose: Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle-specific tyrosine kinase (MuSK) MG., Methods: Human leukocyte antigen (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence-specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence-specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors., Results: Significant association of MuSK MG with alleles DRB1*14 [odds ratio (OR) 3.8], DRB1*16 (OR 3.3) (P < 0.01) and DQB1*05 (OR 2.2) (P < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects (OR 0) (P < 0.01). The HLA DRB1*16-DQB1*05 (OR 2.9) haplotype was found to be associated with MuSK MG (P < 0.05)., Conclusions: The strong association of MuSK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of MuSK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of MuSK MG, at least in our population., (© 2014 EAN.)

The aim of this study was to assess cognitive status in a large group of patients with myotonic dystrophy type 2 (DM2) compared to type 1 (DM1) subjects matched for gender and age, using a comprehensive battery of neuropsychological tests. Thirty-four genetically confirmed adult DM2 patients were recruited and matched for gender and age with 34 adult-onset DM1 subjects. All patients underwent detailed classic pen and pencil neuropsychological investigation and also computerized automated battery-CANTAB. More than half of DM2 patients had abnormal results on executive tests [Intra/Extradimensional Set Shift (IED), Stockings of Cambridge (SOC)] and verbal episodic memory (Ray Auditory Verbal Learning Test). Regarding DM1, abnormal results in more than 50 % of subjects were achieved in even ten tests, including visuospatial, language, executive, cognitive screening and visual memory tests. Direct comparison between patient groups showed that lower percentage of DM2 patients had abnormal results on following tests: Addenbrooke's Cognitive Examination-Revised, Raven Standard Progressive Matrices, Block Design, copy and recall of Rey-Osterieth Complex Figure, number of categories and perseverative responses on Wisconsin Card Sorting Test and Boston Naming Test (p < 0.01), as well as Trail Making Test-B and Spatial Span (p < 0.05). Our results showed significant dysexecutive syndrome and certain impairment of episodic verbal memory in DM2 patients that are reflective of frontal (especially frontostriatal) and temporal lobe dysfunction. On the other hand, dysexecutive and visuospatial/visuoconstructional deficits predominate in DM1 which correspond to the frontal, parietal (and occipital) lobe dysfunction.

Introduction: Myasthenia gravis (MG) may be associated with extrathymic malignancies, especially in patients with thymoma., Aim: To determine the frequency and type of extrathymic malignancies in MG patients from the Belgrade area, and to identify potential risk factors associated with tumors., Patients and Method: The study comprised 390 patients with MG. Different sociodemographic and clinical variables potentially associated with extrathymic neoplasms were analyzed., Results: Extrathymic malignancies were present in 42 (10.8%) MG patients - 22 (52.4%) males and 20 (47.6%) females. The most frequently detected were breast (40%) and lung (40%) neoplasms. The tumors appeared with similar frequency before (45.2%) and after the onset of MG (42.9%). Significant predictors for the development of extrathymic malignancies were current age (p = 0.001) and immunoglobulin (IVIg) therapy (p = 0.021). On the other hand, current age (p=0.001), longer MG duration (p = 0.001) and generalized form of MG (p = 0.002) were significant predictors of malignancy occurring after the MG onset., Conclusion: Our study revealed that older MG patients, as well as those with longer duration of the disease, and those who received IVIg therapy had a higher oncogenic risk for the development of extrathymic malignancies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To assess an impact of cognitive and behavioral impairment on QoL in a larger cohort of patients with DM1., Methods: Sixty six genetically confirmed DM1 patients (22 with juvenile (jDM1) and 44 with adult form (aDM1) of the disease) were recruited. Following behavioral tests were used: Hamilton scales for depression and anxiety (HamD and HamA), Daytime Sleepiness Scale (DSS), and Krupp's Fatigue Severity Scale (FSS). Patients also underwent detailed classic neuropsychological investigation and Cambridge Neuropsychological Test Automated Battery (CANTAB). Individualized Neuromuscular Quality of Life questionnaire (INQoL) was used as a measure of QoL., Results: Patients with jDM1 scored lower than aDM1 patients regarding total INQoL score and all INQoL subdomains, except for myotonia. Significant predictors of total INQoL score in patients with jDM1 were severity of fatigue (β=+0.60, p<0.01) and percentage of correct responses on Spatial Recognition Memory test from CANTAB that measures visuospatial abilities (β=-0.38, p<0.05). The most important predictors of total INQoL score in patients with aDM1 were severity of fatigue (β=+0.36, p<0.05) and level of education (β=-0.29, p<0.05)., Conclusion: Our results showed clear influence of different central manifestations on QoL in patients with both aDM1 and jDM1., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: In this study we analyzed transcranial sonography (TCS) in patients with myotonic dystrophy type 1 (DM1)., Methods: This cross-sectional study included 66 DM1 patients and 55 matched healthy controls (HCs). Echogenicity of the brainstem raphe (BR) and substantia nigra (SN) and third ventricle width (DTV) were assessed by TCS., Results: BR hypoechogenicity was more common in DM1 patients than in HCs (37.7% vs. 7.8%, P < 0.01). Patients with depression or fatigue were more likely to have BR hypoechogenicity (80.0% vs. 29.4%, P < 0.01 and 51.9% vs. 24.2%, P < 0.05, respectively). Both hypoechogenicity and hyperechogenicity of SN were more frequent in DM1 patients than in controls (26.2% vs. 10.9% and 13.1% vs. 1.8%, respectively, P < 0.01). DTV was increased in DM1 patients compared with HCs (6.0 ± 1.4 vs. 4.9 ± 0.9 mm, P < 0.01)., Conclusion: TCS can offer new insight into structural changes of several cerebral areas in patients with DM1., (Copyright © 2014 Wiley Periodicals, Inc.)

Objectives: To analyze frequency and type of personality pattern in patients with myotonic dystrophy type 1 (DM1), to correlate these findings with clinical data, and to assess its possible influence on quality of life (QoL)., Materials and Methods: This cross-sectional study comprised 62 patients with DM1. Following measures were used: Muscular Impairment Rating Scale, Raven's Standard Progressive Matrices (RSPM), Millon Multiaxial Clinical Inventory I (MMCI), SF-36, and Individualized Neuromuscular Quality of Life (INQoL) questionnaires., Results: The presence of at least one pathological personality trait with score above 85 on MMCI was found in 47 (75.8%) patients. After clinical interview, 36 (58.1%) subjects had significant personality impairment. The most common personality trait in our cohort of patients was dependent found in 51.6% of patients, followed by paranoid (38.7%). Higher score on dependent personality scale correlated with lower education (rho = -0.251, P = 0.049). Dependent personality scores significantly differed between patients with physical and intellectual work (93.1 ± 8.9 vs 66.9 ± 31.7, P = 0.011). Paranoid score was higher in patients with lower education (rho = -0.293, P = 0.021), lower score on RSPM test (rho = -0.398, P = 0.004) and larger number of CTG repeats (rho = 0.254, P = 0.046). Presence of dependent personality was not in association with QoL scores (P > 0.05). On the other hand, patients with paranoid personality trait had worse QoL than those without it (P < 0.05)., Conclusion: Almost 60% of our patients with DM1 had clinically significant personality impairment, with dependent and paranoid personality patterns being the most common. Paranoid personality may decrease QoL in these patients, which gives us new opportunities for symptomatic therapy in DM1., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: The aim of the present study was to analyze cerebrospinal fluid (CSF) levels of total tau (T-tau), phosphorylated tau (P-tau) and the 42-amino-acid form of β-amyloid (Aβ42 ) in patients with myotonic dystrophy type 1 (DM1), and their possible correlations with cognitive and behavioral manifestations in these patients., Methods: Lumbar puncture was performed in 74 patients with DM1 [27 with the childhood/juvenile form (jDM1) and 47 with the adult form (aDM1) of the disease] and 26 control subjects who were subjected to orthopedic surgery. Sandwich ELISA was used for measuring the levels of T-tau, P-tau and Aβ42., Results: The CSF level of Aβ42 was at its lowest in patients with jDM1 and at its highest in controls (P < 0.05). A tendency of T-tau and P-tau to increase was greater in aDM1 patients than in jDM1 patients and controls (P > 0.05). In both jDM1 and aDM1 patients, significant correlations were found between Aβ42 and T-tau (rho = 0.81 and rho = 0.67, respectively, P < 0.01), as well as between Aβ42 and P-tau (rho = 0.87 and rho = 0.67, respectively, P < 0.01). The Aβ42/P-tau ratio decreased with age in aDM1 patients (rho = -0.30, P < 0.05). Only the level of Aβ42 in the CSF of jDM1 patients was correlated with the size of the CTG expansion (rho = -0.53, P < 0.05). Only a few correlations were observed between levels of biomarkers and neuropsychological testing., Conclusion: The CSF level of Aβ42 was decreased in patients with jDM1, whilst the Aβ42/P-tau ratio was decreased in aDM1 patients. Positive correlations between Aβ42 , T-tau and P-tau were observed in both forms of disease. Further studies with larger cohorts of DM1 patients are necessary., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the amount of mitochondrial DNA in the affected tissue (muscle, liver, brain, or kidneys). We report a case of an infant with myopathy, deafness, peripheral neuropathy, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene.

Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disease usually diagnosed postmortem. The clinical presentation is not typical, but usually implies refractory hypertension and cardiorespiratory failure. We present a case of a newborn with IIAC who had fetal hydrops and refractory hypertension which normalized soon after initialization of peritoneal dialysis. With this case report, we wanted to highlight that peritoneal dialysis may be beneficial an effective therapeutic option for patients with IIAC and severe refractory hypertension. Until now, peritoneal dialysis was never performed in the treatment of patients with IIAC.

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults. It affects many organs and systems besides muscle. Aim of this study was to assess frequency of erectile dysfunction (ED) and hypogonadism, the correlation between them and the impact of ED on quality of life (QoL) in patients with DM1. A series of 25 men (aged from 22 to 58 years) with a diagnosis of DM1 was analyzed. Muscular Impairment Rating Scale (MIRS) was used to assess severity of muscular involvement. Erectile function was assessed using the short form of the International Index of Erectile Function test (IIEF-5). Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were assessed. All patients completed the Serbian version of the SF-36 questionnaire as a measure of health-related QoL. ED was present in 18 (72%) of patients. Seven (28%) patients were euogonadic, 16 (64%) had compensated hypogonadism and 2 (8%) had primary hypogonadism. ED was somewhat more common in patients with hypogonadism (78% vs. 57%). Mental composite score of SF-36 was lower in patients with ED (p<0.05). Our results showed that 72% of men with DM1 had ED and hypogonadism. Studies with larger number of subjects are needed to resolve cascade of events that lays behind ED in DM1. Development of therapeutic strategies may have positive impact on QoL. Substitutive therapy with androgens may be benefitial.

The aim of this study was to analyze survival, causes of death and cardiologic predictors of sudden death in a large cohort of patients with myotonic dystrophy type 1 (DM1). The study was comprised of 171 adult DM1 patients hospitalized at the Neurology Clinic in a 20-year period. Severe electrocardiographic (ECG) abnormality included at least one of the following: rhythm other than sinus, PR interval of ≥240 ms, QRS complex duration of 120 ms or more, and second-degree or third-degree atrioventricular (AV) block. Survival data were analyzed by the Kaplan-Meier test, log-rank test and Cox regression analysis. During the mean follow-up period of 9.4±5.4 years, a pacemaker was implanted in 5.8% of DM1 patients and 14% of patients died. The mean age at death was 55.6±12.5 years. The most common causes of death in our cohort were sudden death (41.7%) and respiratory failure (29.2%). The presence of palpitations (hazard ratio [HR]=4.7, p<0.05) and increased systolic blood pressure (HR=9.8, p<0.05) were significant predictors of sudden death. Among ECG parameters, severe ECG abnormality (HR=4.7, p<0.05), right bundle branch block (RBBB; HR=3.9, p<0.05) and bifascicular block (HR=5.8, p<0.05) were significant predictors of sudden death., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A soft-coated wheaten terrier was examined for lameness with subsequent identification of protein-losing nephropathy, hypoalbuminemia, hyperglobulinemia, and seroconversion to Borrelia burgdorferi. Following doxycycline therapy, the urine protein loss decreased significantly and serum albumin concentration remained close to or within the reference interval for over 3 years, contrary to the reported poor prognosis for renal disease associated with B. burgdorferi or protein-losing nephropathy of soft-coated wheaten terriers.

Background: Myasthenia gravis (MG) and myotonic dystrophy type 2 (DM2) are rare disorders individually, and their coexistence in the same patient is very rare. We present a patient in which these two diseases coexisted., Case Report: The patient complained of diplopia, fluctuating limb weakness, and difficulties in swallowing and speaking. A neurological examination revealed diplopia, facial, weakness of the neck and proximal limb muscles, dysphagia, dysphonia, and myotonia. The patient's mother had DM2 and her maternal grandfather had cataracts. MG was confirmed in our patient by positive results for neostigmine and a repetitive nerve stimulation test, and elevated serum anti-acetylcholine-receptor antibodies, while DM2 was confirmed by electromyography and genetic testing. The patient improved remarkably after treatment with anticholinesterases, corticosteroids, and azathioprine., Conclusions: This is the second reported case of the coexistence of DM2 and MG in the same patient. Since the symptoms of these two diseases overlap it is very important to keep in mind the possibility of their coexistence, so that MG is not overlooked in patients with a family history of myotonic dystrophy.

Objectives: To analyze the predictive value of anti-acetylcholine receptor antibodies (anti-AChR Ab) and anti-muscle specific kinase antibodies (anti-MuSK Ab), as well as the thymus pathology to the clinical outcome in patients with generalized myasthenia gravis (MG)., Methods: We analyzed 138 patients with generalized MG, who were thymectomized and assayed for anti-AChR Ab and anti-MuSK Ab., Results: Anti-AChR Ab were detected in 84% of patients, while anti-MuSK Ab were present in 36% of the AChR Ab negative patients. Severe forms of the disease were more frequent in MuSK Ab positive, compared to the AChR Ab positive and complete seronegative patients. Thymic lymphoid follicular hyperplasia (LFH) was present in 60%, thymoma in 23%, atrophic thymus in 9% and the normal thymus in 8% of patients. LFH was more frequent among women, while thymoma and atrophic thymus were more frequent in men. The younger patients mainly had LFH and normal thymus, while thymoma and atrophic thymus were more frequent in older patients. The mildest clinical presentation was present in patients with normal thymus, while severe forms of the disease were registered in the patients with thymoma. The AChR Ab positive patients had more often LFH and thymoma, while within MuSK Ab positive patients atrophic thymus was most common., Conclusion: The best disease outcome was observed in patients with normal thymus or LFH with anti-AChR Ab or without both types of antibodies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim: To assess health-related quality of life (HRQoL) in patients with DM1, to identify muscular, multisystemic, central and social factors that may affect QoL and to define a DM1 patient in risk of poor QoL., Patients and Method: This cross-sectional study comprised 120 DM1 consecutive patients. The following scales were used: Multidimensional Scale of Perceived Social Support (MSPSS), Muscular Impairment Rating Scale (MIRS), battery of neuropsychological tests, acceptance of illness scale (AIS), Hamilton rating scale for depression (Ham-D), Krupp's Fatigue Severity Scale (FSS), Daytime Sleepiness Scale (DSS) and SF-36 questionnaire., Results: HRQoL was impaired in DM1 patients in both physical and mental domains (PCS was 41.8±23.5, MCS 47.0±24.3 and total SF-36 score 45.6±24.0). The most significant factors correlating with better SF-36 total score were younger age (β=-0.45, p<0.001), shorter duration of disease (β=-0.27, p=0.001), higher education (β=0.20, p=0.009), less severe muscular weakness (β=-0.52, p<0.001), normal swallowing (β=0.22, p=0.005), absence of fainting (β=0.31, p=0.002), absence of snoring (β=0.21, p=0.036), better acceptance of disease (β=-0.17, p=0.036), lower depressiveness (β=-0.46, p=0.001), lower fatigue (β=-0.32, p=0.001), absence of cataract (β=-0.21, p=0.034), absence of kyphosis (β=0.31, p=0.004) and absence of constipation (β=0.24, p=0.016). Second linear regression analysis revealed that depressed (β=-0.38, p<0.001) and elder patients (β=-0.27, p=0.007) and as well as those with poor acceptance of illness (β=-0.21, p=0.006) were in especially higher risk of having poor HRQoL (R(2)=0.68)., Conclusion: We identified different central, social, muscular, cardiorespiratory and other factors correlating with HRQoL. It is of great importance that most of these factors are amenable to treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to analyze the prevalence and incidence of adult-onset myasthenia gravis (MG) in the Belgrade population from 1979 to 2008., Methods: Data on the number of MG patients and their basic demographic and clinical characteristics were collected from hospital records (1979-1992) and the Belgrade MG Registry (1993-2008). Incidence and prevalence were standardized by the direct method (using the world standard population). A time-trend analysis of MG incidence was performed using a linear regression model., Results: During the study period 562 cases (316 women, 246 men) were registered. On December 31st, 2008, the standardized prevalence (according to the world standard population) was 188.3/1,000,000 (women: 237.8/1,000,000; men: 139.4/1,000,000). The average annual standardized incidence rate was 13.3/1,000,000 (women: 14.1/1,000,000; men: 12.2/1,000,000). The incidence rates tended to increase significantly in both sexes during the study period (y = 3.299 + 14.363x, p = 0.002). Age-specific incidence rates for women demonstrated a bimodal pattern, with the first peak in the 20- to 29-year age group and the second one in the ≥70-year group. For both genders, an increase in age-specific incidence rates was registered for all age groups, although this was significant (p = 0.001) only for an MG onset of ≥60 years of age., Conclusions: The study confirms an increase in the incidence of MG in the area of Belgrade during the study period, especially for those with MG onset after 60 years of age., (Copyright © 2013 S. Karger AG, Basel.)

Ninety-six feral cats from Prince Edward Island were used to determine the prevalence of selected infectious agents. The prevalence rates were 5.2% for feline immunodeficiency virus, 3.1% for feline leukemia virus, 3.1% for Mycoplasma haemofelis, 8.4% for Candidatus Mycoplasma haemominutum, 2.1% for Bartonella spp. and 29.8% for exposure to Toxoplasma gondii. Oocysts of T. gondii were detected in 1.3% of the fecal samples that were collected. Gender and retroviral status of the cats were significantly correlated with hemoplasma infections. Use of a flea comb showed that 9.6% of the cats had fleas; however, flea infestation was not associated with any of the infectious agents.

Objective: To evaluate cardiac autonomic control in patients with myasthenia gravis (MG) and thymoma., Materials and Methods: The study was performed on 21 patients with MG and thymoma and the same number of matched healthy volunteers. Standard cardiovascular reflex tests according to Ewing and baroreflex sensitivity (BRS) at rest was applied. Spectral analysis of heart rate variability (HRV) at rest was assessed using a 20-minute ECG recording (normalized low- and high-frequency bands-LFnu-RRI, HFnu-RRI and LF/HF-RRI) Time-domain analysis of HRV was derived from 24-hour ECG monitoring., Results: Overall autonomic score according to Ewing was significantly increased in patients with MG and thymoma (p<0.05), mostly due to parasympathetic dysfunction. Time-domain parameters representing the overall and long-term sympathetic activity of HRV did not differ significantly between the two groups (p>0.05), but there was a significant decrease in measures of the short-term vagal variations in HRV (p<0.01). HFnu-RRI was lower, while LFnu-RRI and LF/HF-RRI were higher in patients with MG and thymoma in comparison to healthy controls but these differences were not of statistical significance (p>0.05). BRS at rest was highly significantly reduced in patients group (p<0.01)., Conclusions: Our results showed mainly parasympathetic cardiac impairment in patients with myasthenia gravis and thymoma. Since autonomic dysfunction may lead to cardiac conduction abnormalities and sudden death, the investigation of autonomic nervous system function in these patients may be significant in everyday clinical practice., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Diabetic ketoacidosis (DKA), a complication of diabetes mellitus, is a severe metabolic disease that often requires intensive treatment. Diagnosis of ketosis associated with DKA can be difficult due to variability in the metabolic state of DKA patients. Recognition of the clinical signs and definitive diagnosis are essential for proper treatment. This article reviews the formation of ketoacids during DKA and the role of β-hydroxybutyric acid in the diagnosis and monitoring of DKA.

Objective: To assess lipid composition of the intrinsic tongue muscles in patients with myasthenia gravis (MG)., Methods: This study included 15 MG patients with antibodies against muscle-specific kinase (MuSK), 15 matched MG patients with antibodies against acetylcholine receptor (AChR) and 15 matched healthy subjects. Middle posterior region of the tongue was analyzed by single voxel point-resolved proton magnetic resonance spectroscopy (MRS) using 1.5T MRI scanner., Results: MRS obtained from subject with AChR MG showed a broad resonance arising from methylene groups of lipids (PMN) with no observable shoulder attributed to methyl groups (PML). Full-width at half maximum (FWHM) of PMN+PML peak showed higher value in patients with AChR MG in comparison to healthy subjects and MuSK MG patients (p<0.05). In patients with MuSK MG, the shape and FWHM of PMN+PML peak was similar as in healthy subjects (p>0.05), with tendency toward increased ratio between PMN and resonance from vinyl protons of lipids (PV). In both AChR and MuSK MG, total creatine resonance (creatine+phosphocreatine, CP) was almost absent with significant increase of PMN/CP ratio in comparison to healthy subjects (p<0.05)., Conclusion: MRS is useful in revealing muscle lipid composition in MG. In patients with AChR MG, MRS showed increased lipid content in the tongue muscles due to the lipid migration from intra- to extramyocellular space. Finding in patients with MuSK MG might reflect intramyocellular lipid deposition in the tongue. CP decrease in tongue muscles indicated impairment of oxidative metabolism in both AChR MG and MuSK MG., (Copyright © 2010. Published by Elsevier B.V.)

Lack of physical activity and/or physical fitness are some reasons epidemiologists suggest for increase in childhood obesity in the last 20 years, with clear correlation between body composition and physical activity and/or physical fitness yet to be determined. The objectives of the study were to (a) investigate the prevalence of overweight and obesity among Serbian school children and (b) determine the relationship between indicators of physical activity and body fatness in Serbian school children aged 6-14 years. The study subjects included a representative sample of Serbian elementary school children (n = 1,121-754 boys and 367 girls-aged 6.2-14.1 years), all of whom were recruited in the OLIMP (Obesity and Physical Activity among Serbian School Children) study. Anthropometric and physical fitness values, including body mass index (BMI), waist-circumference, body-fat, and aerobic capacity, were measured in all the children. Significant differences were found between male and female children regarding the prevalence of obesity (6.8% vs 8.2%, p < 0.05, boys and girls respectively). Boys had significantly lower body mass, BMI, waist-circumference, sum of six skinfolds, and body-fat compared to their female counterparts (p < 0.05). The highest level of weight, BMI, body-fat, and waist-circumference observed in a 14-year old girl (96.3 kg, 40.5 kg/m2, 54.5%, 91.4 cm respectively) implies the existence of extreme obesity in Serbian school children. The negative relationship between body-fat and maximal oxygen (VO2max) uptake was moderately high (r = -0.76; p < 0.05). The study has shown a high prevalence of adiposity among Serbian school children, with a strong negative relationship between aerobic fitness and body fatness. Data of the study emphasize the necessity to identify children with weight problems and to develop early interventions to improve physical activity in children and prevent the increase of childhood obesity.

The aim of our study was to investigate mechanism of action of endothelins 1, 2 and 3 on spontaneous activity, tone and intraluminal pressure of human ureter. Both longitudinal tension and intraluminal pressure were recorded from the isolated segments of proximal human ureter. Endothelins 1, 2 and 3 (5.35x10(-11) M - 5.05x10(-8) M) produced concentration-dependent tonic contraction and sustained increase in intraluminal pressure of isolated preparations of human ureter. Endothelins 1 and 3 produced also concentration-dependent inhibition of spontaneous, phasic contractions of the isolated preparations. Selective antagonist of ET(A) receptors BQ123 and selective antagonist of ET(B) receptors BQ788 produced significant inhibition of endothelin-1-induced tonic contraction (pA(2)=8.80 and 6.55, respectively) and increase in intraluminal pressure (pA(2)=8.68 and 7.02, respectively), while they did not affect endothelin-1-induced inhibition of spontaneous activity. Endothelin 1 produces increase in tone and intraluminal pressure of isolated human ureter acting on both ET(A) and ET(B) receptors, the first one being functionally more important. Only endothelins 1 and 3 inhibit spontaneous, phasic activity of human ureter, but this effect was not blocked by selective antagonists of ET(A) and ET(B) receptors.

Background: The aim of this study was to determine prevalence and 15-year survival in Charcot-Marie-Tooth disease (CMT)., Methods: The study covers the period from 1 January 1988 to 31 December 2007 in the territory of Belgrade. Data on a number of CMT-affected persons and their basic demographic characteristics as well as data on the disease were collected from medical records. Data on the course and outcome of the disease were obtained through direct contact with patients, their families and their physicians., Results: We registered 161 patients with CMT in the population of Belgrade. The most frequent type was CMT1. The crude prevalence of CMT disease in the Belgrade population on 31 December 2007 was 9.7/100,000 for all subtypes, 7.1/100,000 for CMT1, and 2.3/100,000 for CMT2. Gender-specific prevalence was 11.2/100,000 for males and 8.3/100,000 for females. The highest age-specific prevalence was registered in the oldest age group (75+ years; 19.1/100,000), and the lowest one in patients aged 5-14 years (5.0/100,000). The cumulative probability of 15-year survival for CMT patients in Belgrade was 85.6 ± 7.8% (44.9 ± 31.8% for males and 98.2 ± 1.8% for females)., Conclusions: The prevalence of CMT found in Belgrade is similar to the prevalence registered in Southern European countries., (Copyright © 2011 S. Karger AG, Basel.)

Pulmonary hemorrhage is a rare and life-threatening complication of systemic lupus erythematosus. In this report, we described a 17-year-old female with pulmonary hemorrhage as an initial manifestation of systemic lupus erythematosus, along with lupus nephritis and central nervous system lupus. High doses of corticosteroids and pulse cyclophosphamide therapy resulted in rapid improvement of respiratory function in our patient.

The aim of this study was to investigate autonomic cardiac control in patients with amyotrophic lateral sclerosis (ALS). Fifty-five patients with sporadic ALS (28 female and 27 male; average age 56.00 +/- 10.34 years) were compared to 30 healthy controls (17 female and 13 male; average age 42.87 +/- 11.91 years). Patients with previous history of cardiac disease, diabetes mellitus, and impaired respiratory function were excluded from the study. Cardiovascular autonomic tests according to Ewing, power spectrum analysis of RR variability (low- and high-frequency bands - LF and HF, LF/HF index), real-time beat-to-beat ECG signal monitoring with heart rate variability analysis and baroreflex function analysis were carried out in all patients. Time-domain parameters of heart rate variability (mean RR interval, SDNN, SDANN, SDNN index, rMSSD and pNN50%) were obtained from 24-h ECG monitoring. ALS patients had a significantly higher score of sympathetic (p <0.01) and parasympathetic (p <0.001) dysfunction, as well as of the overall score of autonomic dysfunction (p <0.001). LF/HF index was significantly increased; baroreflex sensitivity and time-domain parameters of heart rate variability were highly significantly decreased in ALS patients (p <0.001). Our results demonstrated impaired cardiac autonomic control in ALS with marked parasympathetic dysfunction and sympathetic predominance.

The main aim of this study was to determine the extent to which physical activity and adiposity are associated with blood cholesterol levels in male adolescents. Anthropometric and physical fitness values were measured in all children. Body mass index (BMI) and physical activity index (PAI) were used to split participants into active overweight (ACO) and non-active normal-weight (NAN) groups. The cutoffs for the ACO group were BMI > or = 22.6 kg/m2 and PAI > or = 3.5, respectively, whereas the corresponding cutoffs for the NAN groups were BMI < 20.0 kg/m2 and PAI < 2. A total of 65 children (29 in ACO group, 36 in NAN group) were selected according to the above criteria. ACO group showed significantly higher BMI and body fat as compared to their NAN counterparts (p < 0.05). Adolescents from ACO group attained superior scores for PAI and aerobic fitness (p < 0.05). Most blood lipid variables were significantly lower in ACO group as compared to NAN (p < 0.05) while HDL-cholesterol was higher in ACO group (p < 0.05). There was significant positive correlation between HDL-cholesterol and PAI in ACO group (r = 0.38; p < 0.05). The physical activity index explained the majority of variance in HDL-cholesterol for ACO group (beta = 0.513; p < 0.05). It seems that physical activity in adolescents is a more important factor in balancing blood lipid status than adiposity per se, particularly for HDL-cholesterol.

The aim was to assess factors that might influence health-related quality of life (HRQoL) in patients with two different neuromuscular disorders - myotonic dystrophy type 1 (DM1) and amyotrophic lateral sclerosis (ALS). A cross-sectional study was performed on 79 patients with DM1 and 74 with ALS. The HRQoL was evaluated by SF-36, Serbian version. Depressive and anxiety symptoms were assessed using the Hamilton rating scale for depression and the Hamilton rating scale for anxiety respectively. Severity of muscular involvement in DM1 was measured with MRC scale and severity of ALS with ALSFRSr score. The mean total score as well as all domain scores of SF-36 were similar in DM1 and ALS patients (p > 0.05), except that ALS patients experienced less bodily pain (p < 0.05). Depressiveness was found in 51% and marked anxiety in 38% of DM1 patients. Emotional status and severity of muscular involvement emerged as significant independent contributing factors to the total SF-36 in DMI patients (p < 0.05). Only 3% of ALS patients showed depressiveness and 4% anxiety symptoms. The factors found to contribute to HRQoL in ALS patients were severity of disease and educational level ofpatients (p < 0.05). We found significant percentage of potentially treatable emotional disturbances which together with severity of disease significantly contributed to HRQoL in DM1 patients. On the other hand, in ALS patients depressiveness and anxious symptoms were uncommon and the factors found to contribute to HRQoL were severity of disease and educational level.

Objectives: To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1)., Materials and Methods: This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI)., Results: DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 +/- 6.6 ng/ml vs 3.6 +/- 2.9 ng/ml in men, and 13.9 +/- 10.0 ng/ml vs 10.9 +/- 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01)., Conclusions: The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.

The case of intrauterine idiopathic bladder rupture with consecutive urinary ascites is presented. Conservative management resulted in complete resolution of the lesion.

A number of urethral stents made of different materials, with different time of indwelling and different designs, primarily based on the vascular stent concept, have been applied in the clinical practice so far. According to the published studies, urethral stents have justified their clinical application, however with certain limitations. Within an attempt to overcome the limitations, a covered, temporary urethral stent was initially designed by Daniel Yachie and Zeljko Markovic in Allium corporation from Israel. With its triangular shape, the stent is a replica of the obstructive urethral lumen. The follow-up of resuIts was done according to a priori established protocol including the following: UCG, uroflowmetry and interview with patients. Due to stent migration, the stent over stent technique was applied in two case, while reposition by balloon-catheter outward traction was performed in two cases of caudal migration. No irritative discomforts were reported in the first 6 months after stent dwelling. Uroflowmetric controls verified at least four times better results than before the insertion. Given it is the question of covered stent, there is no possibility of proliferative secondary lumen obstruction. On account of soft structure and conic shape of posterior part of stent, no lesions of the external urethral sphincter were manifested. The stent is simply withdrawn after 12 months by outward traction using the forceps at the time when the stent construction turns into soft and straight wire. After 12-16 months in all cases we removel stent and in all patients we find complete recanalisation without any disuric problem. In 5 cases we find new "contact" stricture on anterior part of stent and treated succeed with balloon recanalisation.

The aim of this study was to estimate the incidence and prevalence of myotonic dystrophy type 1 (DM1) in Belgrade during the period 1983-2002. The patients who had DM1 were ascertained through hospital records from all neurological departments in Belgrade during 1983-2002. The molecular genetic analysis was performed in all patents included in the study. We identified 101 DM1 patients (52 males and 49 females). The average annual incidence rate of DM1 in Belgrade for the period observed was 2.0/1,000,000 (95% confidence interval (CI), 0.3-8.3), 2.1/1,000,000 (95% CI, 0.3-8.3) for males and 2.0/1,000,000 (95% CI, 0.3-8.3) for females. The highest age-specific DM1 incidence was registered in the age group 20-49: 3.4/1,000,000 (95% CI, 0.5-7.6), 4.0/1,000,000 (95% CI, 1.1-10.2) in males and 2.5/1,000,000 (95% CI, 0.5-7.6) in females. In the population of Belgrade, a cumulative probability of acquiring DM1 was 1 per 8621 for men and 1 per 9259 for women (1 per 8940 of the population for both sexes). The prevalence of DM1 in Belgrade on 31 December 2002 was 5.3/100,000 (95% CI, 4.2-6.6).

The purpose of this investigation was to determine survival and mortality in patients with myotonic dystrophy type 1 (DM1) in the Belgrade population within the period from 1983 to 2002. Data of a number of diagnosed DM1 patients with their demographic, clinical and genetic characteristics were gathered from hospital records in all neurologic institutions in Belgrade for the period 1983-2002. Death certificates were reviewed to determine the cause of death. Survival analysis by life table method and Cox proportional hazard model was performed. Within the observed period, in the population of Belgrade, 15 fatal outcomes among 101 patients with DM1 were registered. Average DM1 mortality rate was 0.5/1,000,000 (95% CI 0.3-0.8), and standardized mortality ratio (SMR) was 5.3. A significant inverse correlation was found between age at onset of DM1 and CTG repeats (P=0.023). The cumulative probability of 15-year survival for DM1 patients in Belgrade was 49+/-5% (48+/-2% for males and 50+/-7% for females). Younger age at onset was a significant unfavorable prognostic factor (hazard ratio=4.2; P=0.012).

Congenital myopathy with uniform type 1 fibers is a rare form of nonprogressive congenital neuromuscular disease. We report a 40 year old woman with proximal muscle weakness, waddling gait and decreased deep tendon reflexes. The serum creatine kinase level was decreased. Peripheral nerve conduction velocity as well as electrocardiogram and echocardiogram were normal. The electromyogram showed myopathic changes. A biopsy specimen from the left deltoid muscle revealed a uniformity of type 1 fibers. This is the first case of congenital myopathy with uniform type 1 fibers reported in Serbia.

Objectives: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG., Methods: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients., Results: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died., Conclusions: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.

Estrogens have been recognized as a major regulator of vascular tone and structure, particularly in the skin. The objective of this study was to investigate the effects of endogenous estrogens on the skin microcirculation. Skin blood flow was measured at the forearm at rest and during postischemic hyperemia using laser Doppler flowmetry in 32 healthy women (mean age 34.5 +/- 3.9 years) involved in an in-vitro fertilization program. Women were treated for 10 to 12 days with gonadotropin-releasing hormone agonist (total dose 40.3 +/- 3.3 mg) and human menopausal gonadotropin (1942 +/- 801 IE) or follicle-stimulating hormone (2544 +/- 1071 IE) according to individual estrogen levels. Plasma estrogen levels increased from 132 +/- 90 pmol/L (36 +/- 25 pg/mL) to 8471 +/- 4386 pmol/L (2308 +/- 1195 pg/mL) during treatment (P < 0.0001). Maximal hyperemic blood flow increased from 353 +/- 81% before treatment to 516 +/- 144% after hormonal stimulation (P < 0.0001), whereas basal skin flow was not altered. This study shows that endogenous estrogens enhance the postischemic hyperemic response of the skin microcirculation.

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.

Objectives: The present study aims to investigate whether laser Doppler flowmetry can be used to monitor improvements in vascular function during statin therapy., Background: Endothelial dysfunction is an early feature of atherosclerosis in hypercholesterolemic patients and can be improved by statins. There are several methods to assess endothelial function in vivo, none of them being feasible in everyday practice., Methods: Skin perfusion, measured by laser Doppler flowmetry, was assessed at rest and during reactive hyperemia. Nineteen hypercholesterolemic patients (age 42 to 73 years, total cholesterol 5.4 to 9.6 mmol/l) were studied before and during statin therapy. To further investigate the mechanisms, postischemic skin hyperemia was measured before and after intradermal injection of the nitric oxide synthase inhibitor L-NAME and its inactive isoform D-NAME (0.5 micromol/10 microl each). On a separate day, the healthy volunteers were reexamined before and 2 h after 1,000 mg aspirin., Results: Postischemic skin blood flow was markedly reduced in hypercholesterolemic patients (45 +/- 11%) compared with healthy controls (238 +/- 20%, p < 0.0001) and improved after statin therapy (113 +/- 15%, p = 0.0005 vs. pre-treatment). In the healthy volunteers, the hyperemic responses were not significantly different after L-NAME and D-NAME. Aspirin reduced hyperemia from 274 +/- 49% to 197 +/- 40% (p = 0.025)., Conclusions: Reactive hyperemia of the skin microcirculation can be easily and reproducibly assessed by laser Doppler flowmetry. Vasodilator prostaglandins are the major mediators of postischemic skin hyperemia, which is impaired in hypercholesterolemic patients and can be enhanced by cholesterol-lowering therapy. Thus, laser Doppler flowmetry may represent a tool to assess and monitor vascular function during therapy in everyday practice.

Myotonic dystrophy type 1 (DM1) is associated with an expansion of CTG repeats in the 3'UTR of the DMPK gene. It is accepted, as in other trinucleotide diseases, that the number of the repeats is correlated with age at onset and severity of the disease. However, assessment of genotype-phenotype correlation in DM1 is complicated with the expansion-biased somatic instability of mutant alleles over time and difficulties in precise assessment of the number of repeats by standard Southern blot hybridization. In order to clarify this issue we defined DM1 expansion size in lymphocytes by three parameters: size of progenitor, average, and largest allele, using a more precise small-pool/long-range PCR technique. We found a negative linear correlation of age at onset and average expansion size in juvenile-adult DM1 patients (35 out of 46) whose progenitor allele is less than 245 repeats long. Our result favors the hypothesis of the existence of a threshold in the progenitor allele size beyond which number of CTG repeats does not influence age at onset. Potential clinical significance is that the average allele size could be a useful indicator for the age at onset in juvenile-adult DM1 patients with relatively short progenitor allele. To test whether somatic instability of mutant alleles influences the progression of DM1, patients were divided in three phenotypic classes according to the severity of neuromuscular symptoms. We showed that the largest expansion in each DM1 phenotypic class reflects somatic instability of mutant allele over time independently of progenitor allele size and patient's age at sampling. The mean of the largest expansion was significantly different between phenotypic classes, implying the possible association between expansion-biased somatic instability of mutant alleles over time and progression of neuromuscular symptoms., (Copyright 2002 Wiley-Liss, Inc.)