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  1. The effect of time-of-day and chest physiotherapy on multiple breath washout measures in children with clinically stable cystic fibrosis.

    Science.gov (United States)

    Voldby, Christian; Green, Kent; Rosthøj, Susanne; Kongstad, Thomas; Philipsen, Lue; Buchvald, Frederik; Skov, Marianne; Pressler, Tania; Gustafsson, Per; Nielsen, Kim G

    2018-01-01

    In this pilot study we investigated daytime variation of multiple breath nitrogen washout (N2MBW) measures in children with clinically stable cystic fibrosis. To our knowledge the effect of time-of-day on multiple breath washout measures in patients with cystic fibrosis has not previously been reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW measures. Ten school children with cystic fibrosis performed N2MBW followed by spirometry and plethysmography in the morning and afternoon at three visits that were one month apart. Chest physiotherapy was performed immediately before the afternoon measurements at visit 2 and immediately before morning and afternoon measurements at visit 3. The influence of time-of-day and chest physiotherapy on the measures was evaluated using linear mixed models. There were adequate quality data from 8 children with median age (range) 9.6 (6.0; 15.1) years. Baseline lung clearance index (LCI) (range) was 9.0 (7.1; 13.0) and baseline FEV1% predicted was 97.5 (78.5; 117.9). No N2MBW measures were significantly influenced by time-of-day or chest physiotherapy. LCI (95% confidence interval) decreased non-significantly 0.05 (-0.32; 0.22) during the day and increased non-significantly 0.08 (-0.26; 0.42) after chest physiotherapy. All spirometric measures were unaffected by time-of-day and chest physiotherapy. For plethysmographic measures FRCpleth decreased significantly (pphysiotherapy performed immediately prior to N2MBW had no consistent or significant influence on N2MBW measures. However, we emphasize that further studies of the effect of both daytime variation and the effect of chest physiotherapy on multiple breath washout measures are warranted.

  2. Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients.

    Science.gov (United States)

    Mostert, J P; Blaauw, Y; Koch, M W; Kuiper, A J; Hoogduin, J M; De Keyser, J

    2008-08-01

    N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with (1)H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies.

  3. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  4. Reproducibility over a 1-month period of (1)H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients

    NARCIS (Netherlands)

    Mostert, J. P.; Blaauw, Y.; Koch, M. W.; Kuiper, A. J.; Hoogduin, J. M.; De Keyser, J.

    N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in

  5. Biomedical applications of mass spectrometry. Clinical uses of stable isotopes

    International Nuclear Information System (INIS)

    Krahmer, U.I.; McCloskey, J.A.

    1978-01-01

    The review covers typical or important examples of stable isotope usage in clinical fields during the period since the last triennial mass spectrometry conference in 1973. Items are included which involve uses of stable isotopes in human or clinically oriented studies, including measurements carried out on materials of human origin. 163 references. (U.K.)

  6. Vegetation engineers marsh morphology through multiple competing stable states

    Science.gov (United States)

    Marani, Marco; Da Lio, Cristina; D’Alpaos, Andrea

    2013-01-01

    Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological–biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes. PMID:23401529

  7. Defining the clinical course of multiple sclerosis

    DEFF Research Database (Denmark)

    Lublin, Fred D; Reingold, Stephen C; Cohen, Jeffrey A

    2014-01-01

    Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts...

  8. Clinical aspects of multiple pregnancy

    NARCIS (Netherlands)

    J.G. Santema

    1996-01-01

    textabstractThe natural wonder of multiple pregnancy and birth has fascinated mankind since ancient times and twins figure prominently in legends, folktales and myths. One of the best known traditional stories is that of Romulus and Remus, the twins who were abandoned on the banks of the Tiber and

  9. Multiple stable isotope fronts during non-isothermal fluid flow

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    Fekete, Szandra; Weis, Philipp; Scott, Samuel; Driesner, Thomas

    2018-02-01

    Stable isotope signatures of oxygen, hydrogen and other elements in minerals from hydrothermal veins and metasomatized host rocks are widely used to investigate fluid sources and paths. Previous theoretical studies mostly focused on analyzing stable isotope fronts developing during single-phase, isothermal fluid flow. In this study, numerical simulations were performed to assess how temperature changes, transport phenomena, kinetic vs. equilibrium isotope exchange, and isotopic source signals determine mineral oxygen isotopic compositions during fluid-rock interaction. The simulations focus on one-dimensional scenarios, with non-isothermal single- and two-phase fluid flow, and include the effects of quartz precipitation and dissolution. If isotope exchange between fluid and mineral is fast, a previously unrecognized, significant enrichment in heavy oxygen isotopes of fluids and minerals occurs at the thermal front. The maximum enrichment depends on the initial isotopic composition of fluid and mineral, the fluid-rock ratio and the maximum change in temperature, but is independent of the isotopic composition of the incoming fluid. This thermally induced isotope front propagates faster than the signal related to the initial isotopic composition of the incoming fluid, which forms a trailing front behind the zone of transient heavy oxygen isotope enrichment. Temperature-dependent kinetic rates of isotope exchange between fluid and rock strongly influence the degree of enrichment at the thermal front. In systems where initial isotope values of fluids and rocks are far from equilibrium and isotope fractionation is controlled by kinetics, the temperature increase accelerates the approach of the fluid to equilibrium conditions with the host rock. Consequently, the increase at the thermal front can be less dominant and can even generate fluid values below the initial isotopic composition of the input fluid. As kinetics limit the degree of isotope exchange, a third front may

  10. Increasing atmospheric CO2 overrides the historical legacy of multiple stable biome states in Africa.

    Science.gov (United States)

    Moncrieff, Glenn R; Scheiter, Simon; Bond, William J; Higgins, Steven I

    2014-02-01

    The dominant vegetation over much of the global land surface is not predetermined by contemporary climate, but also influenced by past environmental conditions. This confounds attempts to predict current and future biome distributions, because even a perfect model would project multiple possible biomes without knowledge of the historical vegetation state. Here we compare the distribution of tree- and grass-dominated biomes across Africa simulated using a dynamic global vegetation model (DGVM). We explicitly evaluate where and under what conditions multiple stable biome states are possible for current and projected future climates. Our simulation results show that multiple stable biomes states are possible for vast areas of tropical and subtropical Africa under current conditions. Widespread loss of the potential for multiple stable biomes states is projected in the 21st Century, driven by increasing atmospheric CO2 . Many sites where currently both tree-dominated and grass-dominated biomes are possible become deterministically tree-dominated. Regions with multiple stable biome states are widespread and require consideration when attempting to predict future vegetation changes. Testing for behaviour characteristic of systems with multiple stable equilibria, such as hysteresis and dependence on historical conditions, and the resulting uncertainty in simulated vegetation, will lead to improved projections of global change impacts. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  11. Clinically stable angina pectoris is not necessarily associated with histologically stable atherosclerotic plaques

    NARCIS (Netherlands)

    van der Wal, A. C.; Becker, A. E.; Koch, K. T.; Piek, J. J.; Teeling, P.; van der Loos, C. M.; David, G. K.

    1996-01-01

    OBJECTIVE: To investigate the extent of plaque inflammation in culprit lesions of patients with chronic stable angina. DESIGN: Retrospective study. SETTING: Amsterdam reference centre. SUBJECTS: 89 consecutive patients who underwent directional coronary atherectomy, 58 of whom met the following

  12. Ivabradine in stable coronary artery disease without clinical heart failure

    DEFF Research Database (Denmark)

    Fox, Kim; Ford, Ian; Steg, Philippe Gabriel

    2014-01-01

    minute or more. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12......,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily......, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction. RESULTS: At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group...

  13. Platinum stable isotope ratio measurements by double-spike multiple collector ICPMS

    DEFF Research Database (Denmark)

    Creech, John; Baker, Joel; Handler, Monica

    2013-01-01

    We present a new technique for the precise determination of platinum (Pt) stable isotope ratios by multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS) using two different Pt double-spikes ( Pt-Pt and Pt-Pt). Results are expressed relative to the IRMM-010 Pt isotope standard......) can be obtained on Pt stable isotope ratios with either double-spike. Elemental doping tests reveal that double-spike corrected Pt stable isotope ratios are insensitive to the presence of relatively high (up to 10%) levels of matrix elements, although the Pt-Pt double-spike is affected by an isobaric...... = 7.308%) results in a redefined Pt atomic weight of 195.08395 ± 0.00068. Using our technique we have measured small, reproducible and statistically significant offsets in Pt stable isotope ratios between different Pt element standards and the IRMM-010 standard, which potentially indicates...

  14. [Multiple primary colorectal cancer: Clinical aspects].

    Science.gov (United States)

    Soldatkina, N V; Kit, O I; Gevorkyan, Yu A; Milakin, A G

    to define some clinical characteristics of synchronous and metachronous colorectal cancer (CRC). The investigation was concerned with the data of 150 patients with T1-4N0-2M0-1 multiple primary CRC. The clinical, biological, and morphological characteristics of synchronous and metachronous tumors were analyzed. Multiple primary tumors were 6.01% of all the cases of CRC. There was a preponderance of synchronous CRC (63.75%) with the tumor localized in the sigmoid colon and rectum. In women, synchronous colorectal tumors were more often concurrent with breast tumors; metachronous ones were detected after treatment for genital tumors. In men, synchronous colorectal tumors were more frequently concurrent with kidney cancer; metachronous ones were identified after treatment for gastric cancer. The found characteristics of multiple primary colorectal tumors may be taken in account in programs for both primary diagnosis and follow-up after treatment for malignant tumors, which will be able to improve the early detection of cancer patients and their treatment results.

  15. Stable multiple-layer stationary solutions of a semilinear parabolic equation in two-dimensional domains

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    Arnaldo Simal do Nascimento

    1997-12-01

    Full Text Available We use $Gamma$--convergence to prove existence of stable multiple--layer stationary solutions (stable patterns to the reaction--diffusion equation. $$ eqalign{ {partial v_varepsilon over partial t} =& varepsilon^2, hbox{div}, (k_1(xabla v_varepsilon + k_2(x(v_varepsilon -alpha(Beta-v_varepsilon (v_varepsilon -gamma_varepsilon(x,,hbox{ in }Omegaimes{Bbb R}^+ cr &v_varepsilon(x,0 = v_0 quad {partial v_varepsilon over partial widehat{n}} = 0,, quadhbox{ for } xin partialOmega,, t >0,.} $$ Given nested simple closed curves in ${Bbb R}^2$, we give sufficient conditions on their curvature so that the reaction--diffusion problem possesses a family of stable patterns. In particular, we extend to two-dimensional domains and to a spatially inhomogeneous source term, a previous result by Yanagida and Miyata.

  16. Nonlinear behavior of multiple-helicity resistive interchange modes near marginally stable states

    International Nuclear Information System (INIS)

    Sugama, Hideo; Nakajima, Noriyoshi; Wakatani, Masahiro.

    1991-05-01

    Nonlinear behavior of resistive interchange modes near marginally stable states is theoretically studied under the multiple-helicity condition. Reduced fluid equations in the sheared slab configuration are used in order to treat a local transport problem. With the use of the invariance property of local reduced fluid model equations under a transformation between the modes with different rational surfaces, weakly nonlinear theories for single-helicity modes by Hamaguchi and Nakajima are extended to the multiple-helicity case and applied to the resistive interchange modes. We derive the nonlinear amplitude equations of the multiple-helicity modes, from which the convective transport in the saturated state is obtained. It is shown how the convective transport is enhanced by nonlinear interaction between modes with different rational surfaces compared with the single-helicity case. We confirm that theoretical results are in good agreement with direct numerical simulations. (author)

  17. Clinical features of multiple spontaneous intracerebral hemorrhages

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    Tao CHANG

    2016-01-01

    Full Text Available Objective To analyze the clinical features of multiple spontaneous intracerebral hemorrhages (MICH. Methods Conservative therapy, puncture and drainage, hematoma removal and/or decompressive craniectomy were used in the treatment of 630 intracerebral hemorrhage (ICH patients, who were divided into 2 groups: 30 cases with MICH and another 600 cases with solitary intracerebral hemorrhage (SICH. Three months after onset, modified Rankin Scale (mRS was used to evaluate the prognosis of all cases. Results Compared with patients in SICH group, the occurrence rate of hypertension > 5 years (P = 0.008, diabetes mellitus (P = 0.024, hypercholesterolemia (P = 0.050 and previous ischemic stroke (P = 0.026 were all significantly higher in MICH group. The mean arterial pressure (MAP level (P = 0.002 and the incidence of limb movement disorder (P = 0.000 were significantly higher in patients with MICH than those with SICH. Basal ganglia and thalamus were the predilection sites of hematoma (P = 0.001. Patients with MICH had worse prognosis compared to those with SICH 3 months after onset (P = 0.006. Conclusions Hypertension > 5 years, diabetes mellitus, hypercholesterolemia and ischemic stroke were identified to be the pathophysiological basis of MICH in this study. All patients with MICH had more serious clinical manifestations after onset and worse prognosis. DOI: 10.3969/j.issn.1672-6731.2016.01.008

  18. Reduced α-stable dynamics for multiple time scale systems forced with correlated additive and multiplicative Gaussian white noise

    Science.gov (United States)

    Thompson, William F.; Kuske, Rachel A.; Monahan, Adam H.

    2017-11-01

    Stochastic averaging problems with Gaussian forcing have been the subject of numerous studies, but far less attention has been paid to problems with infinite-variance stochastic forcing, such as an α-stable noise process. It has been shown that simple linear systems driven by correlated additive and multiplicative (CAM) Gaussian noise, which emerge in the context of reduced atmosphere and ocean dynamics, have infinite variance in certain parameter regimes. In this study, we consider the stochastic averaging of systems where a linear CAM noise process in the infinite variance parameter regime drives a comparatively slow process. We use (semi)-analytical approximations combined with numerical illustrations to compare the averaged process to one that is forced by a white α-stable process, demonstrating consistent properties in the case of large time-scale separation. We identify the conditions required for the fast linear CAM process to have such an influence in driving a slower process and then derive an (effectively) equivalent fast, infinite-variance process for which an existing stochastic averaging approximation is readily applied. The results are illustrated using numerical simulations of a set of example systems.

  19. Clinical and Biochemical Uses of Stable Iodine Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Koutras, D. A. [Thyroid Section, Alexandra Hospital, Athens (Greece)

    1970-07-01

    Iodine and thyroid function are closely linked, since the only known role of iodine is its participation in the synthesis of thyroid hormones. Iodine metabolism may be represented as a metabolic cycle consisting of three main pools: the Plasma Inorganic Iodine (PIl) pool into which dietary iodine goes and from where it is either taken up by the thyroid or excreted by the kidneys, the intrathyroidal iodine pool, where. thyroid hormone synthesis occurs, and finally the peripheral pool of thyroid hormones, of which about 80% are deiodinated and 20% excreted with the faeces. Endemic goitre is usually due to iodine deficiency. There is no renal homeostatic mechanism to keep the PII level constant, and so adaptation to iodine deficiency occurs by increasing the thyroidal iodide clearance rate. Stable iodine measurements are necessary for a complete study of iodine metabolism. Estimates of the serum Protein-Bound Iodine (PBl) are the best index of thyroid function, estimates of the PII and of the urinary iodine are the best indices of iodine nutrition. (author)

  20. Effects of marine protected areas on overfished fishing stocks with multiple stable states.

    Science.gov (United States)

    Takashina, Nao; Mougi, Akihiko

    2014-01-21

    Marine protected areas (MPAs) have attracted much attention as a tool for sustainable fisheries management, restoring depleted fisheries stocks and maintaining ecosystems. However, even with total exclusion of fishing effort, depleted stocks sometimes show little or no recovery over a long time period. Here, using a mathematical model, we show that multiple stable states may hold the key to understanding the tendency for fisheries stocks to recover because of MPAs. We find that MPAs can have either a positive effect or almost no effect on the recovery of depleted fishing stocks, depending on the fish migration patterns and the fishing policies. MPAs also reinforce ecological resilience, particularly for migratory species. In contrast to previous reports, our results show that MPAs have small or sometimes negative effects on the recovery of sedentary species. Unsuitable MPA planning might result in low effectiveness or even deterioration of the existing condition. © 2013 Elsevier Ltd. All rights reserved.

  1. Gender differences in the management and clinical outcome of stable angina

    DEFF Research Database (Denmark)

    Daly, Caroline; Clemens, Felicity; Sendon, Jose L. Lopez

    2006-01-01

    Background- We sought to examine the impact of gender on the investigation and subsequent management of stable angina and to assess gender differences in clinical outcome at 1 year. Methods and Results- The Euro Heart Survey of Stable Angina enrolled patients with a clinical diagnosis of stable...... angina on initial assessment by a cardiologist. Baseline clinical details and cardiac investigations planned or performed within a 4-week period of the assessment were recorded, and follow-up data were collected at 1 year. A total of 3779 patients were included in the survey; 42% were female. Women were......, 1.13 to 3.85), even after multivariable adjustment for age, abnormal ventricular function, severity of coronary disease, and diabetes. Conclusions- Significant gender bias has been identified in the use of investigations and evidence-based medical therapy in stable angina. Women were also less...

  2. Computed tomography imaging of early coronary artery lesions in stable individuals with multiple cardiovascular risk factors

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    Xi Yang

    2015-04-01

    Full Text Available OBJECTIVES: To investigate the prevalence, extent, severity, and features of coronary artery lesions in stable patients with multiple cardiovascular risk factors. METHODS: Seventy-seven patients with more than 3 cardiovascular risk factors were suspected of having coronary artery disease. Patients with high-risk factors and 39 controls with no risk factors were enrolled in the study. The related risk factors included hypertension, impaired glucose tolerance, dyslipidemia, smoking history, and overweight. The characteristics of coronary lesions were identified and evaluated by 64-slice coronary computed tomography angiography. RESULTS: The incidence of coronary atherosclerosis was higher in the high-risk group than in the no-risk group. The involved branches of the coronary artery, the diffusivity of the lesion, the degree of stenosis, and the nature of the plaques were significantly more severe in the high-risk group compared with the no-risk group (all p < 0.05. CONCLUSION: Among stable individuals with high-risk factors, early coronary artery lesions are common and severe. Computed tomography has promising value for the early screening of coronary lesions.

  3. Explaining clinical behaviors using multiple theoretical models

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    Eccles Martin P

    2012-10-01

    Full Text Available Abstract Background In the field of implementation research, there is an increased interest in use of theory when designing implementation research studies involving behavior change. In 2003, we initiated a series of five studies to establish a scientific rationale for interventions to translate research findings into clinical practice by exploring the performance of a number of different, commonly used, overlapping behavioral theories and models. We reflect on the strengths and weaknesses of the methods, the performance of the theories, and consider where these methods sit alongside the range of methods for studying healthcare professional behavior change. Methods These were five studies of the theory-based cognitions and clinical behaviors (taking dental radiographs, performing dental restorations, placing fissure sealants, managing upper respiratory tract infections without prescribing antibiotics, managing low back pain without ordering lumbar spine x-rays of random samples of primary care dentists and physicians. Measures were derived for the explanatory theoretical constructs in the Theory of Planned Behavior (TPB, Social Cognitive Theory (SCT, and Illness Representations specified by the Common Sense Self Regulation Model (CSSRM. We constructed self-report measures of two constructs from Learning Theory (LT, a measure of Implementation Intentions (II, and the Precaution Adoption Process. We collected data on theory-based cognitions (explanatory measures and two interim outcome measures (stated behavioral intention and simulated behavior by postal questionnaire survey during the 12-month period to which objective measures of behavior (collected from routine administrative sources were related. Planned analyses explored the predictive value of theories in explaining variance in intention, behavioral simulation and behavior. Results Response rates across the five surveys ranged from 21% to 48%; we achieved the target sample size for three of

  4. Explaining clinical behaviors using multiple theoretical models.

    Science.gov (United States)

    Eccles, Martin P; Grimshaw, Jeremy M; MacLennan, Graeme; Bonetti, Debbie; Glidewell, Liz; Pitts, Nigel B; Steen, Nick; Thomas, Ruth; Walker, Anne; Johnston, Marie

    2012-10-17

    In the field of implementation research, there is an increased interest in use of theory when designing implementation research studies involving behavior change. In 2003, we initiated a series of five studies to establish a scientific rationale for interventions to translate research findings into clinical practice by exploring the performance of a number of different, commonly used, overlapping behavioral theories and models. We reflect on the strengths and weaknesses of the methods, the performance of the theories, and consider where these methods sit alongside the range of methods for studying healthcare professional behavior change. These were five studies of the theory-based cognitions and clinical behaviors (taking dental radiographs, performing dental restorations, placing fissure sealants, managing upper respiratory tract infections without prescribing antibiotics, managing low back pain without ordering lumbar spine x-rays) of random samples of primary care dentists and physicians. Measures were derived for the explanatory theoretical constructs in the Theory of Planned Behavior (TPB), Social Cognitive Theory (SCT), and Illness Representations specified by the Common Sense Self Regulation Model (CSSRM). We constructed self-report measures of two constructs from Learning Theory (LT), a measure of Implementation Intentions (II), and the Precaution Adoption Process. We collected data on theory-based cognitions (explanatory measures) and two interim outcome measures (stated behavioral intention and simulated behavior) by postal questionnaire survey during the 12-month period to which objective measures of behavior (collected from routine administrative sources) were related. Planned analyses explored the predictive value of theories in explaining variance in intention, behavioral simulation and behavior. Response rates across the five surveys ranged from 21% to 48%; we achieved the target sample size for three of the five surveys. For the predictor variables

  5. Multiple Eccrine Spiradenoma- An Unusual Clinical Presentation

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    Anita P. Javalgi

    2017-04-01

    Full Text Available Eccrine spiradenoma is an uncommon benign adnexal tumour of apocrine differentiation. It is commonly seen in young adults with no sex predilection on upper ventral aspect of body as a solitary papule or nodule. Here we are reporting a rare case of Multiple Eccrine Spiradenoma (MES in a 29 year male patient, who presented with multiple nodules on the anterior chest wall.

  6. Alternative stable states generated by ontogenetic niche shift in the presence of multiple resource use.

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    Takefumi Nakazawa

    2011-02-01

    Full Text Available It has been suggested that when juveniles and adults use different resources or habitats, alternative stable states (ASS may exist in systems coupled by an ontogenetic niche shift. However, mainly the simplest system, i.e., the one-consumer-two-resource system, has been studied previously, and little is known about the development of ASS existing in more complex systems. Here, I theoretically investigated the development of ASS caused by an ontogenetic niche shift in the presence of multiple resource use. I considered three independent scenarios; (i additional resources, (ii multiple habitats, and (iii interstage resource sharing. The model analyses illustrate that relative balance between the total resource availability in the juvenile and adult habitats is crucial for the development of ASS. This balance is determined by factors such as local habitat productivity, subsidy inputs, colonization area, and foraging mobility. Furthermore, it is also shown that interstage resource sharing generally suppresses ASS. These results suggest that the anthropogenic impacts of habitat modifications (e.g., fragmentation and destruction or interaction modifications (e.g., changes in ontogeny and foraging behavior propagate through space and may cause or prevent regime shifts in the regional community structure.

  7. Multiple stable isotope tracer technique for studying the metabolic kinetics of amino acids in hepatic failure

    Energy Technology Data Exchange (ETDEWEB)

    Zongqin, Xia; Tengchang, Dai; Jianhua, Zhang; Yaer, Hu; Bingyao, Yu; Xingrong, Xu; Guanlu, Huang; Gengrong, Shen; Yaqiu, Zhou; Hong, Yu

    1987-08-01

    In order to study the mechanism of the imbalance of amino acid metabolism during hepatic failure, a stable isotope tracer method for observing simultaneously the metabolic kinetics of several amino acids has been established. /sup 15/N-L-Ala, (2,3-D/sub 3/)-Leu and (2,3-D/sub 3/)-Phe were chosen as nonessential, branched chain and aromatic amino acids. A single iv injection of 40 mg N-Ala, 20 mg deuterated Leu and 20 mg deuterated Phe was given to each human subject. Blood samples were taken just before and at different times (up to 60 min) after the injection. Total free amino acids were isolated from the plasma with a small dowex 50 x 8 column and converted to trifluoroacetyl derivatives. Their abundances were then analyzed with a GC-MS system and typical double exponential time course curves were found for all the three labelled amino acids. A two-pool model was designed and applied for compartmental analysis. Significant changes were found in the kinetic parameters of Phe and Leu in patients with fulminant hepatitis or heptic cirrhosis. The half-lives of both Phe pools were longer and the pool sizes were larger than normal subjects, while the half-lives and pool sizes of Leu changes in the opposite direction. No marked change was found in Ala. The significance of intracellular imbalance of Phe and Leu metabolism was discussed. It is evident that the combination of GCMS technique and multiple-tracers labelled with stable isotopes is of great potential for similar purposes.

  8. Assuring Quality Control of Clinical Education in Multiple Clinical Affiliates.

    Science.gov (United States)

    Davis, Judith A.

    A plan was developed to assure equivalency of clinical education among the medical laboratory technician (MLT) programs affiliated with Sandhills Community College. The plan was designed by faculty to monitor the quality of clinical courses offered by the clinical affiliates. The major strategies were to develop competencies, slide/tape modules, a…

  9. Climatic signals in multiple highly resolved stable isotope records from Greenland

    DEFF Research Database (Denmark)

    Vinther, Bo Møllesøe; Dahl-Jensen, Dorthe; Johnsen, Sigfus Johann

    2010-01-01

    are found to correspond better with winter stable isotope data than with summer or annual average stable isotope data it is suggested that a strong local Greenland temperature signal can be extracted from the winter stable isotope data even on centennial to millennial time scales. Udgivelsesdato: Feb....

  10. Generation and monitoring of discrete stable random processes using multiple immigration population models

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, J O; Hopcraft, K I; Jakeman, E [Applied Mathematics Division, School of Mathematical Sciences, University of Nottingham, Nottingham, NG7 2RD (United Kingdom)

    2003-11-21

    Some properties of classical population processes that comprise births, deaths and multiple immigrations are investigated. The rates at which the immigrants arrive can be tailored to produce a population whose steady state fluctuations are described by a pre-selected distribution. Attention is focused on the class of distributions with a discrete stable law, which have power-law tails and whose moments and autocorrelation function do not exist. The separate problem of monitoring and characterizing the fluctuations is studied, analysing the statistics of individuals that leave the population. The fluctuations in the size of the population are transferred to the times between emigrants that form an intermittent time series of events. The emigrants are counted with a detector of finite dynamic range and response time. This is modelled through clipping the time series or saturating it at an arbitrary but finite level, whereupon its moments and correlation properties become finite. Distributions for the time to the first counted event and for the time between events exhibit power-law regimes that are characteristic of the fluctuations in population size. The processes provide analytical models with which properties of complex discrete random phenomena can be explored, and in addition provide generic means by which random time series encompassing a wide range of intermittent and other discrete random behaviour may be generated.

  11. Generation and monitoring of discrete stable random processes using multiple immigration population models

    International Nuclear Information System (INIS)

    Matthews, J O; Hopcraft, K I; Jakeman, E

    2003-01-01

    Some properties of classical population processes that comprise births, deaths and multiple immigrations are investigated. The rates at which the immigrants arrive can be tailored to produce a population whose steady state fluctuations are described by a pre-selected distribution. Attention is focused on the class of distributions with a discrete stable law, which have power-law tails and whose moments and autocorrelation function do not exist. The separate problem of monitoring and characterizing the fluctuations is studied, analysing the statistics of individuals that leave the population. The fluctuations in the size of the population are transferred to the times between emigrants that form an intermittent time series of events. The emigrants are counted with a detector of finite dynamic range and response time. This is modelled through clipping the time series or saturating it at an arbitrary but finite level, whereupon its moments and correlation properties become finite. Distributions for the time to the first counted event and for the time between events exhibit power-law regimes that are characteristic of the fluctuations in population size. The processes provide analytical models with which properties of complex discrete random phenomena can be explored, and in addition provide generic means by which random time series encompassing a wide range of intermittent and other discrete random behaviour may be generated

  12. Explaining clinical behaviors using multiple theoretical models

    OpenAIRE

    Eccles, Martin P; Grimshaw, Jeremy M; MacLennan, Graeme; Bonetti, Debbie; Glidewell, Liz; Pitts, Nigel B; Steen, Nick; Thomas, Ruth; Walker, Anne; Johnston, Marie

    2012-01-01

    Abstract Background In the field of implementation research, there is an increased interest in use of theory when designing implementation research studies involving behavior change. In 2003, we initiated a series of five studies to establish a scientific rationale for interventions to translate research findings into clinical practice by exploring the performance of a number of different, commonly used, overlapping behavioral theories and models. We reflect on the strengths and weaknesses of...

  13. Stochastic resonance in a time-delayed mono-stable system with correlated multiplicative and additive white noise

    International Nuclear Information System (INIS)

    Zhou Yu-Rong

    2011-01-01

    This paper considers the stochastic resonance for a time-delayed mono-stable system, driven by correlated multiplicative and additive white noise. It finds that the output signal-to-noise ratio (SNR) varies non-monotonically with the delayed times. The SNR varies non-monotonically with the increase of the intensities of the multiplicative and additive noise, with the increase of the correlation strength between the two noises, as well as with the system parameter. (general)

  14. Sample size determination in clinical trials with multiple endpoints

    CERN Document Server

    Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2015-01-01

    This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...

  15. Multiple stable states of a periodically driven electron spin in a quantum dot using circularly polarized light

    Science.gov (United States)

    Korenev, V. L.

    2011-06-01

    The periodical modulation of circularly polarized light with a frequency close to the electron spin resonance frequency induces a sharp change of the single electron spin orientation. Hyperfine interaction provides a feedback, thus fixing the precession frequency of the electron spin in the external and the Overhauser field near the modulation frequency. The nuclear polarization is bidirectional and the electron-nuclear spin system (ENSS) possesses a few stable states. The same physics underlie the frequency-locking effect for two-color and mode-locked excitations. However, the pulsed excitation with mode-locked laser brings about the multitudes of stable states in ENSS in a quantum dot. The resulting precession frequencies of the electron spin differ in these states by the multiple of the modulation frequency. Under such conditions ENSS represents a digital frequency converter with more than 100 stable channels.

  16. Stable isotope ratiometer-multiple ion detector (SIRMID) unit for quantitative and qualitative stable isotope studies by gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Klein, P.D.; Haumann, J.R.; Hachey, D.L.

    1975-01-01

    A stable isotope ratiometer-multiple ion detector (SIRMID) unit which can drive existing gas chromatograph-quadrupole or magnetic sector mass spectrometers to monitor up to six ions in turn is described. Each of the three pairs of ions can be selected for quantitation; thus three different or successive components can be analyzed in a single GC run. A background subtraction option permits the ion intensity in the absence of sample to be subtracted automatically during sample measurement. Displays of accumulated counts and isotope ratio are updated twice per second during the measurement and can be printed out at its conclusion. All six ions can be monitored in the analog mode by parallel outputs to a multipen recorder. Experience gained in the construction of this prototype indicates that SIRMID units could be commercially available for $10K, or about 1 / 3 rd to 1 / 6 th of the cost of even an inexpensive computer system. (U.S.)

  17. Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

    Science.gov (United States)

    Reyskens, M; Sleurs, K; Verresen, L; Janssen, M; van den Bergh, J; van den Berg, J; Geusens, P

    2015-07-01

    An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

  18. Stable Flocking of Multiple Agents Based on Molecular Potential Field and Distributed Receding Horizon Control

    International Nuclear Information System (INIS)

    Zhang Yun-Peng; Duan Hai-Bin; Zhang Xiang-Yin

    2011-01-01

    A novel distributed control scheme to generate stable flocking motion for a group of agents is proposed. In this control scheme, a molecular potential field model is applied as the potential field function because of its smoothness and unique shape. The approach of distributed receding horizon control is adopted to drive each agent to find its optimal control input to lower its potential at every step. Experimental results show that this proposed control scheme can ensure that all agents eventually converge to a stable flocking formation with a common velocity and the collisions can also be avoided at the same time. (general)

  19. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis

    DEFF Research Database (Denmark)

    Rocca, Maria A; Amato, Maria P; De Stefano, Nicola

    2015-01-01

    In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter damage and cognitive impairment has been lent support by findings from clinical and MRI studies. However...... that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive deficits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow...

  20. Applications of stable isotopes of 2H, 13C and 15N to clinical problems

    International Nuclear Information System (INIS)

    Klein, P.D.; Szczepanik, P.A.; Hachey, D.L.

    1974-01-01

    The function of the Argonne Program is to provide synthetic, analytical instrumental capability in a core facility for the clinical investigator who needs to use 2 H, 13 C, or 15 N labelled compounds for metabolic or clinical research on pregnant women, newborn infants, young children, or for mass screening. To carry out such application development, there were six stages which were recurrent steps in every application. Five fundamental strategies should be adopted to establish the use of stable isotopes in clinical work. The instrument required for measurements was a combined gas chromatograph-mass spectrometer, and its use was schematically illustrated. Some of the successful experiences with compounds labelled by stable isotopes, such as deuterium labelled chenodeoxycholic acid, and respective 13 C and 15 N-labelled glycine were described. Deutrium labelled bile acid enabled easy and safe determination of the size of the bile acid pool and the replacement rate, providing clearer diagnoses for cholestatic liver disease and gallstones. 13 C and 15 N labelled compounds were used in clinical studies, of children with genetic disorders of amino acid metabolism, i.e., non ketotic hyperflycinemia, B 12 -responsive methyl malonic acidemia, and Lesch-Nyhan syndrome. 15 N-labelled glycine was also studied in a child with Lesch-Nyhan syndrome. (Mukohata, S.)

  1. Testing sequential extraction methods for the analysis of multiple stable isotope systems from a bone sample

    Science.gov (United States)

    Sahlstedt, Elina; Arppe, Laura

    2017-04-01

    Stable isotope composition of bones, analysed either from the mineral phase (hydroxyapatite) or from the organic phase (mainly collagen) carry important climatological and ecological information and are therefore widely used in paleontological and archaeological research. For the analysis of the stable isotope compositions, both of the phases, hydroxyapatite and collagen, have their more or less well established separation and analytical techniques. Recent development in IRMS and wet chemical extraction methods have facilitated the analysis of very small bone fractions (500 μg or less starting material) for PO43-O isotope composition. However, the uniqueness and (pre-) historical value of each archaeological and paleontological finding lead to preciously little material available for stable isotope analyses, encouraging further development of microanalytical methods for the use of stable isotope analyses. Here we present the first results in developing extraction methods for combining collagen C- and N-isotope analyses to PO43-O-isotope analyses from a single bone sample fraction. We tested sequential extraction starting with dilute acid demineralization and collection of both collagen and PO43-fractions, followed by further purification step by H2O2 (PO43-fraction). First results show that bone sample separates as small as 2 mg may be analysed for their δ15N, δ13C and δ18OPO4 values. The method may be incorporated in detailed investigation of sequentially developing skeletal material such as teeth, potentially allowing for the investigation of interannual variability in climatological/environmental signals or investigation of the early life history of an individual.

  2. Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings

    DEFF Research Database (Denmark)

    Boonen, Susanne E; Pörksen, Sven; Mackay, Deborah Jg

    2008-01-01

    We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternal...

  3. Multiple myeloma in Nigeria: An insight to the clinical, laboratory ...

    African Journals Online (AJOL)

    ... the clinician to investigate along the lines of MM. Majority of patients have osteolytic lesions on X‑ray and pathological fractures, and benefit from melphalan based combinations in situations where facilities for transplant are not available. Key words: Clinical features, chemotherapy, laboratory features, multiple myeloma, ...

  4. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS...... therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy...

  5. Magnetic resonance imaging in clinically-definite multiple sclerosis

    International Nuclear Information System (INIS)

    Noakes, J.B.; Herkes, G.K.; Frith, J.A.

    1990-01-01

    Forty-two patients with clinically-definite multiple sclerosis were examined by magnetic resonance imaging using a 1.5-T instrument. Magnetic resonance imaging detected an abnormality in 90% of patients. In four patients, no lesions were demonstrated. The number, size and site of the lesions by magnetic resonance imaging were compared with the patients' clinical status and other variables. The Kurtzke disability status scale score increased in patients with corpus callosum atrophy, brainstem and basal ganglia lesions, and correlated with the total number of lesions. No correlation was shown between the findings of magnetic resonance imaging and disease duration, age, sex or pattern-reversal visual-evoked potentials. The variety of magnetic resonance images that could be obtained in patients with clinically-definite multiple sclerosis is highlighted. 24 refs., 8 figs., 1 tab

  6. The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Peng, Song; Zhao, Min; Wan, Jing; Fang, Qi; Fang, Dong; Li, Kaiyong

    2014-12-20

    This meta-analysis aimed to evaluate the efficacy of trimetazidine in combination with other anti-anginal drugs versus other anti-anginal drugs in the treatment of stable angina pectoris (SAP). Randomized controlled trials (RCTs) published in English and Chinese were retrieved from computerized databases: Embase, PubMed, and CNKI. Primary outcomes consist of clinical parameters (numbers of weekly angina attacks and nitroglycerin use) and ergometric parameters (time to 1mm ST-segment depression, and total work (in Mets) and exercise duration (in seconds) at peak exercise) in stable angina pectoris treated by trimetazidine or not. The quality of studies was evaluated using Jadad score. Data analysis of 13 studies was performed using Stata 12.0 software. Results showed that treatment of trimetazidine and other anti-anginal drugs was associated with a smaller weekly mean number of angina attacks (WMD=-0.95, 95%CI: -1.30 to -0.61, Z=5.39, Pangina pectoris. Sensitivity analysis was performed. Sub-group analysis showed that treatment duration was not a significant moderator and patients treated within 8 weeks and above 12 weeks had no difference in the outcomes addressed in this meta-analysis. No publish bias was detected. This meta-analysis confirms the efficacy of trimetazidine in the treatment of stable angina pectoris, in comparison with conventional antianginal agents, regardless of treatment duration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Angular-stable locking plate fixation of tibial plateau fractures-clinical and radiological midterm results in 101 patients

    OpenAIRE

    Sven Mardian; Felix Landmann; Florian Wichlas; Norbert P Haas; Klaus-Dieter Schaser; Philipp Schwabe

    2015-01-01

    Background: Articular reconstruction and stable fixation of tibial plateau fractures and its various subtypes continue to represent a surgical challenge. Only few trials have studied results following angular stable plate fixation. The present study aimed to investigate the clinical, radiological, functional and quality of life results following tibial plateau fractures using angular stable plate fixation. Materials and Methods: 101 patients were retrospectively studied using functional (...

  8. Incidence of mitral valve prolapse in one hundred clinically stable newborn baby girls: an echocardiographic study.

    Science.gov (United States)

    Chandraratna, P A; Vlahovich, G; Kong, Y; Wilson, D

    1979-09-01

    Clinical and echocardiographic examinations were performed on 100 clinically stable, newborn baby girls. Mitral valve prolapse was noted on the echocardiograms of seven babies. Three subjects had systolic clicks, two of whom had systolic murmurs following the click. The four other babies who had echocardiographic evidence of mitral valve prolapse had no abnormal auscultatory signs. Of the 93 babies without evidence of mitral prolapse, 91 had normal echocardiograms and auscultatory features; one was noted to have a murmur consistent with a ventricular septal defect, and another had an eccentric aortic valve on the echocardiogram which was suggestive of a bicuspid aortic valve. Serial studies on our group of subjects will yield useful information regarding the natural history of mitral valve prolapse.

  9. Stable isotope sup 15 N-urea and clinical research in nephrology

    Energy Technology Data Exchange (ETDEWEB)

    Sugino, Nobuhiro; Arai, Junko; Akimoto, Mitsuko; Miwa, Toichiro; Takuma, Takehide (Tokyo Women' s Medical Coll. (Japan))

    1990-08-01

    Stable isotope {sup 15}N-compound, {sup 15}N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. {sup 15}N-urea incorporation into plasma albumin in addition to plasma {sup 15}N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered {sup 15}N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through {sup 15}N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of {sup 15}N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive {sup 15}N-compounds should be provided and more simple but accurate measurement of {sup 15}N activity should be developed for the further clinical application of the stable isotope. (author).

  10. Stable isotope 15N-urea and clinical research in nephrology

    International Nuclear Information System (INIS)

    Sugino, Nobuhiro; Arai, Junko; Akimoto, Mitsuko; Miwa, Toichiro; Takuma, Takehide

    1990-01-01

    Stable isotope 15 N-compound, 15 N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. 15 N-urea incorporation into plasma albumin in addition to plasma 15 N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered 15 N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through 15 N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of 15 N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive 15 N-compounds should be provided and more simple but accurate measurement of 15 N activity should be developed for the further clinical application of the stable isotope. (author)

  11. Stable carbon isotope fractionation of chlorinated ethenes by a microbial consortium containing multiple dechlorinating genes.

    Science.gov (United States)

    Liu, Na; Ding, Longzhen; Li, Haijun; Zhang, Pengpeng; Zheng, Jixing; Weng, Chih-Huang

    2018-08-01

    The study aimed to determine the possible contribution of specific growth conditions and community structures to variable carbon enrichment factors (Ɛ- carbon ) values for the degradation of chlorinated ethenes (CEs) by a bacterial consortium with multiple dechlorinating genes. Ɛ- carbon values for trichloroethylene, cis-1,2-dichloroethylene, and vinyl chloride were -7.24% ± 0.59%, -14.6% ± 1.71%, and -21.1% ± 1.14%, respectively, during their degradation by a microbial consortium containing multiple dechlorinating genes including tceA and vcrA. The Ɛ- carbon values of all CEs were not greatly affected by changes in growth conditions and community structures, which directly or indirectly affected reductive dechlorination of CEs by this consortium. Stability analysis provided evidence that the presence of multiple dechlorinating genes within a microbial consortium had little effect on carbon isotope fractionation, as long as the genes have definite, non-overlapping functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

    Science.gov (United States)

    Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

    2017-07-01

    To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Characterizing the Effective Bandwidth of Nonlinear Vibratory Energy Harvesters Possessing Multiple Stable Equilibria

    Science.gov (United States)

    Panyam Mohan Ram, Meghashyam

    In the last few years, advances in micro-fabrication technologies have lead to the development of low-power electronic devices spanning critical fields related to sensing, data transmission, and medical implants. Unfortunately, effective utilization of these devices is currently hindered by their reliance on batteries. In many of these applications, batteries may not be a viable choice as they have a fixed storage capacity and need to be constantly replaced or recharged. In light of such challenges, several novel concepts for micro-power generation have been recently introduced to harness, otherwise, wasted ambient energy from the environment and maintain these low-power devices. Vibratory energy harvesting is one such concept which has received significant attention in recent years. While linear vibratory energy harvesters have been well studied in the literature and their performance metrics have been established, recent research has focused on deliberate introduction of stiffness nonlinearities into the design of these devices. It has been shown that, nonlinear energy harvesters have a wider steady-state frequency bandwidth as compared to their linear counterparts, leading to the premise that they can used to improve performance, and decrease sensitivity to variations in the design and excitation parameters. This dissertation aims to investigate this premise by developing an analytical framework to study the influence of stiffness nonlinearities on the performance and effective bandwidth of nonlinear vibratory energy harvesters. To achieve this goal, the dissertation is divided into three parts. The first part investigates the performance of bi-stable energy harvesters possessing a symmetric quartic potential energy function under harmonic excitations and carries out a detailed analysis to define their effective frequency bandwidth. The second part investigates the relative performance of mono- and bi-stable energy harvesters under optimal electric loading

  14. A major and stable QTL associated with seed weight in soybean across multiple environments and genetic backgrounds.

    Science.gov (United States)

    Kato, Shin; Sayama, Takashi; Fujii, Kenichiro; Yumoto, Setsuzo; Kono, Yuhi; Hwang, Tae-Young; Kikuchi, Akio; Takada, Yoshitake; Tanaka, Yu; Shiraiwa, Tatsuhiko; Ishimoto, Masao

    2014-06-01

    We detected a QTL for single seed weight in soybean that was stable across multiple environments and genetic backgrounds with the use of two recombinant inbred line populations. Single seed weight (SSW) in soybean is a key determinant of both seed yield and the quality of soy food products, and it exhibits wide variation. SSW is under genetic control, but the molecular mechanisms of such control remain unclear. We have now investigated quantitative trait loci (QTLs) for SSW in soybean and have identified such a QTL that is stable across multiple environments and genetic backgrounds. Two populations of 225 and 250 recombinant inbred lines were developed from crosses between Japanese and US cultivars of soybean that differ in SSW by a factor of ~2, and these populations were grown in at least three different environments. A whole-genome panel comprising 304 simple sequence repeat (SSR) loci was applied to mapping in each population. We identified 15 significant QTLs for SSW dispersed among 11 chromosomes in the two populations. One QTL located between Sat_284 and Sat_292 on chromosome 17 was detected (3.6 soybean.

  15. Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

    Science.gov (United States)

    Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Seyfferth, Ansgar; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Fernández-Paredes, Lidia; Albert, Matthew L.; Sánchez-Ramón, Silvia

    2015-01-01

    Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. PMID:26039252

  16. Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure.

    Science.gov (United States)

    Sorbets, Emmanuel; Labreuche, Julien; Simon, Tabassome; Delorme, Laurent; Danchin, Nicolas; Amarenco, Pierre; Goto, Shinya; Meune, Christophe; Eagle, Kim A; Bhatt, Deepak L; Steg, Philippe Gabriel

    2014-07-01

    The aim of this study was to determine whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) use is associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD) but without heart failure (HF) receiving contemporary medical management. Using data from the Reduction of Atherothrombosis for Continued Health (REACH) registry, we examined, using propensity score approaches, relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20 909 outpatients with stable CAD and free of HF at baseline. As internal control, we assessed the relation between statin use and outcomes. At 4-year follow-up, the risk of cardiovascular death, MI, or stroke (primary outcome) was similar in ACEI/ARB users compared with non-users (hazard ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.66). Similarly, the risk of the primary outcome and cardiovascular hospitalization for atherothrombotic events (secondary outcome) was not reduced in ACEI/ARB users (hazard ratio, 1.08; 95% CI, 1.01-1.16; P = 0.04), nor were the rates of any of its components. Analyses using propensity score matching yielded similar results, as did sensitivity analyses accounting for missing covariates, changes in medications over time, or analysing separately ACEI and ARB use. In contrast, in the same cohort, statin use was associated with lower rates for all outcomes. Use of ACEI/ARB was not associated with better outcomes in stable CAD outpatients without HF. The benefit of ACEI/ARB seen in randomized clinical trials was not replicated in this large contemporary cohort, which questions their value in this specific subset. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  17. Interrogating pollution sources in a mangrove food web using multiple stable isotopes.

    Science.gov (United States)

    Souza, Iara da C; Arrivabene, Hiulana P; Craig, Carol-Ann; Midwood, Andrew J; Thornton, Barry; Matsumoto, Silvia T; Elliott, Michael; Wunderlin, Daniel A; Monferrán, Magdalena V; Fernandes, Marisa N

    2018-06-01

    Anthropogenic activities including metal contamination create well-known problems in coastal mangrove ecosystems but understanding and linking specific pollution sources to distinct trophic levels within these environments is challenging. This study evaluated anthropogenic impacts on two contrasting mangrove food webs, by using stable isotopes (δ 13 C, δ 15 N, 87 Sr/ 86 Sr, 206 Pb/ 207 Pb and 208 Pb/ 207 Pb) measured in sediments, mangrove trees (Rhizophora mangle, Laguncularia racemosa, Avicennia schaueriana), plankton, shrimps (Macrobranchium sp.), crabs (Aratus sp.), oysters (Crassostrea rhizophorae) and fish (Centropomus parallelus) from both areas. Strontium and Pb isotopes were also analysed in water and atmospheric particulate matter (PM). δ 15 N indicated that crab, shrimp and oyster are at intermediate levels within the local food web and fish, in this case C. parallelus, was confirmed at the highest trophic level. δ 15 N also indicates different anthropogenic pressures between both estuaries; Vitória Bay, close to intensive human activities, showed higher δ 15 N across the food web, apparently influenced by sewage. The ratio 87 Sr/ 86 Sr showed the primary influence of marine water throughout the entire food web. Pb isotope ratios suggest that PM is primarily influenced by metallurgical activities, with some secondary influence on mangrove plants and crabs sampled in the area adjacent to the smelting works. To our knowledge, this is the first demonstration of the effect of anthropogenic pollution (probable sewage pollution) on the isotopic fingerprint of estuarine-mangrove systems located close to a city compared to less impacted estuarine mangroves. The influence of industrial metallurgical activity detected using Pb isotopic analysis of PM and mangrove plants close to such an impacted area is also notable and illustrates the value of isotopic analysis in tracing the impact and species affected by atmospheric pollution. Copyright © 2018 Elsevier B

  18. Ultra-sensitive, stable isotope assisted quantification of multiple urinary mycotoxin exposure biomarkers.

    Science.gov (United States)

    Šarkanj, Bojan; Ezekiel, Chibundu N; Turner, Paul C; Abia, Wilfred A; Rychlik, Michael; Krska, Rudolf; Sulyok, Michael; Warth, Benedikt

    2018-08-17

    There is a critical need to better understand the patterns, levels and combinatory effects of exposures we are facing through our diet and environment. Mycotoxin mixtures are of particular concern due to chronic low dose exposures caused by naturally contaminated food. To facilitate new insights into their role in chronic disease, mycotoxins and their metabolites are quantified in bio-fluids as biomarkers of exposure. Here, we describe a highly sensitive urinary assay based on ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) and 13 C-labelled or deuterated internal standards covering the most relevant regulated and emerging mycotoxins. Utilizing enzymatic pre-treatment, solid phase extraction and UHPLC separation, the sensitivity of the method was significantly higher (10-160x lower LODs) than in a previously described method used for comparison purpose, and stable isotopes provided compensation for challenging matrix effects. This method was in-house validated and applied to re-assess mycotoxin exposure in urine samples obtained from Nigerian children, adolescent and adults, naturally exposed through their regular diet. Owing to the methods high sensitivity, biomarkers were detected in all samples. The mycoestrogen zearalenone was the most frequently detected contaminant (82%) but also ochratoxin A (76%), aflatoxin M 1 (73%) and fumonisin B 1 (71%) were quantified in a large share of urines. Overall, 57% of 120 urines were contaminated with both, aflatoxin M 1 and fumonisin B 1 , and other co-exposures were frequent. These results clearly demonstrate the advanced performance of the method to assess lowest background exposures (pg mL -1 range) using a single, highly robust assay that will allow for the systematic investigation of low dose effects on human health. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  19. CT abnormality in multiple sclerosis analysis based on 28 probable cases and correlation with clinical manifestations

    International Nuclear Information System (INIS)

    Kakigi, Ryusuke; Shibasaki, Hiroshi; Tabira, Takeshi; Kuroiwa, Yoshigoro; Numaguchi, Yuji.

    1981-01-01

    In order to investigate the occurrence and nature of CT abnormality and its correlation with clinical manifestations in multiple sclerosis, 34 CT records obtained from 28 consecutive patients with probable multiple sclerosis were reviewed. Forty-six percent of all cases showed abnormal CT. Dilatation of cortical sulci was found in 39%; dilatation of the lateral ventricle in 36%; dilatation of prepontine or cerebello-pontine cistern and the fourth ventricle, suggesting brainstem atrophy, in 18%; dilatation of cerebellar sulci, superior cerebellar cistern and cisterna magna, suggesting cerebellar atrophy, in 11%. Low density area was found in the cerebral hemisphere in 11% of cases. Contrast enhancement, performed on 25 CT records, did not show any change. There was no correlation between CT abnormality and duration of the illness. Although abnormal CT tended to occur more frequently during exacerbations and chronic stable state than during remissions, the difference was not statistically significant. CT abnormalities suggesting brainstem atrophy, cerebellar atrophy or plaques were found exclusively during exacerbations and chronic stable state. The occurrence of CT abnormalities was not significantly different among various clinical forms which were classified based on clinically estimated sites of lesion, except that abnormal CT tended to occur less frequently in cases classified as the optic-spinal form. It is noteworthy that cerebral cortical atrophy and/or dilatation of the lateral ventricle were found in 31% of cases who did not show any clinical sign of cerebral involvement. There was a statistically significant correlation between CT abnormalities and levels of clinical disability. Eighty percent of the bedridden or severely disabled patients showed abnormal CT, in contrast with only 29% of those with moderate, slight or no disability. (author)

  20. CT abnormality in multiple sclerosis analysis based on 28 probable cases and correlation with clinical manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Kakigi, R.; Shibasaki, H.; Tabira, T.; Kuroiwa, Y. (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine); Numaguchi, Y.

    1981-10-01

    In order to investigate the occurrence and nature of CT abnormality and its correlation with clinical manifestations in multiple sclerosis, 34 CT records obtained from 28 consecutive patients with probable multiple sclerosis were reviewed. Forty-six percent of all cases showed abnormal CT. Dilatation of cortical sulci was found in 39%; dilatation of the lateral ventricle in 36%; dilatation of prepontine or cerebello-pontine cistern and the fourth ventricle, suggesting brainstem atrophy, in 18%; dilatation of cerebellar sulci, superior cerebellar cistern and cisterna magna, suggesting cerebellar atrophy, in 11%. Low density area was found in the cerebral hemisphere in 11% of cases. Contrast enhancement, performed on 25 CT records, did not show any change. There was no correlation between CT abnormality and duration of the illness. Although abnormal CT tended to occur more frequently during exacerbations and chronic stable state than during remissions, the difference was not statistically significant. CT abnormalities suggesting brainstem atrophy, cerebellar atrophy or plaques were found exclusively during exacerbations and chronic stable state. The occurrence of CT abnormalities was not significantly different among various clinical forms which were classified based on clinically estimated sites of lesion, except that abnormal CT tended to occur less frequently in cases classified as the optic-spinal form. It is noteworthy that cerebral cortical atrophy and/or dilatation of the lateral ventricle were found in 31% of cases who did not show any clinical sign of cerebral involvement. There was a statistically significant correlation between CT abnormalities and levels of clinical disability. Eighty percent of the bedridden or severely disabled patients showed abnormal CT, in contrast with only 29% of those with moderate, slight or no disability.

  1. Perfusion index variations in clinically and hemodynamically stable preterm newborns in the first week of life

    Directory of Open Access Journals (Sweden)

    Farinasso Daniela

    2010-01-01

    Full Text Available Abstract Background The perfusion index, derived from the pulse oximeter signal, seems to be an accurate predictor for high illness severity in newborns. The aim of this study was to determine the perfusion index values of clinically and hemodynamically stable preterm newborns in the first week of life. Methods Perfusion index recordings were performed on the first, third and seventh day of life on 30 preterm newborns. Their state of health was assessed according to clinical and behaviour evaluation and to the Score for Neonatal Acute Physiology. Results The median(interquartile range perfusion index values were 0.9(0.6 on the first, 1.2(1.0 on the third, and 1.3(0.9 on the seventh day, with a significant increase between the first and the third day. Conclusions Perfusion index proved to be an easily applicable, non-invasive method for monitoring early postnatal changes in peripheral perfusion. Its trend during the first week of life suggests that its clinical application should take age into account. Further studies are needed to obtain reference perfusion index values from a larger sample of preterm newborns, to identify specific gestational age-related cut-off values for illness and to test the role of perfusion index in monitoring critically ill neonates.

  2. Stable Isotopic Shifts in Fish Bones from Multiple Archeological Coastal Middens in Penobscot Bay, Maine

    Science.gov (United States)

    Harris, C.; Johnson, B.; Ambrose, W. G.; Bourque, B.; Dostie, P.; Crowley, E.

    2010-12-01

    The carbon and nitrogen stable isotope compositions of collagen extracted from well-preserved archeological fish bones has the potential to provide useful information on fish diets and food web dynamics over time. Previous work on the Turner Farm archaeological site in Penobscot Bay, Gulf of Maine, reveals significant shifts in fish diets have occurred since European colonization (post 1620’s). The objective of the present study was to analyze samples from other archaeological sites within Penobscot Bay to characterize the spatial extent of the isotopic shift measured at Turner Farm. Stratified cod, flounder, and sculpin bones were analyzed from eight coastal middens located approximately 50km apart from one another within Penobscot Bay. The bones were sampled from three time horizons (0kya, 0.5-1kya, and 2.2-2.4kya). All bone samples were demineralized in 0.2M HCl at 4°C for 2 to 7 days and then extracted in 0.25M NaOH at 4°C for 1 to 2 hours. After freeze-drying, the bulk isotopic composition of each sample was analyzed using the EA-IRMS. In all stratigraphic horizons analyzed, cod were more enriched in δ13C and δ15N than sculpin, and flounder were the most depleted in δ13C and δ15N . However, the isotopic offsets between the fish species decreased from 2.4kya to the present. The nitrogen isotope composition was relatively constant over time and space for all species, implying that trophic levels for the fishes analyzed have not changed significantly in Penobscot Bay for the last 2,400 years. The carbon isotope composition also appears to be constant spatially in Penobscot Bay, however, the modern signal was more depleted than the paleo signal in all three species. The difference between the modern and paleo δ13C is ~5‰ for cod and flounder, and ~9‰ for sculpin. These shifts may, in part, be explained by decreases in both primary producer and prey species diversity, as kelp forests replace eelgrass beds in the Gulf of Maine.

  3. Disability outcome measures in multiple sclerosis clinical trials

    DEFF Research Database (Denmark)

    Cohen, Jeffrey A; Reingold, Stephen C; Polman, Chris H

    2012-01-01

    Many of the available disability outcome measures used in clinical trials of multiple sclerosis are insensitive to change over time, inadequately validated, or insensitive to patient-perceived health status or quality of life. Increasing focus on therapies that slow or reverse disability...... recommend practical refinements. Conversely, although substantial data support the multiple sclerosis functional composite as an alternative measure, changes to its component tests and scoring method are needed. Novel approaches, including the use of composite endpoints, patient-reported outcomes...... progression makes it essential to refine existing measures or to develop new tools. Major changes to the expanded disability status scale should be avoided to prevent the loss of acceptance by regulators as a measure for primary outcomes in trials that provide substantial evidence of effectiveness. Rather, we...

  4. Engineering a horseradish peroxidase C stable to radical attacks by mutating multiple radical coupling sites.

    Science.gov (United States)

    Kim, Su Jin; Joo, Jeong Chan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

    2015-04-01

    Peroxidases have great potential as industrial biocatalysts. In particular, the oxidative polymerization of phenolic compounds catalyzed by peroxidases has been extensively examined because of the advantage of this method over other conventional chemical methods. However, the industrial application of peroxidases is often limited because of their rapid inactivation by phenoxyl radicals during oxidative polymerization. In this work, we report a novel protein engineering approach to improve the radical stability of horseradish peroxidase isozyme C (HRPC). Phenylalanine residues that are vulnerable to modification by the phenoxyl radicals were identified using mass spectrometry analysis. UV-Vis and CD spectra showed that radical coupling did not change the secondary structure or the active site of HRPC. Four phenylalanine (Phe) residues (F68, F142, F143, and F179) were each mutated to alanine residues to generate single mutants to examine the role of these sites in radical coupling. Despite marginal improvement of radical stability, each single mutant still exhibited rapid radical inactivation. To further reduce inactivation by radical coupling, the four substitution mutations were combined in F68A/F142A/F143A/F179A. This mutant demonstrated dramatic enhancement of radical stability by retaining 41% of its initial activity compared to the wild-type, which was completely inactivated. Structure and sequence alignment revealed that radical-vulnerable Phe residues of HPRC are conserved in homologous peroxidases, which showed the same rapid inactivation tendency as HRPC. Based on our site-directed mutagenesis and biochemical characterization, we have shown that engineering radical-vulnerable residues to eliminate multiple radical coupling can be a good strategy to improve the stability of peroxidases against radical attack. © 2014 Wiley Periodicals, Inc.

  5. Are there long-term benefits in following stable heart failure patients in a heart failure clinic?

    DEFF Research Database (Denmark)

    Leetmaa, Tina; Villadsen, Henrik; Mikkelsen, Kirsten

    2008-01-01

    Objectives and Design. This study describes the long-term outcome of 163 patients with stable mild to moderate heart failure (NYHA II-III), who already were enrolled in a heart failure clinic and now were randomized to continued follow-up in the heart failure (HF) clinic or else to usual care (UC...

  6. Self-organized criticality: An interplay between stable and turbulent regimes of multiple anodic double layers in glow discharge plasma

    Science.gov (United States)

    Alex, Prince; Carreras, Benjamin Andres; Arumugam, Saravanan; Sinha, Suraj Kumar

    2018-05-01

    The role of self-organized criticality (SOC) in the transformation of multiple anodic double layers (MADLs) from the stable to turbulent regime has been investigated experimentally as the system approaches towards critical behavior. The experiment was performed in a modified glow discharge plasma setup, and the initial stable state of MADL comprising three concentric perceptible layers was produced when the drift velocity of electrons towards the anode exceeds the electron thermal velocity (νd ≥ 1.3νte). The macroscopic arrangement of both positive and negative charges in opposite layers of MADL is attributed to the self-organization scenario. Beyond νd ≥ 3νte, MADL begins to collapse and approaches critical and supercritical states through layer reduction which continue till the last remaining layer of the double layer is transformed into a highly unstable radiant anode glow. The avalanche resulting from the collapse of MADL leads to the rise of turbulence in the system. Long-range correlations, a key signature of SOC, have been explored in the turbulent floating potential fluctuations using the rescaled-range analysis technique. The result shows that the existence of the self-similarity regime with self-similarity parameter H varies between 0.55 and 0.91 for time lags longer than the decorrelation time. The power law tail in the rank function, slowly decaying tail of the autocorrelation function, and 1/f behavior of the power spectra of the fluctuations are consistent with the fact that SOC plays a conclusive role in the transformation of MADL from the stable to turbulent regime. Since the existence of SOC gives a measure of complexity in the system, the result provides the condition under which complexity arises in cold plasma.

  7. Prevalence, demographics and clinical characteristics of multiple sclerosis in Qatar.

    Science.gov (United States)

    Deleu, Dirk; Mir, Danial; Al Tabouki, Ahmed; Mesraoua, Rim; Mesraoua, Boulenouar; Akhtar, Naveed; Al Hail, Hassan; D'souza, Atlantic; Melikyan, Gayane; Imam, Yahia Z B; Osman, Yasir; Elalamy, Osama; Sokrab, Tageldin; Kamran, Sadaat; Ruiz Miyares, Francisco; Ibrahim, Faiza

    2013-05-01

    No published epidemiologic data on multiple sclerosis (MS) in Qatar exist. Our objectives were to determine the prevalence, demographics and clinical characteristics of MS in the Middle Eastern country of Qatar. We analyzed data for Qatari MS patients fulfilling the McDonald diagnostic criteria. A total of 154 patients fulfilled the inclusion criteria. On 31 April 2010, the crude prevalence of MS in Qatar was 64.57 per 100,000 inhabitants (95% CI: 58.31-70.37). The female-to-male ratio was 1.33:1. A positive family history was found in 10.4% of included MS patients. We conclude that Qatar is now a medium-to-high risk area for MS, with some important differences in clinical characteristics as compared to other countries in the region.

  8. Terminology development towards harmonizing multiple clinical neuroimaging research repositories.

    Science.gov (United States)

    Turner, Jessica A; Pasquerello, Danielle; Turner, Matthew D; Keator, David B; Alpert, Kathryn; King, Margaret; Landis, Drew; Calhoun, Vince D; Potkin, Steven G; Tallis, Marcelo; Ambite, Jose Luis; Wang, Lei

    2015-07-01

    Data sharing and mediation across disparate neuroimaging repositories requires extensive effort to ensure that the different domains of data types are referred to by commonly agreed upon terms. Within the SchizConnect project, which enables querying across decentralized databases of neuroimaging, clinical, and cognitive data from various studies of schizophrenia, we developed a model for each data domain, identified common usable terms that could be agreed upon across the repositories, and linked them to standard ontological terms where possible. We had the goal of facilitating both the current user experience in querying and future automated computations and reasoning regarding the data. We found that existing terminologies are incomplete for these purposes, even with the history of neuroimaging data sharing in the field; and we provide a model for efforts focused on querying multiple clinical neuroimaging repositories.

  9. Return to work after thoracic organ transplantation in a clinically-stable population.

    Science.gov (United States)

    Petrucci, Lucia; Ricotti, Susanna; Michelini, Ilaria; Vitulo, Patrizio; Oggionni, Tiberio; Cascina, Alessandro; D'Armini, Andrea M; Goggi, Claudio; Campana, Carlo; Viganò, Mario; Dalla-Toffola, Elena; Tinelli, Carmine; Klersy, Catherine

    2007-11-01

    To evaluate the rate of return to work after transplantation and its determinants in a clinically-stable population of patients transplanted and followed-up at a single institution in Italy. 151 thoracic organ transplant recipients (72 lung, 79 heart) were examined. Patients were asked about daily activities, level of education, employment and clinical condition. A six-minute walking test was performed with measurement of dyspnoea using the Borg scale. Quality of Life was evaluated with the SF-36 and GHQ questionnaires. Before transplantation 131 patients (87%), (70 heart and 61 lung) worked. After transplantation, 51 patients (39%) went back to work and 3 more started working. We found that younger age, a better quality of life (mainly in the mental domain), having had an occupation previously (particularly as an entrepreneur/freelancer), and having been off work for less than 24 months, were independent predictors of return to work. Considering their good, objective and subjective, functional status, some patients who could have returned to work, chose not to. Identifying factors which affect return to work might help health professionals to adopt the best course of treatment and psychological support in order to fulfil this goal; however, return to work should not be considered as the only expression of a patient's real psychophysical condition.

  10. Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate.

    Directory of Open Access Journals (Sweden)

    Tarah Lynch

    Full Text Available BACKGROUND: Clostridium difficile are gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15-35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. CONCLUSIONS/SIGNIFICANCE: This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.

  11. 3T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing-remitting multiple sclerosis: a 3-year pilot study.

    Science.gov (United States)

    Zhang, Y; Metz, L M; Yong, V W; Mitchell, J R

    2010-10-15

    Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients. Copyright 2010 Elsevier B.V. All rights reserved.

  12. Multiple intraductal papillomas of breast clinically masquerading as malignancy

    Directory of Open Access Journals (Sweden)

    Singh Pallavi

    2010-01-01

    Full Text Available Background: Intraductal papilloma is characterized by proliferation of epithelial and myoepithelial cells overlying fibro-vascular stalks creating an arborescent structure within the lumen of duct. Some times multiple papillomas with florid proliferation of epithelium may be confused with malignancy. A case of multiple intraductal papillomas of breast with ulceration of overlying skin and large lump leading to clinical diagnosis of malignancy is documented here. Case Report: A 45-year-old female presented with ulcerated mass of six months duration in the left breast. On examination, a firm, immobile lump of 8× 10 cm in size involving nipple with excoriation of surrounding skin and serosanguinous discharge from nipple was present. There was no axillary lymphadenopathy. No family history of carcinoma breast was present. Fine needle aspiration smears showed benign cellular changes with apocrine metaplasia. Biopsy from an area adjacent to nipple showed intraductal papilloma. Simple mastectomy showed lobulated dirty white mass with well circumscribed nodules below the nipple and areola. On histology with immunohistochemistry a diagnosis of multiple intraductal papillomas was made. Patient is on regular follow-up and doing well. Conclusion: The case highlights the problem in differentiating marked papillomatosis from a malignant lesion of breast and importance of biopsy with immunohistochemistry in such cases for proper management.

  13. Clinical and MRI features in pediatric multiple sclerosis

    International Nuclear Information System (INIS)

    Zhao Cailei; Xie Sheng; Xiao Jiangxi; Wang Shuang

    2011-01-01

    Objective: To investigate the clinical and MRI features of multiple sclerosis in children, including the clinically isolated syndrome (CIS) and relapse. Methods: In total, 16 cases of pediatric multiple sclerosis were included in this study. Of them, 11 patients were female and 5 were male, with the mean onset age of 10.1 years. They were followed up for 4 months to 7 years and found to have 1- 5 relapses. The clinical manifestations of CIS and relapse were analyzed by a pediatric neurologist. An experienced neuroradiologist reviewed the MRI images of CIS and relapse. Information on the location, size, and pattern of the lesions was gathered. The location of lesions included subcortical, central, and periventricular white matter, cortex, deep gray matter, brain stem, and cerebellum. Results: CIS episode presented acute onsets in 13/16 cases, with symptoms of cortices in 10 cases and visual impairment in 6 cases. Relapse occurred in 14/16 cases within one year. The incidence of symptoms of cortices was less frequent and severe in the second episode of MS, whereas the visual impairment had a high incidence. All patients had full recovery after the last episode. MRI of CIS showed confluent subcortical white matter lesions in 13/16 cases, abutting on central white matter lesions. The most frequently involved brain part was the frontal lobe, followed by the parietal lobe. Cortical involvement was observed in 9/16 cases. In 6 cases, periventricular white matter lesions were detected. Bilateral deep gray matter was abnormal in 4 cases. Other abnormalities included brain stem lesions in 5 cases, cerebellum lesions in 3 cases, optic nerve involvement in 3 cases, and pyramidal tract lesions in 2 cases. MRI of relapse revealed more small lesions in the subcortical and periventricular white matter in the patients. In the second episode, only 2 cases presented cortical involvement. Lesions were found in the brain stem in 4 cases and in the cerebellum in 5 cases. Pyramidal tract

  14. Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

    Science.gov (United States)

    El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

    2016-09-01

    Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

  15. Smoking, season, and detection of chlamydia pneumoniae DNA in clinically stable COPD patients

    Directory of Open Access Journals (Sweden)

    Goldsmith Charles H

    2002-07-01

    Full Text Available Abstract Background The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD remain unclear. Methods Peripheral blood mononuclear cells were obtained from 100 outpatients with smoking-related, clinically stable COPD, and induced sputum was obtained in 62 patients. Results Patients had mean age (standard deviation of 65.8 (10.7 years, mean forced expiratory volume in one second of 1.34 (0.61 L, and 61 (61.0% were male. C. pneumoniae nucleic acids were detected by nested polymerase chain reaction in 27 (27.0%. Current smoking (odds ratio {OR} = 2.6, 95% confidence interval {CI}: 1.1, 6.6, P = 0.04, season (November to April (OR = 3.6, 95% CI: 1.4, 9.2, P = 0.007, and chronic sputum production (OR = 6.4, 95% CI: 1.8, 23.2, P = 0.005 were associated with detection of C. pneumoniae DNA. Conclusions Prospective studies are needed to examine the role of C. pneumoniae nucleic acid detection in COPD disease symptoms and progression.

  16. Residual Negative Symptoms Differentiate Cognitive Performance in Clinically Stable Patients with Schizophrenia and Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Rajeev Krishnadas

    2014-01-01

    Full Text Available Cognitive deficits in various domains have been shown in patients with bipolar disorder and schizophrenia. The purpose of the present study was to examine if residual psychopathology explained the difference in cognitive function between clinically stable patients with schizophrenia and bipolar disorder. We compared the performance on tests of attention, visual and verbal memory, and executive function of 25 patients with schizophrenia in remission and 25 euthymic bipolar disorder patients with that of 25 healthy controls. Mediation analysis was used to see if residual psychopathology could explain the difference in cognitive function between the patient groups. Both patient groups performed significantly worse than healthy controls on most cognitive tests. Patients with bipolar disorder displayed cognitive deficits that were milder but qualitatively similar to those of patients with schizophrenia. Residual negative symptoms mediated the difference in performance on cognitive tests between the two groups. Neither residual general psychotic symptoms nor greater antipsychotic doses explained this relationship. The shared variance explained by the residual negative and cognitive deficits that the difference between patient groups may be explained by greater frontal cortical neurophysiological deficits in patients with schizophrenia, compared to bipolar disorder. Further longitudinal work may provide insight into pathophysiological mechanisms that underlie these deficits.

  17. Malignant multiple sclerosis: clinical and demographic prognostic factors

    Directory of Open Access Journals (Sweden)

    Fabrício Hampshire-Araújo

    Full Text Available ABSTRACT Patients with malignant multiple sclerosis (MMS reach a significant level of disability within a short period of time (Expanded Disability Status Scale score of 6 within five years. The clinical profile and progression of the disease were analyzed in a Brazilian cohort of 293 patients. Twenty-five (8,53% patients were found to have MMS and were compared with the remaining 268 (91,47%. Women, non-white patients, older age at disease onset, shorter intervals between the first attacks, and more attacks in the first two years of the disease were all more common in the MMS group. These findings could serve as prognostic factors when making therapeutic decisions.

  18. Meniscectomy versus meniscal repair: 10 years radiological and clinical results in vertical lesions in stable knee.

    Science.gov (United States)

    Lutz, C; Dalmay, F; Ehkirch, F P; Cucurulo, T; Laporte, C; Le Henaff, G; Potel, J F; Pujol, N; Rochcongar, G; Salledechou, E; Seil, R; Gunepin, F-X; Sonnery-Cottet, B

    2015-12-01

    Surgical management of meniscal lesion consists of either a meniscectomy or meniscal repair. Although repair offers immediate recovery after surgery, it is also associated with higher rates of revision. A meniscectomy, on the other hand is known to be associated with an early onset of osteoarthritis. The present study compared clinical and radiological results at 10 years between meniscectomy and meniscal repair in isolated vertical lesion in an otherwise stable knee. The hypothesis was that repair shows functional and radiological benefit over meniscectomy. A multi-centric retrospective comparative study of 32 patients (24 male, 8 female). Mean follow-up was 10.6 years (range, 10-13 years). There were 10 meniscal repairs (group R) and 22 meniscectomies (group M), in 17 right and 15 left knees. Mean age at surgery was 33.45±12.3 years (range, 9-47 years). There were 28 medial and 4 lateral meniscal lesions; 26 were in the red-red zone and 6 in red-white zone. Functional score: KOOS score was significantly higher in group R than M on almost all parameters: 98±4.69 versus 77.38±21.97 for symptoms (P=0.0043), 96.89±7.20 versus 78.57±18.9 for pain (P=0.0052), 99.89±0.33 versus 80.88±19.6 for daily life activities (P=0.0002), 96.11±9.83 versus 54.05±32.85 for sport and leisure (P=0.0005), but 91±16.87 versus 68.15±37.7 for quality of life (P=0.1048). Radiology score: in group R, 7 patients had no features of osteoarthritis, and 2 had grade 1 osteoarthritis. In group M, 5 patients had grade 1 osteoarthritis, 10 grade 2, 3 grade 3 and 3 grade 4. Mean quantitative score was 0 (mean, 0.22±0.44) in-group R and 2 (mean, 2.19±0.98) in group M (P<0.0001). At more than 10year's follow-up, functional scores were significantly better with meniscal repair than meniscectomy on all parameters of the KOOS scale except quality of life. Functional and radiological scores correlated closely. These results show that meniscal repair for vertical lesions in stable knees

  19. Chaos theory for clinical manifestations in multiple sclerosis.

    Science.gov (United States)

    Akaishi, Tetsuya; Takahashi, Toshiyuki; Nakashima, Ichiro

    2018-06-01

    Multiple sclerosis (MS) is a demyelinating disease which characteristically shows repeated relapses and remissions irregularly in the central nervous system. At present, the pathological mechanism of MS is unknown and we do not have any theories or mathematical models to explain its disseminated patterns in time and space. In this paper, we present a new theoretical model from a viewpoint of complex system with chaos model to reproduce and explain the non-linear clinical and pathological manifestations in MS. First, we adopted a discrete logistic equation with non-linear dynamics to prepare a scalar quantity for the strength of pathogenic factor at a specific location of the central nervous system at a specific time to reflect the negative feedback in immunity. Then, we set distinct minimum thresholds in the above-mentioned scalar quantity for demyelination possibly causing clinical relapses and for cerebral atrophy. With this simple model, we could theoretically reproduce all the subtypes of relapsing-remitting MS, primary progressive MS, and secondary progressive MS. With the sensitivity to initial conditions and sensitivity to minute change in parameters of the chaos theory, we could also reproduce the spatial dissemination. Such chaotic behavior could be reproduced with other similar upward-convex functions with appropriate set of initial conditions and parameters. In conclusion, by applying chaos theory to the three-dimensional scalar field of the central nervous system, we can reproduce the non-linear outcome of the clinical course and explain the unsolved disseminations in time and space of the MS patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Diabetes mellitus and cardiovascular clinical characteristics of Spanish women with stable ischaemic heart disease: Data from the SIRENA study.

    Science.gov (United States)

    Gámez, José M; Masmiquel, Luis; Ripoll, Tomás; Barrios, Vivencio; Anguita, Manuel

    2017-01-01

    The relationship between diabetes and the cardiovascular clinical characteristics of Spanish women with stable ischaemic heart disease was studied in a nationwide cross-sectional study. Diabetes was related to a higher burden of risk factors, comorbidity, multivessel disease and coronary surgery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD

    Directory of Open Access Journals (Sweden)

    Singh Dave

    2011-01-01

    Full Text Available Abstract Introduction COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales. Method We assessed 120 patients with moderate COPD (FEV1% 52, men 62%, age 66. Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6. Results A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007. TNF-α remained positively correlated with depression (p = 0.024 after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV1%, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044. Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7 had higher mean CES-D depression score than the rest of the sample (p = 0.03. Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054. Conclusion This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.

  2. Stratifying a Risk for an Increased Variation of Airway Caliber among the Clinically Stable Asthma

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    Atsushi Hayata

    2013-01-01

    Conclusions: These results indicate that ACQ, %FEV1 and FENO can stratify the risk for increased variation in airway caliber among patients with stable asthma. This may help identify subjects in whom further monitoring of lung function fluctuations is indicated.

  3. Systematic review of clinical practice guidelines related to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Jia Guo

    Full Text Available BACKGROUND: High quality clinical practice guidelines (CPGs can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS has not been evaluated. OBJECTIVE: To evaluate the methodological quality of CPGs on MS using the AGREE II instrument. METHODS: According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC, and Chinese Biomedical Literature database (CBM. The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0. RESULTS: A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70. The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05 ± 16.13, stakeholder involvement (mean ± SD: 29.53 ± 17.67, rigor of development (mean ± SD: 31.52 ± 21.50, clarity of presentation (mean ± SD: 60.39 ± 13.73, applicability (mean ± SD: 27.08 ± 17.66, editorial independence (mean ± SD: 28.70 ± 22.03. CONCLUSIONS: The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.

  4. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-12-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses.

  5. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    International Nuclear Information System (INIS)

    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-01-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses

  6. Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities

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    Oh YM

    2013-01-01

    Full Text Available Yeon-Mok Oh,1 Arvind B Bhome,2 Watchara Boonsawat,3 Kirthi Dias Gunasekera,4 Dushantha Madegedara,5 Luisito Idolor,6 Camilo Roa,6 Woo Jin Kim,7 Han-Pin Kuo,8 Chun-Hua Wang,8 Le Thi Tuyet Lan,9 Li-Cher Loh,10 Choo-Khoon Ong,10 Alan Ng,11 Masaharu Nishimura,12 Hironi Makita,12 Edwin K Silverman,13 Jae Seung Lee,1 Ting Yang,14 Yingxiang Lin,14 Chen Wang,14 Sang-Do Lee1  1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care, "Friends of the Breathless" Foundation, Pune, India; 3Department of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Central Chest Clinic, Colombo and National Hospital of Sri Lanka; 5Respiratory Disease Treatment Unit and Teaching Hospital Kandy, Sri Lanka; 6Section of Respiratory Services and Physical Therapy and Rehabilitation Lung Center of the Philippines, Quezon City, Philippines; 7Department of Internal Medicine, Kangwon National University, Kang Won, Korea; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 9Respiratory Care Center, University Medical Center Ho Chi Minh City, Vietnam; 10Department of Medicine, Penang Medical College, Penang, Malaysia; 11Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore; 12Division of Respiratory Medicine, Department of Internal Medicine, Hokkaido University Hospital, Sapporo, Japan; 13Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 14Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaAll authors made an equal contribution to this studyBackground and objectives: Chronic obstructive pulmonary disease (COPD is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in

  7. Challenges in clinical studies with multiple imaging probes

    International Nuclear Information System (INIS)

    Krohn, Kenneth A.; O'Sullivan, Finbarr; Crowley, John; Eary, Janet F.; Linden, Hannah M.; Link, Jeanne M.; Mankoff, David A.; Muzi, Mark; Rajendran, Joseph G.; Spence, Alexander M.; Swanson, Kristin R.

    2007-01-01

    This article addresses two related issues: (a) When a new imaging agent is proposed, how does the imager integrate it with other biomarkers, either sampled or imaged? (b) When we have multiple imaging agents, is the information additive or duplicative and how is this objectively determined? Molecular biology is leading to new treatment options with reduced normal tissue toxicity, and imaging should have a role in objectively evaluating new treatments. There are two roles for molecular characterization of disease. Molecular imaging measurements before therapy help predict the aggressiveness of disease and identify therapeutic targets and, therefore, help choose the optimal therapy for an individual. Measurements of specific biochemical processes made during or after therapy should be sensitive measures of tumor response. The rules of evidence are not fully developed for the prognostic role of imaging biomarkers, but the potential of molecular imaging provides compelling motivation to push forward with convincing validation studies. New imaging procedures need to be characterized for their effectiveness under realistic clinical conditions to improve the management of patients and achieve a better outcome. The purpose of this article is to promote a critical discussion within the molecular imaging community because our future value to the overall biomedical community will be in supporting better treatment outcomes rather than in detection

  8. Analyzing clinical symptoms in multiple sclerosis using data mining

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    Zahra Raeisi

    2017-04-01

    Full Text Available Background: One of the today most common and incurable diseases that is associated with central neural system is ‘MS’ disease. Multiple sclerosis (MS is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. In this disease become apparent a wide spectrum of symptoms such as lose muscles control and their coordination and vision derangement. The goal of this research is to consider to two problems: 1- Recognition of effective clinical symptoms on MS disease and 2- Considering levels of effectiveness of age, sex and education levels factors on MS disease and association between these factors according to verity of categories of this disease. Methods: Data mining science in medicine is worthy of attention with main application in diagnosis, therapy and prognosis, respectively high volume of collected datum. The data that were used in this article are about patients of Chaharmahal and Bakhtiari Province and collected by cure assistance. In this paper classification and association methods in software engineering field are used. Classification is a general process related to categorization, the process in which ideas and objects are recognized, differentiated, and understood. Association rules are created by analyzing data for frequent if/then patterns and using the criteria support and confidence to identify the most important relationships. Results: In consideration of first problem in this paper, concluded vision-clinical symptoms are the most effective symptoms and in consideration of second problem, concluded that from 584 records, women affected four times more than men. In other word 70% of MS patients with high graduate are in relapsing-remitting category and 62.5% of MS patients are 20-40 years old. Conclusion: Some of symptoms are quite temporary and transitory and are ignored by people. Awareness of clinical-symptoms prevalence manner can be warning for people before starting

  9. Clinical application of stable xenon CT-CBF studies without denitrogenation

    Energy Technology Data Exchange (ETDEWEB)

    Touho, Hajime; Karasawa, Jun; Shishido, Hisashi; Yamada, Keisuke [Osaka Neurological Institute, Toyonaka (Japan)

    1990-08-01

    Noninvasive and simplified methods for estimating regional cerebral blood flow (CBF) and regional partition coefficient ({lambda}) using the inhalation of stable xenon (Xe{sup s}) and computed tomographic (CT) scanning are described. Thirty percent Xe{sup s} in 70% oxygen was inhaled for 240 seconds and exhaled for 160 seconds during serial CT scanning without denitrogenation in 26 patients with cerebrovascular diseases and four volunteer controls. During the investigation, the end-tidal Xe{sup s} concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) of the artery by the curve fitting method. Calculated A and K values were corrected by the following formulae reported previously: for patients aged 0-20 years, A{sub e} = 0.75A{sub a} + 2.15, K{sub e} = 0.67K{sub a} + 0.69; 21-40 years, A{sub e} = 0.56A{sub a} + 3.24, K{sub e} = 0.38K{sub a} + 1.12; 41-60 years, A{sub e} = 0.91A{sub a} + 1.95, K{sub e} = 0.38K{sub a} + 1.32; over 61 years, A{sub e} = 0.52A{sub a} + 3.81, K{sub e} = 0.31K{sub a} + 1.55 (A{sub e} and K{sub e} were calculated with end-tidal Xe{sup s} concentration, A{sub a} and K{sub a} were calculated by direct sampling of arterial blood). A CBF map (f map) and {lambda} map made with corrected A and K values demonstrated reliable distribution. The CBF was high in the gray matter, low in the white matter, and much lower in the infarcted area. {lambda} was high in the white matter, low in the gray matter, and much lower in the infarcted area. Eight patients were examined with and without denitrogenation. Both the f map and {lambda} map with denitrogenation were compatible with those without denitrogenation. Xe{sup s} CT-CBF studies without denitrogenation are useful in clinical neurosurgery and outpatients for estimating regional cerebral circulation. (author).

  10. Evolution of Subaerial Coastal Fluvial Delta Island Topography into Multiple Stable States Under Influence of Vegetation and Stochastic Hydrology

    Science.gov (United States)

    Moffett, K. B.; Smith, B. C.; O'Connor, M.; Mohrig, D. C.

    2014-12-01

    Coastal fluvial delta morphodynamics are prominently controlled by external fluvial sediment and water supplies; however, internal sediment-water-vegetation feedbacks are now being proposed as potentially equally significant in organizing and maintaining the progradation and aggradation of such systems. The time scales of fluvial and climate influences on these feedbacks, and of their responses, are also open questions. Historical remote sensing study of the Wax Lake Delta model system (Louisiana, USA) revealed trends in the evolution of the subaerial island surfaces from a non-systematic arrangement of elevations to a discrete set of levees and intra-island platforms with distinct vegetation types, designated as high marsh, low marsh, and mudflat habitat. We propose that this elevation zonation is consistent with multiple stable state theory, e.g. as applied to tidal salt marsh systems but not previously to deltas. According to zonally-distributed sediment core analyses, differentiation of island elevations was not due to organic matter accumulation as in salt marshes, but rather by differential mineral sediment accumulation with some organic contributions. Mineral sediment accumulation rates suggested that elevation growth was accelerating or holding steady over time, at least to date in this young delta, in contrast to theory suggesting rates should slow as elevation increases above mean water level. Hydrological analysis of island flooding suggested a prominent role of stochastic local storm events in raising island water levels and supplying mineral sediment to the subaerial island surfaces at short time scales; over longer time scales, the relative influences of local storms and inland/regional floods on the coupled sediment-water-vegetation system of the subaerial delta island surfaces remain the subject of ongoing study. These results help provide an empirical foundation for the next generation of coupled sediment-water-vegetation modeling and theory.

  11. Progress in stable isotope analysis and new possibilities of clinical investigations

    International Nuclear Information System (INIS)

    Roth, E.

    1989-01-01

    The use of stable isotopes in medicine rests on three possibilities offered by labelling: identification of an element, a molecule, or a fragment of a molecule along its biological pathway; quantification of biological pools by isotopic dilution; measurement of metabolization rates, and more generally of clearances. Whenever a corporal function experiences a disregulation reflected either by changes in metabolic activity or modifications of the importance of pools of certain molecules, the possibility exists of making use of isotopes in diagnosis. Examples of practical applications of stable isotopes are given and analytical problems that had to be solved are underlined

  12. Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

    Science.gov (United States)

    Lorente Fernández, L; Monte Boquet, E; Pérez-Miralles, F; Gil Gómez, I; Escutia Roig, M; Boscá Blasco, I; Poveda Andrés, J L; Casanova-Estruch, B

    2014-06-01

    Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  13. Clinical Holistic Medicine: The Patient with Multiple Diseases

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    Søren Ventegodt

    2005-01-01

    Full Text Available In clinical practice, patients can present with many different diseases, often both somatic and mental. Holistic medicine will try to see the diseases as a whole, as symptoms of a more fundamental imbalance in the state of being. The holistic physician must help the patient to recover existence and a good relationship with self. According to the life mission theory, theory of character, and holistic process theory of healing, recovering the purpose of life (the life mission is essential for the patient to regain life, love, and trust in order to find happiness and realize the true purpose of life. We illustrate the power of the holistic medical approach with a case study of an invalidated female artist, aged 42 years, who suffered from multiple severe health problems, many of which had been chronic for years. She had a combination of neurological disturbances (tinnitus, migraine, minor hallucinations, immunological disturbances (recurrent herpes simplex, phlegm in the throat, fungal infection in the crotch, hormonal disturbances (14 days of menstruation in each cycle, muscle disturbances (neck tensions, mental disturbances (tendency to cry, inferiority feeling, mild depression, desolation, anxiety, abdominal complaints, hemorrhoids, and more. The treatment was a combined strategy of improving the general quality of life, recovering her human character and purpose of life (“renewing the patients life energy”, “balancing her global information system”, and processing the local blockages, thus healing most of her many different diseases in a treatment using 30 h of intense holistic therapy over a period of 18 months.

  14. Clinical and MRI correlation in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Negoro, Kiyoshi; Morimatsu, Mitsunori (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1994-05-01

    By using magnetic resonance imaging (MRI), we studied 11 patients with multiple system atrophy (MSA): 5 olivo-pontocerebellar atrophy (OPCA), 2 Shy-Drager syndrome (SDS), and 4 striatonigral degeneration (SND). The diagnoses of OPCA, SDS and SND were clinically made. The MR images were performed on 1.5 tesla MRI unit (Siemens Asahi Medical, Magnetom H15), using a T[sub 2]-weighted spin echo (SE) sequence (TR: 2000-3000 ms, TE: 80-90 ms), a T[sub 1]-weighted SE sequence (TR: 550, TE: 15), and a proton density-weighted (PD) SE sequence (TR: 2000-3000, TE: 12-22). In the patients with OPCA, MRI revealed cerebellar and brainstem atrophy and degeneration of pontine transverse fibers more marked than in the patients with SDS and SND. T[sub 2]-weighted images showed low intensity in posterolateral putamina in one OPCA patient and all of SDS and SND patients. PD images demonstrated the abnormal slit-like high signals in posterolateral putamina in three SND. The degree of cerebellar ataxia was not well correlated with cerebellar and brainstem atrophy and degeneration of pontine transverse fibers. There was a positive correlation between the atrophy of cerebellum and brainstem and the duration of cerebellar ataxia. In most of the patients with Parkinsonism, MRI demonstrated abnormal low signals in putamina on T[sub 2]-weighted images. There were positive correlations between the abnormal low signals putamina and the duration and severity of Parkinsonism. Though abnormal low signals in lateral putamina may be seen in normal aging and other disorders on T[sub 2]-weighted images, it is useful to evaluate Parkinsonism in MSA. We believe that the abnormal slit-like high signals in posterolateral putamina in MSA may suggest loss of neurons and gliosis. (author).

  15. Role of ivabradine in management of stable angina in patients with different clinical profiles

    Science.gov (United States)

    Kaski, Juan Carlos; Gloekler, Steffen; Ferrari, Roberto; Fox, Kim; Lévy, Bernard I; Komajda, Michel; Vardas, Panos; Camici, Paolo G

    2018-01-01

    In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD. PMID:29632676

  16. Neurocognitive function in clinically stable individuals with long-term bipolar I disorder: Comparisons with schizophrenia patients and controls

    Directory of Open Access Journals (Sweden)

    Pei-Yun Lin

    2017-05-01

    Full Text Available This study compared the levels of the five domains of neurocognitive function—executive function, attention, memory, verbal comprehension, and perceptual organization—among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale—Third Edition (WAIS-III, Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale—Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale—Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function.

  17. Periodontal status affects C-reactive protein and lipids in patients with stable heart disease from a tertiary care cardiovascular clinic.

    Science.gov (United States)

    Flores, Manuela F; Montenegro, Marlon M; Furtado, Mariana V; Polanczyk, Carisi A; Rösing, Cassiano K; Haas, Alex N

    2014-04-01

    There are scarce data on the impact of the periodontal condition in the control of biomarkers in patients with cardiovascular disease (CVD). The aim of this study is to assess whether periodontal inflammation and tissue breakdown are associated with C-reactive protein (CRP) and lipids in patients with stable heart disease. This cross-sectional study included 93 patients with stable coronary artery disease (57 males; mean age: 63.5 ± 9.8 years) who were in outpatient care for at least 6 months. After applying a structured questionnaire, periodontal examinations were performed by two calibrated periodontists in six sites per tooth at all teeth. Blood samples were collected from patients on the day of periodontal examination to determine levels of CRP, lipids, and glycated hemoglobin. Multiple linear regression models were fitted to evaluate the association among different periodontal and blood parameters controlling for sex, body mass index, glycated hemoglobin, use of oral hypoglycemic drugs, and smoking. Overall, the sample presented high levels of periodontal inflammation and tissue breakdown. Unadjusted mean concentrations of triglycerides (TGs), very-low-density lipoprotein cholesterol, and glucose were significantly higher in individuals with severe periodontitis. When multiple linear regression models were applied, number of teeth with clinical attachment loss ≥6 mm and presence of severe periodontitis were significantly associated with higher CRP concentrations. Bleeding on probing was significantly associated with TGs, total cholesterol, and non-high-density lipoprotein cholesterol. In this sample of patients with stable CVD, current periodontal inflammation and tissue breakdown are associated with cardiovascular inflammatory markers, such as CRP and lipid profile.

  18. Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Sadia Masood

    2014-03-01

    Full Text Available Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome. The case we are reporting features multiple autoimmune syndrome with five different conditions. The patient had type 1 diabetes mellitus, autoimmune hemolytic anemia, systemic lupus erythematosus, vitiligo, and psoriasis. Psoriasis has rarely been reported previously under the spectrum of autoimmune syndrome. Although the relationship of autoimmune conditions with each other has been explored in the past, this case adds yet another dimension to the unique evolution of autoimmune pathologies. The patient presented with a combination of five autoimmune diseases, which makes it consistent type three multiple autoimmune syndromes with the addition of psoriasis. The current case is unique in this aspect that the combination of these five autoimmune disorders has never been reported in the past.

  19. Very early feeding in stable small for gestational age preterm infants: a randomized clinical trial.

    Science.gov (United States)

    Arnon, Shmuel; Sulam, Daniella; Konikoff, Fred; Regev, Rivka H; Litmanovitz, Ita; Naftali, Timna

    2013-01-01

    To examine the effect of initiating very early feeding on time-to-reach full feeding in stable, small for gestational age (SGA) preterm infants. Preterm infants with gestational age below 37 weeks and birth weight below the 10(th) percentile were randomly allocated to a very early (within 24 hours of birth) feeding regimen or delayed (after 24 hours of birth) feeding. All infants had in utero evidence of absent or reverse diastolic flow. Infants unable to start early feeding were excluded. Time-to-reach full feeding, feeding progression, and related morbidity were compared. Electrogastrography (EGG) was used to measure pre- and postprandial gastric motility on the second and seventh day after feeding initiation. Sixty infants were included in the study, 30 in each group. Infants included in the very early feeding regimen achieved full enteral feeding sooner than controls (98±80-157 vs. 172±123-261 hours of age, respectively; p= 0.004) and were discharged home earlier (p=0.04). No necrotizing enterocolitis (NEC) was documented in both study groups. Gastric motility was improved at day seven after feeding initiation in both study groups, with no difference between groups. Stable SGA preterm infants on a very early feeding regimen achieved full enteral feeding and were discharged home significantly earlier than those on a delayed regimen, with no excess morbidity. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. Clinical Manifestations of Multiple Sclerosis in Taiwanese Children

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    J Gordon Millichap

    2006-11-01

    Full Text Available Twenty-one patients with multiple sclerosis (MS and onset before 18 years were treated over the past 22 years and their records retrospectively analyzed at the National Taiwan University Hospital, Taipei, and Min-Sheng General Hospital, Taoyuan, Taiwan.

  1. Multiple Epiphyseal Dysplasia: A Clinical and Molecular Genetic Study

    NARCIS (Netherlands)

    J.B.A. van Mourik (Jan)

    1998-01-01

    textabstractMultiple epiphyseal dysplasia (MED) is one of the most common osteochondrodysplasias [Wynne-Davies and Gormley 1985]. During childhood and adolescence it affects the epiphyses of the tubular bones, resulting in axial deformities and shorter limbs.·Later in life MED can lead to

  2. Numerical analysis of Markov-perfect equilibria with multiple stable steady states : A duopoly application with innovative firms

    NARCIS (Netherlands)

    Dawid, H.; Keoula, M.Y.; Kort, Peter

    2017-01-01

    This paper presents a numerical method for the characterization of Markov-perfect equilibria of symmetric differential games exhibiting coexisting stable steady states. The method relying on the calculation of ‘local value functions’ through collocation in overlapping parts of the state space, is

  3. Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

    Directory of Open Access Journals (Sweden)

    S. Viswanathan

    2013-01-01

    Full Text Available Background. Multiple sclerosis (MS is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

  4. Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

    Science.gov (United States)

    Viswanathan, S.; Rose, N.; Masita, A.; Dhaliwal, J. S.; Puvanarajah, S. D.; Rafia, M. H.; Muda, S.

    2013-01-01

    Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

  5. Angular stable plates in proximal meta-epiphyseal tibial fractures: study of joint restoration and clinical and functional evaluation.

    Science.gov (United States)

    Giannotti, S; Giovannelli, D; Dell'Osso, G; Bottai, V; Bugelli, G; Celli, F; Citarelli, C; Guido, G

    2016-04-01

    The tibial plateau fractures involve one of the main weight bearing joints of the human body. The goals of surgical treatment are anatomical reduction, articular surface reconstruction and high primary stability. The aim of this study was to evaluate the clinical and functional outcomes after internal plate fixation of this kind of fractures. From January 2009 to December 2012, we treated 75 cases of tibial plateau fracture with angular stable plates. We used Rasmussen Score and the Knee Society Score for the clinical and functional evaluation. Twenty-five cases that underwent hardware removal had arthroscopic and CT evaluation of the joint. No complications occurred. The clinical and functional evaluation, performed by the KSS and Rasmussen Score, highlighted the high percentage of good-to-excellent results (over 90 %). In every case, the range of motion was good with flexion >90°. Arthroscopy showed the presence of chondral damage in 100 % of patients. In all the cases, we found that X-ray images seem better than the CT images. Angular stable plates allow to obtain a good primary stability, permitting an early joint recovery with an excellent range of motion. Avoiding to perform a knee arthrotomy at the time of fracture reduction could prove to be an advantage in terms of functional recovery. The meniscus on the injured bone should be preserved in order to maintain good function of the joint. X-ray images remain the gold standard in checking the progression of post-traumatic osteoarthritis.

  6. The establishment of a multiple sclerosis model for clinical MRI study

    International Nuclear Information System (INIS)

    Zhang Haiqin; Li Kuncheng; Yu Chunshui; Ma Jia; Qin Wen; Ji Zhijuan; Piao Yueshan

    2009-01-01

    Objective: To establish a rat model of multiple sclerosis (MS) for clinical MRI study. Methods: The Lewis (LEW) rats were immunized by myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 35-55 ) emulsified with complete Freunds adjuvant/incomplete Freunds adjuvant. Twenty LEW rats were selected. Group A rats were 5, group B rats were 10 and control group rats were 5. MRI and histopathology analysis were observed on group A and control group, and clinical course were observed on group B. The clinical course was observed and the brain and spinal cord of EAE rats were scanned on 3.0 T MR system with quadrature wrist joint coil on the third day of the acute stage of disease. The T 2 /T 1 weighted images and Gadolinium enhanced T 1 weighted images in 3D volume were obtained respectively. The magnetization transfer ratio (MTR) images were calculated with special software in workstation. Rats were sacrificed within 24 h after MRI, and the histopathological changes of central nervous system were observed. Results: Twice immunization of MOG 35-55 was used and a rat model of MS was successfully induced with all the rats. The model had varied clinical symptoms. The lesions of central nervous system at acute stage on group A (5 rats) were depicted on MRI. The lesions located in the brain and the spinal cord with main manifestation of hyperintensity on T 2 weighed images and hypointensity on T 1 weighted images. Some lesions had Gd-DTPA enhancement, and the value of MTR decreased. The infiltration of mononuclear cells around blood vessels and the extensive distribution of lesions of demyelination in brain and spinal cord were verified by histological examination. Conclusions: Twice immunization of MOG 35-55 could produce a rat model which mimics MS. The model is stable with higher incidence, and the antigen is cheap and obtained easily. The intravital monitoring of brain and spinal cord lesions in MOG 35-55 induced rat model is possible on 3.0 T clinical whole- body MR

  7. Multiple cutaneous inverted papillomas in a dog : clinical communication

    Directory of Open Access Journals (Sweden)

    E.P. Lane

    2007-06-01

    Full Text Available Cutaneous inverted papillomas are described in an 8-month-old mixed breed domestic dog from Windhoek, Namibia. Multiple firm, rapidly growing, doughnut-shaped masses formed on the ventral abdomen, which histologically consisted of a cup-shaped rim of marked epithelial hyperplasia, giant keratohyaline granules and prominent koilocytes and marked hyperkeratosis filling the centre of the mass. Current literature on canine papillomas is briefly reviewed.

  8. Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease.

    Science.gov (United States)

    Ferrari, Roberto; Abergel, Hélène; Ford, Ian; Fox, Kim M; Greenlaw, Nicola; Steg, Ph Gabriel; Hu, Dayi; Tendera, Michal; Tardif, Jean-Claude

    2013-09-10

    Contemporary generalizable data on the demographics and management of outpatients with stable coronary artery disease (CAD) in routine clinical practice are sparse. Using the data from the CLARIFY registry we describe gender- and age-related differences in baseline characteristics and management of these patients across broad geographic regions. This international, prospective, observational, longitudinal registry enrolled stable CAD outpatients from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central, and South America. Baseline data were available for 33280 patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female. The prevalence of CAD risk factors was generally higher in women than in men. Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67 bpm), and were less physically active. Smoking and a history of myocardial infarction were more common in men. Women were more likely to have angina (28% vs 20%), but less likely to have undergone revascularization procedures. CAD was more likely to be asymptomatic in older patients perhaps because of reduced levels of physical activity. Prescription of evidence-based medication for secondary prevention varied with age, with patients ≥ 75 years treated less often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors than patients age groups of outpatients with stable CAD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Diet-tissue stable isotope (Δ(13)C and Δ(15)N) discrimination factors for multiple tissues from terrestrial reptiles.

    Science.gov (United States)

    Steinitz, Ronnie; Lemm, Jeffrey M; Pasachnik, Stesha A; Kurle, Carolyn M

    2016-01-15

    Stable isotope analysis is a powerful tool for reconstructing trophic interactions to better understand drivers of community ecology. Taxon-specific stable isotope discrimination factors contribute to the best use of this tool. We determined the first Δ(13)C and Δ(15)N values for Rock Iguanas (Cyclura spp.) to better understand isotopic fractionation and estimate wild reptile foraging ecology. The Δ(13)C and Δ(15)N values between diet and skin, blood, and scat were determined from juvenile and adult iguanas held for 1 year on a known diet. We measured relationships between iguana discrimination factors and size/age and quantified effects of lipid extraction and acid treatment on stable isotope values from iguana tissues. Isotopic and elemental compositions were determined by Dumas combustion using an elemental analyzer coupled to an isotope ratio mass spectrometer using standards of known composition. The Δ(13)C and Δ(15)N values ranged from -2.5 to +6.5‰ and +2.2 to +7.5‰, respectively, with some differences among tissues and between juveniles and adults. The Δ(13)C values from blood and skin differed among species, but not the Δ(15)N values. The Δ(13)C values from blood and skin and Δ(15)N values from blood were positively correlated with size/age. The Δ(13)C values from scat were negatively correlated with size (not age). Treatment with HCl (scat) and lipid extraction (skin) did not affect the isotope values. These results should aid in the understanding of processes driving stable carbon and nitrogen isotope discrimination factors in reptiles. We provide estimates of Δ(13)C and Δ(15)N values and linear relationships between iguana size/age and discrimination factors for the best interpretation of wild reptile foraging ecology. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Conversion from clinically isolated syndrome to multiple sclerosis

    DEFF Research Database (Denmark)

    Kuhle, J; Disanto, G; Dobson, R

    2015-01-01

    with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were...

  11. Multiple antimicrobial resistance in bacterial isolates from clinical ...

    African Journals Online (AJOL)

    A total of 545 clinical specimens (pus, blood, urine, and stool) and environmental specimens (air sample, saline solution, nasal swabs etc) were cultured for isolation and identification of aerobic bacteria and antimicrobial susceptibility testing. Out of these, 356(65%) specimens yielded one or more bacterial strains. Frequent ...

  12. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2016-03-01

    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  13. Clinical evaluation of multiple exostoses (17 cases) on bonescintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takayuki; Nakamura, Mamoru; Sugita, Reiji; Satou, Akihiro; Sakamoto, Kiyohiko (Tohoku Univ., Sendai (Japan). School of Medicine)

    1991-03-01

    Seventeen patients with multiple exostoses were examined on bone scintigraphy. Inheritance was recognized on seven patients (41%). Onset age of 15 patients was under 20 years old and 10 patients were under 10. The number of lesions was 211 and they were usually recognized at metaphyses of long bones. The degree of accumulation was classified into four grades: 0 (non increased), 1 (slightly-mild), 2 (moderate), and 3 (strong). One hundred and fifty-three lesions (73%) did not show definite increased activity (Grade 0, 1). Grade 3 included 14 lesions and they tended to be strongly calcified on X-P. This disease was said to transform into chondrosarcoma in 10 to 20%. Transformation was said to occur preferably in adults at heavily calcified lesion or one which showed irregularly thick hyaline cartilage. Such lesions showed more increased accumulation than normal bones. In our cases three cases were resected for this reason but turned out to be benign histologically. One case showed malignant transformation. In this case, a large malignant tumor replaced the parent bone and bone scan showed the cold lesion. Bone scintigraphy was considered useful to evaluate the biological activity of multiple exostoses. (author).

  14. Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Wei, Jiafu; Wu, Taixiang; Yang, Qing; Chen, Mao; Ni, Juan; Huang, Dejia

    2011-01-07

    To assess the effect (harms and benefits) of nitrates for stable angina. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma.

    Science.gov (United States)

    Zwitserloot, Annelies; Fuchs, Susanne I; Müller, Christina; Bisdorf, Kornelia; Gappa, Monika

    2014-09-01

    Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400 μg). Healthy controls performed baseline MBW only. 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant effect on LCI for the group. These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The Diagnostic importance of clinical and radiologic features of the Multiple Cemento-osseous dysplasia

    International Nuclear Information System (INIS)

    Han, M. R.; Kim, Y. H.; Kang, B. C.

    1998-01-01

    This case was diagnosed as multiple cementoosseous dysplasia on the basis of clinical and radiological features but was diagnosed as ossifying fibroma on the basis of histopathological feature. The histopathologic features of the multiple cementoosseous dysplasia and cementoossifying fibroma have common features of cementum, fibrous network and bone. Multiple cementoosseous dysplasia is reactive lesion and shows restricted lesion size, occurred on anterior and posterior tooth of the mandible and needs no treatment except periodic follow up. But Cementoossifying fibroma is the true neoplasm and grows continuously and needs surgical removal. The final diagnosis of the multiple cementoosseous dysplasia requires good correlation of the clinical histopathological, and radiological features.

  17. Replication of clinical innovations in multiple medical practices.

    Science.gov (United States)

    Henley, N S; Pearce, J; Phillips, L A; Weir, S

    1998-11-01

    Many clinical innovations had been successfully developed and piloted in individual medical practice units of Kaiser Permanente in North Carolina during 1995 and 1996. Difficulty in replicating these clinical innovations consistently throughout all 21 medical practice units led to development of the interdisciplinary Clinical Innovation Implementation Team, which was formed by using existing resources from various departments across the region. REPLICATION MODEL: Based on a model of transfer of best practices, the implementation team developed a process and tools (master schedule and activity matrix) to quickly replicate successful pilot projects throughout all medical practice units. The process involved the following steps: identifying a practice and delineating its characteristics and measures (source identification); identifying a team to receive the (new) practice; piloting the practice; and standardizing, including the incorporation of learnings. The model includes the following components for each innovation: sending and receiving teams, an innovation coordinator role, an innovation expert role, a location expert role, a master schedule, and a project activity matrix. Communication depended on a partnership among the location experts (local knowledge and credibility), the innovation coordinator (process expertise), and the innovation experts (content expertise). Results after 12 months of working with the 21 medical practice units include integration of diabetes care team services into the practices, training of more than 120 providers in the use of personal computers and an icon-based clinical information system, and integration of a planwide self-care program into the medical practices--all with measurable improved outcomes. The model for sequential replication and the implementation team structure and function should be successful in other organizational settings.

  18. Use of Chest Computed Tomography in Stable Patients with Blunt Thoracic Trauma: Clinical and Forensic Perspective

    Directory of Open Access Journals (Sweden)

    Makbule Ergin

    2011-01-01

    fractures were the most common injury. Thorax computed tomography was significantly superior to chest radiography in detecting pneumothorax , hemothorax and lung contusion. Eightyone life threatening lesions were detected and 50 (61%; pneumothorax 13, hemothorax 24, lung contusion 9,and pneumomediastinum 4 of these lesions could not be detected with plain chest radiography. The clinical management [in 15 patients (30%], and the forensic assesment was changed [in 14 (28%] patients were changed.  Conclusion:We concluded that using Computed Tomography of the thorax in thoracic travmas prive meticulous assesment in management of patients and forens icissues.

  19. Stable radiation pressure acceleration of ions by suppressing transverse Rayleigh-Taylor instability with multiple Gaussian pulses

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, M. L.; Liu, B.; Hu, R. H.; Shou, Y. R.; Lin, C.; Lu, H. Y.; Lu, Y. R.; Ma, W. J., E-mail: wenjun.ma@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, and Key Laboratory of HEDP of the Ministry of Education, CAPT, Peking University, Beijing 100871 (China); Gu, Y. Q. [Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China); Yan, X. Q., E-mail: x.yan@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, and Key Laboratory of HEDP of the Ministry of Education, CAPT, Peking University, Beijing 100871 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006 (China)

    2016-08-15

    In the case of a thin plasma slab accelerated by the radiation pressure of an ultra-intense laser pulse, the development of Rayleigh-Taylor instability (RTI) will destroy the acceleration structure and terminate the acceleration process much sooner than theoretical limit. In this paper, a new scheme using multiple Gaussian pulses for ion acceleration in a radiation pressure acceleration regime is investigated with particle-in-cell simulation. We found that with multiple Gaussian pulses, the instability could be efficiently suppressed and the divergence of the ion bunch is greatly reduced, resulting in a longer acceleration time and much more collimated ion bunch with higher energy than using a single Gaussian pulse. An analytical model is developed to describe the suppression of RTI at the laser-plasma interface. The model shows that the suppression of RTI is due to the introduction of the long wavelength mode RTI by the multiple Gaussian pulses.

  20. Four hundred or more participants needed for stable contingency table estimates of clinical prediction rule performance

    DEFF Research Database (Denmark)

    Kent, Peter; Boyle, Eleanor; Keating, Jennifer L

    2017-01-01

    OBJECTIVE: To quantify variability in the results of statistical analyses based on contingency tables and discuss the implications for the choice of sample size for studies that derive clinical prediction rules. STUDY DESIGN AND SETTING: An analysis of three pre-existing sets of large cohort data......, odds ratios and risk/prevalence ratios, for each sample size was calculated. RESULTS: There were very wide, and statistically significant, differences in estimates derived from contingency tables from the same dataset when calculated in sample sizes below 400 people, and typically this variability...... stabilized in samples of 400 to 600 people. Although estimates of prevalence also varied significantly in samples below 600 people, that relationship only explains a small component of the variability in these statistical parameters. CONCLUSION: To reduce sample-specific variability, contingency tables...

  1. Beyond clinical utility: The multiple values of DTC genetics

    Directory of Open Access Journals (Sweden)

    Mauro Turrini

    2016-03-01

    Full Text Available One point of consensus in the otherwise very controversial discussion about the benefits and dangers of DTC genetics in the health domain is the lack of substantial clinical utility. At the same time, both the empirical and conceptual literature indicate that health-related DTC tests can have value and utility outside of the clinic. We argue that a broader and multi-faceted conceptualization of utility and value would enrich the ethical and social discussion of DTC testing in several ways: First, looking at ways in which DTC testing can have personal and social value for users – in the form of entertainment, learning, or a way to relate to others – can help to explain why people still take DTC tests, and will, further down the line, foster a more nuanced understanding of secondary and tertiary uses of DTC test results (which could very well unearth new ethical and regulatory challenges. Second, considering the economic value and broader utility of DTC testing foregrounds wider social and political aspects than have been dominant in the ethical and regulatory debates surrounding DTC genetics so far. These wider political aspects include the profound power asymmetries that characterize the collection and use of personal genetic data in many contexts.

  2. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  3. Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

    Directory of Open Access Journals (Sweden)

    Zhang XD

    2014-04-01

    Full Text Available Xiao-Dong Zhang,1 Jiang Yang,2 Sha-Sha Song,1 Wei Long,1 Jie Chen,1 Xiu Shen,1 Hao Wang,1 Yuan-Ming Sun,1 Pei-Xun Liu,1 Saijun Fan11Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI, USAAbstract: The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.Keywords: in vivo clearance, gold nanoparticles, small size

  4. Clinical Application of {sup 18}F-FDG PET in Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    This review focuses on the clinical use of {sup 18}F-FDG PET to evaluate multiple myeloma. {sup 18}F-FDG PET is useful for diagnosis, staging of multiple myeloma and differential diagnosis of myeloma related disease such as monoclonal gammopathy of undetermined significance or plasmacytoma. For therapy response, {sup 18}F-FDG PET may be effective after chemotherapy for multiple myeloma and radiotherapy for plasmacytoma.

  5. Clinical Application of 18F-FDG PET in Multiple Myeloma

    International Nuclear Information System (INIS)

    Lee, Su Jin; Choi, Joon Young

    2009-01-01

    This review focuses on the clinical use of 18 F-FDG PET to evaluate multiple myeloma. 18 F-FDG PET is useful for diagnosis, staging of multiple myeloma and differential diagnosis of myeloma related disease such as monoclonal gammopathy of undetermined significance or plasmacytoma. For therapy response, 18 F-FDG PET may be effective after chemotherapy for multiple myeloma and radiotherapy for plasmacytoma

  6. Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

    Science.gov (United States)

    Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

    2012-01-01

    The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

  7. Economic and clinical impact of multiple myeloma to managed care.

    Science.gov (United States)

    Cook, Richard

    2008-09-01

    Because of the development of novel agents such as immunomodulators, proteasome inhibitors, and bisphosphonates, the standards of care for the multiple myeloma (MM) patient have changed. The costs associated with current and emerging therapies, as well as supportive care, are significant and pose a tremendous financial burden to both patients and managed care. To review the economic impact of MM and to weigh the advantages and disadvantages of current treatments in bringing value for prolonged life versus the cost of treatment. This chapter will also discuss the need for thorough data review and pharmacoeconomic analyses to determine the most cost-effective therapies. Although MM accounts for only a small percentage of all cancer types, the costs associated with treating and managing it are among the highest. Recent developments in diagnosing, treating, and managing myeloma have led to novel treatment strategies. Immunomodulators, proteasome inhibitors, and bisphosphonates are improving response rates and preserving quality of life. However, these agents are not replacing older treatment modalities, but being used in addition to them. Intensive chemotherapy, stem cell transplantation, and supportive care are all important components in achieving treatment goals. Costs associated with stem cell transplants and complications of the disease add to the economic burden of myeloma. Additional costs for routine diagnostics to measure the progression of the disease or response to treatment need to be considered. Complications (e.g., lytic bone disease, infection, anemia, and renal failure) also add to morbidity and mortality, thus increasing the burden to the patient and the health care system as a whole. Financial and time constraints of caregivers must also be considered, as well as the added administrative burdens to health care providers. New standards of care in the treatment and management of myeloma are likely to lead to significant increases in costs. Although

  8. Ivabradine in combination with beta-blocker therapy for the treatment of stable angina pectoris in every day clinical practice.

    Science.gov (United States)

    Koester, Ralf; Kaehler, Jan; Ebelt, Henning; Soeffker, Gerold; Werdan, Karl; Meinertz, Thomas

    2010-10-01

    The anti-anginal efficacy of the selective I(f) inhibitor ivabradine has been demonstrated in controlled clinical trials. However, there is limited information about the safety and efficacy of a combined treatment of ivabradine with beta-blockers, particularly outside of clinical trials in every day practice. This analysis from the REDUCTION study evaluated the safety and efficacy of a combined therapy of beta-blockers and ivabradine in every day practice. In this multi-center study 4,954 patients with stable angina pectoris were treated with ivabradine in every day routine practice and underwent a clinical follow-up for 4 months. 344 of these patients received a co-medication with beta-blockers. Heart rate (HR), angina pectoris episodes, nitrate consumption, overall efficacy and tolerance were analyzed. After 4 months of treatment with ivabradine HR was reduced by 12.4 ± 11.6 bpm from 84.3 ± 14.6 to 72.0 ± 9.9 bpm, p every day practice.

  9. Danish evidence-based clinical guideline for use of nutritional support in pulmonary rehabilitation of undernourished patients with stable COPD

    DEFF Research Database (Denmark)

    Beck, Anne Marie; Iepsen, Ulrik Winning; Topperup, Randi

    2015-01-01

    Background and aims Disease-related under-nutrition is a common problem in individuals with COPD. The rationale for nutritional support in pulmonary rehabilitation therefore seems obvious. However there is limited evidence regarding the patient-relevant outcomes i.e. activities of daily living (ADL......) or quality of life. Therefore the topic was included in The Danish Health and Medicines Authority's development of an evidence-based clinical guideline for rehabilitation of patients with stable COPD. Methods The methods were specified by The Danish Health and Medicines Authority as part of a standardized...... studies had been published. There were evidence of moderate quality that nutritional support for undernourished patients with COPD lead to a weight gain of 1.7 kg (95% confidence interval: 1.3 to 2.2 kg), but the effect was quantified as a mean change from baseline, which is less reliable. There were...

  10. Analysis of Grassland Ecosystem Physiology at Multiple Scales Using Eddy Covariance, Stable Isotope and Remote Sensing Techniques

    Science.gov (United States)

    Flanagan, L. B.; Geske, N.; Emrick, C.; Johnson, B. G.

    2006-12-01

    Grassland ecosystems typically exhibit very large annual fluctuations in above-ground biomass production and net ecosystem productivity (NEP). Eddy covariance flux measurements, plant stable isotope analyses, and canopy spectral reflectance techniques have been applied to study environmental constraints on grassland ecosystem productivity and the acclimation responses of the ecosystem at a site near Lethbridge, Alberta, Canada. We have observed substantial interannual variation in grassland productivity during 1999-2005. In addition, there was a strong correlation between peak above-ground biomass production and NEP calculated from eddy covariance measurements. Interannual variation in NEP was strongly controlled by the total amount of precipitation received during the growing season (April-August). We also observed significant positive correlations between a multivariate ENSO index and total growing season precipitation, and between the ENSO index and annual NEP values. This suggested that a significant fraction of the annual variability in grassland productivity was associated with ENSO during 1999-2005. Grassland productivity varies asymmetrically in response to changes in precipitation with increases in productivity during wet years being much more pronounced than reductions during dry years. Strong increases in plant water-use efficiency, based on carbon and oxygen stable isotope analyses, contribute to the resilience of productivity during times of drought. Within a growing season increased stomatal limitation of photosynthesis, associated with improved water-use efficiency, resulted in apparent shifts in leaf xanthophyll cycle pigments and changes to the Photochemical Reflectance Index (PRI) calculated from hyper-spectral reflectance measurements conducted at the canopy-scale. These shifts in PRI were apparent before seasonal drought caused significant reductions in leaf area index (LAI) and changes to canopy-scale "greenness" based on NDVI values. With

  11. Associations of alcohol consumption with clinical and MRI measures in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, Marie B.; De Keyser, Jacques

    Evaluation of: Foster M, Zivadinov R, Weinstock-Guttman B et al. Associations of alcohol consumption with clinical and MRI measures in multiple sclerosis. J. Neuroimmunol. 243(1-2), 61-68 (2012). While the harmful effects of alcohol abuse are well documented, experimental and clinical data support a

  12. Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

    Science.gov (United States)

    Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

    2015-01-01

    The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

  13. The CRESST-III iStick veto. Stable operation of multiple transition edge sensors in one readout circuit

    Energy Technology Data Exchange (ETDEWEB)

    Rothe, Johannes [Max-Planck-Institut f. Physik (Werner-Heisenberg-Institut) (Germany); Ludwig-Maximilians-Universitaet Muenchen (Germany); Collaboration: CRESST-Collaboration

    2016-07-01

    To enable complete rejection of holder-related events in the upcoming CRESST-III dark matter search experiment, the scintillating target crystals are held by calcium tungstate sticks (iSticks) instrumented with tungsten transition edge sensors (TESs). Since the iStick signals are used exclusively for vetoing, it is sufficient to register if an event happened in any stick, without knowing which one. This allows the operation of all iSticks in a single readout circuit, requiring just one SQUID magnetometer. The talk describes the effect of bias current heating and corresponding hysteresis phenomena known in single-TES circuits, and the resulting conditions for stability in multiple-TES circuits. The fundamentally different behaviour of parallel and series circuits and resulting design choices are explored.

  14. In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis

    DEFF Research Database (Denmark)

    Larsson, H B; Frederiksen, J; Kjaer, L

    1988-01-01

    investigated, using a whole-body superconductive MR scanner, operating at 1.5 T. By employing 12-point (or 6-point) partial saturation inversion recovery (PSIR) and 32-echo multiple spin-echo sequences we measured T1 and T2 in MS plaques, white matter, and cortical gray matter. We also focused on the issue......, whether T1 and T2 relaxation processes in fact were monoexponential. T1 and T2 in plaques were found to cover a wide range, which could be explained only by inherent biophysical dissimilarity of the plaques, possibly due to differences in disease activity, edema and gliosis. T1 appeared monoexponential...... in all the plaques, but in seven cases T2 showed biexponential behavior. This was found to be most pronounced near the cerebrospinal fluid of the ventricles, probably caused by partial volume effects or increased free water content. The T2 of apparently normal white matter was significantly longer in MS...

  15. Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

    Science.gov (United States)

    Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

    2018-01-01

    Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

  16. Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

    Science.gov (United States)

    Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

    2018-01-01

    Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with

  17. High Precision Zinc Stable Isotope Measurement of Certified Biological Reference Materials Using the Double Spike Technique and Multiple Collector-ICP-MS.

    Science.gov (United States)

    Moore, Rebekah E T; Larner, Fiona; Coles, Barry J; Rehkämper, Mark

    2017-04-01

    Biological reference materials with well-characterised stable isotope compositions are lacking in the field of 'isotope biochemistry', which seeks to understand bodily processes that rely on essential metals by determining metal stable isotope ratios. Here, we present Zn stable isotope data for six biological reference materials with certified trace metal concentrations: fish muscle, bovine muscle, pig kidney, human hair, human blood serum and human urine. Replicate analyses of multiple aliquots of each material achieved reproducibilities (2sd) of 0.04-0.13‰ for δ 66/64 Zn (which denotes the deviation of the 66 Zn/ 64 Zn ratio of a sample from a pure Zn reference material in parts per 1000). This implies only very minor isotopic heterogeneities within the samples, rendering them suitable as quality control materials for Zn isotope analyses. This endorsement is reinforced by (i) the close agreement of our Zn isotope data for two of the samples (bovine muscle and human blood serum) to previously published results for different batches of the same material and (ii) the similarity of the isotopic data for the samples (δ 66/64 Zn ≈ -0.8 to 0.0‰) to previously published Zn isotope results for similar biological materials. Further tests revealed that the applied Zn separation procedure is sufficiently effective to enable accurate data acquisition even at low mass resolving power (M/ΔM ≈ 400), as measurements and analyses conducted at much higher mass resolution (M/ΔM ≈ 8500) delivered essentially identical results.

  18. Transition of spiral calcium waves between multiple stable patterns can be triggered by a single calcium spark in a fire-diffuse-fire model

    Science.gov (United States)

    Tang, Ai-Hui; Wang, Shi-Qiang

    2009-01-01

    Spiral patterns have been found in various nonequilibrium systems. The Ca2+-induced Ca2+ release system in single cardiac cells is unique for highly discrete reaction elements, each giving rise to a Ca2+ spark upon excitation. We imaged the spiral Ca2+ waves in isolated cardiac cells and numerically studied the effect of system excitability on spiral patterns using a two-dimensional fire-diffuse-fire model. We found that under certain conditions, the system was able to display multiple stable patterns of spiral waves, each exhibiting different periods and distinct routines of spiral tips. Transition between these different patterns could be triggered by an internal fluctuation in the form of a single Ca2+ spark. PMID:19792039

  19. Transition of spiral calcium waves between multiple stable patterns can be triggered by a single calcium spark in a fire-diffuse-fire model.

    Science.gov (United States)

    Tang, Ai-Hui; Wang, Shi-Qiang

    2009-09-01

    Spiral patterns have been found in various nonequilibrium systems. The Ca(2+)-induced Ca(2+) release system in single cardiac cells is unique for highly discrete reaction elements, each giving rise to a Ca(2+) spark upon excitation. We imaged the spiral Ca(2+) waves in isolated cardiac cells and numerically studied the effect of system excitability on spiral patterns using a two-dimensional fire-diffuse-fire model. We found that under certain conditions, the system was able to display multiple stable patterns of spiral waves, each exhibiting different periods and distinct routines of spiral tips. Transition between these different patterns could be triggered by an internal fluctuation in the form of a single Ca(2+) spark.

  20. Multiple daily fractionation in radiotherapy: biological rationale and preliminary clinical experiences

    Energy Technology Data Exchange (ETDEWEB)

    Arcangeli, G [Instituto Medico Scientifico, Rome (Italy). Dept. of Oncology; Mauro, F; Morelli, D; Nervi, C

    1979-09-01

    The biological bases of radiation dose fractionation are reviewed and discussed with special emphasis on reassortment. Experimental data on animal model systems are presented to clarify that reassortment has to be added to sublethal damage repair and reoxygenation in the rationale for an optimized radiotherapy course according to tumor cell kinetics. Clinical results on several human tumors treated with twice or thrice daily fractions are described. These results show that some clinically radioresistant tumors (especially if not characterized by a relatively long clinical doubling line) can be satisfactorily dealt with using multiple daily fractionation. Clinical observations indicate that a relatively high cumulative daily dose (200 + 150 + 150 rad) can be safely administered.

  1. Group-Sequential Strategies in Clinical Trials with Multiple Co-Primary Outcomes

    Science.gov (United States)

    Hamasaki, Toshimitsu; Asakura, Koko; Evans, Scott R; Sugimoto, Tomoyuki; Sozu, Takashi

    2015-01-01

    We discuss the decision-making frameworks for clinical trials with multiple co-primary endpoints in a group-sequential setting. The decision-making frameworks can account for flexibilities such as a varying number of analyses, equally or unequally spaced increments of information and fixed or adaptive Type I error allocation among endpoints. The frameworks can provide efficiency, i.e., potentially fewer trial participants, than the fixed sample size designs. We investigate the operating characteristics of the decision-making frameworks and provide guidance on constructing efficient group-sequential strategies in clinical trials with multiple co-primary endpoints. PMID:25844122

  2. Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

    Science.gov (United States)

    Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Virizuela Echaburu, Juan; Antonio, Maite; Font, Carme; Biosca, Mercè; Ramchandani, Avinash; Martínez, Jerónimo; Hernando Cubero, Jorge; Espinosa, Javier; Martínez de Castro, Eva; Ghanem, Ismael; Beato, Carmen; Blasco, Ana; Garrido, Marcelo; Bonilla, Yaiza; Mondéjar, Rebeca; Arcusa Lanza, María Ángeles; Aragón Manrique, Isabel; Manzano, Aránzazu; Sevillano, Elena; Castañón, Eduardo; Cardona, Mercé; Gallardo Martín, Elena; Pérez Armillas, Quionia; Sánchez Lasheras, Fernando; Ayala de la Peña, Francisco

    2015-02-10

    To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes. © 2015 by American Society of Clinical Oncology.

  3. Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

    Science.gov (United States)

    Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

    2012-03-15

    Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

  4. The clinical impact of cerebellar grey matter pathology in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Alfredo Damasceno

    Full Text Available BACKGROUND: The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. OBJECTIVE: To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. METHODS: Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS and cerebellar functional system (FS score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT and the Symbol-Digit Modalities Test (SDMT. Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. RESULTS: After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001, cerebellar FS (p = 0.002, arm function (p = 0.049, and for leg function (p<0.001. Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013, while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015. CONCLUSIONS: Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

  5. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

    2010-01-01

    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

  6. Danish evidence-based clinical guideline for use of nutritional support in pulmonary rehabilitation of undernourished patients with stable COPD.

    Science.gov (United States)

    Beck, Anne Marie; Iepsen, Ulrik Winning; Tobberup, Randi; Jørgensen, Karsten Juhl

    2015-02-01

    Disease-related under-nutrition is a common problem in individuals with COPD. The rationale for nutritional support in pulmonary rehabilitation therefore seems obvious. However there is limited evidence regarding the patient-relevant outcomes i.e. activities of daily living (ADL) or quality of life. Therefore the topic was included in The Danish Health and Medicines Authority's development of an evidence-based clinical guideline for rehabilitation of patients with stable COPD. The methods were specified by The Danish Health and Medicines Authority as part of a standardized approach to evidence-based national clinical practice guidelines. They included formulation of a PICO with pre-defined criteria for the Population, Intervention, Control and Outcomes. Existing guidelines or systematic reviews were used after assessment using the AGREE II tool or AMSTAR, if possible. We identified primary studies by means of a systematic literature search (July to December 2013), and any identified studies were then quality assessed using the Cochrane risk of bias tool and the GRADE approach. The extracted data on our pre-defined outcomes were summarized in meta-analyses when possible, or meta-analyses from existing guidelines or systematic reviews were adapted. The results were used for labeling and wording of the recommendations. Data from 12 randomized controlled trials were included in a systematic review, which formed the basis for our recommendations as no new primary studies had been published. There were evidence of moderate quality that nutritional support for undernourished patients with COPD lead to a weight gain of 1.7kg (95% confidence interval: 1.3 to 2.2kg), but the effect was quantified as a mean change from baseline, which is less reliable. There were evidence of moderate quality that nutritional therapy does not increase in the 6 minute walking distance of 13 m (95% confidence interval: -27 to 54 m) when results in the intervention and control groups were

  7. Revealing the uncultivated majority: combining DNA stable-isotope probing, multiple displacement amplification and metagenomic analyses of uncultivated Methylocystis in acidic peatlands.

    Science.gov (United States)

    Chen, Yin; Dumont, Marc G; Neufeld, Josh D; Bodrossy, Levente; Stralis-Pavese, Nancy; McNamara, Niall P; Ostle, Nick; Briones, Maria J I; Murrell, J Colin

    2008-10-01

    Peatlands represent an enormous carbon reservoir and have a potential impact on the global climate because of the active methanogenesis and methanotrophy in these soils. Uncultivated methanotrophs from seven European peatlands were studied using a combination of molecular methods. Screening for methanotroph diversity using a particulate methane monooxygenase-based diagnostic gene array revealed that Methylocystis-related species were dominant in six of the seven peatlands studied. The abundance and methane oxidation activity of Methylocystis spp. were further confirmed by DNA stable-isotope probing analysis of a sample taken from the Moor House peatland (England). After ultracentrifugation, (13)C-labelled DNA, containing genomic DNA of these Methylocystis spp., was separated from (12)C DNA and subjected to multiple displacement amplification (MDA) to generate sufficient DNA for the preparation of a fosmid metagenomic library. Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using denaturing gradient gel electrophoresis for low-template amplification (0.01 ng template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias and chimeric artefacts were minimized by using an enzymatic treatment of MDA-generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic library revealed one fosmid containing methanol dehydrogenase and two fosmids containing 16S rRNA genes from these Methylocystis-related species as well as one fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa. Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the assembly of a gene cluster encoding polypeptides involved in bacterial methanol utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA and metagenomics provided access to genomic information of a relatively large DNA fragment of these thus far uncultivated, predominant and active methanotrophs in peatland soil.

  8. Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis

    DEFF Research Database (Denmark)

    Giorgio, Antonio; Battaglini, Marco; Rocca, Maria Assunta

    2013-01-01

    OBJECTIVES: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS). METHODS: In this multicenter, retrospective study, clinical and MRI data at onset......: In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed...... in the converting group in projection, association, and commissural WM tracts, with larger clusters being in the corpus callosum, corona radiata, and cingulum. CONCLUSIONS: Higher frequency of lesion occurrence in clinically eloquent WM tracts can characterize CIS subjects with different types of onset...

  9. Stable Boundary Layer Issues

    OpenAIRE

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The development of robust stable boundary layer parameterizations for use in NWP and climate models is hampered by the multiplicity of processes and their unknown interactions. As a result, these models suffer ...

  10. Clinical commentary on "Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis" and "Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients".

    Science.gov (United States)

    Pareés, Isabel

    2017-11-01

    This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger studies to better understand this unusual clinical association.

  11. IOM and DHHS meeting on making clinical practice guidelines appropriate for patients with multiple chronic conditions.

    Science.gov (United States)

    Goodman, Richard A; Boyd, Cynthia; Tinetti, Mary E; Von Kohorn, Isabelle; Parekh, Anand K; McGinnis, J Michael

    2014-01-01

    The increasing prevalence of Americans with multiple (2 or more) chronic conditions raises concerns about the appropriateness and applicability of clinical practice guidelines for patient management. Most guidelines clinicians currently rely on have been designed with a single chronic condition in mind, and many such guidelines are inattentive to issues related to comorbidities. In response to the need for guideline developers to address comorbidities in guidelines, the Department of Health and Human Services convened a meeting in May 2012 in partnership with the Institute of Medicine to identify principles and action options. Eleven principles to improve guidelines' attentiveness to the population with multiple chronic conditions were identified during the meeting. They are grouped into 3 interrelated categories: (1) principles intended to improve the stakeholder technical process for developing guidelines; (2) principles intended to strengthen content of guidelines in terms of multiple chronic conditions; and (3) principles intended to increase focus on patient-centered care. This meeting built upon previously recommended actions by identifying additional principles and options for government, guideline developers, and others to use in strengthening the applicability of clinical practice guidelines to the growing population of people with multiple chronic conditions. The suggested principles are helping professional societies to improve guidelines' attentiveness to persons with multiple chronic conditions.

  12. In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs against multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Maria Teresa Di Martino

    Full Text Available Multiple myeloma (MM is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs, master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later time points by caspase-6 and -3 activation and apoptosis induction. To improve the in vivo delivery, we encapsulated miR-34a mimics in stable nucleic acid lipid particles (SNALPs. We found that SNALPs miR-34a were highly efficient in vitro in inhibiting growth of MM cells. Then, we investigated the activity of the SNALPs miR-34a against MM xenografts in SCID mice. We observed significant tumor growth inhibition (p<0.05 which translated in mice survival benefits (p=0.0047. Analysis of miR-34a and NOTCH1 expression in tumor retrieved from animal demonstrated efficient delivery and gene modulation induced by SNALPs miR-34a in the absence of systemic toxicity. We here therefore provide evidence that SNALPs miR-34a may represent a promising tool for miRNA-therapeutics in MM.

  13. Clinically significant fatigue: prevalence and associated factors in an international sample of adults with multiple sclerosis recruited via the internet.

    Directory of Open Access Journals (Sweden)

    Tracey J Weiland

    Full Text Available Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS. Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors.To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate and modifiable lifestyle, disease-modifying drugs (DMD and supplement use in a large international sample of PwMS.PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate.Of 2469 participants with confirmed MS, 2138 (86.6% completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7-67.7 screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil.This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this sample may help clarify the contribution

  14. Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

    Science.gov (United States)

    Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

    2016-03-01

    [Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

  15. Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM).

    Science.gov (United States)

    Yang, Ye; Fan, Teresa W-M; Lane, Andrew N; Higashi, Richard M

    2017-07-11

    Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different elemental isotopes can trace the allocation of e.g. C and N atoms through the network. Such dual-label experiments however challenge the resolution of conventional mass spectrometers, which must distinguish the neutron mass differences among different elemental isotopes. This requires ultrahigh resolution Fourier transform mass spectrometry (UHR-FTMS). When combined with direct infusion nano-electrospray ion source (nano-ESI), UHR-FTMS can provide rapid, global, and quantitative analysis of all possible mass isotopologues of metabolites. Unfortunately, very low mass polar metabolites such as amino acids can be difficult to analyze by current models of UHR-FTMS, plus the high salt content present in typical cell or tissue polar extracts may cause unacceptable ion suppression for sources such as nano-ESI. Here we describe a modified method of ethyl chloroformate (ECF) derivatization of amino acids to enable rapid quantitative analysis of stable isotope labeled amino acids using nano-ESI UHR-FTMS. This method showed excellent linearity with quantifiable limits in the low nanomolar range represented in microgram quantities of biological specimens, which results in extracts with total analyte abundances in the low to sub-femtomole range. We have

  16. Clinical Features in a Danish Population-Based Cohort of Probable Multiple System Atrophy Patients

    DEFF Research Database (Denmark)

    Starhof, Charlotte; Korbo, Lise; Lassen, Christina Funch

    2016-01-01

    Background: Multiple system atrophy (MSA) is a rare, sporadic and progressive neurodegenerative disorder. We aimed to describe the clinical features of Danish probable MSA patients, evaluate their initial response to dopaminergic therapy and examine mortality. Methods: From the Danish National...... the criteria for probable MSA. We recorded clinical features, examined differences by MSA subtype and used Kaplan-Meier survival analysis to examine mortality. Results: The mean age at onset of patients with probable MSA was 60.2 years (range 36-75 years) and mean time to wheelchair dependency was 4.7 years...

  17. Morphological and clinical aspects of the occurrence of accessory (multiple) renal arteries

    Science.gov (United States)

    Gulas, Ewelina; Wysiadecki, Grzegorz; Szymański, Jacek; Majos, Agata; Stefańczyk, Ludomir; Topol, Mirosław

    2016-01-01

    Renal vascularization variants vastly differ between individuals due to the very complex embryogenesis of the kidneys. Moreover, each variant may have implications for clinical and surgical interventions. The number of operating procedures continues to grow, and includes renal transplants, aneurysmorrhaphy and other vascular reconstructions. In any surgical technique, unawareness of the presence of multiple renal arteries may result in a fatal outcome, especially if laparoscopic methods are used. The aim of this review is to comprehensively identify the variation within multiple renal arteries and to highlight the connections between the presence of accessory renal arteries and the coexistence of other variants of vascularization. Another aim is to determine the potential clinical implications of the presence of accessory renal arteries. This study is of particular importance for surgeons, intervention radiologists, nephrologists and vascular surgeons. PMID:29593819

  18. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

    2016-01-01

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

  19. Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

    Directory of Open Access Journals (Sweden)

    O.V. Gudym

    2017-08-01

    Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

  20. MRD Testing in Multiple Myeloma: From a Surrogate Marker of Clinical Outcomes to an Every-Day Clinical Tool.

    Science.gov (United States)

    Landgren, Ola

    2018-01-01

    Minimal residual disease (MRD) testing in multiple myeloma is here to stay. Studies show that MRD negativity is consistently associated with longer progression-free survival (PFS). It is just a matter of time until MRD negativity will become a regulatory endpoint for drug approval. Until that can happen, more analysis will be required to define the exact details of MRD in the regulatory setting. For example, for randomized studies there is need to define the amount of improvement in MRD negativity between the experimental arm and the control arm at a given time-point for a drug to obtain regulatory accelerated approval. Such efforts are underway. For the multiple myeloma field as a whole, important tasks for the (near) coming future are as follows: (1) to conduct or finalize the expanded analysis to define the exact details of MRD in the regulatory setting, (2) to develop new and better MRD assays-both more sensitive MRD assays for bone marrow aspirates and nonbone marrow aspirate-based assays (eg, blood-based and imaging-based MRD assays), and (3) to design novel clinical studies to formally assess the effect of MRD negativity in clinical decision making. The aim with this issue of the Journal is to provide a deep and comprehensive summary of the latest MRD knowledge in the field, and to outline future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

    Science.gov (United States)

    Reece, D; Imrie, K; Stevens, A; Smith, C A

    2006-10-01

    In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?What is the toxicity associated with the use of bortezomib?Which patients are more or less likely to benefit from treatment with bortezomib? Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback. Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events. A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc. The literature review found one randomized controlled trial (rct)-the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma. The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is

  2. Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

    OpenAIRE

    K???k, Fadime; Kara, Bilge; Poyraz, Esra ?o?kuner; ?diman, Egemen

    2016-01-01

    [Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression ...

  3. Rehabilitation and multiple limb amputations: A clinical report of patients injured in combat.

    Science.gov (United States)

    Melcer, Ted; Pyo, Jay; Walker, Jay; Quinn, Kimberly; Lebedda, Martin; Neises, Kamaran; Nguyen, Christina; Galarneau, Michael

    2016-01-01

    This clinical report describes the outpatient rehabilitation program for patients with multiple limb amputations enrolled in the Comprehensive Combat and Complex Casualty Care facility at the Naval Medical Center San Diego. Injury-specific data for 29 of these patients wounded by blast weaponry in Afghanistan in 2010 or 2011 were captured by the Expeditionary Medical Encounter Database at the Naval Health Research Center and were reviewed for this report. Their median Injury Severity Score was 27 (N = 29; range, 11-54). Patients averaged seven moderate to serious injuries (Abbreviated Injury Scale scores ≥2), including multiple injuries to lower limbs and injuries to the torso and/or upper limbs. All patients received care from numerous clinics, particularly physical therapy during the first 6 mo postinjury. Clinic use generally declined after the first 6 mo with the exception of prosthetic devices and repairs. The clinical team implemented the Mayo-Portland Adaptability Inventory, 4th Revision (MPAI-4) to assess functioning at outpatient program initiation and discharge (n = 23). At program discharge, most patients had improved scores for the MPAI-4 items assessing mobility, pain, and transportation, but not employment. Case reports described rehabilitation for two patients with triple amputations and illustrated multispecialty care and contrasting solutions for limb prostheses.

  4. Clinical, psychological and demographic parameters of body pain in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Ghasem Salehpoor

    2017-02-01

    Full Text Available Background: Body pain in multiple sclerosis (MS is a common phenomenon that can create or exacerbate by different parameters of clinical, psychological and demographic. The aim of this study was to investigate the relationship between parameters of clinical (fatigue, clinical course, body mass index and duration, psychological (depression, anxiety and stress and demographic (age, gender, marital status and education characters with multiple sclerosis patient’s body pain. Methods: This cross-sectional study has been performed in the Multiple Sclerosis Society of Guilan Province and Imam Reza Specialized and Sub-specialized Clinic, Rasht City, Iran during June to February 2010. In this study 162 patients with MS were selected by consecutive sampling. We used the clinical and demographic variables inventory, body pain subscale of the health survey questionnaire, depression, anxiety and stress scale and fatigue severity scale along with identical analog-spring balance. The data were analyzed by Pearson correlation coefficient and point bi-serial, one-way analysis of variance, Gabriel test and stepwise multiple regression. Results: The findings showed that patients who scored 3 or higher in relapses experienced significantly more body pain than patients who scored 1-2 times of relapses (P= 0.031. In the meantime, significant differences were not found between the two groups of patients with a score of 3 or higher in relapses and non-relapse and between non-relapse patients and with a score 1-2 times of relapses in terms of body pain. Also, significant differences were not found in different groups of hospitalization in terms of body pain. However, anxiety and fatigue together could explain significantly 25% of the shared variance of body pain (F= 26.29, P≤ 0.0009. Conclusion: This study showed the effect of psychological and clinical factors on body pain exacerbation in MS patients. Therefore, it is necessary for clinicians to consider

  5. A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

    Science.gov (United States)

    Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

    2003-09-01

    Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

  6. Multiple Sclerosis and autoimmune diseases: clinical cases and review of the literature

    Directory of Open Access Journals (Sweden)

    A. Protti

    2011-09-01

    Full Text Available Multiple sclerosis (MS, the most frequent demyelinating disease in adults, is thought to be an autoimmune disease. Symptoms and signs observed in MS reflect lesions present mainly in the white matter of the central nervous system (CNS. The diagnosis remains difficult, at least concerning presenting symptoms, because of their low specificity. Diagnosis criteria are usually based on dissemination of signs in time and space, evoked potentials, findings of magnetic resonance imaging, results of cerebrospinal fluid examination, and the exclusion of other diagnosis possibly explaining the clinical signs. However, no clinical and paraclinical investigation can distinguish with certainity MS from other conditions such as autoimmune or inflammatory diseases predominantly affecting the central nervous system. These other disorders include systemic lupus erythematosus, antiphospholipid syndrome, Behcet disease, Sjogren syndrome, sarcoidosis and vasculitides. We present four clinical cases showing the difficulty in reaching a proper diagnosis...

  7. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

    Science.gov (United States)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

    2013-02-01

    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  8. Multiple sclerosis, from referral to confirmed diagnosis: an audit of clinical practice.

    LENUS (Irish Health Repository)

    Kelly, S B

    2012-02-01

    BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) guidelines recommend a timeline of 6 weeks from referral to neurology consultation and then 6 weeks to a diagnosis of multiple sclerosis (MS). OBJECTIVES: We audited the clinical management of all new outpatient referrals diagnosed with MS between January 2007 and May 2010. METHODS: We analysed the timelines from referral to first clinic visit, to MRI studies and lumbar puncture (LP) (if performed) and the overall interval from first visit to the time the diagnosis was given to the patient. RESULTS: Of the 119 diagnoses of MS\\/Clinically Isolated Syndrome (CIS), 93 (78%) were seen within 6 weeks of referral. MRI was performed before first visit in 61% and within 6 weeks in a further 27%. A lumbar puncture (LP) was performed in 83% of all patients and was done within 6 weeks in 78%. In total, 63 (53%) patients received their final diagnosis within 6 weeks of their first clinic visit, with 57 (48%) patients having their diagnosis delayed. The main rate-limiting steps were the availability of imaging and LP, and administrative issues. CONCLUSIONS: We conclude that, even with careful scheduling, it is difficult for a specialist service to obtain MRI scans and LP results so as to fulfil NICE guidelines within the optimal six-week period. An improved service would require MRI scans to be arranged before the first clinic visit in all patients with suspected MS.

  9. Evaluation of Clinical Gait Analysis parameters in patients affected by Multiple Sclerosis: Analysis of kinematics.

    Science.gov (United States)

    Severini, Giacomo; Manca, Mario; Ferraresi, Giovanni; Caniatti, Luisa Maria; Cosma, Michela; Baldasso, Francesco; Straudi, Sofia; Morelli, Monica; Basaglia, Nino

    2017-06-01

    Clinical Gait Analysis is commonly used to evaluate specific gait characteristics of patients affected by Multiple Sclerosis. The aim of this report is to present a retrospective cross-sectional analysis of the changes in Clinical Gait Analysis parameters in patients affected by Multiple Sclerosis. In this study a sample of 51 patients with different levels of disability (Expanded Disability Status Scale 2-6.5) was analyzed. We extracted a set of 52 parameters from the Clinical Gait Analysis of each patient and used statistical analysis and linear regression to assess differences among several groups of subjects stratified according to the Expanded Disability Status Scale and 6-Minutes Walking Test. The impact of assistive devices (e.g. canes and crutches) on the kinematics was also assessed in a subsample of patients. Subjects showed decreased range of motion at hip, knee and ankle that translated in increased pelvic tilt and hiking. Comparison between the two stratifications showed that gait speed during 6-Minutes Walking Test is better at discriminating patients' kinematics with respect to Expanded Disability Status Scale. Assistive devices were shown not to significantly impact gait kinematics and the Clinical Gait Analysis parameters analyzed. We were able to characterize disability-related trends in gait kinematics. The results presented in this report provide a small atlas of the changes in gait characteristics associated with different disability levels in the Multiple Sclerosis population. This information could be used to effectively track the progression of MS and the effect of different therapies. Copyright © 2017. Published by Elsevier Ltd.

  10. Proinsulin is stable at room temperature for 24 hours in EDTA: A clinical laboratory analysis (adAPT 3.

    Directory of Open Access Journals (Sweden)

    Jane Davidson

    Full Text Available Reference laboratories advise immediate separation and freezing of samples for the assay of proinsulin, which limit its practicability for smaller centres. Following the demonstration that insulin and C-peptide are stable in EDTA at room temperature for at least 24hours, we undertook simple stability studies to establish whether the same might apply to proinsulin.Venous blood samples were drawn from six adult women, some fasting, some not, aliquoted and assayed immediately and after storage at either 4°C or ambient temperature for periods from 2h to 24h.There was no significant variation or difference with storage time or storage condition in either individual or group analysis.Proinsulin appears to be stable at room temperature in EDTA for at least 24h. Immediate separation and storage on ice of samples for proinsulin assay is not necessary, which will simplify sample transport, particularly for multicentre trials.

  11. Long-term outcome of FFR-guided PCI for stable coronary artery disease in daily clinical practice

    DEFF Research Database (Denmark)

    De Backer, Ole; Biasco, Luigi; Lønborg, Jacob

    2016-01-01

    AIMS: Our aim was to investigate the strength of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) in daily practice. METHODS AND RESULTS: For this study, 3,512 patients with stable CAD and at least one 50-89% coronary stenosis...... were identified; those patients thought to require PCI (n=1,716) were selected. Of these, 962 (56%) were treated based on angiography (XA) alone, whereas 754 patients (44%) had an FFR-guided treatment. In the latter group, 321 patients (43%) were reallocated to another treatment, predominantly medical...... treatment. After propensity score matching, the number of indicated lesions was 957 in the XA-guided group and 947 in the FFR-guided group. FFR guidance resulted in PCI deferral in 462 lesions (48.8%). In a seven-day landmark analysis, the rate of periprocedural myocardial infarction (MI) was less than half...

  12. Study on the clinical usefulness of magnetic resonance imaging in cases of multiple cerebral infarction

    International Nuclear Information System (INIS)

    Miyashita, Kotaro

    1991-01-01

    The clinical significance of MRI in thrombotic multiple cerebral infarction was examined in 9 patients having recent lacunar stroke. Recent infarct was identified on Gd-enhanced MRI in 4 patients. For patients multiple small infarction, Gd-enhanced MRI made it possible to differentiate recent from other lesions. To clarify the significance of periventricular high intensity lesion (PVH) on T2-weighted MRI, hemodynamic and neuropsychologic examinations were carried out in 41 patients with multiple cerebral infarction. All the patients had PVH, which was classified into three grades as follows: grade I (n=16) showing only a thin high intensity band along the body of lateral ventricles; grade 2 (n=15) showing a definite high intensity area around the lateral ventricles; grade 3 (n=10) showing diffuse thick and irregular foci around the whole ventricle. In these patients, rCBF was measured by 133 Xe inhalation methods. Initial slope index was significantly higher in patients with grade 3 than those with grade I. Mini-mental state test score was significantly higher in patients with grade l than those with grade 2 and 3. Progression of PVH may be related with the reduction of the cerebral circulation and mental function in cases of multiple cerebral infarction. Ischemic and hemorrhagic lesions can be distinguished by MRI, because old intracerebral hemorrhage appear as hypointensity areas with or without hyperintensity area on T2w images. In 92 patients with multiple infarction, MRI was used to evaluate the incidence and distribution of coexisting old intracerebral hemorrhage. Old hemorrhage were found in 15 patients (16.3%). locating the site where hypertensive hemorrhage commonly occurred. High-field MRI is useful for assessing the coexistence of hemorrhage in hypertensive patients with multiple cerebral infarction. (N.K.)

  13. Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Gajofatto A

    2015-12-01

    Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

  14. Assessment of Early Cognitive Impairment in Patients with Clinically Isolated Syndromes and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Leyla Baysal Kıraç

    2014-01-01

    Full Text Available Objective. The aim of our study was to investigate the frequency and pattern of cognitive impairment in patients with clinically isolated syndromes and definite diagnosis of multiple sclerosis within the last 2 years. Methods. We assessed the cognitive status of 46 patients aged 18–49 years with clinically isolated syndromes or definite diagnosis of multiple sclerosis who have onset of their symptoms within the last 2 years. Patients were matched with 40 healthy participants for age, sex, and educational level. Neuropsychological assessment was performed by stroop test, paced auditory serial addition test (PASAT, controlled oral word association test (COWAT, clock drawing test, trail making test (TMT, faces symbol test (FST. Hamilton Depression Scale and Modified Fatigue Impact Scale were used to quantify the severity of any depression and fatigue the subjects might suffer. Results. 19.6% of early MS/CIS group failed at 4 and more tests and had significant cognitive impairment focused on attention, executive functions, memory, and learning. No significant relationship was found between cognitive impairment and disability and fatigue scores. Discussion. Cognitive impairment can be present from the earliest stage of multiple sclerosis. It should be considered among the main manifestations of MS even in the earliest stages of the disease.

  15. Heart rate modulation in stable coronary artery disease without clinical heart failure: What we have already learned from SIGNIFY?

    Directory of Open Access Journals (Sweden)

    Gian Piero Perna

    2016-12-01

    In conclusion, heart rate is a marker of risk but is not a risk factor and/or a target of therapy in patients with stable coronary artery disease and preserved ventricular systolic function. Standard doses of ivabradine are indicated for treatment of angina as an alternative or in addition to beta-blockers, but should not be administered in association with CYP3A4 inhibitors or heart rate-lowering calcium-channel blockers.

  16. Initial Clinical Experience in Multiple Myeloma Staging by Means of Whole-Body Resonance Techniques

    International Nuclear Information System (INIS)

    Gallego, J. I.; Concepcion, L.; Alonso, S.; Sanchez, B.; Manzi, F.

    2003-01-01

    To develop a magnetic resonance (MR) exploratory technique equivalent to serial bone X-ray, and to compare their precision in the staging of multiple myeloma (MM) patients. Multiple acquisition T1-weights TSE and STIR sequences in the coronal plane were performed. Ten healthy volunteers and 11 multiple myeloma diagnosed patients were included. The visualization of bony structures was particularly noted,with special attention given to those which would normally be included in a serial bone X-ray. In the case of the patients, a comparison was made between diagnostic capacities of the MR sequences. MR highlighters significantly more (p<0.05) bony elements than did the serial bone X-ray. This was greatly due to a sequential displacement of the scanner bed, allowing for field-of-views which were minimally from head to third proximal of the leg. Magnetic resonance detected a significantly higher number (p<0.05) of lesions. It was, in turn, capable of revealing greater lesion extensions, even to the point of implying staging classification changes in 18% of the patients. The utilization of whole-body MR techniques in multiple myeloma patients is feasible and clinically beneficial. MR is both more sensitive and more specific than serial bone X-ray for evaluation of bony lesions in MM. It is currently serving as a valid alternative in a growing numbers of patients. (Author) 10 refs

  17. Multiple sclerosis presented as clinically isolated syndrome: the need for early diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Sigliti-Henrietta Pelidou

    2008-06-01

    Full Text Available Sigliti-Henrietta Pelidou, Sotirios Giannopoulos, Sotiria Tzavidi, Georgios Lagos, Athanassios P KyritsisDepartment of Neurology, University of Ioannina School of Medicine, GreeceObjective: To aid in the timely diagnosis of patients who present with clinically isolated syndrome (CIS.Patients and methods: We studied 25 patients (18 women, 7 men, originally presented in our clinic with a CIS suggestive of multiple sclerosis (MS. All patients underwent the full investigation procedure including routine tests, serology, cerebrospinal fluid (CSF examinations, evoked potentials (EPs, and magnetic resonance imaging (MRI of brain and cervical spinal cord. Patients were imaged at baseline, and every three months thereafter up to a year.Results: The CIS was consisted of optic neuritis in 12 cases, incomplete transverse myelitis (ITM in 7 cases, Lhermitte sign in 2 cases, internuclear ophthalmoplegia (INO in 2 cases, mild brainstem syndrome in 1 case, and tonic-clonic seizures in 1 case. Using the baseline and three-month scans 18/25 (72% patients developed definite MS in one year of follow up while 7 (28% had no further findings during this observation period. Immunomodulatory treatments were applied to all definite MS patients.Conclusion: In light of new treatments available, MRIs at 3 month intervals are helpful to obtain the definite diagnosis of MS as early as possible.Keywords: multiple sclerosis, clinically isolated syndrome, optic neuritis, transverse myelitis

  18. The headache to subjects with multiple sclerosis: clinical and imaging study

    International Nuclear Information System (INIS)

    Moldovanu, Ion; Voiticovschi-Iosob, Cristina

    2011-01-01

    The present study showed clinical and imaging particularities of primary headache to subjects with multiple sclerosis. From the total number of 28 patients included in this study 22 (78,57%) had headache accuses (3 men and 19 women). Was observed a high prevalence of tension type headache, present to 10 of the 22 patients (45.45%). Migraine was diagnosed to 8 respondents (36.36 %). In 4 cases was found a combination of migraine and tension type headache (8.1%). Headache was more common to women with multiple sclerosis (MS) than to men. Neuroimaging of MS patients indicates the fact that the presence of demyelinating disease in the brainstem, midbrain, periaqueductal gray substance is associated with an increased risk of headache, migraine characteristics (migraine-like). Psychometric test have revealed a high level of depression and anxiety in patients with MS and chronic headache. (authors)

  19. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

    Directory of Open Access Journals (Sweden)

    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  20. T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

    Science.gov (United States)

    Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

    2015-01-01

    Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). Clinical-radiological correlations in MS patients are

  1. Ties that bind: multiple relationships between clinical researchers and the pharmaceutical industry.

    Science.gov (United States)

    Henry, David; Doran, Evan; Kerridge, Ian; Hill, Suzanne; McNeill, Paul M; Day, Richard

    2005-11-28

    It is believed that pharmaceutical industry sponsorship of clinical research leads to the development of multiple ties between clinicians and the pharmaceutical industry. To quantify this relationship we conducted a survey of medical specialists listed in the Medical Directory of Australia in 2002 and 2003. A questionnaire was mailed that elicited information about all aspects of research relationships between clinicians and pharmaceutical companies. The odds of reporting multiple additional ties (financial and professional) with pharmaceutical companies by clinicians who had an active research relationship were compared with those who did not. All clinicians who returned a completed questionnaire about their research activities were included in the study. A questionnaire was mailed to 2120 medical specialists; 823 (39%) responded. Of these, 338 (41%) reported involvement in industry-sponsored research in the previous year. They were more likely than others to have been offered industry-sponsored items or activities valued at more than 500 AU dollars (>382 US dollars; odds ratio [OR], 3.5; 95% confidence interval [CI], 2.6-4.7) and support for attending international conferences (OR, 5.4; 95% CI, 3.9-7.4). The strongest associations were seen for acting as a paid consultant to industry (OR, 9.0; 95% CI, 3.9-20.4) and for membership on advisory boards (OR, 6.9; 95% CI, 5.1-9.6). There was a strong relationship between research collaboration and accumulation of industry ties. For 1 additional tie the OR was 2.2 (95% CI, 1.2-3.8) and rose to 6.3 (95% CI, 3.5-11.1) with 3 ties and 41.8 (95% CI, 14.5-143.4) with 6 or more ties. Medical specialists who have research relationships with the pharmaceutical industry are much more likely to have multiple additional ties than those who do not have research relationships. Institutional review should discourage clinical researchers from developing multiple ties.

  2. Stable isotopes

    International Nuclear Information System (INIS)

    Evans, D.K.

    1986-01-01

    Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

  3. Design of clinical trials involving multiple hypothesis tests with a common control.

    Science.gov (United States)

    Schou, I Manjula; Marschner, Ian C

    2017-07-01

    Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Elskamp, I.J. van den; Boden, B.; Barkhof, F. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); Dattola, V. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); University of Messina, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina (Italy); Knol, D.L. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Filippi, M. [Scientific Institute and University Ospedale San Raffaele, Neuroimaging Research Unit, Milan (Italy); Kappos, L. [University Hospital, University of Basel, Department of Neurology, Basel (Switzerland); Fazekas, F. [Medical University of Graz, Department of Neurology, Graz (Austria); Wagner, K. [Bayer-Schering Pharma, Berlin (Germany); Pohl, C. [Bayer-Schering Pharma, Berlin (Germany); University Hospital Bonn, Department of Neurology, Bonn (Germany); Sandbrink, R. [Bayer-Schering Pharma, Berlin (Germany); Heinrich-Heine-University Dusseldorf, Department of Neurology, Dusseldorf (Germany); Polman, C.H. [VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands); Uitdehaag, B.M.J. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands)

    2010-10-15

    Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. (orig.)

  5. Topological characteristics of brainstem lesions in clinically definite and clinically probable cases of multiple sclerosis: An MRI-study

    International Nuclear Information System (INIS)

    Brainin, M.; Omasits, M.; Reisner, T.; Neuhold, A.; Wicke, L.

    1987-01-01

    Disseminated lesions in the white matter of the cerebral hemispheres and confluent lesions at the borders of the lateral ventricles as seen on MRI are both considered acceptable paraclinical evidence for the diagnosis of multiple sclerosis. Similar changes are, however, also found in vascular diseases of the brain. We therefore aimed at identifying those additional traits in the infratentorial region, which in our experience are not frequently found in cerebrovascular pathology. We evaluated MR brain scans of 68 patients and found pontine lesions in 71% of cases with a clinically definite diagnosis (17 out of 24) and in 33% of cases with a probable diagnosis (14 out of 43). Lesions in the medulla oblongata were present in 50% and 16%, respectively, and in the midbrain in 25% and 7%, respectively. With rare exceptions all brainstem lesions were contiguous with the cisternal or ventricular cerebrospinal fluid spaces. In keeping with post-mortem reports the morphological spectrum ranged from large confluent patches to solitary, well delineated paramedian lesions or discrete linings of the cerebrospinal fluid border zones and were most clearly depicted from horizontal and sagittal T2 weighted SE-sequences. If there is a predilection for the outer or inner surfaces of the brainstem, such lesions can be considered an additional typical feature of multiple sclerosis and can be more reliably weighted as paraclinical evidence for a definite diagnosis. (orig.)

  6. [Geographical differences in clinical characteristics and management of stable outpatients with coronary artery disease: comparison between the Italian and international population included in the Worldwide CLARIFY registry].

    Science.gov (United States)

    Pozzoli, Massimo; Tavazzi, Luigi

    2014-04-01

    Limited data are available regarding specific differences among countries in demographic and clinical characteristics and treatment of patients with stable coronary artery disease. CLARIFY is an international, prospective and longitudinal registry including more than 33 000 patients with stable coronary artery disease enrolled in 45 countries worldwide. Data were used to compare the characteristics of patients enrolled in Italy with those enrolled in Europe and in the rest of the world. Baseline data were available for 33 283 patients, 2112 of whom from Italy and 12 614 from the remaining western European countries. Italian patients were found to be older, more frequently smoker, hypertensive and with sedentary habits. In addition, they presented more frequently a history of myocardial infarction, carotid arterial disease and chronic obstructive pulmonary disease. In addition, when compared with patients of both European and international cohorts, more Italian patients had undergone coronary angiography and angioplasty. As far as treatment was concerned, a greater number of Italian patients were taking ivabradine, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, nitrates, thienopyridines, while those taking beta-blockers, calcium antagonists and other antianginal medications were fewer. Among ambulatory patients with stable coronary artery disease, there are important geographic differences in terms of risk factors, clinical characteristics, surgical and pharmacological treatment.

  7. Brief multiple behavior interventions in a college student health care clinic.

    Science.gov (United States)

    Werch, Chudley E Chad; Bian, Hui; Moore, Michele J; Ames, Steve; DiClemente, Carlo C; Weiler, Robert M

    2007-12-01

    This study examined the effects of brief image-based interventions, including a multiple behavior health contract, a one-on-one tailored consultation, and a combined consultation plus contract intervention, for impacting multiple health behaviors of students in a university health clinic. A total of 155 college students attending a major southern university were recruited to participate in a study evaluating a health promotion program titled Project Fitness during the fall 2005 and spring 2006. Participants were randomly assigned to one of three treatments as they presented at the clinic: 1) a multiple behavior health contract, 2) a one-on-one tailored consultation, or 3) a combined consultation plus contract intervention. Baseline and 1-month post-intervention data were collected using computer-assisted questionnaires in a quiet office within the student health clinic. Omnibus repeated-measures analyses of variance were significant for drinking driving behaviors, F(2,136) = 4.43, p = .01, exercise behaviors, F(5,140) = 6.12, p = .00, nutrition habits, F(3,143) = 5.37, p = .00, sleep habits, F(2,144) = 5.03, p = .01, and health quality of life, F(5,140) = 3.09, p = .01, with improvements on each behavior across time. Analysis of group-by-time interaction effects showed an increase in the use of techniques to manage stress, F(2,144) = 5.48, p = .01, and the number of health behavior goals set in the last 30 days, F(2,143) = 5.35, p = .01, but only among adolescents receiving the consultation, or consultation plus contract. Effect sizes were consistently larger across health behaviors, and medium in size, when both consult and contract were used together. Brief interventions using a positive goal image of fitness, and addressing a number of health habits using a contract and consultation strategy alone, or in combination, have the potential to influence positive changes in multiple health behaviors of college students attending a university primary health care clinic.

  8. Applications of stable isotopes of /sup 2/H, /sup 13/C and /sup 15/N to clinical problems. Experience of a collaborative program at Argonne National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Klein, P D; Szczepanik, P A; Hachey, D L [Argonne National Lab., Evanston, Ill. (USA)

    1974-08-01

    The function of the Argonne Program is to provide synthetic, analytical instrumental capability in a core facility for the clinical investigator who needs to use /sup 2/H, /sup 13/C, or /sup 15/N labelled compounds for metabolic or clinical research on pregnant women, newborn infants, young children, or for mass screening. To carry out such application development, there were six stages which were recurrent steps in every application. Five fundamental strategies should be adopted to establish the use of stable isotopes in clinical work. The instrument required for measurements was a combined gas chromatograph-mass spectrometer, and its use was schematically illustrated. Some of the successful experiences with compounds labelled by stable isotopes, such as deuterium labelled chenodeoxycholic acid, and respective /sup 13/C and /sup 15/N-labelled glycine were described. Deutrium labelled bile acid enabled easy and safe determination of the size of the bile acid pool and the replacement rate, providing clearer diagnoses for cholestatic liver disease and gallstones. /sup 13/C and /sup 15/N labelled compounds were used in clinical studies, of children with genetic disorders of amino acid metabolism, i.e., non ketotic hyperflycinemia, B/sub 12/-responsive methyl malonic acidemia, and Lesch-Nyhan syndrome. /sup 15/N-labelled glycine was also studied in a child with Lesch-Nyhan syndrome.

  9. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jan Lidbeck

    2002-01-01

    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  10. Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

    Science.gov (United States)

    Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

    2016-04-01

    We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

  11. Analyzing Statistical Mediation with Multiple Informants: A New Approach with an Application in Clinical Psychology.

    Science.gov (United States)

    Papa, Lesther A; Litson, Kaylee; Lockhart, Ginger; Chassin, Laurie; Geiser, Christian

    2015-01-01

    Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI) data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454) is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. The new approach allows for a more comprehensive and effective use of MI data when testing mediation models.

  12. Clinical utility and patient consideration in the use of lenalidomide for multiple myeloma in Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang J

    2015-06-01

    Full Text Available Jing Wang, Hongfeng Guo, Xin Zhou Department of Hematology, Wuxi People’s Hospital, Nanjing Medical University, Wuxi, People’s Republic of China Abstract: Multiple myeloma (MM is an incurable hematologic malignancy caused by the autonomous growth of malignant plasma cells. In the last decade, the introduction of novel targeted agents such as thalidomide, bortezomib, and lenalidomide has dramatically improved the clinical outcome of MM patients in both the frontline and recurrent settings. Lenalidomide is a synthetic derivative of thalidomide, which has been shown to significantly improve overall survival, time to progression, and overall response rates in patients with MM. The China Food and Drug Administration approved the use of lenalidomide in patients with MM in 2013. In a Phase II trial, lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with relapsed/refractory MM, including those with renal impairment and IgD subtype. However, lenalidomide will remain as a second-line antimyeloma drug in the near future because of its high price and the policy of health insurance reimbursement in People’s Republic of China. In this review, we summarize the clinical utility and patient considerations in the use of lenalidomide for MM in Chinese patients. Further studies with larger sample sizes are required to investigate the better quality, longer duration, and more clinically meaningful outcomes of lenalidomide in the treatment of MM in Chinese patients. Keywords: lenalidomide, multiple myeloma, clinical efficacy, Chinese patients

  13. Correlation between olfactory dysfunction and various clinical parameters in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kostić Jelena

    2009-01-01

    Full Text Available Background/Aim. Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system (CNS characterized by myelin destruction and axon loss. Among various clinical manifestations of MS cognitive disorders are frequent. Olfactory disorders are also noticed but they are rarely considered in clinical practice. The aim of the present study was to examine frequency of olfactory dysfunction in patients with MS and its relationship to clinical parameters. Methods. Our study comprised 61 consecutive patients with definite MS who were hospitalized at the Department for Multiple Sclerosis and Other Immune- Mediated Disorders of CNS, Institute of Neurology, Clinical Center of Serbia, Belgrade, and 45 gender-, age- and education-matched healthy voluntaries. The Pocket Smell Test (PST was used for examination of olfactory function. Cognitive functions were analyzed using the tests from the Brief Battery of Neuropsychological Tests: Paced Auditory Serial Addition Test 3-minute Version (PASAT 3', Word List Generation (WLG and Symbol Digit Modalities Test (SDMT. Results. Olfactory dysfunction was found in 26 (43% MS patients and 5 (11% controls (p = 0.001. Statistically significant positive correlation was found only between PST score and WLG scores (r = 0.297, p = 0.030. In comparison with the previously published normative values, our subjects with MS had decrease in the mean indices of the PASAT 3' in 28%, SDMT in 51% and WLG in 90% of the subjects. Conclusion. Olfactory dysfunction is frequent in our population of patients with MS. This disturbance correlates with the impairment of cognitive functions in these patients.

  14. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    International Nuclear Information System (INIS)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi; Hirai, Shunsaku

    1998-01-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO 2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO 2 . A correlation between the decrease in rCMRO 2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  15. Cerebral and spinal MRI examination in patients with clinically isolated syndrome and definite multiple sclerosis

    International Nuclear Information System (INIS)

    Sailer, M.; Fazekas, F.; Gass, A.; Kappos, L.; Radue, E.W.; Rieckmann, P.; Toyka, K.; Wiendl, H.; Bendszus, M.

    2008-01-01

    Purpose: magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5-15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria. Materials and methods: for the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent. Results: reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners. (orig.)

  16. [Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

    Science.gov (United States)

    Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

    2013-09-01

    To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  17. Diet-tissue stable isotope (Δ13C and Δ15N) discrimination factors for multiple tissues from terrestrial reptiles

    OpenAIRE

    Steinitz, R; Lemm, JM; Pasachnik, SA; Kurle, CM

    2016-01-01

    Copyright © 2015 John Wiley & Sons, Ltd. Rationale Stable isotope analysis is a powerful tool for reconstructing trophic interactions to better understand drivers of community ecology. Taxon-specific stable isotope discrimination factors contribute to the best use of this tool. We determined the first Δ 13 C and Δ 15 N values for Rock Iguanas (Cyclura spp.) to better understand isotopic fractionation and estimate wild reptile foraging ecology. Methods The Δ 13 C and Δ 15 N values between di...

  18. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    Directory of Open Access Journals (Sweden)

    Douglas W McMillin

    Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

  19. The Effectiveness of Transdermal Opioid in the Management Multiple Rib Fractures: Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Okan Solak

    2013-09-01

    Full Text Available Background: The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. Aims: To investigate the effectiveness of intramuscular opioid (IMO, intravenous patient-controlled analgesia (IVPCA and the Fentanyl transdermal therapeutic system (TTS in the management of rib fracture pain. Study Design: Prospective randomized clinical trial. Methods: In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15, 4x40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15 this was 5 µg/mL continuous intravenous fentanyl and was 50 µg fentanyl TTS in Group TTS (n=15. The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS. The pain during lying down (VASl and mobilisation (VASm was detected. Results: There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05. We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05. Conclusion: In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

  20. The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

    Science.gov (United States)

    Solak, Okan; Oz, Gürhan; Kokulu, Serdar; Solak, Ozlem; Doğan, Gökçen; Esme, Hıdır; Ocalan, Kubilay; Baki, Elif Doğan

    2013-09-01

    The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

  1. The clinical profile of women with stable ischaemic heart disease in Spain. More effort is needed in secondary prevention. SIRENA study.

    Science.gov (United States)

    Gámez, J M; Ripoll, T; Barrios, V; Anguita, M; Pedreira, M; Madariaga, I

    2016-01-01

    Cardiovascular diseases are the leading cause of death for women, especially ischaemic heart disease, which is still considered a man's disease. In Spain, there are various registries on ischaemic heart disease, although none are exclusively for women. The objectives of the SIRENA study were to describe the clinical profile of women with ischaemic heart disease treated in cardiology consultations, to estimate its prevalence of cardiovascular risk factors and understand its clinical management. A multicentre observational study was conducted with a sample of 631 women with stable ischaemic heart disease, consecutively included during cardiology consultations. Forty-one researchers from all over Spain participated in the study. The mean age was 68.5 years. The clinical presentation was in the form of acute coronary syndrome in up to 67.2% of the patients. The prevalence of cardiovascular risk factors was high (77.7% of the patients had hypertension, 40.7% had diabetes and 68% had dyslipidaemia), with 30.7% having uncontrolled hypertension, 78.4% having LDL-cholesterol levels higher than 70mg/dL and 49.2% having HbA1c levels greater than 7%. The considerable majority of the patients underwent optimal medical treatment with antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers and hypolipidaemic agents. Coronary angiography was performed for 88.3% of the patients, and 63.4% underwent percutaneous coronary intervention. Women with stable ischaemic heart disease in Spain initially present some form of acute coronary syndrome and a high prevalence of inadequately controlled cardiovascular risk factors, despite undergoing optimal medical therapy. A high percentage of these women undergo coronary revascularisation. Increased efforts are required for secondary prevention in women with stable ischaemic heart disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  2. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

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    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  3. Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity.

    Science.gov (United States)

    Koehler, Jürgen; Feneberg, Wolfgang; Meier, Martin; Pöllmann, Walter

    2014-09-01

    This detailed medical charts' data collection study conducted at a multiple sclerosis (MS) clinic in Germany evaluated the effectiveness of tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray in patients with resistant MS spasticity. Over a 15-month timeframe, THC:CBD spray was initiated in 166 patients. Mean follow-up was 9 months. In all, 120 patients remained on treatment for a response rate of 72%. THC:CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. Among responders, the mean spasticity 0-10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Most patients who withdrew from treatment (40/46) had been receiving THC:CBD spray for less than 60 days. Main reasons for treatment discontinuation were: adverse drug reactions, mainly dizziness, fatigue and oral discomfort (23 patients; 13.9%); lack of efficacy (14 patients; 8.4%); or need for a baclofen pump (9 patients; 5.4%). No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.

  4. Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma.

    Science.gov (United States)

    Talamo, Giampaolo; Farooq, Umar; Zangari, Maurizio; Liao, Jason; Dolloff, Nathan G; Loughran, Thomas P; Epner, Elliot

    2010-12-01

    Although the typical clinical manifestations of multiple myeloma (MM) are summarized by the CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone lesions), a significant proportion of patients with MM present with a variety of other clinical manifestations. We conducted a study evaluating the presenting symptoms that led to the diagnosis of MM. We conducted a retrospective review of 170 consecutive patients with MM seen at the Penn State Hershey Cancer Institute. Among patients with symptomatic MM, 74% presented with CRAB symptoms, 20% presented with non-CRAB manifestations, and 6% had both clinical features. Ten categories of non-CRAB manifestations were found, in order of decreasing frequency: neuropathy (because of spinal cord compression, nerve root compression, or peripheral neuropathy), extramedullary involvement, hyperviscosity syndrome, concomitant amyloidosis (eg, nephrotic syndrome or cardiopathy), hemorrhage/coagulopathy, systemic symptoms (eg, fever or weight loss), primary plasma cell leukemia, infections, cryoglobulinemia, and secondary gout. Kaplan-Meier estimates of survival in patients with non-CRAB manifestations did not show a significant difference from the survival of patients presenting with CRAB symptoms. Presenting symptoms of MM may be grouped in a total of 14 categories, 4 for the CRAB and 10 for the less common non-CRAB features. Grouped together, non-CRAB manifestations do not appear to confer a negative effect on the prognosis of patients with MM.

  5. The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

    Science.gov (United States)

    Minagar, Alireza; Barnett, Michael H; Benedict, Ralph H B; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott; Zivadinov, Robert

    2013-01-08

    The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

  6. Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

    Science.gov (United States)

    Russo, Margherita; Naro, Antonino; Leo, Antonino; Sessa, Edoardo; D'Aleo, Giangaetano; Bramanti, Placido; Calabrò, Rocco Salvatore

    2016-06-01

    The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

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    Bastianello Stefano

    2011-10-01

    Full Text Available Abstract Background Chronic cerebrospinal venous insufficiency (CCSVI has recently been reported to be associated with multiple sclerosis (MS. However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian. All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients. Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

  8. Adhesion molecules levels in blood correlate with MRI activity and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Enina, G.; Platkajis, A.; Metra, M.; Kukaine, R.

    2002-01-01

    Research into pathogenesis of multiple sclerosis (MS) has prompted efforts to identify immunological markers associated with disease activity. Adhesion molecules ICAM-1 and VCAM-1 are associated with inflammatory mediated blood-brain barrier (BBB) dysfunction. In this study investigates the correlation between blood level of circulating ICAM-1 and VCAM-1 and magnetic resonance imaging (MRI) activity in different clinical phases of patients with MS. We show that RRMS and SPMS patients in clinically active phase with Gd-enhancing lesions in CNS had higher blood levels of cICAM-1 and cVCAM-1 compared these parameters levers of RRMS patients in remission stage. These results suggest that cICAM-1 and cVCAM-1 is a sensitive indicator of disease activity associated with BBB inflammatory dysfunction. Elevated blood level of cICAM-1 more strongly correlated with clinical activity and BBB damage, than cVCAM-1 and that could be used as biological marker of disease activity. Circulating VCAM-1 as an early indicator of BBB disturbance, may also serve as marker of beneficial activity in relapses phase of MS course. (authors)

  9. Lesion classification using clinical and visual data fusion by multiple kernel learning

    Science.gov (United States)

    Kisilev, Pavel; Hashoul, Sharbell; Walach, Eugene; Tzadok, Asaf

    2014-03-01

    To overcome operator dependency and to increase diagnosis accuracy in breast ultrasound (US), a lot of effort has been devoted to developing computer-aided diagnosis (CAD) systems for breast cancer detection and classification. Unfortunately, the efficacy of such CAD systems is limited since they rely on correct automatic lesions detection and localization, and on robustness of features computed based on the detected areas. In this paper we propose a new approach to boost the performance of a Machine Learning based CAD system, by combining visual and clinical data from patient files. We compute a set of visual features from breast ultrasound images, and construct the textual descriptor of patients by extracting relevant keywords from patients' clinical data files. We then use the Multiple Kernel Learning (MKL) framework to train SVM based classifier to discriminate between benign and malignant cases. We investigate different types of data fusion methods, namely, early, late, and intermediate (MKL-based) fusion. Our database consists of 408 patient cases, each containing US images, textual description of complaints and symptoms filled by physicians, and confirmed diagnoses. We show experimentally that the proposed MKL-based approach is superior to other classification methods. Even though the clinical data is very sparse and noisy, its MKL-based fusion with visual features yields significant improvement of the classification accuracy, as compared to the image features only based classifier.

  10. The Role of Clinical and Instrumented Outcome Measures in Balance Control of Individuals with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Neeta Kanekar

    2013-01-01

    Full Text Available Purpose. The aim of the study was to investigate differences in balance control between individuals with multiple sclerosis (MS and healthy control subjects using clinical scales and instrumented measures of balance and determine relationships between balance measures, fatigue, and disability levels in individuals with MS with and without a history of falls. Method. Twelve individuals with MS and twelve healthy controls were evaluated using the Berg Balance and Activities-specific Balance Confidence Scales, Modified Clinical Test of Sensory Interaction on Balance, and Limits of Stability Tests as well as Fatigue Severity Scale and Barthel Index. Results. Mildly affected individuals with MS had significant balance performance deficits and poor balance confidence levels (P<0.05. MS group had higher sway velocities and diminished stability limits (P<0.05, significant sensory impairments, high fatigue and disability levels (P<0.05. Sway velocity was a significant predictor of balance performance and the ability to move towards stability limits for the MS group. For the MS-fallers group, those with lower disability levels had faster movement velocities and better balance performance. Conclusion. Implementation of both clinical and instrumented tests of balance is important for the planning and evaluation of treatment outcomes in balance rehabilitation of people with MS.

  11. Analyzing Statistical Mediation with Multiple Informants: A New Approach with an Application in Clinical Psychology

    Directory of Open Access Journals (Sweden)

    Lesther ePapa

    2015-11-01

    Full Text Available Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454 is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. Advantages and limitations of the new approach are discussed. The new approach can help clinical researchers overcome limitations of prior techniques. It allows for a more comprehensive and effective use of MI data when testing mediation models.

  12. Clinical implications for substandard, nonproprietary medicines in multiple sclerosis: focus on fingolimod

    Directory of Open Access Journals (Sweden)

    Correale J

    2016-06-01

    each ingredient in each capsule/tablet and lower quality. Substandard, nonproprietary copies of medicines that are immunomodulatory or immunosuppressive are of concern to patients due to their possible untoward safety and lack of efficacy events. This article reviews the potential risks associated with nonproprietary medicines that do not meet the regulatory requirements of the United States Food and Drug Administration, the European Medicines Agency, or the World Health Organization. The clinical implications for patients are described. This article focuses on nonproprietary medicines for multiple sclerosis, particularly fingolimod, that are not identical to proprietary versions and could thus fail to meet efficacy expectations or have different impact on the safety of patients with multiple sclerosis.Keywords: bioequivalence, fingolimod, multiple sclerosis, proprietary, substandard copies, toxicity

  13. Barriers and facilitators to reducing frequent laboratory testing for patients who are stable on warfarin: a mixed methods study of de-implementation in five anticoagulation clinics.

    Science.gov (United States)

    Barnes, Geoffrey D; Misirliyan, Sevan; Kaatz, Scott; Jackson, Elizabeth A; Haymart, Brian; Kline-Rogers, Eva; Kozlowski, Jay; Krol, Gregory; Froehlich, James B; Sales, Anne

    2017-07-14

    Patients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative. Using a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice. From the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less

  14. PSEUDOTUMORAL FORM OF MULTIPLE SCLEROSIS WITH SYMPTOMATIC CONVULSIVE SEIZURES (A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    Yu. A. Belova

    2015-01-01

    Full Text Available Multiple sclerosis (MS is prominent among central nervous system diseases. It affects chiefly young people and almost inevitably results in disability. In the past decade, there has been an upward trend for the prevalence of MS worldwide; in particular, the higher prevalence of this disease has been registered in the Moscow Region, which is associated with both an objective increase in its morbidity and improvement of specialized care to the population in the region. MS is characterized by a variety of clinical manifestations. However, paroxysmal disturbances are referred to as the rare symptoms of MS: the incidence of epileptic seizures in this condition is 0.89 to 7.5% according to the literature data. In addition to the clinical form of MS, there are its rare malignant atypical forms that also include its pseudotumoral form characterized by intrinsic neuroimaging and clinical signs that are different from the classical form of MS and another abnormality of the central nervous system. The pseudotumoral form of MS is characterized by the development of acute focal demyelination that appears as a large focus of an increased magnetic resonance signal with perifocal edema as evidenced by magnetic resonance imaging. A pseudotumoral focus of demyelination can occur both at the onset of MS and during its recurrent course. The atypical onset of MS is a special challenge because of diagnostic problems, which may lead to erroneous therapeutic policy and have a negative impact on the late prognosis of the disease. The authors provide a clinical case of the pseudotumoral form of MS with convulsive seizures at the onset of demyelinating disease. The problems of diagnosis and therapeutic approaches are discussed.

  15. Graph Theory-Based Brain Connectivity for Automatic Classification of Multiple Sclerosis Clinical Courses

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    Gabriel Kocevar

    2016-10-01

    Full Text Available Purpose: In this work, we introduce a method to classify Multiple Sclerosis (MS patients into four clinical profiles using structural connectivity information. For the first time, we try to solve this question in a fully automated way using a computer-based method. The main goal is to show how the combination of graph-derived metrics with machine learning techniques constitutes a powerful tool for a better characterization and classification of MS clinical profiles.Materials and methods: Sixty-four MS patients (12 Clinical Isolated Syndrome (CIS, 24 Relapsing Remitting (RR, 24 Secondary Progressive (SP, and 17 Primary Progressive (PP along with 26 healthy controls (HC underwent MR examination. T1 and diffusion tensor imaging (DTI were used to obtain structural connectivity matrices for each subject. Global graph metrics, such as density and modularity, were estimated and compared between subjects’ groups. These metrics were further used to classify patients using tuned Support Vector Machine (SVM combined with Radial Basic Function (RBF kernel.Results: When comparing MS patients to HC subjects, a greater assortativity, transitivity and characteristic path length as well as a lower global efficiency were found. Using all graph metrics, the best F-Measures (91.8%, 91.8%, 75.6% and 70.6% were obtained for binary (HC-CIS, CIS-RR, RR-PP and multi-class (CIS-RR-SP classification tasks, respectively. When using only one graph metric, the best F-Measures (83.6%, 88.9% and 70.7% were achieved for modularity with previous binary classification tasks.Conclusion: Based on a simple DTI acquisition associated with structural brain connectivity analysis, this automatic method allowed an accurate classification of different MS patients’ clinical profiles.

  16. Sjögren Syndrome Which Simulates Relapsing Remitting Multiple Sclerosis Clinical Features: Case Report

    Directory of Open Access Journals (Sweden)

    Haluk Gümüş

    2013-12-01

    Full Text Available Sjögren syndrome (SS is a chronic, inflammatory, autoimmune disease. It emerges as a dry mouth and eyes (sicca symptoms because, it fundamentally affects exocrine glands, frequently, salivary gland and lachrymal gland. Neurological involvement in Sjögren syndrome is observed in the approximately 20-25% of cases. 87% of the neurological involvements are peripheral nervous system involvement and around 13% of the neurological involvements are central nervous system involvement. Cerebral involvement represents heterogeneous features in terms of both localization (focal or diffuse and progress of the statement (acute, progressive or reversible. Affected central nervous system can show clinical and radiological signs similar to Multiple sclerosis (MS. In this paper, the case, which has a complaint of difficulty in walking and instability and MS like lesions in brain magnetic resonance imaging (MRI and is diagnosed as Sjögren syndrome by further research, is discussed

  17. An exploratory study on emotion recognition in patients with a clinically isolated syndrome and multiple sclerosis.

    Science.gov (United States)

    Jehna, Margit; Neuper, Christa; Petrovic, Katja; Wallner-Blazek, Mirja; Schmidt, Reinhold; Fuchs, Siegrid; Fazekas, Franz; Enzinger, Christian

    2010-07-01

    Multiple sclerosis (MS) is a chronic multifocal CNS disorder which can affect higher order cognitive processes. Whereas cognitive disturbances in MS are increasingly better characterised, emotional facial expression (EFE) has rarely been tested, despite its importance for adequate social behaviour. We tested 20 patients with a clinically isolated syndrome suggestive of MS (CIS) or MS and 23 healthy controls (HC) for the ability to differ between emotional facial stimuli, controlling for the influence of depressive mood (ADS-L). We screened for cognitive dysfunction using The Faces Symbol Test (FST). The patients demonstrated significant decreased reaction-times regarding emotion recognition tests compared to HC. However, the results also suggested worse cognitive abilities in the patients. Emotional and cognitive test results were correlated. This exploratory pilot study suggests that emotion recognition deficits might be prevalent in MS. However, future studies will be needed to overcome the limitations of this study. Copyright 2010 Elsevier B.V. All rights reserved.

  18. USE OF DIMETHYL FUMARATE IN THE TREATMENT OF MULTIPLE SCLEROSIS: CLINICAL AND ECONOMIC ANALYSIS

    Directory of Open Access Journals (Sweden)

    V. R. Mkrtchyan

    2016-01-01

    Full Text Available The paper presents a review of an update on the comparative pharmacoeconomic analysis of using dimethyl fumarate in the treatment of multiple sclerosis (MS in European countries. A pharmacoeconomic evaluation was made to study the use of first-line oral dimethyl fumarate versus another first-line oral teriflunomide in the treatment of MS in the Russian Federation (for 1 year and second-line natalizumab and fingolimod. Among first-line oral drugs, dimethyl fumarate was shown to be superior to teriflunomide in a cost-effectiveness ratio and to be slightly ahead of the MS-modifying drugs (MSMDs  and the second-line drugs natalizumab and fingolimod. According to clinical and economic indicators, dimethyl fumarate is the drug of choise among other MSMDs in the treatment of MS.

  19. [Multiple sclerosis. Clinical survey of 50 patients followed at the Ambulatory of Neurology UNIFESP-EPM].

    Science.gov (United States)

    De Oliveira, E M; Annes, M; Oliveira, A S; Gabbai, A A

    1999-03-01

    Multiple sclerosis, seems to be a rare disease however in the population herein studied it is similar to the one described by others, in Brazil and abroad. We studied 50 patients classified according Poser's criteria that were followed at the Department of Neurology UNIFESP-EPM from 1983 to 1995. The clinical findings of these 50 patients were similar to those described in other series. We found a high prevalence among female young patients who presented relapsing-remitting evolution. The most common symptoms were those related to pyramidal and cerebellar dysfunctions. The EDSS score seems to be worse in patients with specific cerebellar and pyramidal signs, higher number of relapses and longer time of disease but it is not related to the number of white matter lesions found at MRI.

  20. The recolonization hypothesis in a full-mouth or multiple-session treatment protocol : a blinded, randomized clinical trial

    NARCIS (Netherlands)

    Zijnge, Vincent; Meijer, Henriette F.; Lie, Mady-Ann; Tromp, Jan A. H.; Degener, John E.; Harmsen, Hermie J. M.; Abbas, Frank

    P>Aim To test recolonization of periodontal lesions after full-mouth scaling and root planing (FM-SRP) or multiple session-SRP (MS-SRP) in a randomized clinical trial and whether FM-SRP and MS-SRP result in different clinical outcomes. Materials and Methods Thirty-nine subjects were randomly

  1. Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator.

    Science.gov (United States)

    Boggild, Mike; Palace, Jackie; Barton, Pelham; Ben-Shlomo, Yoav; Bregenzer, Thomas; Dobson, Charles; Gray, Richard

    2009-12-02

    To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis. Prospective cohort study with historical comparator. Specialist multiple sclerosis clinics in 70 centres in the United Kingdom. Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme. Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists. Observed utility weighted progression in disability at two years' follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials. In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset ("deviation score" of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from -72% (using raw baseline disability status scale scores, rather than applying a "no improvement" algorithm) to 156% (imputing missing data for year two from progression rates for year one). It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the "no improvement" rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.

  2. Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic pregnancies: a retrospective study.

    Science.gov (United States)

    Dai, Quan; Wang, Lu-Lu; Shao, Xiao-Hui; Wang, Si-Ming; Dong, Xiao-Qiu

    2012-10-01

    To study the effect of local interventional treatment of unruptured ectopic pregnancies with multiple-drug injection guided by color Doppler sonography. In this retrospective analysis, 49 patients with an unruptured ectopic pregnancy were treated with two different local injection methods administered under sonographic guidance. The patients were divided into single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they received a locally administered injection of methotrexate alone or a combination including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs, respectively. Overall, local injection treatment was successful in 44 patients. The 5 patients with failed treatment underwent laparotomy about 1 week after single-drug injection. Serum β-human chorionic gonadotropin (β-hCG ) levels, ectopic pregnancy mass sizes, blood flow at various points after treatment, the incidence of pelvic bleeding, and the time for serum β-hCG levels to return to normal and the mass to resolve were analyzed in the remaining 44 patients. Single-drug treatment was successful in 18 patients; 10 of 23 had low to moderate pelvic bleeding after treatment, and 5 were referred for surgery. All 26 patients were successfully treated by multiple-drug injection. Only 2 patients had a small amount of pelvic bleeding. Differences between groups were statistically significant (P injection under color Doppler guidance is a new, safe, and effective method for treating unruptured ectopic pregnancies. It accelerates the serum β-hCG decline and facilitates mass resolution. This regimen is associated with a very low rate of pelvic bleeding, improves the success rate of conservative treatment, and, therefore, has value as an important clinical application.

  3. The clinical application of absorbable intramedullary nail and claw plate on treating multiple rib fractures.

    Science.gov (United States)

    Chai, X; Lin, Q; Ruan, Z; Zheng, J; Zhou, J; Zhang, J

    2013-08-01

    The absorption intramedullary nail and claw plate indications and efficacy were investigated in the treatment of a life-threatening multiple rib fractures. A retrospective analysis of 248 surgically treated rib fracture patients was performed who admitted to our hospital from March 2007 to December 2012. Intramedullary nailing was performed in 28 cases, a claw-type bone plate was fixed in 141 cases, and a combination of both was fixed in 79 cases. All internal fixation patients were clinically cured except 1 patient died 14 days after a massive pulmonary embolism. The patients with flail chest and floating chest wall causing respiratory and circulatory disorders were promptly corrected. Routine follow-up was from 1 to 2 years, displaced fractures were in 2 cases, and there were 11 cases of internal fixation and extraction. Internal fixation is a simple and reliable method for the treatment of multiple rib fractures. Both internal fixation materials have their pros and cons but the claw bone plate is more robust. The actual selection of appropriate treatment options helps to improve the treatment efficacy.

  4. Clinical implications for substandard, nonproprietary medicines in multiple sclerosis: focus on fingolimod

    Science.gov (United States)

    Correale, Jorge; Chiquete, Erwin; Boyko, Alexey; Beran, Roy G; Strauch, Jorge Barahona; Milojevic, Snezana; Frider, Nadina

    2016-01-01

    Both proprietary and nonproprietary medicines are expected to undergo rigorous preapproval testing and both should meet stringent health authority regulatory requirements related to quality to obtain approval. Nonproprietary (also known as copy, or generic) medicines, which base their authorization and use on the proprietary documentation and label, are often viewed as a means to help lower the cost and, thus, increase patient access. If these medicines fail to meet quality standards, such as good manufacturing practice and bioequivalence (in humans), they are then defined as substandard copies and can pose serious risks to patients in terms of safety and efficacy. Potentially noncontrolled or different manufacturing process and excipients in nonproprietary medicines may result in poor batch-to-batch reproducibility (accurate and consistent quantity of each ingredient in each capsule/tablet) and lower quality. Substandard, nonproprietary copies of medicines that are immunomodulatory or immunosuppressive are of concern to patients due to their possible untoward safety and lack of efficacy events. This article reviews the potential risks associated with nonproprietary medicines that do not meet the regulatory requirements of the United States Food and Drug Administration, the European Medicines Agency, or the World Health Organization. The clinical implications for patients are described. This article focuses on nonproprietary medicines for multiple sclerosis, particularly fingolimod, that are not identical to proprietary versions and could thus fail to meet efficacy expectations or have different impact on the safety of patients with multiple sclerosis. PMID:27418809

  5. HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A 1H MRS Study

    Science.gov (United States)

    Cysique, Lucette A.; Moffat, Kirsten; Moore, Danielle M.; Lane, Tammy A.; Davies, Nicholas W. S.; Carr, Andrew; Brew, Bruce J.; Rae, Caroline

    2013-01-01

    Background Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. Methods 92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. Results Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (pHIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. Conclusions In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by

  6. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  7. Impact of a Pelvic Floor Training Program Among Women with Multiple Sclerosis: A Controlled Clinical Trial.

    Science.gov (United States)

    Ferreira, Ana Paula Silva; Pegorare, Ana Beatriz Gomes de Souza; Salgado, Pedro Rippel; Casafus, Filemón Silva; Christofoletti, Gustavo

    2016-01-01

    The objective of this study was to investigate the effects of two programs for strengthening the pelvic floor on the urinary incontinence of patients with multiple sclerosis (MS). This is a prospective study of the clinical trial type, monitored for 6 mos, in which 24 women in the moderate stage of MS participated in a program of exercises for strengthening the pelvic floor-associated (experimental group) or not (control group) with electrotherapy. The variables analyzed were as follows: quality-of-life, overactivity of the bladder, perineal contraction, and level of anxiety and depression. The statistical procedures involved multivariate analyses of repeated measurements, with a significance of 5%. Initial homogeneity being observed in the anthropometric and clinical variables, both protocols resulted in improvements in quality-of-life (P = 0.001), overactive bladder (P = 0.001), perineal contraction (P = 0.004), and level of anxiety (P = 0.001) and depression (P = 0.001), in relation to the initial comparison. The association of electrotherapy with strengthening exercises increased the improvement of the patients regarding overactive bladder (P = 0.039) and perineal contraction (P = 0.001), in comparison with the control group. The results reinforce the benefit of exercises for strengthening the musculature of the pelvic floor in women with overactive bladder in MS and demonstrate a potential of the action when associated with electrotherapy. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Identify common dysfunctions of the lower urinary tract in women with multiple sclerosis; (2) Discuss the relationship between quality-of-life, level of anxiety and depression, degree of perineal contraction, and overactive bladder; and (3) Recognize the benefits promoted by physical therapy for strengthening the pelvic floor in patients with

  8. Interaural multiple frequency tympanometry measures: clinical utility for unilateral conductive hearing loss.

    Science.gov (United States)

    Norrix, Linda W; Burgan, Briana; Ramirez, Nicholas; Velenovsky, David S

    2013-03-01

    Tympanometry is a routine clinical measurement of the acoustic immittance of the ear as a function of ear canal air pressure. The 226 Hz tympanogram can provide clinical evidence for conditions such as a tympanic membrane perforation, Eustachian tube dysfunction, middle ear fluid, and ossicular discontinuity. Multiple frequency tympanometry using a range of probe tone frequencies from low to high has been shown to be more sensitive than a single probe tone tympanogram in distinguishing between mass- and stiffness-related middle ear pathologies (Colletti, 1975; Funasaka et al, 1984; Van Camp et al, 1986). In this study we obtained normative measures of middle ear resonance by using multiple probe tone frequency tympanometry. Ninety percent ranges for middle ear resonance and for interaural differences were calculated. In a mixed design, normative data were collected from both ears of male and female adults. Twelve male and 12 female adults with normal hearing and normal middle ear function participated in the study. Multiple frequency tympanograms were recorded with a commercially available immittance instrument (GSI Tympstar) to obtain estimates of middle ear resonant frequency (RF) using ΔB, positive tail, and negative tail methods. Data were analyzed using three-way mixed analyses of variance with gender as a between-subject variable and ear and method as within-subject variables. T-tests were performed, using the Bonferroni adjustment, to determine significant differences between means. Using the positive and negative tail methods, a wide range of approximately 500 Hz was found for middle ear resonance in adults with normal hearing and normal middle ear function. The difference in RF between an individual's ears is small with 90% ranges of approximately ±200 Hz, indicating that the right ear RF should be either 200 Hz higher or lower in frequency compared to the left ear. This was true for both negative and positive tail methods. Ninety percent ranges were

  9. The effect of alcohol and red wine consumption on clinical and MRI outcomes in multiple sclerosis.

    Science.gov (United States)

    Diaz-Cruz, Camilo; Chua, Alicia S; Malik, Muhammad Taimur; Kaplan, Tamara; Glanz, Bonnie I; Egorova, Svetlana; Guttmann, Charles R G; Bakshi, Rohit; Weiner, Howard L; Healy, Brian C; Chitnis, Tanuja

    2017-10-01

    Alcohol and in particular red wine have both immunomodulatory and neuroprotective properties, and may exert an effect on the disease course of multiple sclerosis (MS). To assess the association between alcohol and red wine consumption and MS course. MS patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) who completed a self-administered questionnaire about their past year drinking habits at a single time point were included in the study. Alcohol and red wine consumption were measured as servings/week. The primary outcome was the Expanded Disability Status Scale (EDSS) at the time of the questionnaire. Secondary clinical outcomes were the Multiple Sclerosis Severity Score (MSSS) and number of relapses in the year before the questionnaire. Secondary MRI outcomes included brain parenchymal fraction and T2 hyperintense lesion volume (T2LV). Appropriate regression models were used to test the association of alcohol and red wine intake on clinical and MRI outcomes. All analyses were controlled for sex, age, body mass index, disease phenotype (relapsing vs. progressive), the proportion of time on disease modifying therapy during the previous year, smoking exposure, and disease duration. In the models for the MRI outcomes, analyses were also adjusted for acquisition protocol. 923 patients (74% females, mean age 47 ± 11 years, mean disease duration 14 ± 9 years) were included in the analysis. Compared to abstainers, patients drinking more than 4 drinks per week had a higher likelihood of a lower EDSS score (OR, 0.41; p = 0.0001) and lower MSSS (mean difference, - 1.753; p = 0.002) at the time of the questionnaire. Similarly, patients drinking more than 3 glasses of red wine per week had greater odds of a lower EDSS (OR, 0.49; p = 0.0005) and lower MSSS (mean difference, - 0.705; p = 0.0007) compared to nondrinkers. However, a faster increase in T2LV was observed in patients consuming 1

  10. Clinical Predictors of Multiple Organ Dysfunction Syndromes in Pediatric patients with Scrub Typhus.

    Science.gov (United States)

    Zhao, Dongying; Zhang, Yongjun; Yin, Zhaoqing; Zhao, Jing; Yang, Defeng; Zhou, Qun

    2017-06-01

    Scrub typhus can produce multiple organ dysfunction syndrome (MODS). Early recognition of the patients at risk of MODS would be helpful in providing timely management and reducing the mortality. In all, 449 children with scrub typhus were enrolled at three hospitals in Yunnan, China from January 2010 to January 2015. The patients' clinical status of organ system dysfunction was evaluated on the day of discharge from hospital by using standard criteria. The patients were classified into MODS present (64 cases, 14.3%) or MODS absent (385 cases, 85.7%). Multivariate logistic regression analyses revealed that the prognostic factors for MODS included skin rash (odds ratio, OR = 3.3, p = 0.037), time interval form treatment to defervescence (OR = 1.2, p = 0.035), hemoglobin (OR = 0.54, p = 0.041), platelet counts (OR = 0.06, p scrub typhus, our study provides clinicians with important information to improve the clinical monitoring and prognostication of MODS. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study

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    Gonzalez-Toledo Eduardo

    2007-10-01

    Full Text Available Abstract Background The presence of antiphospholipid antibodies (APLA in multiple sclerosis (MS patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA. Methods A consecutive cohort of 24 subjects with relapsing-remitting (RR MS were studied of whom 7 were in remission (Rem and 17 in exacerbation (Exc. All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL, β2 glycoprotein I (β2GPI, Factor VII/VIIa (FVIIa, phosphatidylcholine (PC, phosphatidylserine (PS and phosphatidylethanolamine (PE. Results In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p Conclusion The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.

  12. Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis.

    Science.gov (United States)

    Tam, Roger C; Traboulsee, Anthony; Riddehough, Andrew; Li, David K B

    2012-01-01

    The change in T 1-hypointense lesion ("black hole") volume is an important marker of pathological progression in multiple sclerosis (MS). Black hole boundaries often have low contrast and are difficult to determine accurately and most (semi-)automated segmentation methods first compute the T 2-hyperintense lesions, which are a superset of the black holes and are typically more distinct, to form a search space for the T 1w lesions. Two main potential sources of measurement noise in longitudinal black hole volume computation are partial volume and variability in the T 2w lesion segmentation. A paired analysis approach is proposed herein that uses registration to equalize partial volume and lesion mask processing to combine T 2w lesion segmentations across time. The scans of 247 MS patients are used to compare a selected black hole computation method with an enhanced version incorporating paired analysis, using rank correlation to a clinical variable (MS functional composite) as the primary outcome measure. The comparison is done at nine different levels of intensity as a previous study suggests that darker black holes may yield stronger correlations. The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes.

  13. Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Yu Chunshui; Lin Fuchun; Liu Yaou; Duan Yunyun; Lei Hao; Li Kuncheng

    2008-01-01

    Objective: The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases. Materials and methods: DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T 2 WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients. Results: Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS. Conclusion: Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients

  14. Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology.

    Science.gov (United States)

    Harrison, Daniel M; Oh, Jiwon; Roy, Snehashis; Wood, Emily T; Whetstone, Anna; Seigo, Michaela A; Jones, Craig K; Pham, Dzung; van Zijl, Peter; Reich, Daniel S; Calabresi, Peter A

    2015-08-01

    Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing-remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS. © The Author(s), 2015.

  15. [Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

    Science.gov (United States)

    Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

    2018-02-23

    Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

  16. Incidence, clinical features, laboratory findings and outcome of patients with multiple myeloma presenting with extramedullary relapse.

    Science.gov (United States)

    Papanikolaou, Xenofon; Repousis, Panagiotis; Tzenou, Tatiana; Maltezas, Dimitris; Kotsopoulou, Maria; Megalakaki, Katerina; Angelopoulou, Maria; Dimitrakoloulou, Elektra; Koulieris, Efstathios; Bartzis, Vassiliki; Pangalis, Gerasimos; Panayotidis, Panagiotis; Kyrtsonis, Marie-Christine

    2013-07-01

    Extramedullary plasmacytomas constitute a rare and not well studied subset of multiple myeloma (MM) relapses. We report the incidence, clinical-laboratory features and outcome of patients with MM and extramedullary relapse (ExMeR). A total of 303 patients with symptomatic MM were recorded in a 13-year period in two institutions. Twenty-eight cases of ExMeR (9%) were recorded. There was an increased frequency of elevated lactate dehydrogenase (LDH) (p = 0.026), bone plasmacytomas (p = 0.001) and fractures (p = 0.002) at diagnosis, in patients with ExMeR compared to the others. ExMeR was associated with an ominous outcome, high LDH, constitutional symptoms and a statistically significant decrease of monoclonal paraprotein compared to levels at diagnosis (p = 0.009). Prior treatment with bortezomib was associated with a decreased hazard of ExMeR (p = 0.041). Overall survival (OS) was decreased in patients with ExMeR compared to the others (38 vs. 59 months, p = 0.006). Patients with MM with ExMeR have a lower OS and their clinical and laboratory features differ from those without.

  17. Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline.

    Science.gov (United States)

    Morrow, Sarah A; Drake, Allison; Zivadinov, Robert; Munschauer, Frederick; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2010-10-01

    Cognitive dysfunction is common in multiple sclerosis (MS), yet the magnitude of change on objective neuropsychological (NP) tests that is clinically meaningful is unclear. We endeavored to determine NP markers of the transition from employment to work disability in MS, as indicated by degree of decline on individual tests. Participants were 97 employed MS patients followed over 41.3 ± 17.6 months with a NP battery covering six domains of cognitive function. Deterioration at follow-up was designated as documented and paid disability benefits (conservative definition) or a reduction in hours/work responsibilities (liberal definition). Using the conservative definition, 28.9% reported deteriorated employment status and for the liberal definition, 45.4%. The Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test, Total Learning (CVLT2-TL) measures distinguished employed and disabled patients at follow-up. Controlling for demographic and MS characteristics, the odds ratio of a deterioration based on a change of 2.0 on the CVLT2-TL was 3.7 (95% CI 1.2-11.4 and SDMT by 4.0 was 4.2 (95% CI 1.2-14.8), accounting for 86.7% of the area under the ROC curve. We conclude that decline on NP testing over time is predictive of deterioration in vocational status, establishing a magnitude of decline on NP tests that is clinically meaningful.

  18. A neurophysiological study of facial numbness in multiple sclerosis: Integration with clinical data and imaging findings.

    Science.gov (United States)

    Koutsis, Georgios; Kokotis, Panagiotis; Papagianni, Aikaterini E; Evangelopoulos, Maria-Eleftheria; Kilidireas, Constantinos; Karandreas, Nikolaos

    2016-09-01

    To integrate neurophysiological findings with clinical and imaging data in a consecutive series of multiple sclerosis (MS) patients developing facial numbness during the course of an MS attack. Nine consecutive patients with MS and recent-onset facial numbness were studied clinically, imaged with routine MRI, and assessed neurophysiologically with trigeminal somatosensory evoked potential (TSEP), blink reflex (BR), masseter reflex (MR), facial nerve conduction, facial muscle and masseter EMG studies. All patients had unilateral facial hypoesthesia on examination and lesions in the ipsilateral pontine tegmentum on MRI. All patients had abnormal TSEPs upon stimulation of the affected side, excepting one that was tested following remission of numbness. BR was the second most sensitive neurophysiological method with 6/9 examinations exhibiting an abnormal R1 component. The MR was abnormal in 3/6 patients, always on the affected side. Facial conduction and EMG studies were normal in all patients but one. Facial numbness was always related to abnormal TSEPs. A concomitant R1 abnormality on BR allowed localization of the responsible pontine lesion, which closely corresponded with MRI findings. We conclude that neurophysiological assessment of MS patients with facial numbness is a sensitive tool, which complements MRI, and can improve lesion localization. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A full genomic characterization of the development of a stable Small Colony Variant cell-type by a clinical Staphylococcus aureus strain.

    Science.gov (United States)

    Bui, Long M G; Kidd, Stephen P

    2015-12-01

    A key to persistent and recurrent Staphylococcus aureus infections is its ability to adapt to diverse and toxic conditions. This ability includes a switch into a biofilm or to the quasi-dormant Small Colony Variant (SCV). The development and molecular attributes of SCVs have been difficult to study due to their rapid reversion to their parental cell-type. We recently described the unique induction of a matrix-embedded and stable SCV cell-type in a clinical S. aureus strain (WCH-SK2) by growing the cells with limiting conditions for a prolonged timeframe. Here we further study their characteristics. They possessed an increased viability in the presence of antibiotics compared to their non-SCV form. Their stability implied that there had been genetic changes; we therefore determined both the genome sequence of WCH-SK2 and its stable SCV form at a single base resolution, employing Single Molecular Real-Time (SMRT) sequencing that enabled the methylome to also be determined. The genetic features of WCH-SK2 have been identified; the SCCmec type, the pathogenicity and genetic islands and virulence factors. The genetic changes that had occurred in the stable SCV form were identified; most notably being in MgrA, a global regulator, and RsbU, a phosphoserine phosphatase within the regulatory pathway of the sigma factor SigB. There was a shift in the methylomes of the non-SCV and stable SCV forms. We have also shown a similar induction of this cell-type in other S. aureus strains and performed a genetic comparison to these and other S. aureus genomes. We additionally map RNAseq data to the WCH-SK2 genome in a transcriptomic analysis of the parental, SCV and stable SCV cells. The results from this study represent the unique identification of a suite of epigenetic, genetic and transcriptional factors that are implicated in the switch in S. aureus to its persistent SCV form. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The main clinical symptoms of multiple sclerosis at the children in the debut. Own observation

    Directory of Open Access Journals (Sweden)

    Stetsenko T.I.

    2016-05-01

    Full Text Available Objective: evaluate first clinical signs of MS for early diagnosis and prevention of disability. Patients and methods. There are results of examination of 9 patients (5 boys, 4 girls aged 15 to 17 years, who sought a neurological department NDSL «OKHMATDYT» during 2014 for further diagnosis & treatment. Researches included a general clinical examination, immunological parameters, visual evoked potentials, CT, MRI with contrast of brain and spinal cord. Data analysis was performed according to McDonald criteria. Results. The complaints are presented in all cases of violation of the sensitivity of the limbs (numbness of limbs mainly in the left part of a body as a result of stress, during the studies at school, after physical exercises, against a background of full health. Later, they were accompanied by paresis of facial muscles in the central-type, by the central amaurosis of both eyes, by the periodic urinary incontinence in the last 7 years, lower spastic paraparesis and left-side hemiparesis. Clinically: nistahmoyid in extreme abduction of the eyeballs, asymmetry of reflexes, abnormal volatility of iambic signs, violation of statics and coordination. In the first case there were detected 7 exacerbations. In MRI of the brain was detected multiple hiperintense foci of periventricular and subcortical mostly (8 cases, spread to the spinal cord (2 cases. At the previous stages was diagnosed herpes infection, subacute encephalitis, brain volumetric process, ADEM, acute myelitis, tuberous sclerosis, CVA. After the examination in conditions of highly specialized branch was established in RS for appropriate treatment. Conclusions. 1. The manifestation of MS among children 15–17 year old mostly presented monosymptomatic and sensitivity violation almost in all cases. 2. Characteristic remitting and relapsing-remitting-relapsing course of MS, cerebral form (in 2 cases cerebrovascular spinal. 3. A clearly shown dissemination in space and time

  1. Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

    Science.gov (United States)

    Hannoun, Salem; Bagory, Matthieu; Durand-Dubief, Francoise; Ibarrola, Danielle; Comte, Jean-Christophe; Confavreux, Christian; Cotton, Francois; Sappey-Marinier, Dominique

    2012-01-01

    Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients. PMID:22479330

  2. Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course

    Directory of Open Access Journals (Sweden)

    Yun Jin Lee

    2011-06-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is a demyelinating disease of the central nervous system (CNS that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS. Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.

  3. Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

    Directory of Open Access Journals (Sweden)

    Cefaro Luca

    2009-10-01

    Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

  4. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    2014-01-01

    Is entrepreneurship a more stable career choice for high employment turnover individuals? We find that a transition to entrepreneurship induces a shift towards stayer behavior and identify job matching, job satisfaction and lock-in effects as main drivers. These findings have major implications...

  5. Phased implementation of spaced clinic visits for stable HIV-positive patients in Rwanda to support Treat All.

    Science.gov (United States)

    Nsanzimana, Sabin; Remera, Eric; Ribakare, Muhayimpundu; Burns, Tracy; Dludlu, Sibongile; Mills, Edward J; Condo, Jeanine; Bucher, Heiner C; Ford, Nathan

    2017-07-21

    In 2016, Rwanda implemented "Treat All," requiring the national HIV programme to increase antiretroviral (ART) treatment coverage to all people living with HIV. Approximately half of the 164,262 patients on ART have been on treatment for more than five years, and long-term retention of patients in care is an increasing concern. To address these challenges, the Ministry of Health has introduced a differentiated service delivery approach to reduce the frequency of clinical visits and medication dispensing for eligible patients. This article draws on key policy documents and the views of technical experts involved in policy development to describe the process of implementation of differentiated service delivery in Rwanda. Implementation of differentiated service delivery followed a phased approach to ensure that all steps are clearly defined and agreed by all partners. Key steps included: definition of scope, including defining which patients were eligible for transition to the new model; definition of the key model components; preparation for patient enrolment; considerations for special patient groups; engagement of implementing partners; securing political and financial support; forecasting drug supply; revision, dissemination and implementation of ART guidelines; and monitoring and evaluation. Based on the outcomes of the evaluation of the new service delivery model, the Ministry of Health will review and strategically reduce costs to the national HIV program and to the patient by exploring and implementing adjustments to the service delivery model.

  6. Assessment set for evaluation of clinical outcomes in multiple sclerosis: psychometric properties

    Directory of Open Access Journals (Sweden)

    Rasova K

    2012-10-01

    Full Text Available Kamila Rasova,1 Patricia Martinkova,2 Jana Vyskotova,3 Michaela Sedova21Department of Rehabilitation, 3rd Faculty of Medicine, Charles University in Prague and Faculty Hospital Královské Vinohrady, Prague, Czech Republic; 2Center of Biomedical Informatics and Department of Medical Informatics and Biostatistics, Institute of Computer Science, AS CR, Prague, Czech Republic; 3Faculty of Medicine, Ostrava University, Ostrava, Czech RepublicPurpose: Multiple sclerosis (MS manifests itself in a wide range of symptoms. Physiotherapy plays an important role in the treatment of those symptoms connected with mobility. For this therapy to be at its most effective it should be based on a systematic examination that is able to describe and classify damaged clinical functions meaningfully. The purpose of this study was to develop and validate a battery of tests and composite tests that can be used to systematically evaluate clinical features of MS treatable by physiotherapy.Methods: The authors assembled a proposed battery of tests comprising known, standard, and validated assessments (low-contrast letter acuity testing; the Motricity Index; the Modified Ashworth Scale; the Berg Balance Scale; scales of postural reactions, tremor, dysdiadochokinesia, and dysmetria; the Nine-Hole Peg Test; the Timed 25-Foot Walk; and the 3-minute version of the Paced Auditory Serial Addition Test and one test (knee hyperextension of the authors’ own. Normalization was calculated and six composite assessments were measured. Seventeen ambulatory subjects with MS were tested twice with the assessment set before undergoing physiotherapy, and 12 were also tested with the assessment set after the physiotherapy. The test–retest reliability, stability, internal consistency of composite measurements, sensitivity to changes after therapy, and correlation between measurements and the Kurtzke Expanded Disability Status Scale score were evaluated for all tests in the assessment set

  7. Clinical characteristics and usage of statins in patients with stable ischemic heart disease referred for angiography or coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    I.V. Shklianka

    2017-12-01

    Full Text Available The aim – to compare the clinical characteristics and frequency of statins usage in real clinical practice in patients referred to a specialized clinic for angiography or coronary artery bypass grafting. Materials and methods. In a retrospective slice single-center study data from a primary examination of 155 patients with stable ischemic heart disease, consecutively selected for coronary artery bypass grafting surgery, were analyzed. Depending on the inclusion of statins in the list of medicinal prescriptions, patients were retrospectively divided into two groups: those who had been prescribed statins while they were initially referred to a specialized cardiac surgery center for angiography or revascularization (n = 84 and those who were not prescribed statins (n ​​= 71. Results. The studied patients’ cohort was characterized by earlier coronary events, signs of the peripheral artery atherosclerosis and other absolute indications for treatment with statins in vast majority of cases. At the same time, groups of patients who had been and had not been prescribed statins, did not differ by vast majority of demographic, clinical and instrumental characteristics, concomitant diseases and risk factors. No statin therapy was associated with higher levels of total cholesterol and interleukin-6 compared with the group of patients taking statins (total cholesterol, respectively, 4.8 versus 4.2 mmol/l (p = 0.016 and interleukin-6, respectively, 4.4 versus. 3.1 p/ml (p = 0.022. In general, statins were prescribed in 54,2 % of patients, among them high doses – in 17 patients (20.2 %, moderate – 46 patients (54.8 %, low – 21 patients (25 %. Conclusions. The obtained data show the insufficient level of ambulatory statins usage in patients with ischemic heart disease referred for myocardial revascularization and significant discrepancy between clinical characteristics and real statins usage. Therefore, there is a great need to determine the

  8. Stable measures of number sense accuracy in math learning disability: Is it time to proceed from basic science to clinical application?

    Science.gov (United States)

    Júlio-Costa, Annelise; Starling-Alves, Isabella; Lopes-Silva, Júlia Beatriz; Wood, Guilherme; Haase, Vitor Geraldi

    2015-12-01

    Math learning disability (MLD) or developmental dyscalculia is a highly prevalent and persistent difficulty in learning arithmetic that may be explained by different cognitive mechanisms. The accuracy of the number sense has been implicated by some evidence as a core deficit in MLD. However, research on this topic has been mainly conducted in demographically selected samples, using arbitrary cut-off scores to characterize MLD. The clinical relevance of the association between number sense and MLD remains to be investigated. In this study, we aimed at assessing the stability of a number sense accuracy measure (w) across five experimental sessions, in two clinically defined cases of MLD. Stable measures of number sense accuracy estimate are required to clinically characterize subtypes of MLD and to make theoretical inferences regarding the underlying cognitive mechanisms. G. A. was a 10-year-old boy with MLD in the context of dyslexia and phonological processing impairment and his performance remained steadily in the typical scores range. The performance of H. V., a 9-year-old girl with MLD associated with number sense inaccuracy, remained consistently impaired across measurements, with a nonsignificant tendency to worsen. Qualitatively, H. V.'s performance was also characterized by greater variability across sessions. Concomitant clinical observations suggested that H. V.'s difficulties could be aggravated by developing symptoms of mathematics anxiety. Results in these two cases are in line with the hypotheses that at least two reliable patterns of cognitive impairment may underlie math learning difficulties in MLD, one related to number sense inaccuracy and the other to phonological processing impairment. Additionally, it indicates the need for more translational research in order to examine the usefulness and validity of theoretical advances in numerical cognition to the clinical neuropsychological practice with MLD. © 2015 The Institute of Psychology, Chinese

  9. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

    OpenAIRE

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho

    2015-01-01

    Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 contr...

  10. Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis.

    Science.gov (United States)

    Pérez Sánchez, S; Eichau Madueño, S; Rus Hidalgo, M; Domínguez Mayoral, A M; Vilches-Arenas, A; Navarro Mascarell, G; Izquierdo, G

    2018-03-21

    Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the 'as low as reasonably achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Disease progression was significantly correlated with ultrasound findings (P=.041 for the right eye and P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P=.07 for the right eye and P=.043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS). Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Donepezil improved memory in multiple sclerosis in a randomized clinical trial.

    Science.gov (United States)

    Krupp, L B; Christodoulou, C; Melville, P; Scherl, W F; MacAllister, W S; Elkins, L E

    2004-11-09

    To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

  12. Neuropsychological and clinical heterogeneity of cognitive impairment in patients with multiple system atrophy.

    Science.gov (United States)

    Barcelos, Lorena Broseghini; Saad, Flávia; Giacominelli, Carla; Saba, Roberta Arb; de Carvalho Aguiar, Patrícia Maria; Silva, Sonia Maria Azevedo; Borges, Vanderci; Bertolucci, Paulo Henrique Ferreira; Ferraz, Henrique Ballalai

    2018-01-01

    We evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C). This cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinson's disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI). Neuropsychological tests were used to evaluate general cognition, verbal and visual memory, working memory, constructional ability, visuospatial, language, and executive function. The median age of the patients was 62 years, median disease duration was 3.5 years, and median education level was 10 years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the continuous data between the two MSA subtypes and observed that bodily pain reported in the quality of life questionnaire, SF-36, was worse in MSA-P (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA-C than MSA-P (p<0.05). Our comparative study of cognitive impairment in MSA-P and MSA-C showed that both groups had impaired executive and visuospatial functions, while the attention deficit was predominant only in MSA-C. These findings support the concept that cognitive deficit originates from striatofrontal dysfunction and cerebellar degeneration. Our study also suggests that cognitive impairment is relevant in MSA, and clinical neurologists should not neglect evaluation of these aspects in their daily clinical practice. Copyright © 2017. Published by Elsevier B.V.

  13. Effect of photodynamic therapy in the reduction of halitosis in patients with multiple sclerosis: clinical trial.

    Science.gov (United States)

    Gonçalves, Marcela Leticia Leal; Kalil Bussadori, Sandra; Dadalti Fragoso, Yara; da Silva, Vinicius Vieira Belarmino; Melo Deana, Alessandro; da Mota, Ana Carolina Costa; Horácio Pinto, Erika; Horliana, Anna Carolina RattoTempestini; Miranda França, Cristiane

    2017-10-27

    Smell and odours play a vital role in social interaction. Halitosis is a social problem that affects one third of the population, causing a negative impact on the quality of life. There is little knowledge on the prevalence and management of halitosis in multiple sclerosis (MS) patients. The present study aims to evaluate the presence of halitosis in patients with MS when compared to a control group, and also evaluate treatment of the problem with antimicrobial photodynamic therapy (aPDT). This is a case-control clinical study in which 60 patients were evaluated: 30 MS patients in treatment at the Specialties Clinic School of Medicine, and 30 healthy patients, matched in age and gender for the control group. Data was collected on the duration of the disease as well as the degree of disability and medication use in the MS group. For all patients, halitosis was assessed with Oral Chroma™. Individuals with halitosis underwent treatment with tongue scraping and aPDT. The photosensitizer was methylene blue (0.005%) and a THERAPY XT-EC ® laser (660 nm, 9 J, 100 mW for 90 s per point, 320 J cm -2 , 3537 mW cm -2 ) was used. Six points 1 cm apart from each other were irradiated in the tongue dorsum. There was a positive correlation between the disability and disease duration. No parameter was correlated with halitosis. Patients with MS have higher levels of SH 2 compounds when compared to the control group (p = 0.003, Mann-Whitney), but after aPDT both groups significantly reduced the levels to under the halitosis threshold. The aPDT scraping treatment was effective in the immediate reduction of halitosis in both groups.

  14. Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Przemyslaw Kardas

    2007-05-01

    Full Text Available Przemyslaw KardasThe First Department of Family Medicine, Medical University of LodzBackground: A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.Methods: One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.Results: The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01, and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001. The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01. The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01, correct interdose intervals (77.4% v 53.1%, p < 0.0001, and therapeutic coverage (85.6% vs 73.7%, p < 0.001 were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.Conclusions: The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.Keywords: patient compliance, quality of life, stable angina pectoris, randomized controlled trial

  15. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study.

    Science.gov (United States)

    Abedini, Sadollah; Gøransson, Lasse; Cockburn, Elinor; Kilany, Suzanne; Holdaas, Hallvard

    2018-02-01

    This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice. Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events. Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was -0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m 2 ), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal

  16. Clinical and neurophysiological findings in oligoclonal band negative multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Mesaroš Šarlota

    2003-01-01

    Full Text Available Besides magnetic resonance imaging, the presence of locally produced oligoclonal IgG bands (OCB in the cerebrospinal fluid (CSF is the most consistent laboratory abnormality in patients with multiple sclerosis (MS. The most sensitive method for the detection of CSF OCB is isoelectric focusing (IEF [6]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [7, 8]. This study was designed to compare clinical data and evoked potential (EP findings between CSF OCB positive and OCB negative MS patients. The study comprised 22 OCB negative patients with clinically definite MS [11] and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS score [12] and progression rate (PR. All patients underwent multimodal EP: visual (VEPs, brainstem auditory (BAEPs and median somatosensory (mSEPs. The VEPa were considered abnormal if the P100 latency exceeded 117 ms or inter-ocular difference greater than 8 ms was detected. The BAEPs were considered abnormal if waves III or V were absent or the interpeak latencies I-III, III-V, or I-V were increased. The mSEPs were considerd abnormal when N9, N13 and N20 potentials were absent or when increased interpeak latencies were recorded. The severity of the neurophysiological abnormalities was scored for each modality as follows normal EP score 0; every other EP abnormality except the absence of one of the main waves, score 1; absence of one or more of the main waves, score 2 [13]. Both mean EDSS score (4.0 vs. 3.5 and PR (0.6 vs. 0.5 were similar in OCB positive and OCB negative group, (p>0.05. In the first group males were predominant, but without statistical significance (Table 1. Disease started more often with the brainstem symptoms in the OCB positive than in OCB negative MS group (p=0.028, while there was no differences in other initial symptoms between

  17. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  18. Professional competencies in health sciences education: from multiple intelligences to the clinic floor.

    Science.gov (United States)

    Lane, India F

    2010-03-01

    Nontechnical competencies identified as essential to the health professional's success include ethical behavior, interpersonal, self-management, leadership, business, and thinking competencies. The literature regarding such diverse topics, and the literature regarding "professional success" is extensive and wide-ranging, crossing educational, psychological, business, medical and vocational fields of study. This review is designed to introduce ways of viewing nontechnical competence from the psychology of human capacity to current perspectives, initiatives and needs in practice. After an introduction to the tensions inherent in educating individuals for both biomedical competency and "bedside" or "cageside" manner, the paper presents a brief overview of the major lines of inquiry into intelligence theory and how theories of multiple intelligences can build a foundation for conceptualizing professional and life skills. The discussion then moves from broad concepts of intelligence to more specific workplace skill sets, with an emphasis on professional medical education. This section introduces the research on noncognitive variables in various disciplines, the growing emphasis on competency based education, and the SKA movement in veterinary education. The next section presents the evidence that nontechnical, noncognitive or humanistic skills influence achievement in academic settings, medical education and clinical performance, as well as the challenges faced when educational priorities must be made.

  19. [Multiple chemical sensitivity: Clinical evaluation of the severity and psychopathological profile].

    Science.gov (United States)

    Lago Blanco, Eva; Puiguriguer Ferrando, Jordi; Rodríguez Enríquez, Mónica; Agüero Gento, Laura; Salvà Coll, Joan; Pizà Portell, Maria Rosa

    2016-02-05

    Multiple chemical sensitivity (MCS) is a multisystem disorder of controversial etiology, affecting some subjects when exposed to chemicals at no harmful concentrations. The objective of this paper is to describe the epidemiological, clinical and psychological features of a sample of patients with MCS for further specific group treatment. Descriptive study of patients diagnosed with MCS in a toxicology unit. We administered the Quick Environmental Exposure and Sensitivity Inventory, the structured interview SCID-II, the anxiety scale HAS and the type A personality test, PCTA. Seventy-three patients were included. The mean age was 52,6 years (range 33-77; SD 9.29). Sixty-six were females (90.4%). Fifty-three percent were classified as i-ii and ii grade. Sixty-one patients (83%) presented some type of comorbidity, mainly chronic pain, fibromyalgia and chronic fatigue. They exhibited higher levels of anxiety (average score of 19.2), prevalence of phobic-avoidant traits of personality and type A behavior in 31.1%. MCS affects middle-aged women with comorbidities (chronic pain, fibromyalgia and chronic fatigue) and high anxiety and avoidance behaviors. This preliminary analysis should help provide a specific therapeutic approach to these patients. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Clinical presentation and management of stable coronary artery disease: insights from the international prospective CLARIFY registry - results from the Greek national cohort.

    Science.gov (United States)

    Sbarouni, Eftihia; Voudris, Vassilis; Georgiadou, Panagiota; Hamilos, Michalis; Steg, P Gabriel; Fox, Kim M; Greenlaw, Nicola; Ferrari, Roberto; Vardas, Panos E

    2014-01-01

    Coronary artery disease (CAD) is highly prevalent worldwide, yet there is a paucity of data regarding the clinical characteristics and management of outpatients with stable CAD. In this paper, we report the baseline data of the Greek cohort and we compare our national data with the global results of the entire registry, as well as the results from the western European countries. CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis >50%, or chest pain associated with proven myocardial ischemia. A total of 33,283 patients from 45 countries in 4 continents were enrolled between November 2009 and July 2010; of these, 14,726 were from western European countries (Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the United Kingdom) and 559 patients were enrolled in Greece. Compared to their counterparts in western Europe and the entire cohort, Greeks were younger (p<0.0001, p<0.0001, respectively), more predominantly male (p<0.0039, p<0.0001), with a higher body mass index (p<0.0002, p<0.0001) and a larger waist circumference (p<0.0001, p<0.0001), as well as a higher prevalence of family history of CAD (p<0.0008, 0.0005), hyperlipidemia (p<0.0001, p<0.0001) and smoking (p<0.0001, p<0.0001). Noninvasive testing (p<0.0001, p<0.0001, respectively) and coronary angiography (p<0.0001, 0.0013) along with surgical revascularization (CABG) (p<0.0001, 0.0088) were performed more often in Greece. Antiplatelets, b-blockers and lipid lowering medications were used to an equal extent in Greece as in the other two cohorts. There are substantial differences in demographics, clinical profiles and treatment in patients with stable CAD within the data set, which are also observed for Greek data. Interestingly, these differences are consistent in relation to the global

  1. A mobile and self-sufficient lab for high frequency measurements of stable water isotopes and chemistry of multiple water sources

    Science.gov (United States)

    Windhorst, David; Kraft, Philipp; Holly, Hartmut; Sahraei, Amir; Breuer, Lutz

    2017-04-01

    Technical advances over the last years have made instruments for stable water isotope and water chemistry measurements smaller, more durable and energy efficient. It is nowadays feasible to deploy such instruments in situ during field campaigns. Coupled to an automated sample delivery system, high temporal resolution online measurements of various sources are within the bounds of economic and technical possibility. However, the day to day operation of such equipment still requires either a lot of man power and infrastructure or the implementation of a quasi-self-sufficient system. The challenge remains on how to facilitate and remotely operate such a system. We present the design and implementation of the Water Analysis Trailer for Environmental Research (WATER), an autonomous platform consisting of instruments for stable water isotope and water chemistry analysis. The system takes and measures samples in high temporal resolution (operation of up to one week several issues need to be addressed. The essential topics are: - self-sufficient power supply, - automated sample delivery and preparation, and - autonomous measurements and management interfacing all instruments. In addition to the basic requirements we implemented: - communication of all system states, alarm messages and measurement results to an internal as well as an external database via cellular telemetry, - automated storage of up to 300 frozen reference samples (100 mL, stored at -18°C), - climate control for temperature sensitive equipment (±1°C), - a local and remote (up to 20 km using radio telemetry) sensor network (i.e. to record states of the hydrological system and climate and soil conditions), also suitable to trigger specific measurements - automatic fire suppression and security system. The initial instrumentation includes a UV spectrometer (ProPs, Trios GmBH, Germany) to measure NO3-, COD, TOC and total suspended sediments, multiparameter water quality probe (YSI600R, YSI, USA) to measure

  2. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study

    Directory of Open Access Journals (Sweden)

    Sadollah Abedini, MD, PhD

    2018-02-01

    Conclusions. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.

  3. Clinical-scale investigation of stable isotopes in human blood: delta13C and delta15N from 406 patients at the Johns Hopkins Medical Institutions.

    Science.gov (United States)

    Kraft, Rebecca A; Jahren, A Hope; Saudek, Christopher D

    2008-11-01

    Objective chemical biomarkers are needed in clinical studies of diet-related diseases to supplement subjective self-reporting methods. We report on several critical experiments for the development of clinically legitimate dietary stable isotope biomarkers within human blood. Our examination of human blood revealed the following: (1) Within blood clot and serum from anonymous individuals (201 males, 205 females) we observed: mean serum delta13C = -19.1 +/- 0.8 per thousand (standard deviation, SD); clot, -19.3 +/- 0.8 per thousand (SD); range = -15.8 per thousand to -23.4 per thousand. Highly statistically significant differences are observed between clot and serum, males and females for both clot and serum. For 15N (n = 206), mean serum = +8.8 +/- 0.5 per thousand (SD); clot +7.4 +/- 0.4 per thousand (SD); range = +6.3 per thousand to +10.5 per thousand. Blood serum is enriched in 15N relative to blood clot by +1.4 per thousand on average, which may reflect differing protein amino acid content. Serum nitrogen is statistically significantly different for males and females, however, clot shows no statistical difference. (2) Relative to clot, capillary blood is marginally different for 13C, but not 15N. Clot 13C is not significantly different from serum; however, it is depleted in 15N by 1.5 per thousand relative to serum. (3) We assessed the effect of blood additives (sodium fluoride and polymerized acrylamide resin) and laboratory process (autoclaving, freeze drying) commonly used to preserve or prepare venous blood. On average, no alteration in delta13C or delta15N is detected compared with unadulterated blood from the same individual. (4) Storage of blood with and without the additives described above for a period of up to 115 days exhibits statistically significant differences for 13C and 15N for sodium fluoride. However, storage for unadulterated blood and blood preserved with polymerized acrylamide resin does not change the delta13C or delta15N isotopic

  4. Modification of elastic stable intramedullary nailing with a 3rd nail in a femoral spiral fracture model - results of biomechanical testing and a prospective clinical study.

    Science.gov (United States)

    Kaiser, Martin M; Stratmann, Christine; Zachert, Gregor; Schulze-Hessing, Maaike; Gros, Nina; Eggert, Rebecca; Rapp, Marion

    2014-01-08

    Elastic stable intramedullary nailing (ESIN) is the standard treatment for displaced diaphyseal femoral fractures in children. However, high complication rates (10-50%) are reported in complex fractures. This biomechanical study compares the stiffness with a 3rd nail implanted to that in the classical 2C-shaped configuration and presents the application into clinical practice. For each of the 3 configurations of ESIN-osteosynthesis with titanium nails eight composite femoral grafts (Sawbones®) with an identical spiral fracture were used: 2C configuration (2C-shaped nails, 2 × 3.5 mm), 3CM configuration (3rd nail from medial) and 3CL configuration (3rd nail from lateral). Each group underwent biomechanical testing in 4-point bending, internal/external rotation and axial compression. 2C and 3CM configurations showed no significant differences in this spiroid type fracture model. 3CL had a significantly higher stiffness during anterior-posterior bending, internal rotation and 9° compression than 2C, and was stiffer in the lateral-medial direction than 3CM. The 3CL was less stable during p-a bending and external rotation than both the others. As biomechanical testing showed a higher stability for the 3CL configuration in two (a-p corresponding to recurvation and 9° compression to shortening) of three directions associated with the most important clinical problems, we added a 3rd nail in ESIN-osteosynthesis for femoral fractures. 11 boys and 6 girls (2.5-15 years) were treated with modified ESIN of whom 12 were '3CL'; due to the individual character of the fractures 4 patients were treated with '3CM' (third nail from medial) and as an exception 1 adolescent with 4 nails and one boy with plate osteosynthesis. No additional stabilizations or re-operations were necessary. All patients achieved full points in the Harris-Score at follow-up; no limb length discrepancy occurred. The 3CL configuration provided a significantly higher stiffness than 2C and 3CM configurations

  5. Stable isotopes

    International Nuclear Information System (INIS)

    Brazier, J.L.; Guinamant, J.L.

    1995-01-01

    According to the progress which has been realised in the technology of separating and measuring isotopes, the stable isotopes are used as preferable 'labelling elements' for big number of applications. The isotopic composition of natural products shows significant variations as a result of different reasons like the climate, the seasons, or their geographic origins. So, it was proved that the same product has a different isotopic composition of alimentary and agriculture products. It is also important in detecting the pharmacological and medical chemicals. This review article deals with the technology, like chromatography and spectrophotometry, adapted to this aim, and some important applications. 17 refs. 6 figs

  6. Stable Tetraquarks

    Energy Technology Data Exchange (ETDEWEB)

    Quigg, Chris [Fermilab

    2018-04-13

    For very heavy quarks, relations derived from heavy-quark symmetry imply novel narrow doubly heavy tetraquark states containing two heavy quarks and two light antiquarks. We predict that double-beauty states will be stable against strong decays, whereas the double-charm states and mixed beauty+charm states will dissociate into pairs of heavy-light mesons. Observing a new double-beauty state through its weak decays would establish the existence of tetraquarks and illuminate the role of heavy color-antitriplet diquarks as hadron constituents.

  7. Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Yan, Xiaoyu; Clemens, Pamela L; Puchalski, Thomas

    2018-01-01

    OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, ...

  8. Clinically isolated syndromes suggestive of multiple sclerosis: an optical coherence tomography study.

    Directory of Open Access Journals (Sweden)

    Celia Oreja-Guevara

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL, which provides an indirect measurement of axonal damage in multiple sclerosis (MS. This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS suggestive of MS. METHODOLOGY: This was a cross-sectional study. Twenty-four patients with CIS suggestive of MS (8 optic neuritis [ON], 6 spinal cord syndromes, 5 brainstem symptoms and 5 with sensory and other syndromes were prospectively studied. The main outcome evaluated was RNFL thickness at CIS onset. Secondary objectives were to study the relationship between RNFL thickness and MRI criteria for disease dissemination in space (DIS as well as the presence of oligoclonal bands in the cerebrospinal fluid. PRINCIPAL FINDINGS: Thirteen patients had decreased RNFL thickness in at least one quadrant. Mean RNFL thickness was 101.67±10.72 µm in retrobulbar ON eyes and 96.93±10.54 in unaffected eyes. Three of the 6 patients with myelitis had at least one abnormal quadrant in one of the two eyes. Eight CIS patients fulfilled DIS MRI criteria. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P<5% cut-off value had a sensitivity of 75% and a specificity of 56% for predicting DIS MRI. CONCLUSIONS: The findings from this study show that axonal damage measured by OCT is present in any type of CIS; even in myelitis forms, not only in ON as seen up to now. OCT can detect axonal damage in very early stages of disease and seems to have high sensitivity and moderate specificity for predicting DIS MRI. Studies with prospective long-term follow-up would be needed to establish the prognostic value of baseline OCT findings.

  9. Disrupted Module Efficiency of Structural and Functional Brain Connectomes in Clinically Isolated Syndrome and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    2018-04-01

    Full Text Available Recent studies have demonstrated disrupted topological organization of brain connectome in multiple sclerosis (MS. However, whether the communication efficiency between different functional systems is affected in the early stage of MS remained largely unknown. In this study, we constructed the structural connectivity (SC and functional connectivity (FC networks in 41 patients with clinically isolated syndrome (CIS, 32 MS patients and 35 healthy controls (HC based on diffusion and resting-state functional MRI. To quantify the communication efficiency within and between different functional systems, we proposed two measures called intra- and inter-module efficiency. Based on the module parcellation of functional backbone network, the intra- and inter-module efficiency of SC and FC networks was calculated for each participant. For the SC network, CIS showed decreased inter-module efficiency between the sensory-motor network (SMN, the visual network (VN, the default-mode network (DMN and the fronto-parietal network (FPN compared with HC, while MS showed more widespread decreased module efficiency both within and between modules relative to HC and CIS. For the FC network, no differences were found between CIS and HC, and a decreased inter-module efficiency between SMN and FPN and between VN and FPN was identified in MS, compared with HC and CIS. Moreover, both intra- and inter-module efficiency of SC network were correlated with the disability and cognitive scores in MS. Therefore, our results demonstrated early SC changes between modules in CIS, and more widespread SC alterations and inter-module FC changes were observed in MS, which were further associated with cognitive impairment and physical disability.

  10. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

    Science.gov (United States)

    Lahuerta, Juan-Jose; Paiva, Bruno; Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F

    2017-09-01

    Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients

  11. Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method.

    Directory of Open Access Journals (Sweden)

    Veronica Popescu

    Full Text Available Studies disagree on the location of grey matter (GM atrophy in the multiple sclerosis (MS brain.To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition.127 MS patients and 50 controls were included and cortical and deep grey matter (DGM volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen's d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM and vertex-wise FreeSurfer were used for group-level comparisons.The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.

  12. Clinical and Genetic Analysis of Multiple Endocrine Neoplasia Type 1-Related Primary Hyperparathyroidism in Chinese.

    Directory of Open Access Journals (Sweden)

    Jing Kong

    Full Text Available Multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT differs in many aspects from sporadic PHPT (SHPT. The aims of this study were to summarize the clinical features and genetic background of Chinese MHPT patients and compare the severity of the disease with those of SHPT.A total of 40 MHPT (27 sporadic, 7 families and 169 SHPT cases of Chinese descent were retrospectively analyzed. X-rays and ultrasound were used to assess the bone and urinary system. Dual energy x-ray absorptiometry (DXA were performed to measure bone mineral density (BMD. Besides direct sequencing of the MEN1 and CDKN1B genes, multiplex ligation-dependent probe amplification (MLPA was used to screen gross deletion for the MEN1 gene.Compared with SHPT patients, MHPT patients showed lower prevalence of typical X-ray changes related to PHPT (26.3% vs. 55.7%, P = 0.001 but higher prevalence of urolithiasis/renal calcification (40.2% vs. 60.0%, P = 0.024. MHPT patients showed higher phosphate level (0.84 vs. 0.73mmol/L, P<0.05 but lower ALP (103.0 vs. 174.0U/L, P<0.001 and PTH (4.0 vs. 9.8×upper limit, P<0.001 levels than SHPT patients. There were no significant differences in BMD Z-scores at the lumbar spine and femoral neck between the two groups. Mutations in the MEN1 gene were detected in 27 MHPT cases. Among the nine novel mutations were novel, one of them involved the deletion of exon 5 and 6.MHPT patients experienced more common kidney complications but less skeletal issues, and a milder biochemical manifestation compared with SHPT patients. MEN1 mutation detection rate was 79.4% and 9 of the identified mutations were novel.

  13. Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity

    Science.gov (United States)

    Wildburger, Norelle C.; Gyngard, Frank; Guillermier, Christelle; Patterson, Bruce W.; Elbert, Donald; Mawuenyega, Kwasi G.; Schneider, Theresa; Green, Karen; Roth, Robyn; Schmidt, Robert E.; Cairns, Nigel J.; Benzinger, Tammie L. S.; Steinhauser, Matthew L.; Bateman, Randall J.

    2018-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population—those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ) in the brain, which leads to one of the pathological hallmarks of AD—Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging in an approach termed SILK–SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK–SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development. PMID:29623063

  14. Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity

    Directory of Open Access Journals (Sweden)

    Norelle C. Wildburger

    2018-03-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population—those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ in the brain, which leads to one of the pathological hallmarks of AD—Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK and nanoscale secondary ion mass spectrometry (NanoSIMS imaging in an approach termed SILK–SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK–SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.

  15. Clinical diagnostic criteria of multiple sclerosis: the role of magnetic resonance imaging

    International Nuclear Information System (INIS)

    Belair, M.; Girard, M.

    2004-01-01

    The objective of this article is to summarize the diagnostic criteria recommended by the International Panel on the Diagnosis of Multiple Sclerosis in 2001. The recommendations of another working group, the Consortium of Multiple Sclerosis Centers Consensus Meeting, which met in Vancouver in 2001, concerning the diagnosis and follow-up of patients with multiple sclerosis are also presented in an effort to standardize the protocols for magnetic resonance imaging of these patients. (author)

  16. Stable beams

    CERN Multimedia

    2015-01-01

    Stable beams: two simple words that carry so much meaning at CERN. When LHC page one switched from "squeeze" to "stable beams" at 10.40 a.m. on Wednesday, 3 June, it triggered scenes of jubilation in control rooms around the CERN sites, as the LHC experiments started to record physics data for the first time in 27 months. This is what CERN is here for, and it’s great to be back in business after such a long period of preparation for the next stage in the LHC adventure.   I’ve said it before, but I’ll say it again. This was a great achievement, and testimony to the hard and dedicated work of so many people in the global CERN community. I could start to list the teams that have contributed, but that would be a mistake. Instead, I’d simply like to say that an achievement as impressive as running the LHC – a machine of superlatives in every respect – takes the combined effort and enthusiasm of everyone ...

  17. An Interactive Platform to Visualize Data-Driven Clinical Pathways for the Management of Multiple Chronic Conditions.

    Science.gov (United States)

    Zhang, Yiye; Padman, Rema

    2017-01-01

    Patients with multiple chronic conditions (MCC) pose an increasingly complex health management challenge worldwide, particularly due to the significant gap in our understanding of how to provide coordinated care. Drawing on our prior research on learning data-driven clinical pathways from actual practice data, this paper describes a prototype, interactive platform for visualizing the pathways of MCC to support shared decision making. Created using Python web framework, JavaScript library and our clinical pathway learning algorithm, the visualization platform allows clinicians and patients to learn the dominant patterns of co-progression of multiple clinical events from their own data, and interactively explore and interpret the pathways. We demonstrate functionalities of the platform using a cluster of 36 patients, identified from a dataset of 1,084 patients, who are diagnosed with at least chronic kidney disease, hypertension, and diabetes. Future evaluation studies will explore the use of this platform to better understand and manage MCC.

  18. Internal correction of spectral interferences and mass bias for selenium metabolism studies using enriched stable isotopes in combination with multiple linear regression.

    Science.gov (United States)

    Lunøe, Kristoffer; Martínez-Sierra, Justo Giner; Gammelgaard, Bente; Alonso, J Ignacio García

    2012-03-01

    The analytical methodology for the in vivo study of selenium metabolism using two enriched selenium isotopes has been modified, allowing for the internal correction of spectral interferences and mass bias both for total selenium and speciation analysis. The method is based on the combination of an already described dual-isotope procedure with a new data treatment strategy based on multiple linear regression. A metabolic enriched isotope ((77)Se) is given orally to the test subject and a second isotope ((74)Se) is employed for quantification. In our approach, all possible polyatomic interferences occurring in the measurement of the isotope composition of selenium by collision cell quadrupole ICP-MS are taken into account and their relative contribution calculated by multiple linear regression after minimisation of the residuals. As a result, all spectral interferences and mass bias are corrected internally allowing the fast and independent quantification of natural abundance selenium ((nat)Se) and enriched (77)Se. In this sense, the calculation of the tracer/tracee ratio in each sample is straightforward. The method has been applied to study the time-related tissue incorporation of (77)Se in male Wistar rats while maintaining the (nat)Se steady-state conditions. Additionally, metabolically relevant information such as selenoprotein synthesis and selenium elimination in urine could be studied using the proposed methodology. In this case, serum proteins were separated by affinity chromatography while reverse phase was employed for urine metabolites. In both cases, (74)Se was used as a post-column isotope dilution spike. The application of multiple linear regression to the whole chromatogram allowed us to calculate the contribution of bromine hydride, selenium hydride, argon polyatomics and mass bias on the observed selenium isotope patterns. By minimising the square sum of residuals for the whole chromatogram, internal correction of spectral interferences and mass

  19. Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study.

    Science.gov (United States)

    Derancourt, C; Bourdon-Lanoy, E; Grob, J-J; Guillaume, J-C; Bernard, P; Bastuji-Garin, S

    2007-01-01

    Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. To assess whether these lesions are clinical markers of past severe sunburn. A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

  20. Focal cortical thinning in patients with stable relapsing-remitting multiple sclerosis. Cross-sectional-based novel estimation of gray matter kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Orbach, Lior; Menascu, Shay; Hoffmann, Chen; Achiron, Anat [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel); Tel-Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Miron, Shmuel [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel)

    2018-02-15

    The aim of our study is to identify radiological patterns of cortical gray matter atrophy (CGMA) that correlate with disease duration in patients with relapsing-remitting multiple sclerosis (RRMS). RRMS patients were randomly selected from the Sheba Multiple Sclerosis (MS) center computerized data registry based on stratification of disease duration up to 10 years. Patients were scanned by 3.0 T (Signa, GE) MRI, using a T1 weighted 3D high resolution, FSPGR, MS protocol. Neurological disability was assessed by the Expanded Disability Status Scale (EDSS). FreeSurfer was used to obtain brain volumetric segmentation and to perform cortical thickness surface-based analysis. Clusters of change in cortical thickness with correlation to disease duration were produced. Two hundred seventy-one RRMS patients, mean ± SD age 33.0 ± 7.0 years, EDSS 1.6 ± 1.2, disease duration 5.0 ± 3.4 years. Cortical thickness analysis demonstrated focal areas of cerebral thinning that correlated with disease duration. Seven clusters accounting for 11.7% of the left hemisphere surface and eight clusters accounting for 10.6% of the right hemisphere surface were identified, with cluster-wise probability of p < 0.002 and p < 0.02, respectively.The clusters included bilateral involvement of areas within the cingulate, precentral, postcentral, paracentral, superior-parietal, superior-frontal gyri and insular cortex. Mean and cluster-wise cortical thickness negatively correlated with EDSS score, p < 0.001, with stronger Spearman rho for cluster-wise measurements. We identified CGMA patterns in sensitive brain regions which give insight and better understanding of the progression of cortical gray matter loss in relation to dissemination in space and time. These patterns may serve as markers to modulate therapeutic interventions to improve the management of MS patients. (orig.)

  1. Demographic and clinical profile of Multiple Sclerosis in Kashmir: A short report.

    Science.gov (United States)

    Zahoor, Insha; Asimi, Ravouf; Haq, Ehtishamul; Yousuf Wani, Irfan

    2017-04-01

    Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system (CNS). There have been only few population/hospital based studies on MS in India, and at the same time there is no data on its profile in Kashmir. A total of 41 MS patients diagnosed on the basis of 2010 Revised Mc Donald criteria were enrolled in this study from Kashmir region of India. Clinical, demographic, radiological and biochemical parameters were analyzed for most of the patients. Male to female ratio was found to be 1:3.1 with mean age at the time of analysis 32.26±7.54 (range 18-48) years. The mean disease duration was found to be 3.2±3.6 years. The most common course was relapsing-remitting (RR) present in 87.80% of cases followed by secondary progressive (SP) in 9.76% and primary progressive (PP) in 2.44%. Numbness, weakness of limbs, prickling and tingling sensations, muscle stiffness, and visual disturbances were most common manifestations. Condition of bilateral internuclear ophthalmoplegia (INO) and vertigo was rarely observed. Oligoclonal bands (OCB) were present in cerebrospinal fluid (CSF) of majority of the patients. Symptomatic and steroidal treatment mode was given to majority of the patients (92.68%) and only 7.32% patients were given disease modifying drug. This is the first preliminary report on MS profile in Kashmir. The high prevalence of female patients and RR course of MS, low prevalence of progressive cases, predominance of OCB positive cases, insignificant family history in all cases, predominance of cases with low socio-economic status, and high rate of less educated and unemployed cases are the most important findings. By and large MS pattern in Kashmir was found to be relatively similar to West and rest of the Asia. Larger comprehensive studies are mandatory to completely understand MS pattern in Kashmir. There is utmost requirement to maintain a local MS registry in Kashmir so as to get an idea about the actual number of

  2. Single and multiple clinical syndromes in incarcerated offenders : Associations with dissociative experiences and emotionality.

    NARCIS (Netherlands)

    Garofalo, C.; Velotti, P.; Crocamo, Cristina; Carrá, Giuseppe

    2018-01-01

    The present study examined the prevalence and correlates of clinical syndromes in a large group (N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically

  3. Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

    International Nuclear Information System (INIS)

    Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

    1987-01-01

    We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases

  4. A distinct section of the Early Bronze Age society? Stable isotope investigations of burials in settlement pits and multiple inhumations of the Únětice culture in central Germany.

    Science.gov (United States)

    Knipper, Corina; Fragata, Matthias; Nicklisch, Nicole; Siebert, Angelina; Szécsényi-Nagy, Anna; Hubensack, Vera; Metzner-Nebelsick, Carola; Meller, Harald; Alt, Kurt W

    2016-03-01

    Inhumations in so-called settlement pits and multiple interments are subordinate burial practices of the Early Bronze Age Únětice culture in central Germany (2200-1700/1650 BC). The majority of the Únětice population was entombed as single inhumations in rectangular grave pits with a normative position of the body. The goal of the study was to test archaeological hypotheses that the deviant burials may represent socially distinct or nonlocal individuals. The study comprised up to two teeth and one bone each of 74 human individuals from eight sites and faunal comparative samples. The inhumations included regular, deviant burials in so-called settlement or storage pits, and multiple burials. We investigated radiogenic strontium isotope compositions of tooth enamel ((87) Sr/(86) Sr) and light stable isotope ratios of carbon and nitrogen of bone collagen (δ(13) C, δ(15) N) aiming at the disclosure of residential changes and dietary patterns. Site-specific strontium isotope data ranges mirror different geological properties including calcareous bedrock, loess, and glacial till. Independent from burial types, they disclose low portions of nonlocal individuals of up to some 20% at the individual sites. The light stable isotope ratios of burials in settlement pits and rectangular graves overlap widely and indicate highly similar dietary habits. The analytical results let to conclude that inhumations in settlement pits and multiple burials were two of the manifold burial practices of the Early Bronze Age. The selection criteria of the individuals for the different forms of inhumation remained undisclosed. © 2015 Wiley Periodicals, Inc.

  5. ANALYSIS OF COST STRUCTURE FOR PHARMACOTHERAPY OF PATIENTS WITH STABLE ANGINA (THE CASE OF CARDIOLOGY DEPARTMENT OF TVER REGIONAL CLINICAL HOSPITAL

    Directory of Open Access Journals (Sweden)

    M. A. Demidova

    2012-01-01

    Full Text Available Aim. To analyze the cost structure for pharmacotherapy of patients with stable angina (SA, in particular, to compare the cost of pharmacotherapy with drugs, both included and not included into the official Standard of care (SC. Material and methods. Medical records of patients with SA (n=100 admitted to the cardiology department of Tver Regional Clinical Hospital in January-July 2010 were studied retrospectivelly. Costs of treatment with drugs specified in SC for patients with SA as well as drugs not included in SC were considered. Costs of pharmacotherapy and cost structure were determined. Pharmacoeconomical methods, especially ABC analysis, were partially used.  Results. Totally 65502.39 ruble was spent for pharmacotherapy of 100 patients with SA. Cost structure was the following: 32679.34 ruble was spent for drugs recommended by SC, 23698.18 ruble — for drugs not included in SC, and 9124.87 ruble — for drugs to treat concomitant diseases which are not taken into account by SC for patients with SA. Conclusion. SA pharmacotherapy counts 50% of the total cost for drugs recommended by SC, 36% — for drugs not included in SC but belonged to pharmacological class presented in SC, and 14% — drugs from pharmacological class not included in SC. In the process of new SC elaboration for SA patients it is necessary to take into account treatment costs of concomitant diseases especially diabetes mellitus which can account up to 9.5% of total treatment cost of SA patients.

  6. Deciphering diet and monitoring movement: Multiple stable isotope analysis of the viking age settlement at Hofstaðir, Lake Mývatn, Iceland.

    Science.gov (United States)

    Sayle, Kerry L; Hamilton, W Derek; Cook, Gordon T; Ascough, Philippa L; Gestsdóttir, Hildur; McGovern, Thomas H

    2016-05-01

    A previous multi-isotope study of archaeological faunal samples from Skútustaðir, an early Viking age settlement on the southern shores of Lake Mývatn in north-east Iceland, demonstrated that there are clear differences in δ(34)S stable isotope values between animals deriving their dietary protein from terrestrial, freshwater, and marine reservoirs. The aim of this study was to use this information to more accurately determine the diet of humans excavated from a nearby late Viking age churchyard. δ(13)C, δ(15)N, and δ(34)S analyses were undertaken on terrestrial animal (n = 39) and human (n = 46) bone collagen from Hofstaðir, a high-status Viking-period farmstead ∼10 km north-west of Skútustaðir. δ(34)S values for Hofstaðir herbivores were ∼6‰ higher relative to those from Skútustaðir (δ(34)S: 11.4 ± 2.3‰ versus 5.6 ± 2.8‰), while human δ(13)C, δ(15)N, and δ(34)S values were broad ranging (-20.2‰ to -17.3‰, 7.4‰ to 12.3‰, and 5.5‰ to 14.9‰, respectively). Results suggest that the baseline δ(34)S value for the Mývatn region is higher than previously predicted due to a possible sea-spray effect, but the massive deposition of Tanytarsus gracilentus (midges) (δ(34)S: -3.9‰) in the soil in the immediate vicinity of the lake is potentially lowering this value. Several terrestrial herbivores displayed higher bone collagen δ(34)S values than their contemporaries, suggesting trade and/or movement of animals to the region from coastal areas. Broad ranging δ(13)C, δ(15)N, and δ(34)S values for humans suggest the population were consuming varied diets, while outliers within the dataset could conceivably have been migrants to the area. © 2016 Wiley Periodicals, Inc.

  7. Effectiveness of the medication safety review clinics for older adults prescribed multiple medications

    Directory of Open Access Journals (Sweden)

    Ding-Cheng Chan

    2014-02-01

    Conclusion: DRPs were common in geriatric outpatients taking multiple medications and most were solved with appropriate interventions. The MSRC service may improve prescription quality in Taiwan if widely available.

  8. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

    Science.gov (United States)

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-04-01

    Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Comi, G; Martinelli, V; Rodegher, M

    2009-01-01

    treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel Udgivelsesdato: 2009/10/31......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

  10. Microsatellite typing of clinical and environmental Cryptococcus neoformans var. grubii isolates from Cuba shows multiple genetic lineages.

    Directory of Open Access Journals (Sweden)

    Maria-Teresa Illnait-Zaragozi

    Full Text Available BACKGROUND: Human cryptococcal infections have been associated with bird droppings as a likely source of infection. Studies toward the local and global epidemiology of Cryptococcus spp. have been hampered by the lack of rapid, discriminatory, and exchangeable molecular typing methods. METHODOLOGY/PRINCIPAL FINDINGS: We selected nine microsatellite markers for high-resolution fingerprinting from the genome of C. neoformans var. grubii. This panel of markers was applied to a collection of clinical (n = 122 and environmental (n = 68; from pigeon guano C. neoformans var. grubii isolates from Cuba. All markers proved to be polymorphic. The average number of alleles per marker was 9 (range 5-51. A total of 104 genotypes could be distinguished. The discriminatory power of this panel of markers was 0.993. Multiple clusters of related genotypes could be discriminated that differed in only one or two microsatellite markers. These clusters were assigned as microsatellite complexes. The majority of environmental isolates (>70% fell into 1 microsatellite complex containing only few clinical isolates (49 environmental versus 2 clinical. Clinical isolates were segregated over multiple microsatellite complexes. CONCLUSIONS/SIGNIFICANCE: A large genotypic variation exists in C. neoformans var. grubii. The genotypic segregation between clinical and environmental isolates from pigeon guano suggests additional source(s of human cryptococcal infections. The selected panel of microsatellite markers is an excellent tool to study the epidemiology of C. neoformans var. grubii.

  11. Clinical observation of 89Sr treatment efficacy of multiple bone metastases in breast and prostate cancer patients

    International Nuclear Information System (INIS)

    Yuan Chao; Li Weipeng; Hu Yongquan; Tao Jian

    2010-01-01

    Objective: To evaluate the efficacy of 89 Sr in treatment of multiple bone metastases of breast and prostate cancer patients. Methods: Seventy multiple bone metastases patients (30 females with breast cancer and 40 males with prostate cancer) were treated with 89 Sr. The clinical effectiveness was assessed by Karnofsky performance score and whole body bone scanning data. Results: The total pain relief rate was 79% in bone metastases of breast cancer and 85% in bone metastases of prostate cancer, respectively. There was no significant differences between the two groups (χ 2 =0.78, P>0.05). The Karnofsky score was significantly improved in both groups (t=2.46, P 89 Sr treatment was good, and the quality of life was improved in patients with multiple bone metastases breast or prostate cancer. (authors)

  12. Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma

    DEFF Research Database (Denmark)

    Casneuf, Tineke; Xu, Xu Steven; Adams, Homer C

    2017-01-01

    Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and......, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy...

  13. Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Hai Chen

    2016-01-01

    Conclusion: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

  14. Evaluation of the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome.

    Science.gov (United States)

    Kornek, Barbara; Schmitl, Beate; Vass, Karl; Zehetmayer, Sonja; Pritsch, Martin; Penzien, Johann; Karenfort, Michael; Blaschek, Astrid; Seidl, Rainer; Prayer, Daniela; Rostasy, Kevin

    2012-12-01

    Magnetic resonance imaging diagnostic criteria for paediatric multiple sclerosis have been established on the basis of brain imaging findings alone. The 2010 McDonald criteria for the diagnosis of multiple sclerosis, however, include spinal cord imaging for detection of lesion dissemination in space. The new criteria have been recommended in paediatric multiple sclerosis. (1) To evaluate the 2010 McDonald multiple sclerosis criteria in children with a clinically isolated syndrome and to compare them with recently proposed magnetic resonance criteria for children; (2) to assess whether the inclusion of spinal cord imaging provided additional value to the 2010 McDonald criteria. We performed a retrospective analysis of brain and spinal cord magnetic resonance imaging scans from 52 children with a clinically isolated syndrome. Sensitivity, specificity and accuracy of the magnetic resonance criteria were assessed. The 2010 McDonald dissemination in space criteria were more sensitive (85% versus 74%) but less specific (80% versus 100%) compared to the 2005 McDonald criteria. The Callen criteria were more accurate (89%) compared to the 2010 McDonald (85%), the 2005 McDonald criteria for dissemination in space (81%), the KIDMUS criteria (46%) and the Canadian Pediatric Demyelinating Disease Network criteria (76%). The 2010 McDonald criteria for dissemination in time were more accurate (93%) than the dissemination in space criteria (85%). Inclusion of the spinal cord did not increase the accuracy of the McDonald criteria.

  15. Use of Multiple Linear Regression Method for Modelling Seasonal Changes in Stable Isotopes of 18O and 2H in 30 Pouns in Gilan Province

    Directory of Open Access Journals (Sweden)

    M.A. Mousavi Shalmani

    2014-08-01

    Full Text Available In order to assessment of water quality and characterize seasonal variation in 18O and 2H in relation with different chemical and physiographical parameters and modelling of effective parameters, an study was conducted during 2010 to 2011 in 30 different ponds in the north of Iran. Samples were collected at three different seasons and analysed for chemical and isotopic components. Data shows that highest amounts of δ18O and δ2H were recorded in the summer (-1.15‰ and -12.11‰ and the lowest amounts were seen in the winter (-7.50‰ and -47.32‰ respectively. Data also reveals that there is significant increase in d-excess during spring and summer in ponds 20, 21, 22, 24, 25 and 26. We can conclude that residual surface runoff (from upper lands is an important source of water to transfer soluble salts in to these ponds. In this respect, high retention time may be the main reason for movements of light isotopes in to the ponds. This has led d-excess of pond 12 even greater in summer than winter. This could be an acceptable reason for ponds 25 and 26 (Siyahkal county with highest amount of d-excess and lowest amounts of δ18O and δ2H. It seems light water pumped from groundwater wells with minor source of salt (originated from sea deep percolation in to the ponds, could may be another reason for significant decrease in the heavy isotopes of water (18O and 2H for ponds 2, 12, 14 and 25 from spring to summer. Overall conclusion of multiple linear regression test indicate that firstly from 30 variables (under investigation only a few cases can be used for identifying of changes in 18O and 2H by applications. Secondly, among the variables (studied, phytoplankton content was a common factor for interpretation of 18O and 2H during spring and summer, and also total period (during a year. Thirdly, the use of water in the spring was recommended for sampling, for 18O and 2H interpretation compared with other seasons. This is because of function can be

  16. Clinical vocabulary as a boundary object in multidisciplinary care management of multiple chemical sensitivity, a complex and chronic condition.

    Science.gov (United States)

    Sampalli, Tara; Shepherd, Michael; Duffy, Jack

    2011-04-14

    Research has shown that accurate and timely communication between multidisciplinary clinicians involved in the care of complex and chronic health conditions is often challenging. The domain knowledge for these conditions is heterogeneous, with poorly categorized, unstructured, and inconsistent clinical vocabulary. The potential of boundary object as a technique to bridge communication gaps is explored in this study. A standardized and controlled clinical vocabulary was developed as a boundary object in the domain of a complex and chronic health condition, namely, multiple chemical sensitivity, to improve communication among multidisciplinary clinicians. A convenience sample of 100 patients with a diagnosis of multiple chemical sensitivity, nine multidisciplinary clinicians involved in the care of patients with multiple chemical sensitivity, and 36 clinicians in the community participated in the study. Eighty-two percent of the multidisciplinary and inconsistent vocabulary was standardized using the Systematized Nomenclature of Medicine - Clinical Terms (SNOMED(®) CT as a reference terminology. Over 80% of the multidisciplinary clinicians agreed on the overall usefulness of having a controlled vocabulary as a boundary object. Over 65% of clinicians in the community agreed on the overall usefulness of the vocabulary. The results from this study are promising and will be further evaluated in the domain of another complex chronic condition, ie, chronic pain. The study was conducted as a preliminary analysis for developing a boundary object in a heterogeneous domain of knowledge.

  17. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  18. Clinically practical intensity modulation for complex head and neck lesions using multiple, static MLC fields

    International Nuclear Information System (INIS)

    Verhey, L.J.; Xia, P.; Akazawa, P.

    1997-01-01

    Purpose: A number of different beam delivery methods have been proposed for implementing intensity modulated radiotherapy (IMRT), including fixed gantry with multiple static MLC fields (MSMLC - often referred to as 'stop and shoot'), fixed gantry with dynamic MLC (DMLC), intensity modulated arc therapy (IMAT), Tomotherapy and Peacock MIMiC. Using two complex head and neck cases as examples, we have compared dose distributions achievable with 3-D conformal radiotherapy (3DCRT) to those which can be achieved using IMRT delivered with MSMLC, DMLC and Peacock MIMiC. The goal is to demonstrate the potential value of IMRT in the treatment of complex lesions in the head and neck and to determine whether MSMLC, the simplest of the proposed IMRT methods, can produce dose distributions which are competitive with dynamic IMRT methods and which can be implemented in clinically acceptable times. Materials and Methods: Two patients with nasopharyngeal carcinoma were selected from the archives of the Department of Radiation Oncology at the University of California, San Francisco (UCSF). These patients were previously planned and treated with CT-based 3-D treatment planning methods which are routinely used at UCSF, including non-axial beam directions and partial transmission blocks when indicated. The CT data tapes were then read into a test version of CORVUS, an inverse treatment planning program being developed by NOMOS Corporation, target volumes and critical normal structures were outlined on axial CT slices and dose goals and limits were defined for the targets and normal tissues of interest. Optimized dose plans were then obtained for each delivery method including MSMLC (4 or 5 hand-selected beams with 3 levels of intensity), DMLC (9 evenly spaced axial beams with 10 levels of intensity) and Peacock MIMiC (55 axial beams spanning 270 degrees with 10 levels of intensity). Dose-volume histograms (DVH's) for all IMRT plans were then compared with the 3DCRT plans. Treatment

  19. Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics.

    Directory of Open Access Journals (Sweden)

    Daniel D Buchanan

    2010-07-01

    Full Text Available Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC. Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37% individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02. For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004 after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

  20. Clinical Characteristics of Multiple Colorectal Adenoma Patients Without Germline APC or MYH Mutations

    NARCIS (Netherlands)

    Tieu, Alan H; Edelstein, Daniel; Axilbund, Jennifer; Romans, Katharine E; Brosens, Lodewijk; Wiley, Elizabeth; Hylind, Linda; Giardiello, Francis M

    BACKGROUND: Patients with multiple colorectal adenomas (MCRA) without genetic cause are increasingly being diagnosed. The characteristics and natural history of this condition are not well studied. MATERIALS AND METHODS: Twenty-seven patients with MCRA, with cumulatively 10 to 99 colorectal adenomas

  1. Encephalic magnetic resonance imaging in spinal clinical forms of multiple sclerosis

    International Nuclear Information System (INIS)

    Lubetzki, C.; Lyon-Caen, O.; Lhermitte, F.; Iba-Zizen, M.T.

    1988-01-01

    The diagnosis of multiple sclerosis (MS) in patients presenting with signs and symptoms of pure spinal cord involvement is always difficult. Previous studies have shown the usefulness of encephalic magnetic resonance imaging (MRI) of the brain in those cases. The aim was to evaluate the diagnosis value of brain MRI in medullar forms of MS. 3 refs

  2. Clinical trials: odds ratios and multiple regression models--why and how to assess them

    NARCIS (Netherlands)

    Sobh, Mohamad; Cleophas, Ton J.; Hadj-Chaib, Amel; Zwinderman, Aeilko H.

    2008-01-01

    Odds ratios (ORs), unlike chi2 tests, provide direct insight into the strength of the relationship between treatment modalities and treatment effects. Multiple regression models can reduce the data spread due to certain patient characteristics and thus improve the precision of the treatment

  3. Serum homocysteine levels in relation to clinical progression in multiple sclerosis

    NARCIS (Netherlands)

    Teunissen, C.E.; Killestein, J.; Kragt, J.J.; Polman, C.H.; Dijkstra, C.D.; Blom, H.J.

    2008-01-01

    Background: Elevated homocysteine levels are associated with various neurodegenerative diseases and have even been identified as a risk factor for some of these. Homocysteine levels may be elevated in patients with multiple sclerosis (MS) but large studies are lacking and the relation with disease

  4. Development of a novel concept for performing multiple assays on clinical samples using fluidic device

    DEFF Research Database (Denmark)

    Søe, Martin Jensen

    RNA-130a sammenlignet med konventionelle teknikker, hvor der benyttes prober af DNA og LNA. Desuden kunne multiple miRNAer detekteres ved brug af sekventielle inkuberinger af TSA reagens. Dette tillod detektion af to miRNA og et protein på samme vævssnit. Den anden model involverede design og konstruktion...

  5. Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury.

    Science.gov (United States)

    Kawai, Chihiro; Kotani, Hirokazu; Miyao, Masashi; Ishida, Tokiko; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-04-01

    Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Prevalence and clinical outcomes of patients with multiple potential causes of syncope

    NARCIS (Netherlands)

    Chen, Lin Y.; Gersh, Bernard J.; Hodge, David O.; Wieling, Wouter; Hammill, Stephen C.; Shen, Win-Kuang

    2003-01-01

    Objective: To determine the prevalence, predictors, and prognosis of patients with multiple potential causes of syncope. Patients and Methods: This is a retrospective cohort study with prospective follow-up of consecutive patients with syncope of uncertain cause who were referred to the

  7. Movement disorders in multiple sclerosis and neuromyelitis optica: A clinical marker of neurological disability.

    Science.gov (United States)

    Candeias da Silva, Carolina; Bichuetti, Denis Bernardi; Azevedo Silva, Sonia Maria Cesar de; Ferraz, Henrique Ballalai; Oliveira, Enedina Maria Lobato de; Borges, Vanderci

    2018-03-03

    Movement disorders are not rare in demyelinating diseases but there are few studies comparing their frequency between multiple sclerosis and neuromyelitis optica spectrum disorder. Our aim was to determine the frequency and the related features of movement disorders in a cohort of patients with multiple sclerosis and neuromyelitis optica spectrum disorder. It is a cross-sectional study of patients with multiple sclerosis and neuromyelitis optica spectrum disorder. Patients were evaluated by a movement disorder specialist. Data from a personal interview and neurological examination were collected. Fahn-Tolosa-Marin tremor rating scale was used for tremor evaluation. Health-related quality of life was assessed using EuroQol instrument. Two hundred fifty-three patients were included (mean [SD] age, 40 [12] years; 74.3% female; median [IQR] EDSS score 2.5 [1.0-6.0]); 26% presented with movement disorders. Paroxysmal dystonia (n = 32) and tremor (n = 27) were the most common movement disorders. Patients with multiple sclerosis and low Expanded Disability Status Scale score (below 4.0) have fewer movement disorders than patients with neuromyelitis optica spectrum disorder. The diagnosis of neuromyelitis optica spectrum disorder was strongly associated with paroxysmal dystonia (OR = 22.07, 95% CI = 2.56-189.78; p = 0.005). Patients with multiple sclerosis and patients without movement disorders have a slightly better quality of life. Paroxysmal dystonia was the most common movement disorder in demyelinating diseases and strongly associated with neuromyelitis optica spectrum disorder. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

    Science.gov (United States)

    Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

    2017-08-15

    Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings

  9. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

    Directory of Open Access Journals (Sweden)

    Francine Foss

    2016-03-01

    Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

  10. Preprocedural High-Sensitivity Cardiac Troponin T and Clinical Outcomes in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention.

    Science.gov (United States)

    Zanchin, Thomas; Räber, Lorenz; Koskinas, Konstantinos C; Piccolo, Raffaele; Jüni, Peter; Pilgrim, Thomas; Stortecky, Stefan; Khattab, Ahmed A; Wenaweser, Peter; Bloechlinger, Stefan; Moschovitis, Aris; Frenk, Andre; Moro, Christina; Meier, Bernhard; Fiedler, Georg M; Heg, Dik; Windecker, Stephan

    2016-06-01

    Cardiac troponin detected by new-generation, highly sensitive assays predicts clinical outcomes among patients with stable coronary artery disease (SCAD) treated medically. The prognostic value of baseline high-sensitivity cardiac troponin T (hs-cTnT) elevation in SCAD patients undergoing elective percutaneous coronary interventions is not well established. This study assessed the association of preprocedural levels of hs-cTnT with 1-year clinical outcomes among SCAD patients undergoing percutaneous coronary intervention. Between 2010 and 2014, 6974 consecutive patients were prospectively enrolled in the Bern Percutaneous Coronary Interventions Registry. Among patients with SCAD (n=2029), 527 (26%) had elevated preprocedural hs-cTnT above the upper reference limit of 14 ng/L. The primary end point, mortality within 1 year, occurred in 20 patients (1.4%) with normal hs-cTnT versus 39 patients (7.7%) with elevated baseline hs-cTnT (P<0.001). Patients with elevated hs-cTnT had increased risks of all-cause (hazard ratio 5.73; 95% confidence intervals 3.34-9.83; P<0.001) and cardiac mortality (hazard ratio 4.68; 95% confidence interval 2.12-10.31; P<0.001). Preprocedural hs-TnT elevation remained an independent predictor of 1-year mortality after adjustment for relevant risk factors, including age, sex, and renal failure (adjusted hazard ratio 2.08; 95% confidence interval 1.10-3.92; P=0.024). A graded mortality risk was observed across higher tertiles of elevated preprocedural hs-cTnT, but not among patients with hs-cTnT below the upper reference limit. Preprocedural elevation of hs-cTnT is observed in one fourth of SCAD patients undergoing elective percutaneous coronary intervention. Increased levels of preprocedural hs-cTnT are proportionally related to the risk of death and emerged as independent predictors of all-cause mortality within 1 year. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291. © 2016 American Heart Association, Inc.

  11. Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

    Science.gov (United States)

    Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

    2015-03-01

    There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

  12. Clinical values of detection of multiple tumor markers in pleural fluid for diagnosis malignancy

    International Nuclear Information System (INIS)

    Xiao Chuangqing; Jiang Li; Zhou Guanghua; He Yunnan

    2005-01-01

    Objective: To improve the diagnostic accuracy for the differentiation of malignant from tuberculous pleural effusion with determination of multiple tumor markers in pleural fluid. Methods: With a multiple tumor markers combined protein chip diagnostic system, contents of twelve common tumor markers were detected in the chest fluid from 60 patients with malignant pleural effusion and 30 patients with tuberculous pleural effusion. Results: For pulmonary carcinoma related pleural effusion, the contents of four common tumor markers (CEA, NSE, SF, CA125) in chest fluid were significantly higher those in tuberculous related chest fluid. The diagnostic positive rate of combined test of these four marker for malignancy could be as high as 96.7%. Conclusion: Combined determination of chest fluid CEA, NSE, SF, CA125 contents was very sensitive and accurate for differentiation of malignant from tuberculous pleural effusion. (authors)

  13. [Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

    Science.gov (United States)

    Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

    2017-06-01

    Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

  14. Clinical results of single-vessel versus multiple-vessel infrapopliteal intervention

    OpenAIRE

    Darling, Jeremy; McCallum, John C.; Soden, Peter A.; Hon, J.J. (John J.); Guzman, R.J. (Raul J.); Wyers, M.C. (Mark C.); Verhagen, Hence; Schermerhorn, Marc

    2016-01-01

    textabstractObjective The effects of concomitant endovascular interventions on multiple infrapopliteal vessels are not well known, and the short-term and long-term sequelae of such procedures have not been reported. Methods From 2004 to 2014, 673 limbs in 528 patients underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Outcomes included wound healing, RAS eve...

  15. Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline

    OpenAIRE

    Reece, D.; Imrie, K.; Stevens, A.; Smith, C.A.

    2006-01-01

    Questions In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate? What is the toxicity associated with the use of bortezomib? Which patients are more or less likely to benefit from treatment with bortezomib? Perspectives Evidence was selected and reviewed by two members of the Hemato...

  16. Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice

    OpenAIRE

    de Sa, João Carlos Correia; Airas, Laura; Bartholome, Emmanuel; Grigoriadis, Nikolaos; Mattle, Heinrich; Oreja-Guevara, Celia; O’Riordan, Jonathan; Sellebjerg, Finn; Stankoff, Bruno; Vass, Karl; Walczak, Agata; Wiendl, Heinz; Kieseier, Bernd C.

    2011-01-01

    As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Resear...

  17. Clinical problems of multiple primary cancers including head and neck cancers. From the viewpoint of radiotherapy

    International Nuclear Information System (INIS)

    Nishio, Masamichi; Myojin, Miyako; Nishiyama, Noriaki; Taguchi, Hiroshi; Takagi, Masaru; Tanaka, Katsuhiko

    2003-01-01

    A total of 2144 head and neck cancers were treated by radiotherapy at the National Sapporo Hospital between 1974 and 2001. Of these, 313 (14.6%) were found to have other primary cancers besides head and neck cancer, in which double cancers were 79% and triple or more cancers were 21%. Frequency according to primary site of the first head and neck cancer was oral cavity: 107/603 (17.7%), epipharynx cancer: 7/117 (6.0%), oropharyngeal cancer: 63/257 (24.5%), hypopharyngeal cancer: 65/200 (32.5%), laryngeal cancer: 114/558 (20.4%), and nose/paranasal sinus: 4.9% respectively. Esophageal cancer, head and neck cancer, lung cancer and gastric cancer were very frequent as other primary sites combined with the head and neck. The first onset region was the head and neck in 233 out of 313 cases with multiple primary cancers. The five-year survival rate from the onset of head and neck cancers is 52%, 10-year: 30%, and 5-year cause-specific survival rate 82%, and 10-year: 78%, respectively. The treatment possibilities in multiple primary cancers tend to be limited because the treatment areas are sometimes overlapped. New approaches to the treatment of multiple primary cancers should be considered in the future. (author)

  18. Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

    Science.gov (United States)

    Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

    2018-03-22

    Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement

  19. Temporomandibular joint disorder in a patient with multiple sclerosis--review of literature with a clinical report.

    Science.gov (United States)

    Badel, Tomislav; Carek, Andreja; Podoreski, Dijana; Pavicin, Ivana Savić; Lovko, Sandra Kocijan

    2010-09-01

    Temporomandibular disorders are a form of musculoskeletal disorders, which reduce the function of stomatognathic system and they are related to some other diseases causing painful conditions and disorders of oral function. The aim of this paper is to describe a one year follow up clinical case of a female patient with comorbid multiple sclerosis and a relatively rare form of articular disc disorder. Primary clinical diagnostics encompassed manual methods of TMJ examination. Definite diagnosis included radiologic examination. Clinical hyperextensive condyle position was palpated bilaterally and subsequently confirmed by a functional panoramic radiograph of TMJ. The anterior displacement of disc with reduction was diagnosed by magnetic resonance and in the right joint there was a disc displacement upon excursive movement. From relevant literature, the relationship of a number of diseases that can be related to functional disorder of the orofacial system, such as multiple sclerosis, has been described from many aspects. Also, apart from the standard classification of one form of anterior displacement of the disc, made primarily by magnetic resonance, cases of disc displacement upon excursive mandibular movement can rarely be found in literature.

  20. Combined embolization with multiple materials for the treatment of esophagogastric varices: an analysis of clinical therapeutic effect

    International Nuclear Information System (INIS)

    Lu Yanping; Qin Haopu; Zhang Mengzeng

    2011-01-01

    Objective: To evaluate the clinical efficacy of percutaneous transhepatic combined embolization with multiple materials in treating esophagogastric varices. Methods: A total of 48 patients with esophagogastric varices complicated by bleeding due to ruptured varices were enrolled in this study. Percutaneous transhepatic combined embolization with Gelfoam, ethanol and stainless steel coils was carried out in all patients. The clinical results were analyzed. Results: Superselective catheterization and subsequent combined embolization procedure were successfully completed in all patients. In 17 patients with acute upper gastrointestinal bleeding, one died seven days after the treatment because of general failure. Postoperative gastroscopic examination was performed in 33 patients, which showed that esophagogastric varices were completely obliterated in 27 patients and markedly improved in six patients. A total of 35 patients were followed up for 4-36 months. During the follow-up period rebleeding occurred in 5 and death in 2 patients. Conclusion: For the treatment of esophagogastric varices, combined embolization with multiple materials is mini-invasive, safe and effective. It is of value to popularize this technique in clinical practice. (authors)

  1. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    NARCIS (Netherlands)

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  2. Characterization of multiple antibiotic resistant clinical strains of Staphylococcus isolated from pregnant women vagina.

    Science.gov (United States)

    Hetsa, Bakwena Ashton; Kumar, Ajay; Ateba, Collins Njie

    2018-03-29

    Vagina which is one of the important reservoirs for Staphylococcus and in pregnant women pathogenic strains may infect the child during the birth or by vertical transmission. A total of 68 presumptive Staphylococcus strains isolated from human vagina were found to be gram-positive cocci, and only 32 (47%) isolates were found beta-hemolytic. Matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) results confirmed 33 isolates belonged to Staphylococcus which consisting of 6 species, i.e., S. aureus (14), S. vitulinus (7), S. epidermidis (4), S cohnii (3), S. equorum (3), and S. succinus (2). Further, the result of antibiotic susceptibility tests showed that large proportions (76%-100%) of the isolates were resistant to multiple antibiotics and more often resistant to penicillin (100%), ampicillin (100%), oxacillin (97%), oxytetracycline (97%), vancomycin (97%), rifampin (85%), erythromycin (82%), and streptomycin (76%). In the present study, only the sec enterotoxin gene was detected in four S. aureus strains. DNA fingerprints of the 33 isolates that were generated using random amplified polymorphic DNA (RAPD) and enterobacterial repetitive intergenic consensus (ERIC) PCR analysis revealed great genetic relatedness of isolates. High prevalence of vaginal colonization with multiple antibiotic-resistant staphylococci among pregnant women was observed which were emerged from the single respective species clones that underwent evolution. The vertical transmission of these multiple antibiotic-resistant Staphylococcus species to the infant is possible; therefore, the findings of this study emphasize the need for regular surveillance of antibiotic-resistant bacterial strains in pregnant women in this area.

  3. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  4. Clinical and biological features of multiple myeloma involving the gastrointestinal system.

    Science.gov (United States)

    Talamo, Giampaolo; Cavallo, Federica; Zangari, Maurizio; Barlogie, Bart; Lee, Choon-Kee; Pineda-Roman, Mauricio; Kiwan, Elias; Krishna, Somashekar; Tricot, Guido

    2006-07-01

    We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival after diagnosis of GI involvement was 7 months. Among 13 patients treated with stem cell transplantation, the response rate was 92%, and median progression-free survival was 4 months. We conclude that MM involving the GI system is associated with adverse biological features and with short-lasting remissions, even after A high-dose chemotherapy.

  5. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Polman, Chris H; Bertolotto, Antonio; Deisenhammer, Florian

    2010-01-01

    in MS and NAbs to interferon-beta therapy convened in Amsterdam, Netherlands, under the auspices of the Neutralizing Antibodies on Interferon beta in Multiple Sclerosis consortium, a European-based project of the 6th Framework Programme of the European Commission, to review and discuss data on NAbs......The identification of factors that can affect the efficacy of immunomodulatory drugs in relapsing-remitting multiple sclerosis (MS) is important. For the available interferon-beta products, neutralising antibodies (NAb) have been shown to affect treatment efficacy. In June, 2009, a panel of experts...... and their practical consequences for the treatment of patients with MS on interferon beta. The panel believed that information about NAbs and other markers of biological activity of interferons (ie, myxovirus resistance protein A [MxA]) can be integrated with clinical and imaging indicators to guide individual...

  6. Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

    Directory of Open Access Journals (Sweden)

    Zhi-Hai Chen

    Full Text Available Hemorrhagic fevers (HF caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF, 34 with Hemorrhagic Fever with Renal Syndrome (HFRS, one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC, higher levels of creations kinase (CK and alanine aminotransferase (ALT, while HFRS patients presented with an elevation of blood urea nitrogen (BUN and creatinine (CREA. These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

  7. PERSPECTIVE: Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain

    Science.gov (United States)

    Rousche, Patrick; Schneeweis, David M.; Perreault, Eric J.; Jensen, Winnie

    2008-03-01

    A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who

  8. Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain.

    Science.gov (United States)

    Rousche, Patrick; Schneeweis, David M; Perreault, Eric J; Jensen, Winnie

    2008-03-01

    A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who

  9. Associations between multiple indoor environmental factors and clinically confirmed allergic disease in early childhood

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Bekö, Gabriel; Weschler, Charles J.

    2012-01-01

    , rhinoconjunctivitis and atopic dermatitis. Method: A crosssectional case-cohort study (n = 500) based on 2835 children, aged 3–5 years, responding to a questionnaire, consisted of 300 subjects randomly selected and 200 cases with at least two parentally reported doctor diagnosed allergic diseases (asthma, allergic...... rhinoconjunctivitis or atopic dermatitis). The same physician conducted a clinical examination of all the 500 children including structured interview on allergic heredity, clinical and medical history. Specific s-IgE against inhalant and food allergens was determined. The homes were investigated by inspectors...... assessing air change rates, relative humidity, temperature, CO2, and dust samples were collected for analyses of indoor allergens, phthalates, nicotine and polyaromatic hydrocarbons. The diagnosis of allergic disease was based on internationally accepted criteria. Result: In the base group (n = 300) asthma...

  10. Multiple stage MS in analysis of plasma, serum, urine and in vitro samples relevant to clinical and forensic toxicology.

    Science.gov (United States)

    Meyer, Golo M; Maurer, Hans H; Meyer, Markus R

    2016-01-01

    This paper reviews MS approaches applied to metabolism studies, structure elucidation and qualitative or quantitative screening of drugs (of abuse) and/or their metabolites. Applications in clinical and forensic toxicology were included using blood plasma or serum, urine, in vitro samples, liquids, solids or plant material. Techniques covered are liquid chromatography coupled to low-resolution and high-resolution multiple stage mass analyzers. Only PubMed listed studies published in English between January 2008 and January 2015 were considered. Approaches are discussed focusing on sample preparation and mass spectral settings. Comments on advantages and limitations of these techniques complete the review.

  11. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

    2017-01-01

    New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

  12. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    OpenAIRE

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  13. Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core.

    Science.gov (United States)

    Arango-Dávila, Cesar A; Rincón-Hoyos, Hernán G

    A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  14. Quantitative analysis of the clinical data on leukemia, 5. Specificity of clinical features in acute myelocytic leukemia with 8; 21 translocation by multiple logistic discriminant analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ueoka, Hiroshi; Kamada, Nanao; Yamamoto, Hisashi; Ohtaki, Megu; Takimoto, Yasuo; Kuramoto, Atsushi; Munaka, Masaki

    1984-11-01

    In order to determine the necessity of chromosome analysis required for the evaluation of 8;21 translocation, multiple logistic discriminant analysis was made on 124 patients with acute non-lymphocytic leukemia experienced in the authors' institution. Variables which showed positive correlation with the presence of 8;21 translocation were the presence of Auer body and granular abnormality of the cells, numbers of peripheral promyelocytes, myelocytes and metamyelocytes, and bone marrow promyelocytes, myelocytes, and the sum of rods and segments. Those which showed negative correlation with 8;21 translocation were peripheral platelet count, neutrocytealkaline phosphatase (N-AP) score, numbers of eosinocytes, monocytes and erythroblasts, and erythroblasts on myelogram. Auer body, four peripheral hematological features (platelet count, N-AP score, metamyelocytes and monocytes), and three myelogram features (myelocytes, reticular cells and granulocytes/eosionocytes) were used for the multiple logistic discriminant analysis. By the analysis, 2 of the 22 patients (9.1%) with translocation were judged not to have 8;21 translocation and 3 of the 102 patients (2.9%) without translocation were judged to have it. Therefore, this multiple logistic discriminant method has proved to be simple and useful in clinically evaluating acute non-lymphocytic leukemia. (Namekawa, K.).

  15. Body Esteem Among Women with Multiple Sclerosis and its Relationship with Demographic, Clinical and Socio-Psychological Factors.

    Science.gov (United States)

    Wilski, M; Tasiemski, T; Dąbrowski, A

    2016-06-01

    The principal aim of this study was to verify if specific socio-demographic, clinical, and socio-psychological factors are correlates of body esteem in women with multiple sclerosis (MS). The study included 185 women with MS who completed the Body Esteem Scale (BES), Rosenberg Self-Esteem Scale (RSES), Multiple Sclerosis Impact Scale (MSIS-29), Brief Illness Perception Questionnaire (B-IPQ), Actually Received Support Scale (a part of the Berlin Social Support Scale), and Expanded Disability Status Scale (EDSS). The patients were recruited as a result of cooperation with the Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. The demographic characteristics of the participants and their illness-related problems were determined with a self-report survey. A hierarchical multiple regression revealed that four factors, psychological condition (R (2) = 0.23, p ≤ 0.001), received support (R (2) = 0.28, p ≤ 0.001), personal control (R (2) = 0.30, p ≤ 0.001), and physical condition (R (2) = 0.31, p ≤ 0.001), were significant correlates of the general body esteem in our study group of women with MS. The model explained 31 % of variance in body esteem. Positive body esteem, an important component of self-esteem in women with MS, is associated with better social support, overcoming negative illness-related appraisals and improvement of psychological well-being. Subjective perception of a negative impact of MS on one's physical condition may be helpful in the identification of women with MS being at increased risk of decreased body esteem.

  16. A clinical study of multiple trauma combined with acute lung injury

    Directory of Open Access Journals (Sweden)

    Tao Liang

    2016-11-01

    Full Text Available Objective: To study the changes of the contents of inflammatory mediators in serum of polytrauma patients with acute lung injury (ALI and their correlation with the disease. Methods: Patients suffering from multiple trauma combined with ALI were selected as ALI group (n = 54. Patients suffering from multiple trauma without ALI were considered as the control group (n = 117. The severity of the disease of patients in the two groups was assessed. Arterial blood was extracted for blood gas analysis. Venous blood was extracted to detect the contents of inflammatory mediators tumor necrosis factor-a, interleukin-1b (IL-1b, IL-10, granulocyte-macrophage colony stimulating factor, NO, endothelin-1. Results: The scores of injury severity score [(25.42 ± 3.58 vs. (17.03 ± 2.25], systemic inflammatory response syndrome [(3.85 ± 0.52 vs. (2.20 ± 0.36] and acute physiology and chronic health evaluation II [(92.63 ± 11.04 vs. (60.46 ± 8.87] in patients in ALI group were all significantly higher than those in the control group and its correcting shock time [(8.39 ± 1.05 vs. (5.15 ± 0.72 h] was longer than that of the control group. The amount of blood transfusion [(674.69 ± 93.52 vs. (402.55 ± 57.65 mL] was greater than that in the control group. The contents of the arterial partial pressure of oxygen [(76.65 ± 9.68 vs. (86.51 ± 10.56 mmHg], arterial blood pressure of carbon dioxide [(27.76 ± 4.82 vs. (36.78 ± 5.82 mmHg] and arterial partial pressure of oxygen/fraction of inspired oxygen [(236.94 ± 36.49 vs. (353.95 ± 47.76] were all significantly lower than those in the control group. The contents of serum tumor necrosis factor-a, IL-1b, IL- 10, granulocyte-macrophage colony stimulating factor, NO and endothelin-1 were obviously higher than those of control group and also positively correlated with the scores of injury severity score, systemic inflammatory response syndrome and acute physiology and chronic health evaluation II. Conclusions

  17. Clinical multiple sclerosis occurs at one end of a spectrum of CNS pathology: a modified threshold liability model leads to new ways of thinking about the cause of clinical multiple sclerosis.

    Science.gov (United States)

    Haegert, David G

    2005-01-01

    Multiple sclerosis (MS) is a complex trait, the causes of which are elusive. A threshold liability model influences thinking about the causes of this disorder. According to this model, a population has a normal distribution of genetic liability to MS. In addition, a threshold exists, so that MS begins when an individual's liability exceeds the MS threshold; environmental and other causative factors may increase or decrease an individual's MS liability. It is argued here, however, that this model is misleading, as it is based on the incorrect assumption that MS is a disorder that one either has or does not have. This paper hypothesizes, instead, that patients with a diagnosis of MS share identical CNS pathology, termed MS pathology, with some individuals who have a diagnosis of possible MS and with some apparently healthy individuals, who may never have a diagnosis of MS. In order to accommodate this hypothesis, the current threshold liability model is modified as follows. (1) In addition to a normal distribution of MS liability within a population, a spectrum of MS pathology occurs in some who have a high MS liability. (2) A clinical MS threshold exists at a point on this liability distribution, where the burden and distribution of MS pathology permits a diagnosis of clinical MS. (3) Additional thresholds exist that correspond to a lower MS liability and a lesser burden of MS pathology than occur at the clinical MS threshold. This modified threshold model leads to the postulate that causes act at various time points to increase MS liability and induce MS pathology. The accumulation of MS pathology sometimes leads to a diagnosis of clinical MS. One implication of this model is that the MS pathology in clinical MS and in some with possible MS differs only in the extent but not in the type of CNS injury. Thus, it may be possible to obtain insight into the causative environmental factors that increase MS liability and induce MS pathology by focusing on patients who

  18. Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice

    DEFF Research Database (Denmark)

    de Sa, João Carlos Correia; Airas, Laura; Bartholome, Emmanuel

    2011-01-01

    compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking....... This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize......As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors...

  19. Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs.

    Directory of Open Access Journals (Sweden)

    Sarah Gooding

    Full Text Available Double relapsed and/or refractory multiple myeloma (DRMM, MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411-£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM.

  20. The ability of clinical balance measures to identify falls risk in multiple sclerosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Quinn, Gillian; Comber, Laura; Galvin, Rose; Coote, Susan

    2018-05-01

    To determine the ability of clinical measures of balance to distinguish fallers from non-fallers and to determine their predictive validity in identifying those at risk of falls. AMED, CINAHL, Medline, Scopus, PubMed Central and Google Scholar. First search: July 2015. Final search: October 2017. Inclusion criteria were studies of adults with a definite multiple sclerosis diagnosis, a clinical balance assessment and method of falls recording. Data were extracted independently by two reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale and the modified Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was conducted for the cross-sectional studies using Review Manager 5. The mean difference with 95% confidence interval in balance outcomes between fallers and non-fallers was used as the mode of analysis. We included 33 studies (19 cross-sectional, 5 randomised controlled trials, 9 prospective) with a total of 3901 participants, of which 1917 (49%) were classified as fallers. The balance measures most commonly reported were the Berg Balance Scale, Timed Up and Go and Falls Efficacy Scale International. Meta-analysis demonstrated fallers perform significantly worse than non-fallers on all measures analysed except the Timed Up and Go Cognitive ( p Balance Confidence Scale had the highest area under the receiver operating characteristic curve value (0.92), but without reporting corresponding measures of clinical utility. Clinical measures of balance differ significantly between fallers and non-fallers but have poor predictive ability for falls risk in people with multiple sclerosis.

  1. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben

    2011-01-01

    Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically...... (Caw). All patients had spirometry, assessment of symptoms with questionnaires and low-dose CT scan as well as assessment of weight and body composition. We examined the following subgroups of COPD: Patients with 1) Severe emphysema, 2) Chronic bronchitis, 3) Frequent exacerbations, 4) Loss of lean...

  2. Alzheimer’s disease multiple intervention trial (ADMIT: study protocol for a randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Callahan Christopher M

    2012-06-01

    Full Text Available Abstract Background Given the current lack of disease-modifying therapies, it is important to explore new models of longitudinal care for older adults with dementia that focus on improving quality of life and delaying functional decline. In a previous clinical trial, we demonstrated that collaborative care for Alzheimer’s disease reduces patients’ neuropsychiatric symptoms as well as caregiver stress. However, these improvements in quality of life were not associated with delays in subjects’ functional decline. Trial design Parallel randomized controlled clinical trial with 1:1 allocation. Participants A total of 180 community-dwelling patients aged ≥45 years who are diagnosed with possible or probable Alzheimer’s disease; subjects must also have a caregiver willing to participate in the study and be willing to accept home visits. Subjects and their caregivers are enrolled from the primary care and geriatric medicine practices of an urban public health system serving Indianapolis, Indiana, USA. Interventions All patients receive best practices primary care including collaborative care by a dementia care manager over two years; this best practices primary care program represents the local adaptation and implementation of our prior collaborative care intervention in the urban public health system. Intervention patients also receive in-home occupational therapy delivered in twenty-four sessions over two years in addition to best practices primary care. The focus of the occupational therapy intervention is delaying functional decline and helping both subjects and caregivers adapt to functional impairments. The in-home sessions are tailored to the specific needs and goals of each patient-caregiver dyad; these needs are expected to change over the course of the study. Objective To determine whether best practices primary care plus home-based occupational therapy delays functional decline among patients with Alzheimer’s disease compared

  3. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Comi, G; Martinelli, V; Rodegher, M

    2009-01-01

    BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis....... treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

  4. Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities.

    Science.gov (United States)

    Nordvall, Maria; Dziegiel, Morten; Hegaard, Hanne Kristine; Bidstrup, Mogens; Jonsbo, Finn; Christensen, Birgit; Hedegaard, Morten

    2009-10-01

    The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

  5. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: a comparative clinical and immunological study.

    Science.gov (United States)

    Shaheen, Maha Adel; Salem, Samar Abdallah M; Fouad, Dina Adel; El-Fatah, Abeer Aly Abd

    2015-01-01

    Intralesional purified protein derivative (PPD) or mumps, measles, rubella (MMR) were not previously compared regarding their efficacy or mechanism of action in treatment of warts. We aimed to compare their efficacy in treatment of multiple warts and investigate their effect on serum interleukin (IL)-4 and IL-12. Thirty patients with multiple warts were included (10 treated with PPD, 10 with MMR, and 10 with normal saline (control)). Injection was done every 3 weeks until clearance or maximum of three treatments. Clinical response of target and distant warts was evaluated. Serum ILs-4 and -12 were assessed before and after treatment. A significantly higher rate of complete response was found in target and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared with controls (0%), with no significant difference between both treatments. After treatment, the control group showed the lowest serum IL-12 and IL-4 levels compared with the MMR- and PPD-treated groups with statistically significant difference in between. MMR resulted in a significantly higher serum IL-12 than PPD. With PPD, IL-4 was increased with statistically significant change compared with pretreat-ment level. Intralesional PPD and MMR show comparable efficacy and safety in treatment of multiple warts. Serum ILs-4 and-12 increase following antigen injection. © 2015 Wiley Periodicals, Inc.

  6. Imaging and clinical characteristics of children with multiple foci of microsusceptibility changes in the brain on susceptibility-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Aida, Noriko; Fujita, Kazutoshi; Shishikura, Ayako [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Takahara, Taro; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Miyata, Daiki [Kanagawa Children' s Medical Center, Department of Circulation Medicine, Yokohama (Japan); Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2010-10-15

    Microsusceptibility changes in the brain are well known to correspond with microbleeds or micrometal fragments in adults, but this phenomenon has not been explored well in children. To assess imaging and clinical characteristics of children with multiple foci of microsusceptibility changes using susceptibility-weighted imaging (SWI). Between 2006 and 2008, 12 children with multiple foci of microsusceptibility on SWI without corresponding abnormal signal on conventional MRI were identified and were retrospectively assessed. The locations of foci of microsusceptibility included the cerebral white matter, basal ganglia, brainstem and cerebellar white matter, without any clear systematic anatomic distribution. CT (n = 5) showed no calcification at the locations corresponding to the microsusceptibility on SWI. Conventional MR imaging showed white matter volume loss (n = 5), delayed myelination (n = 2), acute infarction (n = 1), chronic infarction (n = 1), meningitis (n = 1), slight signal abnormality in the white matter (n = 1) and no abnormal findings (n = 1). Follow-up SWI (n = 3) showed no change of the microsusceptibility foci. Interestingly, all children had a history of heart surgery under extracorporeal circulation for congenital heart disease. Multiple foci of microsusceptibility can be seen in the brain on SWI in children with congenital heart disease who underwent heart surgery with extracorporeal circulation. (orig.)

  7. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

    Science.gov (United States)

    Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

    2008-02-01

    To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

  8. Serial thallium-201 imaging at rest in patients with unstable and stable angina pectoris: relationship of myocardial perfusion at rest to presenting clinical syndrome

    International Nuclear Information System (INIS)

    Brown, K.A.; Okada, R.D.; Boucher, C.A.; Phillips, H.R.; Strauss, H.W.; Pohost, G.M.

    1983-01-01

    In order to determine whether there are differences in myocardial perfusion at rest among patients with various unstable and stable angina syndromes, serial thallium-201 imaging was performed at rest in 19 patients presenting with rapidly worsening exertional angina (unstable angina, group A), 12 patients with rest angina alone without exertional symptoms (unstable angina, group B), and 34 patients with chronic stable angina. No patient had an episode of angina within 4 hours of study. Nineteen of 19 (100%) patients in group A demonstrated transient defects compared to only 3 of 12 (25%) patients in group B (p less than 0.0001) and 4 of 34 (12%) stable angina patients (p less than 0.0001). The majority of zones demonstrating transient defects in group A were associated with hypokinesis of the corresponding left ventriculogram segment without associated ECG evidence of previous infarction. There were no significant differences in the frequency of persistent thallium defects, severity of angiographic coronary artery disease, or frequency of regional wall motion abnormalities of myocardial segments supplied by stenotic coronary arteries among the three groups of patients. Transient defects have been shown to reflect reduction in regional coronary blood flow to viable myocardium. Therefore, we conclude that regional resting hypoperfusion of viable myocardium is far more common in patients with exertional unstable angina symptoms than in patients with rest angina alone or chronic stable angina

  9. Multiple variations of the renal and testicular vessels: possible embryological basis and clinical importance.

    Science.gov (United States)

    Mazengenya, Pedzisai

    2016-08-01

    During routine dissection of the abdominal cavity of a 55-year-old African male cadaver, multiple anomalies including renal and testicular vessels were encountered. The right kidney was supplied by three right hilar renal arteries arising from the abdominal aorta at different vertebral levels whereas only one left renal artery supplied the left kidney. On the right three renal veins drained the kidney into the inferior vena cava. In contrast, the left kidney was drained by a single renal vein which received a large primary posterior tributary. The primary posterior tributary had three tributaries from the posterior lumbar region. The right testis had two sources of arterial supply; one from the subcostal artery and another from the abdominal aorta. The left testis was supplied normally by a single testicular artery. The right testis was drained by four testicular veins as follows: one drained into the subcostal vein, the other two drained separately for a longer course and joined shortly before draining into the right main renal vein, the fourth one drained into the anterior aspect of the inferior vena cava at the level of the second lumbar vertebra. On the left, the testicle was drained by two testicular veins which travelled separately from the deep inguinal ring and joined shortly before they drain into the left renal vein. This variation may represent an immature form of complicated development of kidneys and testes. Additionally, emphasis must be put on preoperative vascular examination to avoid surgical complications from variant vessels in this region.

  10. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Miller, Robert C.; Lachance, Daniel H.; Lucchinetti, Claudia F.; Keegan, B. Mark; Gavrilova, Ralitza H.; Brown, Paul D.; Weinshenker, Brian G.; Rodriguez, Moses

    2006-01-01

    Purpose: The aim of this study was a retrospective assessment of neurotoxicity in patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT) to the brain. Methods and Materials: We studied 15 consecutively treated patients with MS who received brain EBRT. Neurologic toxicity was assessed with the Common Toxicity Criteria v.3.0. Results: Median follow-up for the 5 living patients was 6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade 4 at 5 years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at 37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT. Univariate analysis showed an association between opposed-field irradiation of the temporal lobes, central white matter, and brainstem and increased risk of neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients treated before 1986. Conclusions: External beam radiotherapy of the brain in patients with MS may be associated with an increased risk of neurotoxicity compared with patients without demyelinating illnesses. However, this risk is associated with treatment techniques that may not be comparable to modern, conformal radiotherapy

  11. Investigating the role of Clinical Nurse Consultants in one health district from multiple stakeholder perspectives: a cooperative inquiry.

    Science.gov (United States)

    Walsh, Kenneth; Bothe, Janine; Edgar, Denise; Beaven, Geraldine; Burgess, Bernadette; Dickson, Vhari; Dunn, Stephen; Horning, Lynda; Jensen, Janice; Kandl, Bronia; Nonu, Miriam; Owen, Fran; Moss, Cheryle

    2015-01-01

    The impetus for this research came from a group of 11 Clinical Nurse Consultants (CNCs) within a health service in NSW, Australia, who wanted to investigate the CNC role from multiple stakeholder perspectives. With support from academic researchers, the CNCs designed and implemented the study. The aim of this research project was to investigate the role of the CNC from the multiple perspectives of CNCs and other stakeholders who work with CNCs in the Health District. This was a co-operative inquiry that utilised qualitative descriptive research approach. Co-operative inquiry methods enabled 11 CNCs to work as co-researchers and to conduct the investigation. The co-researchers implemented a qualitative descriptive design for the research and used interviews (7) and focus groups (16) with CNC stakeholders (n = 103) to gather sufficient data to investigate the role of the CNC in the organisation. Thematic analysis was undertaken to obtain the results. The CNC role is invaluable to all stakeholders and it was seen as the "glue" which holds teams together. Stakeholder expectations of the CNC role were multiple and generally agreed. Five themes derived from the data are reported as "clinical leadership as core", "making a direct difference to patient care", "service development as an outcome", "role breadth or narrowness and boundaries", and "career development". There was clear appreciation of the work that CNCs do in their roles, and the part that the CNC role plays in achieving quality health outcomes. The role of the CNC is complex and the CNCs themselves often negotiate these complexities to ensure beneficial outcomes for the patient and organisation. For the wider audience this study has given further insights into the role of these nurses and the perspectives of those with whom they work.

  12. Linked Clinical Trials – The Development of New Clinical Learning Studies in Parkinson’s Disease Using Screening of Multiple Prospective New Treatments

    Science.gov (United States)

    Brundin, Patrik; Barker, Roger A.; Conn, P. Jeffrey; Dawson, Ted M.; Kieburtz, Karl; Lees, Andrew J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Isaacs, Tom; Duffen, Joy; Matthews, Helen; Wyse, Richard K.H.

    2015-01-01

    Finding new therapies for Parkinson’s disease (PD) is a slow process. We assembled an international committee of experts to examine drugs potentially suitable for repurposing to modify PD progression. This committee evaluated multiple drugs currently used, or being developed, in other therapeutic areas, as well as considering several natural, non-pharmaceutical compounds. The committee prioritized which of these putative treatments were most suited to move immediately into pilot clinical trials. Aspects considered included known modes of action, safety, blood-brain-barrier penetration, preclinical data in animal models of PD and the possibility to monitor target engagement in the brain. Of the 26 potential interventions, 10 were considered worth moving forward into small, parallel ‘learning’ clinical trials in PD patients. These trials could be funded in a multitude of ways through support from industry, research grants and directed philanthropic donations. The committee-based approach to select the candidate compounds might help rapidly identify new potential PD treatment strategies for use in clinical trials. PMID:24018336

  13. Eating disorders, substance use disorders and multiple symptoms: three clinical vignettes.

    Science.gov (United States)

    Fava Vizziello, Graziella; Bellin, Laura

    2018-04-01

    During the longitudinal study of three patients, referred to services at 3, 13, 15 years for eating disorders, reduced food intake and anorexia nervosa, other symptoms appeared depending on difficult development, relational and personality problems. The patients showed the interweaving of symptoms at different times: they were dealing with modified developmental needs and contexts, included new possibilities of attachment that might produce different internal organizations. These changes required different treatments. Anorexia started early in life for these girls, but presented different steps of organization. We wanted to start finding some aspects of a staging model to map the course of ED, because many patients arrived later in life, reported untreated early symptoms, actually personality traits. Mapping the evolution, could allow to take care of patients at the very early stage of problems when few symptoms are present, and better patients' evolution might be possible. Level V opinions of respected authorities based on clinical experience.

  14. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Science.gov (United States)

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Clinical observations of infants with multiple encephalomalacia on cranial computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Eda, I.; Yoshino, K.; Nakai, M.; Takashima, S. (Tottori Univ., Yonago (Japan). School of Medicine); Morita, M.

    1982-09-01

    Four cases whose CT scans showed multi-focal or diffuse low density in both cerebral hemisphere were reported and their clinical histories, roentogenographic and electroencephalographic findings were compared. Out of 2 cases with multi-focal low density, one fatal case (Case 1) was diagnosed neuropathologically as multicystic encephalomalacia (MCEM). He had asphyxia at delivery, convulsion and fever for a few days from the first day. Case 2 was one of twins with a clinical history of intrauterine onset. He had no trouble in delivery but poor feedings in the neonatal period. Two cases showed microcephaly, severe psychomotor retardation and tetraplegia later. Two cases with diffuse low density had the episode of respiratory arrest in early infancy. In one patient (Case 3), several cavities in CT and PEG at 2 months of age were demonstrated, and changed into diffuse low density of cerebral hemispheres at 8 months. Case 4 showed almost normal CT at the age of 16 days and developed diffuse low density at 5 months. They also showed microcephaly, severe psychomotor retardation and tetraplegia. EEG showed irregular slow wave activities in 2 cases with multicystic lesions, and almost flat activities in 2 cases with diffuse cystic lesions. The former was compatible with MCEM and the latter hydranencephaly of postnatal onset described by Friede. It was concluded that diffuse cystic lesion could be classified as an extreme type of MCEM, and both destructive lesions caused by pre-or postnatal hypoxia and circulatory disturbances of different severity. Serial CT scans might demonstrate the onset and progression of these pathological changes. EEG was also useful for monitoring the courses of these diseases.

  16. Clinical observations of infants with multiple encephalomalacia on cranial computerized tomography

    International Nuclear Information System (INIS)

    Eda, Isematsu; Yoshino, Kunio; Nakai, Minako; Takashima, Sachio; Morita, Motoaki.

    1982-01-01

    Four cases whose CT scans showed multi-focal or diffuse low density in both cerebral hemisphere were reported and their clinical histories, roentogenographic and electroencephalographic findings were compared. Out of 2 cases with multi-focal low density, one fatal case (Case 1) was diagnosed neuropathologically as multicystic encephalomalacia (MCEM). He had asphyxia at delivery, convulsion and fever for a few days from the first day. Case 2 was one of twins with a clinical history of intrauterine onset. He had no trouble in delivery but poor feedings in the neonatal period. Two cases showed microcephaly, severe psychomotor retardation and tetraplegia later. Two cases with diffuse low density had the episode of respiratory arrest in early infancy. In one patient (Case 3), several cavities in CT and PEG at 2 months of age were demonstrated, and changed into diffuse low density of cerebral hemispheres at 8 months. Case 4 showed almost normal CT at the ag e of 16 days and developed diffuse low density at 5 months. They also showed microcephaly, severe psychomotor retardation and tetraplegia. EEG showed irregular slow wave activities in 2 cases with multicystic lesions, and almost flat activities in 2 cases with diffuse cystic lesions. The former was compatible with MCEM and the latter hydranencephaly of postnatal onset described by Friede. It was concluded that diffuse cystic lesion could be classified as an extreme type of MCEM, and both destructive lesions caused by pre-or postnatal hypoxia and circulatory disturbances of different severity. Serial CT scans might demonstrate the onset and progression of these pathological changes. EEG was also useful for monitoring the courses of these diseases. (author)

  17. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

    Directory of Open Access Journals (Sweden)

    M Shanmugam

    2015-01-01

    Full Text Available Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20-50 years contributed to 55 sites, each site falling into at least three adjacent Miller′s Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3 rd and 12 th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001 and increasing WKT (1.75 ± 0.78, P < 0.001 were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%. Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved.

  18. Clinical characteristics and survival of lung cancer patients associated with multiple primary malignancies.

    Directory of Open Access Journals (Sweden)

    Shan Shan

    Full Text Available To investigate the characteristics and survival of lung cancer patients with additional malignant primary cancers.Records of lung cancer patients newly diagnosed in Shanghai Pulmonary Hospital between January 2000 and January 2010 were retrospectively reviewed. Patients with second primary lung cancer and those with lung cancer only were included for detailed analysis.Of 27642 newly diagnosed lung cancer patients, 283 patients (1.02% suffered previous additional primary cancers. Compared with single primary lung cancer, patients with secondary lung cancer associated other primary cancers were more often women (female to male ratio 1:1.72 vs 1:2.58, P = 0.018, older (64.2 vs 60.5 years old, P<0.001, more squamous cell type (30.7% vs 20.5%, P = 0.004, less small cell (3.9% vs 15.5%, P<0.001 type, at earlier stages (17.7% vs 11.0% for stage I, P = 0.014, and more frequently with family history of cancers (7.8% vs 3.9%, P = 0.038. The most common previous primary cancers observed were colorectal (22.0%, breast (18.4%, gastric (14.4% and larynx cancers (11.9%. Approximately 42.9% of patients were diagnosed with lung cancer 2 to 6 years after diagnosis of initial primary cancers. The survival of patients with secondary lung cancer associated other malignancies was not significantly different from those with single lung cancer (P = 0.491, while synchronous multiple primary malignancies showed worse prognosis compared with those with metachronous ones or single lung cancer (p = 0.012.The possibility of second primary lung cancer should always be considered during the follow-up of related cancer types, especially those with family history of cancers. Patients with secondary lung cancer associated other primary malignancies have non-inferior survival than those with single lung cancer.

  19. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability

    Directory of Open Access Journals (Sweden)

    Antonio Giorgio

    2017-11-01

    Full Text Available Pediatric-onset multiple sclerosis (POMS may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15 in comparison with age- and disability-matched AOMS patients (n = 14 and to normal controls (NC, n = 20. We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space. POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

  20. The effect of time-of-day and chest physiotherapy on multiple breath washout measures in children with clinically stable cystic fibrosis

    DEFF Research Database (Denmark)

    Voldby, Christian; Green, Kent; Rosthøj, Susanne

    2018-01-01

    not previously been reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW measures. METHODS: Ten school children with cystic fibrosis performed N2MBW followed by spirometry and plethysmography in the morning and afternoon at three visits that were one month apart. Chest physiotherapy...... was performed immediately before the afternoon measurements at visit 2 and immediately before morning and afternoon measurements at visit 3. The influence of time-of-day and chest physiotherapy on the measures was evaluated using linear mixed models. RESULTS: There were adequate quality data from 8 children...... with median age (range) 9.6 (6.0; 15.1) years. Baseline lung clearance index (LCI) (range) was 9.0 (7.1; 13.0) and baseline FEV1% predicted was 97.5 (78.5; 117.9). No N2MBW measures were significantly influenced by time-of-day or chest physiotherapy. LCI (95% confidence interval) decreased non-significantly 0...

  1. Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes.

    Science.gov (United States)

    Arellano, Gabriel; Acuña, Eric; Reyes, Lilian I; Ottum, Payton A; De Sarno, Patrizia; Villarroel, Luis; Ciampi, Ethel; Uribe-San Martín, Reinaldo; Cárcamo, Claudia; Naves, Rodrigo

    2017-01-01

    Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) ( n  = 21), different clinical forms of MS ( n  = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) ( n  = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.

  2. Clinically isolated syndrome. Prognostic markers for conversion to multiple sclerosis and initiation of disease-modifying therapy

    International Nuclear Information System (INIS)

    Kohriyama, Tatsuo

    2011-01-01

    Eighty-five percent of patients with multiple sclerosis (MS) initially present with a single demyelinating event, referred to as a clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Following the onset of CIS, 38 to 68% of patients develop clinically definite MS (CDMS). Clinically silent brain lesions are seen on MRI in 50 to 80% of patients with CIS at first clinical presentation and 56 to 88% of CIS patients with abnormal MRI are at high risk of conversion to CDMS. Axonal damage, that is considered to underlie the development of persistent disability in MS, occurs in the CIS stage. Treatment with disease-modifying therapies (DMTs), that might prevent axonal damage and result in slowing the progression of disability, should be initiated early during the disease course. Clinical trials demonstrated that early treatment of CIS patients with the standard dose of interferon beta (IFNβ) significantly reduced the risk of progression to CDMS by 44 to 50%. After 5 years of follow-up, the results of the IFNβ treatment extension studies confirmed that the risk of conversion to CDMS was significantly reduced by 35 to 37% in patients receiving early treatment compared to that in those receiving delayed treatment. However, not every patient with CIS will progress to CDMS; the IFNβ treatment is appropriately indicated for CIS patients who are diagnosed with MS by McDonald diagnostic criteria based on MRI findings of dissemination in space and time and are at high risk for conversion to CDMS. Development of more reliable prognostic markers will enable DMTs to be targeted for those who are most likely to benefit. (author)

  3. Multiple Sclerosis in Older Adults: The Clinical Profile and Impact of Interferon Beta Treatment

    Directory of Open Access Journals (Sweden)

    Afsaneh Shirani

    2015-01-01

    Full Text Available Background. We examined (1 patient characteristics and disease-modifying drug (DMD exposure in late-onset (LOMS, ≥50 years at symptom onset versus adult-onset (AOMS, 18–<50 years MS and (2 the association between interferon-beta (IFNβ and disability progression in older relapsing-onset MS adults (≥50 years. Methods. This retrospective study (1980–2004, British Columbia, Canada included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90 were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses. Results. LOMS patients (6% were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18–1.22 or historical controls (HR: 0.54; 95% CI: 0.20–1.42 were considered. Conclusion. LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients.

  4. Clinical results of Intracoronary Brachytherapy (ICBT) for multiple in-stent restenosis

    International Nuclear Information System (INIS)

    Stadler, P.; Schaefer, C.; Chaber, S.; Putnik, K.; Treutwein, M.; Koelbl, O.; Muders, F.

    2006-01-01

    Background and purpose: treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. Patients and methods: 40 patients (27 male, 13 female, age: 66 ± 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste registered Beta-Cath trademark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. Results: the 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). Conclusion: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT. (orig.)

  5. Stable Isotope Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tissue samples (skin, bone, blood, muscle) are analyzed for stable carbon, stable nitrogen, and stable sulfur analysis. Many samples are used in their entirety for...

  6. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Science.gov (United States)

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  7. The recolonization hypothesis in a full-mouth or multiple-session treatment protocol: a blinded, randomized clinical trial.

    Science.gov (United States)

    Zijnge, Vincent; Meijer, Henriette F; Lie, Mady-Ann; Tromp, Jan A H; Degener, John E; Harmsen, Hermie J M; Abbas, Frank

    2010-06-01

    To test recolonization of periodontal lesions after full-mouth scaling and root planing (FM-SRP) or multiple session-SRP (MS-SRP) in a randomized clinical trial and whether FM-SRP and MS-SRP result in different clinical outcomes. Thirty-nine subjects were randomly assigned to FM-SRP or MS-SRP groups. At baseline and after 3 months, probing pocket depth (PPD), plaque index (PlI) and bleeding on probing (BoP) were recorded. At baseline, immediately after treatment, after 1, 2, 7, 14 and 90 days, paper point samples from a single site from the maxillary right quadrant were collected for microbiological analysis of five putative pathogens by polymerase chain reaction. FM-SRP and MS-SRP resulted in significant reductions in PPD, BoP and PlI and the overall detection frequencies of the five species after 3 months without significant differences between treatments. Compared with MS-SRP, FM-SRP resulted in less recolonization of the five species, significantly for Treponema denticola, in the tested sites. FM-SRP and MS-SRP result in overall clinically and microbiologically comparable outcomes where recolonization of periodontal lesions may be better prevented by FM-SRP.

  8. Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial

    DEFF Research Database (Denmark)

    Winkel, Per; Hilden, Jørgen; Hansen, Jørgen Fischer

    2015-01-01

    -cause mortality (hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease during 10years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI: 1.04-1.31, and HR: 1.25, 95% CI: 1...... death outside hospital and cerebrovascular morbidity in patients with stable coronary heart disease who were not on statin. The increased cardiovascular mortality was years later compensated, likely through frailty attrition.......BACKGROUND: The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease. This study investigates the effects of clarithromycin versus placebo during 10years follow up. METHODS: The CLARICOR trial is a randomised...

  9. Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives.

    Science.gov (United States)

    Roberts, Sa; McGowan, L; Hirst, Wm; Brison, Dr; Vail, A; Lieberman, Ba

    2010-07-01

    In vitro fertilisation (IVF) treatments involve an egg retrieval process, fertilisation and culture of the resultant embryos in the laboratory, and the transfer of embryos back to the mother over one or more transfer cycles. The first transfer is usually of fresh embryos and the remainder may be cryopreserved for future frozen cycles. Most commonly in UK practice two embryos are transferred (double embryo transfer, DET). IVF techniques have led to an increase in the number of multiple births, carrying an increased risk of maternal and infant morbidity. The UK Human Fertilisation and Embryology Authority (HFEA) has adopted a multiple birth minimisation strategy. One way of achieving this would be by increased use of single embryo transfer (SET). To collate cohort data from treatment centres and the HFEA; to develop predictive models for live birth and twinning probabilities from fresh and frozen embryo transfers and predict outcomes from treatment scenarios; to understand patients' perspectives and use the modelling results to investigate the acceptability of twin reduction policies. A multidisciplinary approach was adopted, combining statistical modelling with qualitative exploration of patients' perspectives: interviews were conducted with 27 couples at various stages of IVF treatment at both UK NHS and private clinics; datasets were collated of over 90,000 patients from the HFEA registry and nearly 9000 patients from five clinics, both over the period 2000-5; models were developed to determine live birth and twin outcomes and predict the outcomes of policies for selecting patients for SET or DET in the fresh cycle following egg retrieval and fertilisation, and the predictions were used in simulations of treatments; two focus groups were convened, one NHS and one web based on a patient organisation's website, to present the results of the statistical analyses and explore potential treatment policies. The statistical analysis revealed no characteristics that

  10. P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations.

    Science.gov (United States)

    Miller, Walter L

    2012-10-23

    Cytochrome P450 enzymes catalyze the biosynthesis of steroid hormones and metabolize drugs. There are seven human type I P450 enzymes in mitochondria and 50 type II enzymes in endoplasmic reticulum. Type II enzymes, including both drug-metabolizing and some steroidogenic enzymes, require electron donation from a two-flavin protein, P450 oxidoreductase (POR). Although knockout of the POR gene causes embryonic lethality in mice, we discovered human POR deficiency as a disorder of steroidogenesis associated with the Antley-Bixler skeletal malformation syndrome and found mild POR mutations in phenotypically normal adults with infertility. Assay results of mutant forms of POR using the traditional but nonphysiologic assay (reduction of cytochrome c) did not correlate with patient phenotypes; assays based on the 17,20 lyase activity of P450c17 (CYP17) correlated with clinical phenotypes. The POR sequence in 842 normal individuals revealed many polymorphisms; amino acid sequence variant A503V is encoded by ~28% of human alleles. POR A503V has about 60% of wild-type activity in assays with CYP17, CYP2D6, and CYP3A4, but nearly wild-type activity with P450c21, CYP1A2, and CYP2C19. Activity of a particular POR variant with one P450 enzyme will not predict its activity with another P450 enzyme: Each POR-P450 combination must be studied individually. Human POR transcription, initiated from an untranslated exon, is regulated by Smad3/4, thyroid receptors, and the transcription factor AP-2. A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism.

  11. Problems in clinical practice of domestic supply of 99Mo/99mTc. The direction and problem of stable supply chain of 99Mo in Japan

    International Nuclear Information System (INIS)

    Inoue, Tomio

    2013-01-01

    The shortage of supply of 99 Mo caused by trouble of old nuclear reactors in Canada and Europe caused international problem in the field of nuclear medicine, which has not been completely resolved yet. Because all of 99 Mo/ 99m Tc generator in Japan has been imported, Japan Atomic Energy Commission (JAEC) suggested the necessity of establishment of stable supply chain of 99 Mo ( 99 Mo/ 99m Tc generator). According this suggestion, an ad hoc committee appointed to consider the stable supply chain, which consisted of persons concerned with industry, academic society, Japan Isotope Association, Ministry of Education, Culture, Sports, Science, and Technology-Japan (MEXT), Ministry of Health, Labour and Welfare (MHLW), Japan Atomic Energy Agency (JAEA), National Institute of Radiological Science (NIRS) et al., evaluated and compared several ways of production and purification of 99 Mo from the view point of technological maturity, regulation compatibility, economic suitability, and stability for supply. In this review, the summary of the committee report is introduced. For short term strategy, we need to keep the variable import routes for 99 Mo. As a mid-term goal, we need to establish the supply chain inside Japan as a conclusion of the committee report but it seems to be not easy for utility of nuclear reactor after nuclear accident of Fukushima Daiichi Nuclear Power Plant. The development of the method for 99 Mo/ 99m Tc production using accelerator is also expected for the establishment of stable supply chain. (author)

  12. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe

    2015-01-01

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11......,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST......-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical...

  13. Measuring standing balance in multiple sclerosis: Further progress towards an automatic and reliable method in clinical practice.

    Science.gov (United States)

    Keune, Philipp M; Young, William R; Paraskevopoulos, Ioannis T; Hansen, Sascha; Muenssinger, Jana; Oschmann, Patrick; Müller, Roy

    2017-08-15

    Balance deficits in multiple sclerosis (MS) are often monitored by means of observer-rated tests. These may provide reliable data, but may also be time-consuming, subject to inter-rater variability, and potentially insensitive to mild fluctuations throughout the clinical course. On the other hand, laboratory assessments are often not available. The Nintendo Wii Balance Board (WBB) may represent a low-cost solution. The purpose of the current study was to examine the methodological quality of WBB data in MS (internal consistency, test-retest reliability), convergent validity with observer-rated tests (Berg Balance Scale, BBS; Timed-Up and Go Test, TUG), and discriminative validity concerning clinical status (Expanded Disability Status Scale, EDSS). Standing balance was assessed with the WBB for 4min in 63 MS patients at two assessment points, four months apart. Additionally, patients were examined with the BBS, TUG and the EDSS. A period of 4min on the WBB provided data characterized by excellent internal consistency and test-retest reliability. Significant correlations between WBB data and results of the BBS and TUG were obtained after merely 2min on the board. An EDSS median-split revealed that higher EDSS values (>3) were associated with significantly increased postural sway on the WBB. WBB measures reflecting postural sway are methodologically robust in MS, involving excellent internal consistency and test-retest reliability. They are also characterized by convergent validity with other considerably lengthier observer-rated balance measures (BBS) and sensitive to broader clinical characteristics (EDSS). The WBB may hence represent an effective, easy-to-use monitoring tool for MS patients in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe

    DEFF Research Database (Denmark)

    Link, Jenny; Ramanujam, Ryan; Auer, Michael

    2017-01-01

    Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta...... positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years...

  15. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  16. IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

    Science.gov (United States)

    Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

    2015-09-01

    IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Optimization of the clinical course of stable angina pectoris with the use of omega-3 polyunsaturated fatty acids and combined magnetotherapy

    Directory of Open Access Journals (Sweden)

    K. O. Zolotarova

    2016-12-01

    Full Text Available The article presents the results of the study of the comparative efficacy of the protocol for angina pectoris medication and combined therapy with the use of ω-3 PUFA and magnetotherapy on the dynamics of the frequency of anginal attacks of patients with stable angina. It was found that the use of ώ-3 PUFA and MT in therapy allows a significantly higher and further reduction in the frequency of attacks compared with standard therapy, and this effect is largely due to the influence of MT and to a lesser extent - the effect of omega-3 polyunsaturated fatty acids.

  18. Reliability and equivalence of alternate forms for the Symbol Digit Modalities Test: implications for multiple sclerosis clinical trials.

    Science.gov (United States)

    Benedict, Ralph H B; Smerbeck, Audrey; Parikh, Rajavi; Rodgers, Jonathan; Cadavid, Diego; Erlanger, David

    2012-09-01

    Cognitive impairment is common in multiple sclerosis (MS), but is seldom assessed in clinical trials investigating the effects of disease-modifying therapies. The Symbol Digit Modalities Test (SDMT) is a particularly promising tool due to its sensitivity and robust correlation with brain magnetic resonance imaging (MRI) and vocational disability. Unfortunately, there are no validated alternate SDMT forms, which are needed to mitigate practice effects. The aim of the study was to assess the reliability and equivalence of SDMT alternate forms. Twenty-five healthy participants completed each of five alternate versions of the SDMT - the standard form, two versions from the Rao Brief Repeatable Battery, and two forms specifically designed for this study. Order effects were controlled using a Latin-square research design. All five versions of the SDMT produced mean values within 3 raw score points of one another. Three forms were very consistent, and not different by conservative statistical tests. The SDMT test-retest reliability using these forms was good to excellent, with all r values exceeding 0.80. For the first time, we find good evidence that at least three alternate versions of the SDMT are of equivalent difficulty in healthy adults. The forms are reliable, and can be implemented in clinical trials emphasizing cognitive outcomes.

  19. The co-occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology.

    Science.gov (United States)

    Tettey, Prudence; Simpson, Steve; Taylor, Bruce V; van der Mei, Ingrid A F

    2015-01-15

    We reviewed the evidence for the co-occurrence of type 1 diabetes mellitus (T1D) and multiple sclerosis (MS), and assessed the clinical significance of this association and the shared aetiological features of the two diseases. T1D and MS contribute considerably to the burden of autoimmune diseases in young adults. The co-occurrence of MS and T1D has been reported by a number of studies, suggesting that the two conditions share one or more aetiological components. Both conditions have been associated with distinct human leukocyte antigen (HLA) haplotypes but share a number of similarities in clinical, epidemiological and immunological features, leading to suggestions of possible common mechanisms of development. While underlying genetic factors may be important for the co-occurrence of both conditions, some evidence suggests that environmental factors such as vitamin D deficiency may also modulate an individual's risk for the development of both conditions. Evidence on whether the co-occurrence of the two autoimmune conditions will affect the disease course and severity of MS is merely absent. Further studies need to be conducted to ascertain whether the neuropathology associated with T1D might influence the disease course and contribute to the severity of MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Two approaches to incorporate clinical data uncertainty into multiple criteria decision analysis for benefit-risk assessment of medicinal products.

    Science.gov (United States)

    Wen, Shihua; Zhang, Lanju; Yang, Bo

    2014-07-01

    The Problem formulation, Objectives, Alternatives, Consequences, Trade-offs, Uncertainties, Risk attitude, and Linked decisions (PrOACT-URL) framework and multiple criteria decision analysis (MCDA) have been recommended by the European Medicines Agency for structured benefit-risk assessment of medicinal products undergoing regulatory review. The objective of this article was to provide solutions to incorporate the uncertainty from clinical data into the MCDA model when evaluating the overall benefit-risk profiles among different treatment options. Two statistical approaches, the δ-method approach and the Monte-Carlo approach, were proposed to construct the confidence interval of the overall benefit-risk score from the MCDA model as well as other probabilistic measures for comparing the benefit-risk profiles between treatment options. Both approaches can incorporate the correlation structure between clinical parameters (criteria) in the MCDA model and are straightforward to implement. The two proposed approaches were applied to a case study to evaluate the benefit-risk profile of an add-on therapy for rheumatoid arthritis (drug X) relative to placebo. It demonstrated a straightforward way to quantify the impact of the uncertainty from clinical data to the benefit-risk assessment and enabled statistical inference on evaluating the overall benefit-risk profiles among different treatment options. The δ-method approach provides a closed form to quantify the variability of the overall benefit-risk score in the MCDA model, whereas the Monte-Carlo approach is more computationally intensive but can yield its true sampling distribution for statistical inference. The obtained confidence intervals and other probabilistic measures from the two approaches enhance the benefit-risk decision making of medicinal products. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. Early Characterization of the Severity and Transmissibility of Pandemic Influenza Using Clinical Episode Data from Multiple Populations.

    Directory of Open Access Journals (Sweden)

    Pete Riley

    2015-09-01

    Full Text Available The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0 and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics.

  2. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

    Directory of Open Access Journals (Sweden)

    Gabriel Bsteh

    Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

  3. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

    Science.gov (United States)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe; Aquino, Melissa; Stone, Gregg W; Sartori, Samantha; Steg, Philippe Gabriel; Wijns, William; Smits, Pieter C; Jeger, Raban V; Leon, Martin B; Windecker, Stephan; Serruys, Patrick W; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Kandzari, David; Dangas, George D; Mastoris, Ioannis; Von Birgelen, Clemens; Galatius, Soren; Kimura, Takeshi; Mikhail, Ghada; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Valgimigli, Marco; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

    2015-09-15

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women. Published by Elsevier Inc.

  4. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  5. A new T2 lesion in a patient with the clinically isolated syndrome does not necessarily imply a conversion to multiple sclerosis.

    Science.gov (United States)

    Capone, Fioravante; Puthenparampil, Marco; Mallio, Carlo Augusto; Celia, Alessandra Ida; Florio, Lucia; Gallo, Paolo; Di Lazzaro, Vincenzo

    2018-01-01

    In the follow-up of patients with the clinically isolated syndrome, both clinical and MRI findings should be carefully evaluated by clinicians to avoid misinterpretation and inappropriate diagnosis of multiple sclerosis. We describe a case of a patient with a previous diagnosis of clinically isolated syndrome who developed a new asymptomatic brain lesion at the MRI follow-up. The careful evaluation of clinical history and radiological findings allowed the correct diagnosis of cocaine-associated ischemic stroke. Our case highlights that, in patients with the clinically isolated syndrome, the appearance of a new lesion on MRI does not necessarily imply a conversion to multiple sclerosis. Among "better explanations", ischemic lesions are of relevance and, in patients without typical risk factors for stroke, rarer causes such as cocaine assumption should be considered. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Long-term follow-up in optimally treated and stable heart failure patients: primary care vs. heart failure clinic. Results of the COACH-2 study.

    Science.gov (United States)

    Luttik, Marie Louise A; Jaarsma, Tiny; van Geel, Peter Paul; Brons, Maaike; Hillege, Hans L; Hoes, Arno W; de Jong, Richard; Linssen, Gerard; Lok, Dirk J A; Berge, Marjolein; van Veldhuisen, Dirk J

    2014-11-01

    It has been suggested that home-based heart failure (HF) management in primary care may be an alternative to clinic-based management in HF patients. However, little is known about adherence to HF guidelines and adherence to the medication regimen in these home-based programmes. The aim of the current study was to determine whether long-term follow-up and treatment in primary care is equally effective as follow-up at a specialized HF clinic in terms of guideline adherence and patient adherence, in HF patients initially managed and up-titrated to optimal treatment at a specialized HF clinic. We conducted a multicentre, randomized, controlled study in 189 HF patients (62% male, age 72 ± 11 years), who were assigned to follow-up either in primary care (n = 97) or in a HF clinic (n = 92). After 12 months, no differences between guideline adherence, as estimated by the Guideline Adherence Indicator (GAI-3), and patient adherence, in terms of the medication possession ratio (MPR), were found between treatment groups. There was no difference in the number of deaths (n = 12 in primary care and n = 8 in the HF clinic; P = 0.48), and hospital readmissions for cardiovascular (CV) reasons were also similar. The total number of unplanned non-CV hospital readmissions, however, tended to be higher in the primary care group (n = 22) than in the HF clinic group (n = 10; P = 0.05). Patients discharged after initial management in a specialized HF clinic can be discharged to primary care for long-term follow-up with regard to maintaining guideline adherence and patient adherence. However, the complexity of the HF syndrome and its associated co-morbidities requires continuous monitoring. Close collaboration between healthcare providers will be crucial in order to provide HF patients with optimal, integrated care. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

  7. Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study

    Directory of Open Access Journals (Sweden)

    Nasim Tabrizi

    2012-01-01

    Full Text Available Background: The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Materials and Methods: Forty patients with aggressive relapsing remitting MS were randomly put into two groups. The first group underwent monthly plasma exchange for three successive months, followed by 12 mg/m 2 mitoxantrone at the end of each course and two more doses of 6 mg/m 2 mitoxantrone in 3-month intervals. The second group received the same doses of mitoxantrone only without plasma exchange. At the end of 8 months treatment course, clinical reassessment and neuroimaging was performed and treatment was continued with interferon-β. Results: At the end of induction therapy, Expanded Disability Status Scale score was significantly improved in both groups (P < 0.001. Number of demyelinating and gadolinium-enhancing plaques in brain magnetic resonance imaging (MRI was prominently reduced in group 2 (P ≤ 0.05, but the changes were not statistically significant in group 1, except for juxtacortical plaques. Conclusion: Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.

  8. Treatment of periodontitis in smokers with multiple sessions of antimicrobial photodynamic therapy or systemic antibiotics: A randomized clinical trial.

    Science.gov (United States)

    Theodoro, Letícia Helena; Assem, Naida Zanini; Longo, Mariéllen; Alves, Márcio Luiz Ferro; Duque, Cristiane; Stipp, Rafael Nobrega; Vizoto, Natália Leal; Garcia, Valdir Gouveia

    2018-06-01

    The aim of this study was to evaluate the effects of non-surgical periodontal therapies on smokers with chronic periodontitis, involving multiple adjunctive applications of antimicrobial photodynamic therapy (aPDT), and systemic metronidazole (MTZ) with amoxicillin (AMX). All participants were treated with scaling and root planing (SRP). Seventeen patients received 400 mg of MTZ and 500 mg of AMX three times per day for 7 days (MTZ + AMX). Additionally, 17 patients received a placebo, and 17 patients were treated with three applications of aPDT (immediately, 48 h and 96 h after SRP). Clinical and microbiological examinations were performed at baseline and at 90 and 180 days post-therapy. Subgingival samples were analyzed using real-time polymerase chain reaction. After 180 days, the patients in groups MTZ + AMX and aPDT had significantly lower mean probing depths, more clinical attachment level gains and less bleeding on probing. At 180 days, in the moderate pocket there was a reduction in the levels of Porphyromonas gingivalis and Prevotella nigrescens in the MTZ + AMX group, while group aPDT showed a reduction in Prevotella nigrescens. Furthermore, at 180 days, in the deep pocket a reduction in Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens was observed in group MTZ + AMX, as well as a reduction in the levels of Prevotella intermedia and Prevotella nigrescens in group aPDT. In smokers with periodontitis, the MTZ + AMX and aPDT treatments significantly improved the effects of SRP. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Long-term follow-up in optimally treated and stable heart failure patients : primary care vs. heart failure clinic. Results of the COACH-2 study

    NARCIS (Netherlands)

    Luttik, Marie Louise A.; Jaarsma, Tiny; van Geel, Peter Paul; Brons, Maaike; Hillege, Hans L.; Hoes, Arno W.; de Jong, Richard; Linssen, Gerard; Lok, Dirk J. A.; Berger, Marjolein; van Veldhuisen, Dirk J.

    2014-01-01

    AimsIt has been suggested that home-based heart failure (HF) management in primary care may be an alternative to clinic-based management in HF patients. However, little is known about adherence to HF guidelines and adherence to the medication regimen in these home-based programmes. The aim of the

  10. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  11. Angina Pectoris (Stable Angina)

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Angina Pectoris (Stable Angina) Updated:Aug 21,2017 You may have heard the term “angina pectoris” or “stable angina” in your doctor’s office, ...

  12. [Local ice application in therapy of kinetic limb ataxia. Clinical assessment of positive treatment effects in patients with multiple sclerosis].

    Science.gov (United States)

    Albrecht, H; Schwecht, M; Pöllmann, W; Parag, D; Erasmus, L P; König, N

    1998-12-01

    Upper limb ataxia is one of the most disabling symptoms of patients with multiple sclerosis (MS). There are some clinically tested therapeutic strategies, especially with regard to cerebellar tremor. But most of the methods used for treatment of limb ataxia in physiotherapy and occupational therapy are not systematically evaluated, e.g. the effect of local ice applications, as reported by MS patients and therapists, respectively. We investigated 21 MS patients before and in several steps 1 up to 45 min after cooling the most affected forearm. We used a series of 6 tests, including parts of neurological status and activities of daily living as well. At each step skin temperature and nerve conduction velocity were recorded. All tests were documented by video for later offline analysis. Standardized evaluation was done by the investigators and separately by an independent second team, both of them using numeric scales for quality of performance. After local cooling all patients showed a positive effect, especially a reduction of intentional tremor. In most cases this effect lasted 45 min, in some patients even longer. We presume that a decrease in the proprioceptive afferent inflow-induced by cooling-may be the probable cause of this reduction of cerebellar tremor. Patients can use ice applications as a method of treating themselves when a short-time reduction of intention tremor is required, e.g. for typing, signing or self-catheterization.

  13. Different types of exercise in Multiple Sclerosis: Aerobic exercise or Pilates, a single-blind clinical study.

    Science.gov (United States)

    Kara, Bilge; Küçük, Fadime; Poyraz, Esra Coşkuner; Tomruk, Melda Soysal; İdıman, Egemen

    2017-01-01

    The aim of our study is to examine effects of aerobic and Pilates exercises on disability, cognition, physical performance, balance, depression and fatigue in relapsing-remitting Multiple Sclerosis (MS) patients as compared to healthy controls. The subjects were divided as aerobic exercise (n = 26), Pilates (n = 9), and the healthy control group (n = 21). We used MSFC, physical performance, Berg balance scale, Beck depression scale, fatigue impact scale. All evaluations were performed before and after exercise training. There are statistically meaningful differences between Nine hole testing, PASAT 3, physical performance and fatique impact scale before and after aerobic exercise. Also we found significant difference for physical performance in the Pilates group. There are no significant differences in measures of fatique impact scale and depression between aerobic exercise group and the healthy controls after exercise. We found significant differences between Pilates and control group's after measurements except depression. There were significant differences between the Pilates and aerobic group for cognitive tests in favor of the Pilates group. Aerobic exercise and clinical Pilates exercises revealed moderate changes in levels of cognitive, physical performance, balance, depression, fatigue in MS patients.

  14. Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

    Science.gov (United States)

    Tortorella, C; Romano, R; Direnzo, V; Taurisano, P; Zoccolella, S; Iaffaldano, P; Fazio, L; Viterbo, R; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

    2013-08-01

    Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

  15. Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

    Science.gov (United States)

    Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

    2017-09-01

    Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Scientific and industrial challenges of developing nanoparticle-based theranostics and multiple-modality contrast agents for clinical application

    Science.gov (United States)

    Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire

    2015-10-01

    Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

  17. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

    Directory of Open Access Journals (Sweden)

    Peter Joseph Jongen

    2015-01-01

    Full Text Available In persons with multiple sclerosis (MS a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS and early Relapsing Remitting MS (eRRMS were assessed for self-efficacy (MSSES-18, cognition (CDR System, fatigue (MFIS-5, depressive symptoms (BDI, disease impact (MSIS-29, and disability (EDSS. Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001, Reaction Time Variability (r= 0.57; P< 0.001, and Speed of Memory (r= 0.53; P< 0.01, and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01. Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy.

  18. Immunological and Clinical Effect of Diet Modulation of the Gut Microbiome in Multiple Sclerosis Patients: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Marina Saresella

    2017-10-01

    Full Text Available Pathogenesis of autoimmune disorders, including multiple sclerosis (MS, has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10 or a “Western Diet” (WD group; N = 10 for at least 12 months. Gut microbiota composition, analyzed by 16 S V4 rRNA gene sequencing and immunological profiles, was examined after a minimum of 12 months of diet. Results showed that, in the HV/LP diet group compared to the WD group: (1 Lachnospiraceae family was significantly more abundant; (2 IL-17-producing T CD4+ lymphocytes (p = 0.04 and PD-1 expressing T CD4+ lymphocytes (p = 0.0004 were significantly decreased; and (3 PD-L1 expressing monocytes (p = 0.009 were significantly increased. In the HV/LP diet group, positive correlations between Lachnospiraceae and both CD14+/IL-10+ and CD14+/TGFβ+monocytes (RSp = 0.707, p = 0.05, and RSp = 0.73, p = 0.04, respectively, as well as between Lachnospiraceae and CD4+/CD25+/FoxP3+ T lymphocytes (RSp = 0.68, p = 0.02 were observed. Evaluation of clinical parameters showed that in the HV/LP diet group alone the relapse rate during the 12 months follow-up period and the Expanded Disability Status Scale score at the end of the study period were significantly reduced. Diet modulates dysbiosis and improves clinical parameters in MS patients by increasing anti-inflammatory circuits. Because Lachnospiraceae favor Treg differentiation as well as TGFβ and IL-10 production this effect could be associated

  19. Enzyme-mediated formulation of stable elliptical silver nanoparticles tested against clinical pathogens and MDR bacteria and development of antimicrobial surgical thread.

    Science.gov (United States)

    Thapa, Rupak; Bhagat, Chintan; Shrestha, Pragya; Awal, Suvash; Dudhagara, Pravin

    2017-05-16

    Silver nanoparticles (AgNPs) are believed to be emerging tool against various infectious diseases including multi-drug resistant (MDR) bacteria. In the present study, in vitro synthesis of AgNPs was optimized using 1:50 ratio of macerozyme (25 μg/μl) and 1 mM AgNO 3 incubated at 80 °C for 8 h. AgNPs were characterized by UV-Visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction (XRD). Characterization studies suggest the synthesis of elliptical, stable and crystalline AgNPs with an average size of 38.26 ± 0.4 nm calculated using TEM. The XRD pattern revealed the face-centered-cubic (fcc) form of metallic silver. Good shape integrity and dispersion of AgNPs after 1 year of incubation confirmed their stability. AgNPs were exibited the antimicrobial property against ten pathogenic bacteria, three molds and one yeast. The AgNPs also revealed remarkable antimicrobial activity against three MDR strains i.e. Extended spectrum beta-lactamase positive Escherichia coli, Staphylococcus aureus (MRSA) and Teicoplanin resistant Streptococcus Pneumoniae. The AgNPs coated surgical threads (suture) were revealed the remarkble antibacterial activity against three MDR strains. This is the first report to synthesize antimicrobial elliptical AgNPs using enzymes. The results suggest the possibilities to develop the nanoparticles coated antimicrobial medical fabric to combat against MDR infection.

  20. Design and validation of realistic breast models for use in multiple alternative forced choice virtual clinical trials.

    Science.gov (United States)

    Elangovan, Premkumar; Mackenzie, Alistair; Dance, David R; Young, Kenneth C; Cooke, Victoria; Wilkinson, Louise; Given-Wilson, Rosalind M; Wallis, Matthew G; Wells, Kevin

    2017-04-07

    A novel method has been developed for generating quasi-realistic voxel phantoms which simulate the compressed breast in mammography and digital breast tomosynthesis (DBT). The models are suitable for use in virtual clinical trials requiring realistic anatomy which use the multiple alternative forced choice (AFC) paradigm and patches from the complete breast image. The breast models are produced by extracting features of breast tissue components from DBT clinical images including skin, adipose and fibro-glandular tissue, blood vessels and Cooper's ligaments. A range of different breast models can then be generated by combining these components. Visual realism was validated using a receiver operating characteristic (ROC) study of patches from simulated images calculated using the breast models and from real patient images. Quantitative analysis was undertaken using fractal dimension and power spectrum analysis. The average areas under the ROC curves for 2D and DBT images were 0.51  ±  0.06 and 0.54  ±  0.09 demonstrating that simulated and real images were statistically indistinguishable by expert breast readers (7 observers); errors represented as one standard error of the mean. The average fractal dimensions (2D, DBT) for real and simulated images were (2.72  ±  0.01, 2.75  ±  0.01) and (2.77  ±  0.03, 2.82  ±  0.04) respectively; errors represented as one standard error of the mean. Excellent agreement was found between power spectrum curves of real and simulated images, with average β values (2D, DBT) of (3.10  ±  0.17, 3.21  ±  0.11) and (3.01  ±  0.32, 3.19  ±  0.07) respectively; errors represented as one standard error of the mean. These results demonstrate that radiological images of these breast models realistically represent the complexity of real breast structures and can be used to simulate patches from mammograms and DBT images that are indistinguishable from

  1. Overall survival patterns in patients with multiple myeloma in the era of novel agents and the role of initial clinical presentation and comorbidities: A population-based study

    NARCIS (Netherlands)

    Oortgiesen, Berdien; Van Roon, Eric N.; Joosten, Peter; Kibbelaar, Robby; Storm, Huib; Hovenga, Sjoerd; Van Rees, Bas P.; Woolthuis, Gerhard; Veeger, Nic J. G. M.; Hoogendoorn, Mels

    2014-01-01

    Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting

  2. An exploratory trial exploring the use of a multiple intelligences teaching approach (MITA) for teaching clinical skills to first year undergraduate nursing students.

    Science.gov (United States)

    Sheahan, Linda; While, Alison; Bloomfield, Jacqueline

    2015-12-01

    The teaching and learning of clinical skills is a key component of nurse education programmes. The clinical competency of pre-registration nursing students has raised questions about the proficiency of teaching strategies for clinical skill acquisition within pre-registration education. This study aimed to test the effectiveness of teaching clinical skills using a multiple intelligences teaching approach (MITA) compared with the conventional teaching approach. A randomised controlled trial was conducted. Participants were randomly allocated to an experimental group (MITA intervention) (n=46) and a control group (conventional teaching) (n=44) to learn clinical skills. Setting was in one Irish third-level educational institution. Participants were all first year nursing students (n=90) in one institution. The experimental group was taught using MITA delivered by the researcher while the control group was taught by a team of six experienced lecturers. Participant preference for learning was measured by the Index of Learning Styles (ILS). Participants' multiple intelligence (MI) preferences were measured with a multiple intelligences development assessment scale (MIDAS). All participants were assessed using the same objective structured clinical examination (OSCE) at the end of semester one and semester two. MI assessment preferences were measured by a multiple intelligences assessment preferences questionnaire. The MITA intervention was evaluated using a questionnaire. The strongest preference on ILS for both groups was the sensing style. The highest MI was interpersonal intelligence. Participants in the experimental group had higher scores in all three OSCEs (pmultiple choice questions as methods of assessment. MITA was evaluated positively. The study findings support the use of MITA for clinical skills teaching and advance the understanding of how MI teaching approaches may be used in nursing education. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Clinical usefulness of serum free light chains measurement in patients with multiple myeloma: comparative analysis of two different tests

    Directory of Open Access Journals (Sweden)

    Tadeusz Kubicki

    2017-01-01

    Full Text Available Introduction: There are two commercially available tests for measurement of serum free light chains (sFLC in multiple myeloma (MM patients – Freelite and N Latex FLC. The aim of this study was to perform an assessment and direct comparison of the usefulness of the methods in routine clinical practice.Methods: 40 refractory/relapsed MM patients underwent routine disease activity assessment studies, along with sFLC analysis using both assays. Correlation and concordance between the tests and sensitivity of studied methods of sFLC assessment were established. Special attention was focused on sFLC results in patients finally evaluated after completing the treatment. Results: A weak correlation for the measurement of both κ [Passing–Bablok slope (PB = 0.7681] and λ chains [(PB = 1.542] was found. Using Bland–Altman plots, a bias of 0.0467 (κ and -0.2133 (λ between the measurements was documented. The concordance coefficient equaled 0.87 for κ, 0.62 for λ and 0.52 for κ/λ ratio. Ten patients had an abnormal Freelite assay κ/λ ratio and normal N Latex FLC κ/λ ratio. Three of these patients had negative serum protein electrophoresis results and fulfilled diagnostic criteria of stringent complete remission (sCR according to N Latex FLC (but not according to Freelite. When the κ/λ ratio obtained by both methods was compared to patients’ serum/urine protein electrophoresis and immunofixation results, sensitivity of Freelite and N Latex FLC was established to be 62.5% and 41%, respectively. Conclusions: There was no strong correlation or concordance between the two assays, and the sensitivity in terms of sFLC detection was different. This may cause problems when diagnosis of sCR is considered.

  4. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

  5. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2012-05-01

    Full Text Available Brendon J Coventry, Martin L AshdownDiscipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, AustraliaAbstract: Over 50 years of cancer therapy history reveals complete clinical responses (CRs from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained?Over some 20 years, realization that (1 chronic inflammation is intricately associated with cancer, and (2 the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of "final common pathways" of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This "missing" aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer

  6. Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

    Science.gov (United States)

    Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

    2016-04-15

    To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Diet-tissue stable isotope (delta¹³C and delta¹⁵N) discrimination factors for multiple tissues from terrestrial reptiles (rock iguanas, Cyclura species)

    OpenAIRE

    Steinitz, Ronnie

    2015-01-01

    Trophic interactions can drive community structure; therefore, studying food webs is key in understanding ecological communities. Stable isotope analysis is a powerful tool for reconstructing foraging patterns. However, stable isotope discrimination factors (delta¹³C and delta¹⁵N) are needed to best use this tool. We determined the first delta¹³C and delta¹⁵N values for Rock Iguanas (Cyclura spp.) to better understand isotope fractionation patterns in reptiles and estimate wild reptile diets....

  8. Microwave Accelerated Green Synthesis of Stable Silver Nanoparticles with Eucalyptus globulus Leaf Extract and Their Antibacterial and Antibiofilm Activity on Clinical Isolates.

    Directory of Open Access Journals (Sweden)

    Khursheed Ali

    Full Text Available A simple and rapid microwave assisted method of green synthesis of silver nanoparticles (AgNPs was developed using aqueous leaf extract of Eucalyptus globulus(ELE, and their antibacterial and antibiofilm potential investigated. With this aim, the aqueous solutions of ELE and AgNO3(1 mM were mixed (1:4 v/v, and microwave irradiated at 2450 Mhz, for 30 sec. The instant color change of the ELE-AgNO3 mixture from pale yellow to dark brown indicated ELE-AgNPs synthesis. The intensity of peak at 428 nm in UV-Vis spectra, due to the surface plasmon resonance of AgNPs, varied with the amount of ELE, AgNO3 concentration, pH and time of incubation. The biosynthesized ELE-AgNPs were characterized by UV-visible spectroscopy, XRD, TEM, SEM-EDX, FTIR and TGA analyses. The size of ELE-AgNPs was determined to be in range of 1.9-4.3 nm and 5-25 nm, with and without microwave treatment, respectively. SEM exhibited the capping of AgNPs with the ELE constituents, and validated by FTIR analysis. The FTIR data revealed the presence of plant organic constituents and metabolites bound to ELE-AgNPs, which contributes for their stability. The antimicrobial activity of ELE-AgNPs was assessed by growth and biofilm inhibition of extended spectrum β-lactamase (ESBL producing Pseudomonas aeruginosa, Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA and methicillin-sensitive Staphylococcus aureus (MSSA clinical bacterial isolates. The results demonstrated that S. aureus were more sensitive to ELE-AgNPs than E. coli and P. aeruginosa. MRSA exhibited higher sensitive than MSSA, whereas P. aeruginosa were more sensitive than E. coli to ELE-AgNPs treatment. Also, significant (83 ± 3% and 84 ± 5% biofilm inhibition was observed in case of S. aureus and P. aeruginosa, respectively. The results elucidated environmentally friendly, economical and quick method for production of colloidal bio-functionalized ELE-AgNPs, for effectual clinical applications, as broad

  9. Longitudinal erythronychia: individual or multiple linear red bands of the nail plate: a review of clinical features and associated conditions.

    Science.gov (United States)

    Cohen, Philip R

    2011-08-01

    Longitudinal erythronychia is a linear red band on the nail plate that originates at the proximal nail fold, traverses the lunula, and extends to the free edge of the nail plate. Longitudinal erythronychia is classified based upon the number of nails affected and the number of red streaks present on each nail as follows: type Ia (monodactylous - single band), type Ib (monodactylous - bifid bands), type IIa (polydactylous - single band), and type IIb (polydactylous - multiple bands). Associated morphologic findings that can be present at the distal tip of the nail with longitudinal erythronychia include fragility, onycholysis, splinter hemorrhage, splitting, subungual keratosis, thinning, and V-shaped nick. Some patients with longitudinal erythronychia seek medical evaluation because of pain in the associated distal digit; however, the linear red nail plate dyschromia is often asymptomatic and the individual is concerned about the cosmetic appearance or distal nail fragility. Longitudinal erythronychia can be a clinical manifestation of an underlying local or systemic condition. Benign tumors (glomus tumor, onychopapilloma, and warty dyskeratoma), malignant neoplasms (malignant melanoma and squamous cell carcinoma), and other conditions (hemiplegia and postsurgical scar) can be associated with monodactylous longitudinal erythronychia or it may be idiopathic or the initial stage of polydactylous longitudinal erythronychia-associated systemic conditions. Polydactylous longitudinal erythronychia is most commonly reported in patients with Darier disease (keratosis follicularis); other associated conditions include acantholytic dyskeratotic epidermal nevus, acantholytic epidermolysis bullosa, acrokeratosis verruciformis of Hopf, amyloidosis, graft-versus-host disease, lichen planus, and pseudobulbar syndrome. Polydactylous longitudinal erythronychia has also been observed as an idiopathic finding. Biopsy of the nail matrix and nail bed may be necessary to establish the

  10. Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Obradović Dragana

    2012-01-01

    Full Text Available Background/Aim. Multiple sclerosis (MS is an immunemediated central nervous system disease characterized by inflammation, demyelination and axonal degeneration. Cytokines are proven mediators of immunological process in MS. The aim of this study was to investigate whether there is a difference in the production of the tumor necrosis factor alpha (TNF-alpha and interleukin-4 (IL-4 in cerebrospinal fluid (CSF and plasma in the MS patients and the controls (other neurological non-inflammatory diseases and to determine a possible difference in these cytokines in plasma and CSF in different clinical forms of MS. Methods. This study involved 60 consecutive MS patients - 48 patients with relapsing-remitting MS (RRMS and 12 patients with secondary progressive MS (SPMS. The control group consisted of 20, age and sex matched, nonimmunological, neurological patients. According to the clinical presentation of MS at the time of this investigation, 34 (56.7% patients had relapse (RRMS, 14 (23.3% were in remission (RRMS, while the rest of the patients, 12 (20.0%, were SPMS. TNF-alpha and IL-4 concentrations were measured in the same time in CSF and plasma in the MS patients and the controls. Extended disability status score (EDSS, albumin ratio and IgG index were determined in all MS patients. Results. The MS patients had significantly higher CSF and plasma levels of TNF-alpha than the controls (p < 0.001 for both samples. IL-4 CSF levels were significantly lower in the MS patients than in the controls (p < 0.001, however plasma levels were similar. The patients in relapse (RRMS and with progressive disease (SPMS had higher concentrations of CSF TNF-alpha levels than the patients in remission (p < 0.001. IL-4 CSF levels in relapse (RRMS and SPMS groups were lower than in the patients in remission. The patients in remission had an unmeasurable plasma TNF-alpha level and the patients with SPMS had significantly lower IL-4 levels in plasma than the patients in

  11. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  12. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General Article Volume 21 Issue 9 September 2016 pp 803- ... Keywords. Evolutionary game theory, evolutionary stable state, conflict, cooperation, biological games.

  13. Stable Boundary Layer Issues

    NARCIS (Netherlands)

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The

  14. Insights on Genomic and Molecular Alterations in Multiple Myeloma and Their Incorporation towards Risk-Adapted Treatment Strategy: Concise Clinical Review

    Directory of Open Access Journals (Sweden)

    Taiga Nishihori

    2017-01-01

    Full Text Available Although recent advances in novel treatment approaches and therapeutics have shifted the treatment landscape of multiple myeloma, it remains an incurable plasma cell malignancy. Growing knowledge of the genome and expressed genomic information characterizing the biologic behavior of multiple myeloma continues to accumulate. However, translation and incorporation of vast molecular understanding of complex tumor biology to deliver personalized and precision treatment to cure multiple myeloma have not been successful to date. Our review focuses on current evidence and understanding of myeloma biology with characterization in the context of genomic and molecular alterations. We also discuss future clinical application of the genomic and molecular knowledge, and more translational research is needed to benefit our myeloma patients.

  15. Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign

    Directory of Open Access Journals (Sweden)

    A. Herrero-Ruiz

    2017-01-01

    Full Text Available We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1. DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

  16. Intrathecal IgM index correlates with a severe disease course in multiple sclerosis: Clinical and MRI results.

    Science.gov (United States)

    Ozakbas, Serkan; Cinar, Bilge Piri; Özcelik, Pinar; Baser, Hatice; Kosehasanoğullari, Gorkem

    2017-09-01

    Intrathecally synthesized IgM can be seen not only in the cerebrospinal fluid (CSF) in infectious and inflammatory diseases of the central nervous system, but also in that of patients with multiple sclerosis (MS). Intrathecal IgM synthesis in MS seems to be correlated with an unfavorable disease course. In one cross-sectional study, intrathecal synthesis of IgM (IgM index) was found to be correlated with cranial magnetic resonance imaging (MRI) parameters. The purpose of this study was to determine the possible relationship between the IgM index and MRI and clinical parameters. Eighty-one patients with MS (58 female) undergoing lumbar puncture were included in the study. Fifty-one patients had a relapsing-remitting (RR) disease course, while 30 cases were secondary progressive MS (SPMS). IgM was detected in paired CSF and serum specimens using ELISA. The IgM index was calculated using the formula CSF IgM/serum IgM: CSF albumin/serum albumin. IgM indexes higher than 0.1 were considered "increased". All patients underwent brain and whole spinal cord MRI. The IgM index was normal in 43 of the 81 patients (53.1%) and increased in 38 (46.9%). A significant correlation was determined between the IgM index and Expanded Disability Status Scale (EDSS) (r=0.638, p=0.001). Most of the subjects with increased IgM indexes were SPMS patients, 28 having a SPMS course and 10 a RRMS course. Only two patients with SPMS courses had normal IgM indexes. EDSS scores were significantly higher in patients with increased IgM indexes (EDSS 4.3 vs EDSS 2.8, p=0.000). All patients with EDSS >3 had increased IgM indexes. All patients with IgM index values higher than 0.2 IgM had SPMS courses and EDSS >6. Time to onset of the secondary progressive phase of the disease was correlated with IgM index values (p=0.004). IgM index values were also correlated with T1 hypointense lesions (r=0.0431, p=0.008) and Gd enhancing lesions (r=0.0396, p=0.006). Patients with increased IgM indexes also had more

  17. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  18. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Letolle, R.; Mariotti, A.; Bariac, T.

    1991-06-01

    This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

  19. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Drent, Esther; Groen, Richard W. J.; Noort, Willy A. Noort

    2016-01-01

    Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody...... sequences to generate second-generation retroviral CD38- chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence......, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite...

  20. Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment.

    Science.gov (United States)

    Kassem, Abeer Ahmed; Issa, Doaa Ahmed Elsayed; Kotry, Gehan Sherif; Farid, Ragwa Mohamed

    2017-01-01

    Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis. Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application. Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects. Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12 h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the -NH groups of metformin and -OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment. The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.

  1. Staff and students' perceptions and experiences of teaching and assessment in Clinical Skills Laboratories: interview findings from a multiple case study.

    Science.gov (United States)

    Houghton, Catherine E; Casey, Dympna; Shaw, David; Murphy, Kathy

    2012-08-01

    The Clinical Skills Laboratory has become an essential structure in nurse education and several benefits of its use have been identified. However, the literature identifies the need to examine the transferability of skills learned there into the reality of practice. This research explored the role of the Clinical Skills Laboratory in preparing nursing students for the real world of practice. This paper focuses specifically on the perceptions of the teaching and assessment strategies employed there. Qualitative multiple case study design. Five case study sites. Interviewees (n=58) included academic staff, clinical staff and nursing students. Semi-structured interviews. The Clinical Skills Laboratory can provide a pathway to practice and its authenticity is significant. Teaching strategies need to incorporate communication as well as psychomotor skills. Including audio-visual recording into assessment strategies is beneficial. Effective relationships between education institutions and clinical settings are needed to enhance the transferability of the skills learned. The Clinical Skills Laboratory should provide an authentic learning environment, with the appropriate use of teaching strategies. It is crucial that effective links between educators and clinical staff are established and maintained. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Combined use of 64-slice computed tomography angiography and gated myocardial perfusion SPECT for the detection of functionally relevant coronary artery stenoses. First results in a clinical setting concerning patients with stable angina

    International Nuclear Information System (INIS)

    Hacker, M.; Hack, N.; Tiling, R.; Jakobs, T.; Nikolaou, K.; Becker, C.; Ziegler, F. von; Knez, A.; Koenig, A.; Klauss, V.

    2007-01-01

    Aim: In patients with stable angina pectoris both morphological and functional information about the coronary artery tree should be present before revascularization therapy is performed. High accuracy was shown for spiral computed tomography (MDCT) angiography acquired with a 64-slice CT scanner compared to invasive coronary angiography (ICA) in detecting obstructive'' coronary artery disease (CAD). Gated myocardial SPECT (MPI) is an established method for the noninvasive assessment of functional significance of coronary stenoses. Aim of the study was to evaluate the combination of 64-slice CT angiography plus MPI in comparison to ICA plus MPI in the detection of hemodynamically relevant coronary artery stenoses in a clinical setting. Patients, methods: 30 patients (63 ± 10.8 years, 23 men) with stable angina (21 with suspected, 9 with known CAD) were investigated. MPI, 64-slice CT angiography and ICA were performed, reversible and fixed perfusion defects were allocated to determining lesions separately for MDCT angiography and ICA. The combination of MDCT angiography plus MPI was compared to the results of ICA plus MPI. Results: Sensitivity, specificity, negative and positive predictive value for the combination of MDCT angiography plus MPI was 85%, 97%, 98% and 79%, respectively, on a vessel-based and 93%, 87%, 93% and 88%, respectively, on a patient-based level. 19 coronary arteries with stenoses =50% in both ICA and MDCT angiography showed no ischemia in MPI. Conclusion: The combination of 64-slice CT angiography and gated myocardial SPECT enabled a comprehensive non-invasive view of the anatomical and functional status of the coronary artery tree. (orig.)

  3. Combined use of 64-slice computed tomography angiography and gated myocardial perfusion SPECT for the detection of functionally relevant coronary artery stenoses. First results in a clinical setting concerning patients with stable angina

    Energy Technology Data Exchange (ETDEWEB)

    Hacker, M.; Hack, N.; Tiling, R. [Klinikum Grosshadern (Germany). Dept. of Nuclear Medicine; Jakobs, T.; Nikolaou, K.; Becker, C. [Klinikum Grosshadern (Germany). Dept. of Clinical Radiology; Ziegler, F. von; Knez, A. [Klinikum Grosshadern (Germany). Dept. of Cardiology; Koenig, A.; Klauss, V. [Medizinische Poliklinik-Innenstadt, Univ. of Munich (Germany). Dept. of Cardiology

    2007-07-01

    Aim: In patients with stable angina pectoris both morphological and functional information about the coronary artery tree should be present before revascularization therapy is performed. High accuracy was shown for spiral computed tomography (MDCT) angiography acquired with a 64-slice CT scanner compared to invasive coronary angiography (ICA) in detecting ''obstructive'' coronary artery disease (CAD). Gated myocardial SPECT (MPI) is an established method for the noninvasive assessment of functional significance of coronary stenoses. Aim of the study was to evaluate the combination of 64-slice CT angiography plus MPI in comparison to ICA plus MPI in the detection of hemodynamically relevant coronary artery stenoses in a clinical setting. Patients, methods: 30 patients (63 {+-} 10.8 years, 23 men) with stable angina (21 with suspected, 9 with known CAD) were investigated. MPI, 64-slice CT angiography and ICA were performed, reversible and fixed perfusion defects were allocated to determining lesions separately for MDCT angiography and ICA. The combination of MDCT angiography plus MPI was compared to the results of ICA plus MPI. Results: Sensitivity, specificity, negative and positive predictive value for the combination of MDCT angiography plus MPI was 85%, 97%, 98% and 79%, respectively, on a vessel-based and 93%, 87%, 93% and 88%, respectively, on a patient-based level. 19 coronary arteries with stenoses =50% in both ICA and MDCT angiography showed no ischemia in MPI. Conclusion: The combination of 64-slice CT angiography and gated myocardial SPECT enabled a comprehensive non-invasive view of the anatomical and functional status of the coronary artery tree. (orig.)

  4. Analysing Stable Time Series

    National Research Council Canada - National Science Library

    Adler, Robert

    1997-01-01

    We describe how to take a stable, ARMA, time series through the various stages of model identification, parameter estimation, and diagnostic checking, and accompany the discussion with a goodly number...

  5. Comparison of the Influence of Different Rehabilitation Programmes on Clinical, Spirometric and Spiroergometric Parameters in Patients with Multiple Sclerosis

    Czech Academy of Sciences Publication Activity Database

    Řasová, K.; Havrdová, E.; Brandejský, P.; Zálišová, M.; Foubíková, B.; Martinková, Patrícia

    2006-01-01

    Roč. 12, č. 2 (2006), s. 227-234 ISSN 1352-4585 Source of funding: V - iné verejné zdroje Keywords : aerobic training * fatigue * multiple sclerosis * neurorehabilitation * spirometric and spiroergometric parameters Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.773, year: 2006

  6. Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis

    DEFF Research Database (Denmark)

    Wu, Xingchen; Hanson, Lars G.; Skimminge, Arnold Jesper Møller

    2014-01-01

    Objective: To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Methods: Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months ...

  7. Overexpression of c-myc is associated with adverse clinical features and worse overall survival in multiple myeloma

    DEFF Research Database (Denmark)

    Szabo, Agoston Gyula; Gang, Anne Ortved; Pedersen, Mette Ølgod

    2016-01-01

    The role of c-myc in multiple myeloma (MM) is controversial. We conducted a retrospective study of 117 patients with MM diagnosed between 2004 and 2010 at Herlev Hospital. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) made from...

  8. Clinical analysis of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lili Xu

    2018-01-01

    Conclusion: Cancer pain in patients with advanced hepatocellular carcinoma can be alleviated with electroacupuncture and multiple acupoint stimulation, but the onset pain relief was slow. To improve the analgesic effects of this technique, the combination of various analgesic methods should be necessary in early stage of the treatment.

  9. [Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease].

    Science.gov (United States)

    Higueras, Javier; Martín-Ventura, José Luis; Blanco-Colio, Luis; Cristóbal, Carmen; Tarín, Nieves; Huelmos, Ana; Alonso, Joaquín; Pello, Ana; Aceña, Álvaro; Carda, Rocío; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Asensio, Dolores; Almeida, Pedro; Rodríguez-Artalejo, Fernando; Farré, Jerónimo; López Bescós, Lorenzo; Egido, Jesús; Tuñón, José

    2015-01-01

    At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); Pvalue improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  10. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

    Energy Technology Data Exchange (ETDEWEB)

    Bellmann-Strobl, J.; Paul, F.; Aktas, O.; Zipp, F. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); Stiepani, H.; Bohner, G.; Klingebiel, R. [Charite - University Medicine Berlin, Department of Neuroradiology, Berlin (Germany); Wuerfel, J. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); University Schleswig-Holstein, Institute of Neuroradiology, Campus Luebeck, Kiel (Germany); Warmuth, C. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Wandinger, K.P. [Charite - University Medicine Berlin, Department of Neurology, Berlin (Germany)

    2009-08-15

    The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0{+-}7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon {beta}-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p<0.05) and correlated to the MSFC score (r=0.476, p<0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p<0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. (orig.)

  11. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

    International Nuclear Information System (INIS)

    Bellmann-Strobl, J.; Paul, F.; Aktas, O.; Zipp, F.; Stiepani, H.; Bohner, G.; Klingebiel, R.; Wuerfel, J.; Warmuth, C.; Wandinger, K.P.

    2009-01-01

    The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0±7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon β-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p<0.05) and correlated to the MSFC score (r=0.476, p<0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p<0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. (orig.)

  12. A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

    Science.gov (United States)

    Derfuss, Tobias; Curtin, François; Guebelin, Claudia; Bridel, Claire; Rasenack, Maria; Matthey, Alain; Du Pasquier, Renaud; Schluep, Myriam; Desmeules, Jules; Lang, Alois B; Perron, Hervé; Faucard, Raphael; Porchet, Hervé; Hartung, Hans-Peter; Kappos, Ludwig; Lalive, Patrice H

    2015-06-01

    GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period. © The Author(s) 2014.

  13. The Effect of Parasite Infection on Stable Isotope Turnover Rates of δ15N, δ13C and δ34S in Multiple Tissues of Eurasian Perch Perca fluviatilis.

    Directory of Open Access Journals (Sweden)

    Elizabeth Yohannes

    Full Text Available Stable isotope analysis of commercially and ecologically important fish can improve understanding of life-history and trophic ecology. However, accurate interpretation of stable isotope values requires knowledge of tissue-specific isotopic turnover that will help to describe differences in the isotopic composition of tissues and diet. We performed a diet-switch experiment using captive-reared parasite-free Eurasian perch (Perca fluviatilis and wild caught specimens of the same species, infected with the pike tapeworm Triaenophorus nodulosus living in host liver tissue. We hypothesize that metabolic processes related to infection status play a major role in isotopic turnover and examined the influence of parasite infection on isotopic turn-over rate of carbon (δ13C, nitrogen (δ15N and sulphur (δ34S in liver, blood and muscle. The δ15N and δ13C turnovers were fastest in liver tissues, followed by blood and muscle. In infected fish, liver and blood δ15N and δ13C turnover rates were similar. However, in infected fish, liver and blood δ13C turnover was faster than that of δ15N. Moreover, in infected subjects, liver δ15N and δ13C turnover rates were three to five times faster than in livers of uninfected subjects (isotopic half-life of ca.3-4 days compared to 16 and 10 days, respectively. Blood δ34S turnover rate were about twice faster in non-infected individuals implying that parasite infection could retard the turnover rate of δ34S and sulphur containing amino acids. Slower turnover rate of essential amino acid could probably decrease individual immune function. These indicate potential hidden costs of chronic and persistent infections that may have accumulated adverse effects and might eventually impair life-history fitness. For the first time, we were able to shift the isotope values of parasites encapsulated in the liver by changing the dietary source of the host. We also report variability in isotopic turnover rates between tissues

  14. Multi-criteria clinical decision support: A primer on the use of multiple criteria decision making methods to promote evidence-based, patient-centered healthcare.

    Science.gov (United States)

    Dolan, James G

    2010-01-01

    Current models of healthcare quality recommend that patient management decisions be evidence-based and patient-centered. Evidence-based decisions require a thorough understanding of current information regarding the natural history of disease and the anticipated outcomes of different management options. Patient-centered decisions incorporate patient preferences, values, and unique personal circumstances into the decision making process and actively involve both patients along with health care providers as much as possible. Fundamentally, therefore, evidence-based, patient-centered decisions are multi-dimensional and typically involve multiple decision makers.Advances in the decision sciences have led to the development of a number of multiple criteria decision making methods. These multi-criteria methods are designed to help people make better choices when faced with complex decisions involving several dimensions. They are especially helpful when there is a need to combine "hard data" with subjective preferences, to make trade-offs between desired outcomes, and to involve multiple decision makers. Evidence-based, patient-centered clinical decision making has all of these characteristics. This close match suggests that clinical decision support systems based on multi-criteria decision making techniques have the potential to enable patients and providers to carry out the tasks required to implement evidence-based, patient-centered care effectively and efficiently in clinical settings.The goal of this paper is to give readers a general introduction to the range of multi-criteria methods available and show how they could be used to support clinical decision-making. Methods discussed include the balance sheet, the even swap method, ordinal ranking methods, direct weighting methods, multi-attribute decision analysis, and the analytic hierarchy process (AHP).

  15. Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons

    Directory of Open Access Journals (Sweden)

    Sunčanica Ljubin-Sternak

    2016-01-01

    Full Text Available The aim of this study was to determine the causative agent of acute respiratory infection (ARI in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV (28.6%, followed by parainfluenza viruses (PIVs types 1–3 (18.4%, rhinovirus (HRV (14.3%, human metapneumovirus (10.1%, adenovirus (AdV (7.1%, influenza viruses types A and B (4.8%, and coronaviruses (4.2%. In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%, bocavirus (HBoV (10.5%, PIV-4 (2.6%, and parechovirus (1.3%. There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P>0.05. AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P<0.001.

  16. Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus

    Directory of Open Access Journals (Sweden)

    Zong Sheng Guo

    2017-12-01

    Full Text Available Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome. Using this improved procedure combined with the SEM system, we have constructed multiple marker-free oncolytic poxviruses expressing different cytokines and other therapeutic genes. The high fidelity of inserted DNA sequences validates the utility of this improved procedure for generation of therapeutic viruses for human patients. We have created an oncolytic poxvirus expressing human chemokine CCL5, designated as vvDD-A34R-hCCL5, with manipulations at two genetic loci in a single virus. Finally, we have produced and purified this virus in clinical grade for its use in a phase I clinical trial and presented data on initial in vitro characterization of the virus.

  17. Uses of stable isotopes

    International Nuclear Information System (INIS)

    Axente, Damian

    1998-01-01

    The most important fields of stable isotope use with examples are presented. These are: 1. Isotope dilution analysis: trace analysis, measurements of volumes and masses; 2. Stable isotopes as tracers: transport phenomena, environmental studies, agricultural research, authentication of products and objects, archaeometry, studies of reaction mechanisms, structure and function determination of complex biological entities, studies of metabolism, breath test for diagnostic; 3. Isotope equilibrium effects: measurement of equilibrium effects, investigation of equilibrium conditions, mechanism of drug action, study of natural processes, water cycle, temperature measurements; 4. Stable isotope for advanced nuclear reactors: uranium nitride with 15 N as nuclear fuel, 157 Gd for reactor control. In spite of some difficulties of stable isotope use, particularly related to the analytical techniques, which are slow and expensive, the number of papers reporting on this subject is steadily growing as well as the number of scientific meetings organized by International Isotope Section and IAEA, Gordon Conferences, and regional meeting in Germany, France, etc. Stable isotope application development on large scale is determined by improving their production technologies as well as those of labeled compound and the analytical techniques. (author)

  18. Calcium stable isotope geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

    2016-08-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  19. Calcium stable isotope geochemistry

    International Nuclear Information System (INIS)

    Gausonne, Nikolaus; Schmitt, Anne-Desiree; Heuser, Alexander; Wombacher, Frank; Dietzel, Martin; Tipper, Edward; Schiller, Martin

    2016-01-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  20. Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.

    Science.gov (United States)

    Filippi, Massimo; Preziosa, Paolo; Meani, Alessandro; Ciccarelli, Olga; Mesaros, Sarlota; Rovira, Alex; Frederiksen, Jette; Enzinger, Christian; Barkhof, Frederik; Gasperini, Claudio; Brownlee, Wallace; Drulovic, Jelena; Montalban, Xavier; Cramer, Stig P; Pichler, Alexander; Hagens, Marloes; Ruggieri, Serena; Martinelli, Vittorio; Miszkiel, Katherine; Tintorè, Mar; Comi, Giancarlo; Dekker, Iris; Uitdehaag, Bernard; Dujmovic-Basuroski, Irena; Rocca, Maria A

    2018-02-01

    In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria. Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis. Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple

  1. Influence of multiple clinical use on fatigue resistance of ProTaper rotary nickel-titanium instruments.

    Science.gov (United States)

    Vieira, E P; França, E C; Martins, R C; Buono, V T L; Bahia, M G A

    2008-02-01

    To examine the influence of clinical use on the occurrence of deformation and fracture and on the fatigue resistance of ProTaper rotary instruments. Root canal treatments were performed on patients using the ProTaper rotary system. Ten sets of instruments were used by an experienced endodontist, each set in five molars. Another 10 sets of instruments were used by the same operator, each set in eight molars. In addition, 10 sets of instruments were used, each set in five molars, by undergraduate students with no clinical experience with the system. After clinical use, S1, S2, F1 and F2 instruments were analysed for damage by optical and scanning electron microscopy. The used sets, along with a control group of 12 sets of new instruments, were then tested in a bench device for fatigue resistance. The use of the ProTaper rotary instruments by an experienced endodontist allowed for the cleaning and shaping of the root canal system of up to eight molars without fracture. During the students work, six instruments fractured. Fatigue resistance decreased upon clinical use for all instruments analysed. Fatigue resistance of used instruments was reduced, but no significant change was observed amongst the instruments used for shaping the canals of five and eight molars. Operator experience affected the occurrence of fracture and plastic deformation during shaping.

  2. An investigation of clinical studies suggests those with multiple objectives should have at least 90% power for each endpoint.

    NARCIS (Netherlands)

    Borm, G.F.; Houben, R.; Welsing, P.M.J.; Zielhuis, G.A.

    2006-01-01

    BACKGROUND AND OBJECTIVES: Many clinical studies have more than one objective, either formally or informally, but this is not usually taken into account in the determination of the sample size. We investigated the overall power of a study, that is, the probability that all the objectives will be

  3. clinical

    African Journals Online (AJOL)

    zone at the squamo-columnar junction, which explains in part why HPV ... immune suppression, cigarette smoke, multiple sexual partners .... established, disease progression may not be affected by CD4 ... PREVEnTiOn OF cERVical cancER.

  4. Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.

    Directory of Open Access Journals (Sweden)

    Johannes Ehler

    Full Text Available Experience with therapeutic plasma exchange (TPE for acute relapses in clinically isolated syndrome (CIS or multiple sclerosis (MS patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years.Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS scoring.A clinical response to TPE was observed in 65 out of 90 patients (72.2%, with marked improvement in 18 (20.0% and moderate improvement in 47 out of 90 patients (52.2%. The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001. Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001, no disease modifying drugs (p = 0.017, gadolinium-positive (Gd+ MRI lesions (p = 0.001 and EDSS ≤ 5.0 before TPE (p = 0.014. In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004.Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.

  5. Clinical significance of combined detection of multiple serum antibodies (AsAb, EmAb, AcAb, AoAb, ToxAb) in infertile women

    International Nuclear Information System (INIS)

    Chen Jing; Jiang Li; Lu Ya

    2005-01-01

    Objective: To determine the clinical significance of combined detection of multiple serum antibodies in infertile women. Methods; Serum multiple antibodies were examined in 120 infertile women, including 88 failed to get pregnancy and 32 with repeated spontaneous abortion. The antibodies tested were: (1) anti-sperm antibody (AsAb) (2) endometrial antibody (EmAb) (3) anti-cardiophospholipid antibody (AcAb) (4) Anti-ovarian antibody (AoAb) and Toxoplasmosis antibody (ToxAb). Results: In 48 of the infertile women, none of the five antibodies were positive (40% of 120). The rest were: one antibody positive--38/120 or 31.6%; two antibodies positive--31/120 or 25.83%, three and four antibodies positive--4/120 or 3.33%. None of the women were positive with all five antibodies. Conclusion: Immune factor was the chief cause of infertility in women. (authors)

  6. Clinical value of assays of multiple serum tumor markers in conjunction with 18F-FDG SPECT for discriminating malignant from benign lung disorders

    International Nuclear Information System (INIS)

    Zhang Chunyan; Wang Linglong; Tu Liping; Yu Yuefang; Zhu Weijie; Cai Ao; Gao Shuxing

    2006-01-01

    Objective: To evaluate the clinical value of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders. Methods: A total of 62 patients with malignant and benign lung diseases un- derwent 18 F-FDG SPECT examination and tests for serum tumor markers CEA, CA50, CA199 and CA242, alone or combined. The sensitivity, specificity, accuracy of these tests were examined. Results: The sensitivity, specificity accuracy of 18 F-FDG SPECT for the diagnosis of malignant lung tumors were 85.7 (30/35), 59.3 (16/27) and 74.2(46/62) respectively, those of each of serum CEA, CA199, CA50, CA242 levels in diagnosing malignant lung tumors were 22.9(8/35), 92.6(25/27), 59.7(33/62), 14.3(5/35), 100(27/27), 51.6 (32/62), 34.3 (12/35), 85.2 (23/27), 56.5 (35/62), 28.6 (10/35), 85.2 (23/27) and 53.2 (33/62) respectively, those of assays of multiple serum tumor markers for diagnosis of malignant lung tumors were 85.7 (30/35), 85.2 (23/27) and 85.5 (53/62) respectively, those of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung nodules were 88.6(31/35), 85.2(23/27) and 87.1 (54/62) respectively. Conclusion: Assays of multiple serum tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders can yield higher sensitivity, specialty and accuracy, making a significant contribution to clinical application. (authors)

  7. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

    Science.gov (United States)

    Sanoobar, Meisam; Dehghan, Parvin; Khalili, Mohammad; Azimi, Amirreza; Seifar, Fatemeh

    2016-01-01

    Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS. We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms. A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P multiple sclerosis.

  8. Comparison and clinical utility evaluation of four multiple allergen simultaneous tests including two newly introduced fully automated analyzers

    Directory of Open Access Journals (Sweden)

    John Hoon Rim

    2016-04-01

    Full Text Available Background: We compared the diagnostic performances of two newly introduced fully automated multiple allergen simultaneous tests (MAST analyzers with two conventional MAST assays. Methods: The serum samples from a total of 53 and 104 patients were tested for food panels and inhalant panels, respectively, in four analyzers including AdvanSure AlloScreen (LG Life Science, Korea, AdvanSure Allostation Smart II (LG Life Science, PROTIA Allergy-Q (ProteomeTech, Korea, and RIDA Allergy Screen (R-Biopharm, Germany. We compared not only the total agreement percentages but also positive propensities among four analyzers. Results: Evaluation of AdvanSure Allostation Smart II as upgraded version of AdvanSure AlloScreen revealed good concordance with total agreement percentages of 93.0% and 92.2% in food and inhalant panel, respectively. Comparisons of AdvanSure Allostation Smart II or PROTIA Allergy-Q with RIDA Allergy Screen also showed good concordance performance with positive propensities of two new analyzers for common allergens (Dermatophagoides farina and Dermatophagoides pteronyssinus. The changes of cut-off level resulted in various total agreement percentage fluctuations among allergens by different analyzers, although current cut-off level of class 2 appeared to be generally suitable. Conclusions: AdvanSure Allostation Smart II and PROTIA Allergy-Q presented favorable agreement performances with RIDA Allergy Screen, although positive propensities were noticed in common allergens. Keywords: Multiple allergen simultaneous test, Automated analyzer

  9. Clinical applications of 153Sm-EDTMP in treatment of multiple bone metastases in 78 patients with lung cancer

    International Nuclear Information System (INIS)

    Xiao Guoyou; Li Dangsheng; Liang Yihua; Yao Xinjuan

    2001-01-01

    Objective: To evaluate the effect of 153 Sm-EDTMP in treating patients with lung cancer and multiple bone metastases. Methods: A dose of 18.5-25.9 MBq/Kg 153 Sm-EDTMP was administered once a month to each patient through vein injection according to disease severity and body weight. 3 injections made up one therapy cycle. Results: Pain relieves were obtained in 65 patients, with an effective rate of 83.3%. Pain relief of grade I was observed in 19 patients (24.3%), grade II in 46 patients (59%) and grade III in 13 patients (16.7%), respectively. Lesions of bone metastases disappeared or shrunk in 9 patients, with a positive rate of 11.5%, which included 3 cases of grade I and 6 cases of grade II, respectively. Better effects were obtained in adenocarcinoma and squamous carcinoma than in small cell lung cancer. Conclusion: 153 Sm-EDTMP is safe and effective in treating patients with lung cancer and multiple bone metastases

  10. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

  11. Clinical and genetic spectrum of Birt–Hogg–Dubé syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature

    Science.gov (United States)

    Kunogi, Makiko; Kurihara, Masatoshi; Ikegami, Takako Shigihara; Kobayashi, Toshiyuki; Shindo, Noriko; Kumasaka, Toshio; Gunji, Yoko; Kikkawa, Mika; Iwakami, Shin-ichiro; Hino, Okio; Takahashi, Kazuhisa

    2010-01-01

    Background Birt–Hogg–Dubé syndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. Objectives BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. Methods This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. Results An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3′-end of the FLCN gene including exons 12 and 13 (13/25=52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. Conclusions BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations. PMID:20413710

  12. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  13. Application of multiple geochemical indicators, including the stable isotopes of water, to differentiate water quality evolution in a region influenced by various agricultural practices and domestic wastewater treatment and disposal

    International Nuclear Information System (INIS)

    Butler, Thomas W.

    2007-01-01

    Spatial and temporal variations in groundwater chemistry indicate that the use of low TDS lake water for irrigation, on land located just south of the City of Dixon, Solano County, California, is primarily responsible for improving groundwater quality with regards to salts. The stable isotopes of water further support this finding and suggest that TDS concentrations decrease as groundwater evolves to a more highly evaporated state. This seemingly contradictory finding was primarily attributed to infiltration of low TDS Lake Berryessa surface water, which has an isotopic signature indicative of an evaporated source and is used extensively for irrigation in the area, mixing with poorer quality locally recharged shallow groundwater. Geochemical modeling using the program PHREEQC further supports the anthropogenic aquifer freshening hypotheses through computed reductions in the saturation state of carbonate minerals in the vicinity of land irrigated by lake derived water, which is undersaturated with regards to modeled carbonates. Additionally, δ 18 O and δ 2 H were found to be useful in estimating climatic variables such as temperature and humidity, illustrating the potential for applying these models in hydrologic investigations within the area. It was however found that USDA NRCS soils data and measured water chemistry were not well correlated and thus the use of soils classifications to assess potential groundwater quality impacts was of limited utility

  14. Health technology assessment on the use of magnetic resonance imaging (MRI) and computed tomography (CT) in the diagnosis of multiple sclerosis (MS) and clinically isolated syndromes (CIS)

    Energy Technology Data Exchange (ETDEWEB)

    Achten, Eric [Department of Radiology, Ghent University, De Pintelaan 185, B-9000 Gent (Belgium)], E-mail: rik.achten@ugent.be; Deblaere, Karel [Department of Radiology, Ghent University, De Pintelaan 185, B-9000 Gent (Belgium)], E-mail: karel.deblaere@ugent.be

    2008-02-15

    This work is the result of a health technology assessment for the Flemish regional government, Belgium, performed in 2006. A search of the available literature in the databases Medline and EMBASE was performed to find evidence for a rational choice between CT and MRI techniques in the work-up of patients with clinically isolated syndrome (CIS) with a suspicion for multiple sclerosis (MS), and in follow-up exams performed in such patients. From the presented evidence, in patients referred for CIS or MS, MR is superior to CT for detection and characterization of brain and spine lesions.

  15. Antibacterial effect of Allium sativum cloves and Zingiber officinale rhizomes against multiple-drug resistant clinical pathogens.

    Science.gov (United States)

    Karuppiah, Ponmurugan; Rajaram, Shyamkumar

    2012-08-01

    To evaluate the antibacterial properties of Allium sativum (garlic) cloves and Zingiber officinale (ginger) rhizomes against multi-drug resistant clinical pathogens causing nosocomial infection. The cloves of garlic and rhizomes of ginger were extracted with 95% (v/v) ethanol. The ethanolic extracts were subjected to antibacterial sensitivity test against clinical pathogens. Anti-bacterial potentials of the extracts of two crude garlic cloves and ginger rhizomes were tested against five gram negative and two gram positive multi-drug resistant bacteria isolates. All the bacterial isolates were susceptible to crude extracts of both plants extracts. Except Enterobacter sp. and Klebsiella sp., all other isolates were susceptible when subjected to ethanolic extracts of garlic and ginger. The highest inhibition zone was observed with garlic (19.45 mm) against Pseudomonas aeruginosa (P. aeruginosa). The minimal inhibitory concentration was as low as 67.00 µg/mL against P. aeruginosa. Natural spices of garlic and ginger possess effective anti-bacterial activity against multi-drug clinical pathogens and can be used for prevention of drug resistant microbial diseases and further evaluation is necessary.

  16. Stable isotope studies

    International Nuclear Information System (INIS)

    Ishida, T.

    1992-01-01

    The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

  17. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salvi, Marco; Kolb, Craig

    2017-01-01

    Interactive ray tracing applications running on commodity hardware can suffer from objectionable temporal artifacts due to a low sample count. We introduce stable ray tracing, a technique that improves temporal stability without the over-blurring and ghosting artifacts typical of temporal post-pr...

  18. The Stable Concordance Genus

    OpenAIRE

    Kearney, M. Kate

    2013-01-01

    The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.

  19. Stable radiographic scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

  20. Some stable hydromagnetic equilibria

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J L; Oberman, C R; Kulsrud, R M; Frieman, E A [Project Matterhorn, Princeton University, Princeton, NJ (United States)

    1958-07-01

    We have been able to find and investigate the properties of equilibria which are hydromagnetically stable. These equilibria can be obtained, for example, by wrapping conductors helically around the stellarator tube. Systems with I = 3 or 4 are indicated to be optimum for stability purposes. In some cases an admixture of I = 2 fields can be advantageous for achieving equilibrium. (author)

  1. Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol.

    Science.gov (United States)

    Gaudino, Mario; Alexander, John H; Bakaeen, Faisal G; Ballman, Karla; Barili, Fabio; Calafiore, Antonio Maria; Davierwala, Piroze; Goldman, Steven; Kappetein, Peter; Lorusso, Roberto; Mylotte, Darren; Pagano, Domenico; Ruel, Marc; Schwann, Thomas; Suma, Hisayoshi; Taggart, David P; Tranbaugh, Robert F; Fremes, Stephen

    2017-12-01

    The primary hypothesis of the ROMA trial is that in patients undergoing primary isolated non-emergent coronary artery bypass grafting, the use of 2 or more arterial grafts compared with a single arterial graft (SAG) is associated with a reduction in the composite outcome of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization. The secondary hypothesis is that in these patients, the use of 2 or more arterial grafts compared with a SAG is associated with improved survival. The ROMA trial is a prospective, unblinded, randomized event-driven multicentre trial comprising at least 4300 subjects. Patients younger than 70 years with left main and/or multivessel disease will be randomized to a SAG or multiple arterial grafts to the left coronary system in a 1:1 fashion. Permuted block randomization stratified by the centre and the type of second arterial graft will be used. The primary outcome will be a composite of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization. The secondary outcome will be all-cause mortality. The primary safety outcome will be a composite of death from any cause, any stroke and any myocardial infarction. In all patients, 1 internal thoracic artery will be anastomosed to the left anterior descending coronary artery. For patients randomized to the SAG group, saphenous vein grafts will be used for all non-left anterior descending target vessels. For patients randomized to the multiple arterial graft group, the main target vessel of the lateral wall will be grafted with either a radial artery or a second internal thoracic artery. Additional grafts for the multiple arterial graft group can be saphenous veins or supplemental arterial conduits. To detect a 20% relative reduction in the primary outcome, with 90% power at 5% alpha and assuming a time-to-event analysis, the sample size must include 845 events (and 3650 patients). To detect a 20% relative

  2. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  3. Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor.

    Science.gov (United States)

    Devito, Liani; Petrova, Anastasia; Miere, Cristian; Codognotto, Stefano; Blakely, Nicola; Lovatt, Archie; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

    2014-10-01

    Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. ©AlphaMed Press.

  4. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial.

    Science.gov (United States)

    Leist, Thomas P; Comi, Giancarlo; Cree, Bruce A C; Coyle, Patricia K; Freedman, Mark S; Hartung, Hans-Peter; Vermersch, Patrick; Casset-Semanaz, Florence; Scaramozza, Matthew

    2014-03-01

    Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5.0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Of 903 participants assessed for eligibility, 616 patients received cladribine 5.25 mg/kg (n=204), cladribine 3.5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5.25 mg/kg=0.38, 95% CI 0.25-0.58, pMS diagnosis compared with placebo. The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS. Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS. Merck Serono SA Geneva

  5. Expression Analysis of Multiple Genes May Involve in Antimony Resistance among Leishmania major Clinical Isolates from Fars Province, Central Iran

    Directory of Open Access Journals (Sweden)

    Nafiseh GHOBAKHLOO

    2016-10-01

    Full Text Available Background: Treatment of Cutaneous Leishmaniasis (CL is being faced with serious difficulties in Fars Province, due to emerging of resistance against meglumine antimonite (Glucantime®. In this context, determining some biomarkers for drug sensitivity monitoring seems to be highly essential. Different studies have been carried out to decipher the genes might be involved in antimony resistant phenotype in Leishmania spp. Here, we selected three genes: AQP (as drug transporter, TDR-1-1(as drug activator, and γ-GCS (inducing reduction environment for comparative expression analysis on clinical resistant and sensitive isolates of L. major.Methods: The clinical isolates of L. major were collected from CL patients referred to Valfajr Health Center, Shiraz from Oct 2011 to Feb 2012. The susceptibility test was performed to confirm drug sensitivity of strains in vitro as well. Then, the gene expression analysis was performed by quantitative real-time PCR using SYBR® Green.Results: By comparison of expression level between strains, up regulation of γ-GCS gene and down regulation of AQP gene were observed in resistant strains compared to the sensitive isolates; however, down regulation of AQP was not statistically specific. Analysis of TDR-1-1 gene unexpectedly showed a high level of expression in the non-responsive cases.Conclusion: The γ-GCS, at least, can be considered as a suitable molecular marker for screening antimony sensitivity in clinical isolates, although AQP and TDR-1-1gene seem not to be reliable resistant markers. 

  6. Psychometric characteristics of Clinical Reasoning Problems (CRPs) and its correlation with routine multiple choice question (MCQ) in Cardiology department.

    Science.gov (United States)

    Derakhshandeh, Zahra; Amini, Mitra; Kojuri, Javad; Dehbozorgian, Marziyeh

    2018-01-01

    Clinical reasoning is one of the most important skills in the process of training a medical student to become an efficient physician. Assessment of the reasoning skills in a medical school program is important to direct students' learning. One of the tests for measuring the clinical reasoning ability is Clinical Reasoning Problems (CRPs). The major aim of this study is to measure psychometric qualities of CRPs and define correlation between this test and routine MCQ in cardiology department of Shiraz medical school. This study was a descriptive study conducted on total cardiology residents of Shiraz Medical School. The study population consists of 40 residents in 2014. The routine CRPs and the MCQ tests was designed based on similar objectives and were carried out simultaneously. Reliability, item difficulty, item discrimination, and correlation between each item and the total score of CRPs were all measured by Excel and SPSS software for checking psycometeric CRPs test. Furthermore, we calculated the correlation between CRPs test and MCQ test. The mean differences of CRPs test score between residents' academic year [second, third and fourth year] were also evaluated by Analysis of variances test (One Way ANOVA) using SPSS software (version 20)(α=0.05). The mean and standard deviation of score in CRPs was 10.19 ±3.39 out of 20; in MCQ, it was 13.15±3.81 out of 20. Item difficulty was in the range of 0.27-0.72; item discrimination was 0.30-0.75 with question No.3 being the exception (that was 0.24). The correlation between each item and the total score of CRP was 0.26-0.87; the correlation between CRPs test and MCQ test was 0.68 (preasoning in residents. It can be included in cardiology residency assessment programs.

  7. Regulation of the CD56 promoter and its association with proliferation, anti-apoptosis and clinical factors in multiple myeloma

    DEFF Research Database (Denmark)

    Damgaard, Tina; Knudsen, Lene M; Dahl, Inger Marie S

    2009-01-01

    the regulation of the CD56 promoter in relation to typical clinical factors. We used qPCR and FACS to measure the expression levels of CD56, and potential regulatory factors in patients with MM and related these with MM progression/prognosis. The transcription factors BTBD3, Pax5, RUNX1 and MMSET were positively...... associated with CD56 expression, as was CYCLIN D1, which is involved in disease progression, anti-apoptosis and proliferation. RUNX1 was negatively associated with the survival of stem-cell transplanted patients. Our findings propose four potential activators of the CD56 promoter and for CD56 to be involved...

  8. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2012-06-15

    To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

  9. Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria

    DEFF Research Database (Denmark)

    Filippi, Massimo; Preziosa, Paolo; Meani, Alessandro

    2018-01-01

    of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic......, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0......·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0...

  10. Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

    Science.gov (United States)

    Abidin, Anas Z.; Chockanathan, Udaysankar; DSouza, Adora M.; Inglese, Matilde; Wismüller, Axel

    2017-03-01

    Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with