Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings

International Nuclear Information System (INIS)

Baur, A.; Staebler, A.; Reiser, M.; Lamerz, R.; Bartl, R.

1998-01-01

The clinical, histopathological, and imaging findings on MRI of a 56-year-old woman with light chain deposition disease occurring in multiple myeloma are presented. Light chain deposition disease is a variant of multiple myeloma with distinct clinical and histological characteristics. MRI of this patient also revealed an infiltration pattern in the bone marrow distinct from that of typical multiple myeloma. Multiple small foci of low signal intensity were present on T1- and T2-weighted spin echo and STIR images, corresponding to conglomerates of light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo images show diffuse enhancement of 51% over all vertebral bodies, with a minor enhancement of the focal conglomerates of light chains. Light chain deposition disease in multiple myeloma should be added to the list of those few entities with normal radiographs and discrete low-signal marrow lesions on T1- and T2-weighted spin echo pulse sequences. (orig.)

A simplified approach for evaluating multiple test outcomes and multiple disease states in relation to the exercise thallium-201 stress test in suspected coronary artery disease

International Nuclear Information System (INIS)

Pollock, S.G.; Watson, D.D.; Gibson, R.S.; Beller, G.A.; Kaul, S.

1989-01-01

This study describes a simplified approach for the interpretation of electrocardiographic and thallium-201 imaging data derived from the same patient during exercise. The 383 patients in this study had also undergone selective coronary arteriography within 3 months of the exercise test. This matrix approach allows for multiple test outcomes (both tests positive, both negative, 1 test positive and 1 negative) and multiple disease states (no coronary artery disease vs 1-vessel vs multivessel coronary artery disease). Because this approach analyzes the results of 2 test outcomes simultaneously rather than serially, it also negates the lack of test independence, if such an effect is present. It is also demonstrated that ST-segment depression on the electrocardiogram and defects on initial thallium-201 images provide conditionally independent information regarding the presence of coronary artery disease in patients without prior myocardial infarction. In contrast, ST-segment depression on the electrocardiogram and redistribution on the delayed thallium-201 images may not provide totally independent information regarding the presence of exercise-induced ischemia in patients with or without myocardial infarction

A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

Science.gov (United States)

Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

2015-01-01

Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people

[Retinopathy of prematurity in multiple births: risk analysis for plus disease].

Science.gov (United States)

García-Serrano, J L; Ramírez-García, M C; Piñar-Molina, R

2009-04-01

To analyze the risk factors associated with plus disease in retinopathy of prematurity (ROP). Over a period of 8.5 years we carried out a prospective study of ROP in twins and triplets. Fifty-four multiple-birth infants with low birth weight (large area of avascular retina, low gestational age, low birth weight, a patent ductus arteriosus, length of mechanical ventilation, adverse events increase, low 5 min Apgar scores and poor postnatal weight gain (in the first 4 to 6 weeks of life). Using multiple logistic regression, only the grade of ROP (OR: 5.5; p disease gained an average 3.9 +/- 3.1 g/day in the first 6 weeks of life, compared to a mean of 11.84 +/- 8.3 g/day for those without plus disease (p < 0.0001). Advanced ROP stages and poor weight gain were the most significant factors associated with plus disease. Twins who gained weight at more than 7 g/day in the first 4-6 weeks of life had a significantly reduced risk of plus disease. A good weight gain is an effective strategy against avoidable blindness due to ROP.

Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease.

Science.gov (United States)

Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

2017-01-01

Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz - neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach's coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low

Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP

International Nuclear Information System (INIS)

Cohen, M.B.; Graham, L.S.; Lake, R.

1986-01-01

Tomographic imaging of the brain was performed using a rotating slant hole collimator and [ 123 I]N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of 123 I appears to be a useful technique for the evaluation of demented patients

A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

KAUST Repository

Kannan, Venkateshan

2017-03-29

Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.

Serological prevalence of celiac disease in Brazilian population of multiple sclerosis, neuromyelitis optica and myelitis.

Science.gov (United States)

de Oliveira, Pérola; de Carvalho, Daniel Rocha; Brandi, Ivar Viana; Pratesi, Riccardo

2016-09-01

Comorbidity of celiac disease with demyelinating diseases of the central nervous system has been reported since the 1960s. The objective of this study was to determine the serological prevalence of celiac disease in the largest series of patients diagnosed with multiple sclerosis, neuromyelitis optica, or myelitis. A prevalence study was conducted with patients evaluated at Sarah Network of Rehabilitation Hospitals between March 2012 and September 2013. They were previously diagnosed with multiple sclerosis, neuromyelitis optica, or idiopathic myelitis. The serum levels of antibodies against tissue transglutaminase and endomysium were assessed. Of the 379 patients evaluated, 249 (65.70%) were diagnosed with multiple sclerosis, 37 (9.56%) with neuromyelitis optica, and 96 (24.54%) with idiopathic myelitis. Two patients (0.53%), one with multiple sclerosis and other with myelitis, tested positive for both antibodies. Our study do not confirm the relationship between celiac serological antibodies with multiple sclerosis, neuromyelitis optica and inflammatory myelitis of an unknown etiology. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple concurrent primary extramammary Paget’s disease

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Leelavathi Muthupalaniappen

2016-11-01

Full Text Available Extramammary Paget’s disease (EMPD is a rare malignant disorder of the skin, which was described in as early as the nineteenth century. EMPD usually occurs as a single lesion in the apocrine sweat gland–bearing skin with abundant hair follicles. Here, we present an elderly man who suffered from a non-resolving chronic genital pruritus for 8 months. Initially, he was managed for recurrent fungal infection and eczema. Later, a diagnosis of the rare condition multiple primary EMPD was made based on the histopathology findings and appropriate treatment was given.

Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma.

Science.gov (United States)

Bhowmik, Debajyoti; Song, Xue; Intorcia, Michele; Kent, Shia T; Shi, Nianwen

2018-01-01

Objectives Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US. Methods In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases. Chronic kidney disease patients had ≥1 diagnosis of chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date = index date) on or after the first multiple myeloma diagnosis, and were propensity score matched 1:1 to multiple myeloma patients without chronic kidney disease, end-stage renal disease, dialysis, or other type of chronically impaired renal function. All patients had ≥six-month continuous enrollment prior to index date and were followed for ≥one month from index date until the earliest of inpatient death, end of continuous enrollment, or end of the study period (30 September 2015). The per-patient per-year healthcare resource utilization and costs were measured during follow-up. Costs were total reimbursed amount in 2016 US dollars. Results A total of 2541 multiple myeloma patients with chronic kidney disease stages 1-5 and 2541 matched controls met the study criteria and were respectively 69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of follow up. Compared to controls, chronic kidney disease patients had significantly (all P chronic kidney disease, end-stage renal disease, or dialysis had $78,455 ( P chronic kidney disease in patients with multiple myeloma was estimated to be between $34,754 and $78,455 per-patient per-year. Given its substantial clinical and economic impact, preservation of renal function is important in

Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

Science.gov (United States)

Stefan, V.

2013-03-01

A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

Evaluation of prevalence of headache in Multiple Sclerosis patients before & after the disease

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H. Mozhdehipanah

2017-08-01

Full Text Available Background: Multiple Sclerosis disease is a chronic disease of nervous system which causes different symptoms. Although headache is not a major symptom of this disease, but a lot of patients suffer from it. To specify the prevalence of headache and its’ types has an important role in diagnose, treatment and improvement the quality of patients’ life. Objective: Our goal of this study was to determine the prevalence of headache in multiple sclerosis patients, before and after the diagnosis of this disease. Methods: This cross-sectional descriptive epidemiologic study was performed on 150 multiple sclerosis patients referred to the neurology clinic of Qazvin in 2015. Data were recorded by history taking & physical examination the existence of headache before the MS diagnosis and at the time of study was evaluated by the patients’ data. Findings: Among participants, prevalence of headache before the MS diagnosis was 40%, which increased to 64% after that (P<0.001. The most common type of headache, before and after the affection was tension headache, which formed 58.3% and 70.8% of all headaches, respectively. The average rate of headache in the group with headache, before and after the diagnosis of MS was 5.8 and 5.76 days in month, which calculated 2.32 and 3.68 days in month in all patients, respectively. Conclusion: Prevalence of headache increases in multiple sclerosis patients. Patients suffer from headache almost 13% of their life days.

Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

International Nuclear Information System (INIS)

Weber, Marc-Andre; Delorme, Stefan; Hillengass, Jens

2014-01-01

Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

Designed multiple ligands in metabolic disease research: from concept to platform.

Science.gov (United States)

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human endogenous retroviruses and multiple sclerosis: innocent bystanders or disease determinants?

Science.gov (United States)

Antony, Joseph M; Deslauriers, Andre M; Bhat, Rakesh K; Ellestad, Kristofer K; Power, Christopher

2011-02-01

Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies. 2010 Elsevier B.V. All rights reserved.

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

Science.gov (United States)

Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

2017-06-01

Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

A Case of Multiple Sclerosis and Celiac Disease

Directory of Open Access Journals (Sweden)

H. Z. Batur-Caglayan

2013-01-01

Full Text Available Objectives. Multiple sclerosis (MS is an inflammatory autoimmune disorder of the central nervous system (CNS. Since a correlation between gluten intake and incidence of MS had been reported, the relationship of antigliadin antibodies and MS was debated. Case Report. We report the case of a 45-year-old female MS patient who is under interferon treatment. After seven years of monitoring, during her routine gastroenterological assessment, she was diagnosed with celiac disease. Conclusion. Beside the neurological manifestations that have been demonstrated in about 10% of celiac disease (CD patients, white-matter abnormalities in brain MRI are uncommon and controversial. But in the literature, MS seems to be associated with CD as in our patient. We suggest that MS patients with gastroenterological complaints should undergo an assessment for CD.

Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

NARCIS (Netherlands)

Visser, Leo H.; Heerings, Marco A.; Jongen, Peter J.; van der Hiele, Karin

2016-01-01

Background: The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study

Health-related needs of people with multiple chronic diseases: differences and underlying factors.

NARCIS (Netherlands)

Hopman, P.; Schellevis, F.G.; Rijken, M.

2016-01-01

Purpose: To examine the health-related needs of people with multiple chronic diseases in the Netherlands compared to people with one chronic disease, and to identify different subgroups of multimorbid patients based on differences in their health problems. Methods: Participants were 1092 people with

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

Science.gov (United States)

Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

2013-01-01

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

Default mode network links to visual hallucinations: A comparison between Parkinson's disease and multiple system atrophy.

Science.gov (United States)

Franciotti, Raffaella; Delli Pizzi, Stefano; Perfetti, Bernardo; Tartaro, Armando; Bonanni, Laura; Thomas, Astrid; Weis, Luca; Biundo, Roberta; Antonini, Angelo; Onofrj, Marco

2015-08-01

Studying default mode network activity or connectivity in different parkinsonisms, with or without visual hallucinations, could highlight its roles in clinical phenotypes' expression. Multiple system atrophy is the archetype of parkinsonism without visual hallucinations, variably appearing instead in Parkinson's disease (PD). We aimed to evaluate default mode network functions in multiple system atrophy in comparison with PD. Functional magnetic resonance imaging evaluated default mode network activity and connectivity in 15 multiple system atrophy patients, 15 healthy controls, 15 early PD patients matched for disease duration, 30 severe PD patients (15 with and 15 without visual hallucinations), matched with multiple system atrophy for disease severity. Cortical thickness and neuropsychological evaluations were also performed. Multiple system atrophy had reduced default mode network activity compared with controls and PD with hallucinations, and no differences with PD (early or severe) without hallucinations. In PD with visual hallucinations, activity and connectivity was preserved compared with controls and higher than in other groups. In early PD, connectivity was lower than in controls but higher than in multiple system atrophy and severe PD without hallucinations. Cortical thickness was reduced in severe PD, with and without hallucinations, and correlated only with disease duration. Higher anxiety scores were found in patients without hallucinations. Default mode network activity and connectivity was higher in PD with visual hallucinations and reduced in multiple system atrophy and PD without visual hallucinations. Cortical thickness comparisons suggest that functional, rather than structural, changes underlie the activity and connectivity differences. © 2015 International Parkinson and Movement Disorder Society.

A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

KAUST Repository

Kannan, Venkateshan; Kiani, Narsis A.; Piehl, Fredrik; Tegner, Jesper

2017-01-01

Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving

Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism.

Science.gov (United States)

Yi, Hyon-Seung; Kim, Ji Min; Ju, Sang Hyeon; Lee, Younghak; Kim, Hyun Jin; Kim, Koon Soon

2016-02-01

Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea.

Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

DEFF Research Database (Denmark)

Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

2012-01-01

The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

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Lewei Duan

2013-01-01

Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

Impulse control disorders are associated with multiple psychiatric symptoms in Parkinson's disease.

Science.gov (United States)

Jaakkola, Elina; Kaasinen, Valtteri; Siri, Chiara; Martikainen, Kirsti; Cilia, Roberto; Niemelä, Solja; Joutsa, Juho

2014-01-01

Impulse control disorders can have serious adverse consequences to the life of a patient with Parkinson's disease. Although impulse control disorders are common, a possible psychiatric comorbidity has not been fully characterized. The aim of this study was to investigate the psychiatric symptoms exhibited by Parkinson's disease patients with impulse control disorders. The study was conducted as a postal survey to patients in the registry of the Finnish Parkinson Association. A total of 290 Parkinson's disease patients were evaluated for impulse control disorders using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Psychiatric symptoms were systematically screened using the Symptom Checklist 90. We found that 108 of the evaluated patients had one or more impulse control disorders. Patients with impulse control disorders had markedly higher scores for symptoms of psychoticism (Bonferroni corrected p disorder (p impulse control disorders. Impulse control disorders were shown to be independently associated with these symptoms. Patients with multiple impulse control disorders had higher scores for depression and obsessive-compulsive symptoms when compared with patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our results confirm the previous observations that impulse control disorders in Parkinson's disease are linked with multiple psychiatric symptoms, including psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and depression. Clinicians treating these patients should acknowledge the concomitant psychiatric symptoms.

Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

LENUS (Irish Health Repository)

Shortt, Conor P

2009-04-01

The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs

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Xue Fuzhong

2010-01-01

Full Text Available Abstract Background Genetic association study is currently the primary vehicle for identification and characterization of disease-predisposing variant(s which usually involves multiple single-nucleotide polymorphisms (SNPs available. However, SNP-wise association tests raise concerns over multiple testing. Haplotype-based methods have the advantage of being able to account for correlations between neighbouring SNPs, yet assuming Hardy-Weinberg equilibrium (HWE and potentially large number degrees of freedom can harm its statistical power and robustness. Approaches based on principal component analysis (PCA are preferable in this regard but their performance varies with methods of extracting principal components (PCs. Results PCA-based bootstrap confidence interval test (PCA-BCIT, which directly uses the PC scores to assess gene-disease association, was developed and evaluated for three ways of extracting PCs, i.e., cases only(CAES, controls only(COES and cases and controls combined(CES. Extraction of PCs with COES is preferred to that with CAES and CES. Performance of the test was examined via simulations as well as analyses on data of rheumatoid arthritis and heroin addiction, which maintains nominal level under null hypothesis and showed comparable performance with permutation test. Conclusions PCA-BCIT is a valid and powerful method for assessing gene-disease association involving multiple SNPs.

Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

LENUS (Irish Health Repository)

Lonergan, Roisin

2012-02-01

Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

Science.gov (United States)

English, Clayton; Aloi, Joseph J

2015-04-01

Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

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Sahar Vesal

2016-01-01

Full Text Available Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS disease duration on personality type A and B in relation to individuals' behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18 based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years, 38% (5-10 years, 20% (10-20 years, and 12% (more than 20 years. Significant relationship was observed between disease duration and tendency to type A (higher stress. This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

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Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Genomic Physics. Multiple Laser Beam Treatment of Alzheimer's Disease

Science.gov (United States)

Stefan, V. Alexander

2014-03-01

The synapses affected by Alzheimer's disease can be rejuvenated by the multiple ultrashort wavelength laser beams.[2] The guiding lasers scan the whole area to detect the amyloid plaques based on the laser scattering technique. The scanning lasers pinpoint the areas with plaques and eliminate them. Laser interaction is highly efficient, because of the focusing capabilities and possibility for the identification of the damaging proteins by matching the protein oscillation eigen-frequency with laser frequency.[3] Supported by Nikola Tesla Labs, La Jolla, California, USA.

The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

Science.gov (United States)

Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa

2015-01-01

Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status. Copyright © 2014 Elsevier B.V. All rights reserved.

CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

2000-01-01

Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

[Disease concept, etiology and mechanisms of multiple sclerosis].

Science.gov (United States)

Kira, Jun-Ichi

2014-11-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

Feasibility of large-scale deployment of multiple wearable sensors in Parkinson's disease

NARCIS (Netherlands)

Silva de Lima, A.L.; Hahn, T.; Evers, L.J.W.; Vries, N.M. de; Cohen, E.; Afek, M.; Bataille, L.; Daeschler, M.; Claes, K.; Boroojerdi, B.; Terricabras, D.; Little, M.A.; Baldus, H.; Bloem, B.R.; Faber, M.J.

2017-01-01

Wearable devices can capture objective day-to-day data about Parkinson's Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort

Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Richard A Awad

2011-01-01

Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

Speech and Pause Characteristics Associated with Voluntary Rate Reduction in Parkinson's Disease and Multiple Sclerosis

Science.gov (United States)

Tjaden, Kris; Wilding, Greg

2011-01-01

The primary purpose of this study was to investigate how speakers with Parkinson's disease (PD) and Multiple Sclerosis (MS) accomplish voluntary reductions in speech rate. A group of talkers with no history of neurological disease was included for comparison. This study was motivated by the idea that knowledge of how speakers with dysarthria…

Multiple disease resistance to fungal and oomycete pathogens using a recombinant inbred line population in pepper

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Incorporating disease resistance into cultivars is a primary focus of modern breeding programs. Resistance to pathogens is often introgressed from landrace or wild individuals with poor fruit quality into commercial-quality cultivars. Sites of multiple disease resistance (MDR) are regions or “hotspo...

Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

Science.gov (United States)

Xu, You-hai; Xu, Kui; Sun, Ying; Liou, Benjamin; Quinn, Brian; Li, Rong-hua; Xue, Ling; Zhang, Wujuan; Setchell, Kenneth D R; Witte, David; Grabowski, Gregory A

2014-08-01

Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD. © The Author 2014. Published by Oxford University

Multiple sclerosis: patients’ information sources and needs on disease symptoms and management

Directory of Open Access Journals (Sweden)

Albert I Matti

2010-06-01

Full Text Available Albert I Matti1, Helen McCarl2, Pamela Klaer2, Miriam C Keane1, Celia S Chen11Department of Ophthalmology, Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia; 2The Multiple Sclerosis Society of South Australia and Northern Territory, Klemzig, SA, AustraliaObjective: To investigate the current information sources of patients with multiple sclerosis (MS in the early stages of their disease and to identify patients’ preferred source of information. The relative amounts of information from the different sources were also compared.Methods: Participants at a newly diagnosed information session organized by the Multiple Sclerosis Society of South Australia were invited to complete a questionnaire. Participants were asked to rate on a visual analog scale how much information they had received about MS and optic neuritis from different information sources and how much information they would like to receive from each of the sources.Results: A close to ideal amount of information is being provided by the MS society and MS specialist nurses. There is a clear deficit between what information patients are currently receiving and the amount of information they actually want from various sources. Patients wish to receive significantly more information from treating general practitioners, eye specialists, neurologists, and education sessions. Patients have identified less than adequate information received on optic neuritis from all sources.Conclusion: This study noted a clear information deficit regarding MS from all sources. This information deficit is more pronounced in relation to optic neuritis and needs to be addressed in the future.Practice implications: More patient information and counselling needs to be provided to MS patients even at early stages of their disease, especially in relation to management of disease relapse.Keywords: information sources, information needs, MS patients, optic neuritis

Multiple schwannomas of cauda equine in the absence of von Recklinghausen's disease

International Nuclear Information System (INIS)

Kayaoglu, Cetin R.; Sengul, G.; Aydin, Ismail H.

2007-01-01

Multiple schwannomas in the absence of neurofibromatosis is rarely reported in the literature. We present a 56-year-old female with a history of severe leg and back pain on the left side for one year. Magnetic resonance imaging revealed 4 schwannomas located in the cauda equine in the absence of von Recklinghausen's disease. (author)

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...

Staphylococcus cohnii as a cause of multiple brain abscesses in Weber-Christian disease.

Science.gov (United States)

Yamashita, Satoshi; Yonemura, Kiminobu; Sugimoto, Ryoko; Tokunaga, Makoto; Uchino, Makoto

2005-11-15

We report a patient with multiple brain abscesses due to Staphylococcus cohnii. While these brain abscesses markedly responded to the antibiotics, this patient was subsequently suffered from subcutaneous inflammatory nodules in the adipose tissue, which diagnosed him as having Weber-Christian disease (WCD). This is the first report that subcutaneous inflammatory nodules in the adipose tissue, which lead the diagnosis of WCD, followed multiple brain abscesses. To our knowledge, S. cohnii has not yet been reported to cause multiple brain abscesses in humans. Although the etiology of WCD is unknown, an immune mechanism has been implicated in the pathogenesis. Therefore, we should notice that patients with WCD could be immunocompromised hosts with a higher risk to suffer from severe opportunistic infections.

Target intervention against multiple-risk markers to reduce cardiovascular disease in patients with type 2 diabetes

DEFF Research Database (Denmark)

Gaede, Peter; Pedersen, Oluf

2004-01-01

The risk of cardiovascular disease is markedly increased in patients with type 2 diabetes with a prevalence twice as high compared to the background population. With the recognition of multiple concomitant risk factors for both microvascular as well as cardiovascular disease in type 2 diabetic pa...

Infections in patients with multiple sclerosis: Implications for disease-modifying therapy.

Science.gov (United States)

Celius, E G

2017-11-01

Patients with multiple sclerosis have an increased risk of infections compared to the general population. The increased risk has been described for decades and is not alone attributed to the use of disease-modifying drugs, but secondary to the disability. The introduction of more potent immunomodulatory drugs may cause an additional challenge, and depending on the mechanism of action, a treatment-induced increased risk of bacterial, viral, fungal or parasitic infections is observed. The choice of treatment in the individual patient with infections and multiple sclerosis must be guided by the drugs' specific mechanism of action, the drug-specific risk of infection and comorbidities. Increased monitoring and follow-up through treatment registries is warranted to increase our understanding and thereby improve management. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predictors of activity and participation across neurodegenerative conditions: a comparison of people with motor neurone disease, multiple sclerosis and Parkinson's disease.

Science.gov (United States)

Morley, David; Dummett, Sarah; Kelly, Laura; Fitzpatrick, Ray; Jenkinson, Crispin

2018-02-17

Comparisons between neurological conditions have the potential to inform service providers by identifying particular areas of difficulty experienced by affected individuals. This study aimed to identify predictors of activity and participation in people with motor neurone disease (MND), people with multiple sclerosis (MS) and people with Parkinson's Disease (PD). The Oxford Participation and Activities Questionnaire (Ox-PAQ) and Medical Outcomes Study 36-Item Short Form Survey (MOS SF-36) were administered by postal survey to 386 people with a confirmed diagnosis of MND, MS or PD. Data analyses focused on stepwise regression analyses in order to identify predictors of activity and participation in the three conditions assessed. Three hundred and thirty four participants completed the survey, a response rate of 86.5%. Regression analyses identified multiple predictors of activity and participation dependent on Ox-PAQ domain and disease group, the most prominent being social and physical functioning as measured by the MOS SF-36. Results indicate that the physical and social consequences of neurological illness are of greatest relevance to people experiencing the conditions assessed. Whilst the largely inevitable physical implications of disease take hold, emphasis should be placed on the avoidance of social withdrawal and isolation, and the maintenance of social engagement should become a significant priority.

Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience

OpenAIRE

Casamento, K.; Laverty, A.; Wilsher, M.; Twiss, J.; Gabbay, E.; Glaspole, I.; Jaffe, A.

2016-01-01

Background We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. Methods A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were s...

Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

Energy Technology Data Exchange (ETDEWEB)

Sowa, Piotr [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Owren Nygaard, Gro [Oslo University Hospital, Department of Neurology, Oslo (Norway); Bjoernerud, Atle [Intervention Center, Oslo University Hospital, Oslo (Norway); University of Oslo, Department of Physics, Oslo (Norway); Gulowsen Celius, Elisabeth [Oslo University Hospital, Department of Neurology, Oslo (Norway); University of Oslo, Institute of Health and Society, Faculty of Medicine, Oslo (Norway); Flinstad Harbo, Hanne [University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Oslo University Hospital, Department of Neurology, Oslo (Norway); Kristiansen Beyer, Mona [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Department of Life Sciences and Health, Oslo (Norway)

2017-07-15

The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

International Nuclear Information System (INIS)

Sowa, Piotr; Owren Nygaard, Gro; Bjoernerud, Atle; Gulowsen Celius, Elisabeth; Flinstad Harbo, Hanne; Kristiansen Beyer, Mona

2017-01-01

The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

Directory of Open Access Journals (Sweden)

James E Peters

2016-03-01

Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

Relationship between contrast sensitivity test and disease severity in multiple sclerosis patients.

Science.gov (United States)

Soler García, A; González Gómez, A; Figueroa-Ortiz, L C; García-Ben, A; García-Campos, J

2014-09-01

To assess the importance of the Pelli-Robson contrast sensitivity test in multiple sclerosis patients according to the Expanded Disability Status Scale (EDSS). A total of 62 patients with multiple sclerosis were included in a retrospective study. Patients were enrolled from the Neurology Department to Neuroophthalmology at Virgen de la Victoria Hospital. Patients were classified into 3 groups according to EDSS: group A) lower than 1.5, group B) between 1.5 and 3.5 and group C) greater than 3.5. Visual acuity and monocular and binocular contrast sensitivity were performed with Snellen and Pelli-Robson tests respectively. Twelve disease-free control participants were also recruited. Correlations between parameter changes were analyzed. The mean duration of the disease was 81.54±35.32 months. Monocular and binocular Pelli-Robson mean values in the control group were 1.82±0.10 and 1.93±0.43 respectively, and 1.61±0.29 and 1.83±0.19 in multiple sclerosis patients. There were statistically significant differences in the monocular analysis for a level of significance P<.05. Mean monocular and binocular Pelli-Robson values in relation to gravity level were, in group A: 1.66±0.24 and 1.90±0.98, group B: 1.64±0.21 and 1.82±0.16, and group C: 1.47±0.45 and 1.73±0.32 respectively. Group differences were statistically significant in both tests: P=.05 and P=.027. Monocular and binocular contrast discrimination analyzed using the Pelli-Robson test was found to be significantly lower when the severity level, according EDSS, increases in multiple sclerosis patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

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.

Visual field impairment captures disease burden in multiple sclerosis.

Science.gov (United States)

Ortiz-Perez, Santiago; Andorra, Magí; Sanchez-Dalmau, Bernardo; Torres-Torres, Rubén; Calbet, David; Lampert, Erika J; Alba-Arbalat, Salut; Guerrero-Zamora, Ana M; Zubizarreta, Irati; Sola-Valls, Nuria; Llufriu, Sara; Sepúlveda, María; Saiz, Albert; Villoslada, Pablo; Martinez-Lapiscina, Elena H

2016-04-01

Monitoring disease burden is an unmeet need in multiple sclerosis (MS). Identifying patients at high risk of disability progression will be useful for improving clinical-therapeutic decisions in clinical routine. To evaluate the role of visual field testing in non-optic neuritis eyes (non-ON eyes) as a biomarker of disability progression in MS. In 109 patients of the MS-VisualPath cohort, we evaluated the association between visual field abnormalities and global and cognitive disability markers and brain and retinal imaging markers of neuroaxonal injury using linear regression models adjusted for sex, age, disease duration and use of disease-modifying therapies. We evaluated the risk of disability progression associated to have baseline impaired visual field after 3 years of follow-up. Sixty-two percent of patients showed visual field defects in non-ON eyes. Visual field mean deviation was statistically associated with global disability; brain (normalized brain parenchymal, gray matter volume and lesion load) and retinal (peripapillary retinal nerve fiber layer thickness and macular ganglion cell complex thickness) markers of neuroaxonal damage. Patients with impaired visual field had statistically significative greater disability, lower normalized brain parenchymal volume and higher lesion volume than patients with normal visual field testing. MS patients with baseline impaired VF tripled the risk of disability progression during follow-up [OR = 3.35; 95 % CI (1.10-10.19); p = 0.033]. The association of visual field impairment with greater disability and neuroaxonal injury and higher risk of disability progression suggest that VF could be used to monitor MS disease burden.

Comparison between cerebral ischemia disease and multiple sclerosis by using MR diffusion tensor imaging

International Nuclear Information System (INIS)

Lou Xin; Cai Youquan; Ma Lin; Cai Jianming

2007-01-01

Objective: To assess the value of MR diffusion tensor imaging (DTI) in the differentiation between the patients with cerebral ischemia disease and multiple sclerosis. Methods: MR diffusion tensor imaging was performed in thirty-two patients with internal carotid artery stenosis ≥70% and eighteen patients with clinical diagnosed multiple sclerosis. Fractional anisotropy (FA) value of the germ, splenium, body of the corpus callosum, and the white matter of the frontal and occipital lobe were measured respectively, and independent-sample t-test statistical analysis was performed. Results: The FA value was decreased obviously in the anterior and posterior body and splenium of the corpus callosumin the MS patients compared with the ICA severe stenosis patients (0.67 ± 0.12 vs. 0.75 ± 0.05, t=3.443, P 0.05; 0.34 ± 0.08 vs. 0.34 ± 0.05, t=0.137, P> 0.05; 0.29 ± 0.06 vs. 0.40 ± 0.06, t=5.449, P>0.05). Conclusion: DTI can noninvasive detect the potential disorder of corpus callosum in vivo, thus providing useful information to differentiate the cerebral ischemia disease from multiple sclerosis. (authors)

CD4 T cell activation and disease activity at onset of multiple sclerosis

DEFF Research Database (Denmark)

Jensen, J; Langkilde, Annika Reynberg; Fenst, C

2004-01-01

We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

International Nuclear Information System (INIS)

Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail; Topalkara, Kamil; Erkoc, Mustafa F.

2015-01-01

Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm 2 . ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm 2 which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10 -3 mm 2 /s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10 -3 mm 2 /s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10 -3 mm 2 /s in MS patients, and (0.75 ± 0.08) x 10 -3 mm 2 /s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

Energy Technology Data Exchange (ETDEWEB)

Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey); Topalkara, Kamil [Bayindir Hospital, Department of Neurology, Ankara (Turkey); Erkoc, Mustafa F. [Bozok University School of Medicine, Department of Radiology, Yozgat (Turkey)

2015-04-01

Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm{sup 2}. ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm{sup 2} which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10{sup -3} mm{sup 2}/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10{sup -3} mm{sup 2}/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10{sup -3} mm{sup 2}/s in MS patients, and (0.75 ± 0.08) x 10{sup -3} mm{sup 2}/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

Multiple sclerosis

International Nuclear Information System (INIS)

Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

2008-01-01

Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

LENUS (Irish Health Repository)

O'Brien, M

2012-02-01

BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

Payment for multiple forest benefits alters the effect of tree disease on optimal forest rotation length.

Science.gov (United States)

Macpherson, Morag F; Kleczkowski, Adam; Healey, John R; Hanley, Nick

2017-04-01

Forests deliver multiple benefits both to their owners and to wider society. However, a wave of forest pests and pathogens is threatening this worldwide. In this paper we examine the effect of disease on the optimal rotation length of a single-aged, single rotation forest when a payment for non-timber benefits, which is offered to private forest owners to partly internalise the social values of forest management, is included. Using a generalisable bioeconomic framework we show how this payment counteracts the negative economic effect of disease by increasing the optimal rotation length, and under some restrictive conditions, even makes it optimal to never harvest the forest. The analysis shows a range of complex interactions between factors including the rate of spread of infection and the impact of disease on the value of harvested timber and non-timber benefits. A key result is that the effect of disease on the optimal rotation length is dependent on whether the disease affects the timber benefit only compared to when it affects both timber and non-timber benefits. Our framework can be extended to incorporate multiple ecosystem services delivered by forests and details of how disease can affect their production, thus facilitating a wide range of applications.

Exploration of machine learning techniques in predicting multiple sclerosis disease course

OpenAIRE

Zhao, Yijun; Healy, Brian C.; Rotstein, Dalia; Guttmann, Charles R. G.; Bakshi, Rohit; Weiner, Howard L.; Brodley, Carla E.; Chitnis, Tanuja

2017-01-01

Objective To explore the value of machine learning methods for predicting multiple sclerosis disease course. Methods 1693 CLIMB study patients were classified as increased EDSS?1.5 (worsening) or not (non-worsening) at up to five years after baseline visit. Support vector machines (SVM) were used to build the classifier, and compared to logistic regression (LR) using demographic, clinical and MRI data obtained at years one and two to predict EDSS at five years follow-up. Results Baseline data...

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

Science.gov (United States)

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

MKRMDA: multiple kernel learning-based Kronecker regularized least squares for MiRNA-disease association prediction.

Science.gov (United States)

Chen, Xing; Niu, Ya-Wei; Wang, Guang-Hui; Yan, Gui-Ying

2017-12-12

Recently, as the research of microRNA (miRNA) continues, there are plenty of experimental evidences indicating that miRNA could be associated with various human complex diseases development and progression. Hence, it is necessary and urgent to pay more attentions to the relevant study of predicting diseases associated miRNAs, which may be helpful for effective prevention, diagnosis and treatment of human diseases. Especially, constructing computational methods to predict potential miRNA-disease associations is worthy of more studies because of the feasibility and effectivity. In this work, we developed a novel computational model of multiple kernels learning-based Kronecker regularized least squares for MiRNA-disease association prediction (MKRMDA), which could reveal potential miRNA-disease associations by automatically optimizing the combination of multiple kernels for disease and miRNA. MKRMDA obtained AUCs of 0.9040 and 0.8446 in global and local leave-one-out cross validation, respectively. Meanwhile, MKRMDA achieved average AUCs of 0.8894 ± 0.0015 in fivefold cross validation. Furthermore, we conducted three different kinds of case studies on some important human cancers for further performance evaluation. In the case studies of colonic cancer, esophageal cancer and lymphoma based on known miRNA-disease associations in HMDDv2.0 database, 76, 94 and 88% of the corresponding top 50 predicted miRNAs were confirmed by experimental reports, respectively. In another two kinds of case studies for new diseases without any known associated miRNAs and diseases only with known associations in HMDDv1.0 database, the verified ratios of two different cancers were 88 and 94%, respectively. All the results mentioned above adequately showed the reliable prediction ability of MKRMDA. We anticipated that MKRMDA could serve to facilitate further developments in the field and the follow-up investigations by biomedical researchers.

Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI

Directory of Open Access Journals (Sweden)

Antonio Jose da Rocha

2013-09-01

Full Text Available The current diagnostic criteria for multiple sclerosis (MS confirm the relevant role of magnetic resonance imaging (MRI, supporting the possibility of characterizing the dissemination in space (DIS and the dissemination in time (DIT in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diagnosis list, including diseases with exacerbation, remitting periods and numerous treatable infectious diseases, which can mimic the MRI features of MS. We discuss the most relevant imaging features in several infectious diseases that resemble MS and examine the primary spatial distributions of lesions and the gadolinium enhancement patterns related to MS. Recognizing imaging "red flags" can be useful for the proper diagnostic evaluation of suspected cases of MS, facilitating the correct differential diagnosis by assessing the combined clinical, laboratory and MR imaging information.

Cat-scratch disease presenting as multiple hepatic lesions: case report and literature review.

Science.gov (United States)

Baptista, Mariana Andrade; Lo, Denise Swei; Hein, Noely; Hirose, Maki; Yoshioka, Cristina Ryoka Miyao; Ragazzi, Selma Lopes Betta; Gilio, Alfredo Elias; Ferronato, Angela Esposito

2014-01-01

Although infectious diseases are the most prevalent cause of fevers of unknown origin (FUO), this diagnosis remains challenging in some pediatric patients. Imaging exams, such as computed tomography (CT) are frequently required during the diagnostic processes. The presence of multiple hypoattenuating scattered images throughout the liver associated with the history of cohabitation with cats should raise the suspicion of the diagnosis of cat-scratch disease (CSD), although the main etiologic agent of liver abscesses in childhood is S taphylococcus aureus . Differential diagnosis by clinical and epidemiological data with Bartonella henselae is often advisable. The authors report the case of a boy aged 2 years and 9 months with 16-day history of daily fever accompanied by intermittent abdominal pain. Physical examination was unremarkable. Abdominal ultrasound performed in the initial work up was unrevealing, but an abdominal CT that was performed afterwards disclosed multiple hypoattenuating hepatic images compatible with the diagnosis of micro abscesses. Initial antibiotic regimen included cefotaxime, metronidazole, and oxacillin. Due to the epidemiology of close contact with kittens, diagnosis of CSD was considered and confirmed by serologic tests. Therefore, the initial antibiotics were replaced by clarithromycin orally for 14 days followed by fever defervescence and clinical improvement. The authors call attention to this uncommon diagnosis in a child presenting with FUO and multiple hepatic images suggestive of micro abscesses.

Cat-scratch disease presenting as multiple hepatic lesions: case report and literature review

Directory of Open Access Journals (Sweden)

Mariana Andrade Baptista

2014-06-01

Full Text Available Although infectious diseases are the most prevalent cause of fevers of unknown origin (FUO, this diagnosis remains challenging in some pediatric patients. Imaging exams, such as computed tomography (CT are frequently required during the diagnostic processes. The presence of multiple hypoattenuating scattered images throughout the liver associated with the history of cohabitation with cats should raise the suspicion of the diagnosis of cat-scratch disease (CSD, although the main etiologic agent of liver abscesses in childhood is Staphylococcus aureus. Differential diagnosis by clinical and epidemiological data with Bartonella henselae is often advisable. The authors report the case of a boy aged 2 years and 9 months with 16-day history of daily fever accompanied by intermittent abdominal pain. Physical examination was unremarkable. Abdominal ultrasound performed in the initial work up was unrevealing, but an abdominal CT that was performed afterwards disclosed multiple hypoattenuating hepatic images compatible with the diagnosis of micro abscesses. Initial antibiotic regimen included cefotaxime, metronidazole, and oxacillin. Due to the epidemiology of close contact with kittens, diagnosis of CSD was considered and confirmed by serologic tests. Therefore, the initial antibiotics were replaced by clarithromycin orally for 14 days followed by fever defervescence and clinical improvement. The authors call attention to this uncommon diagnosis in a child presenting with FUO and multiple hepatic images suggestive of micro abscesses.

Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

Directory of Open Access Journals (Sweden)

Jose Flores

2012-01-01

Full Text Available Multiple Sclerosis (MS is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases

Directory of Open Access Journals (Sweden)

Azzam Maghazachi

2016-07-01

Full Text Available Several drugs have been approved for treatment of multiple sclerosis. Dimethyl fumarate (DMF is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF, a related compound has not been examined in greater details although it has the potential as a therapeutic drug for multiple sclerosis and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species. However, other mechanisms have also been described which include effects on monocytes, dendritic cells, T cells, and natural killer cells. It is also reported that DMF might be useful for treating psoriasis, asthma, aggressive breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. In this article we will touch on some of these diseases with an emphasis on the effects of DMF and MMF on various immune cells.

Growth Hormone and Disease Severity in Early Stage of Multiple Sclerosis

Directory of Open Access Journals (Sweden)

M. Gironi

2013-01-01

Full Text Available Evidence suggests that neurohormones such as GH and IGF-I are involved in the neuroreparative processes in multiple sclerosis (MS. GH and IGF-I blood levels in naïve MS patients with different disease courses were investigated in this study. Serum GH and IGF-I in untreated MS patients (n=64, healthy controls (HC, n=62, and patients affected by other neurological diseases (OND, n=46 were evaluated with a solid-phase-enzyme-labeled-chemiluminescent-immunometric assay. No differences were detected in GH across MS, OND, and HC (MS=0.87±1.32 ng/mL; OND=1.66±3.7; and HC=1.69±3.35; P=0.858 when considering gender, disease duration, and disease course. However, GH was lower (P=0.007 in patients with more severe disease (expanded disability scale score, EDSS≥4.0 compared with milder forms (EDSS<4. IGF-I l did not differ across the 3 groups (P=0.160, as far as concern disease course, disability, and gender were. Lower IGF-I levels were detected in subjects older than 50 years compared to younger ones for all 3 groups. Lower GH was detected in patients with more severe MS, and age was confirmed as the main factor driving IGF-I levels in all subjects. These findings, relying on the natural course of the disease, could help in shedding lights on the mechanisms involved in autoreparative failure associated with poorer prognosis in MS.

Combined influence of multiple climatic factors on the incidence of bacterial foodborne diseases.

Science.gov (United States)

Park, Myoung Su; Park, Ki Hwan; Bahk, Gyung Jin

2018-01-01

Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (Pclimatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

DEFF Research Database (Denmark)

Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy

DEFF Research Database (Denmark)

Comabella, M; Balashov, K; Issazadeh-Navikas, Shohreh

1998-01-01

Multiple sclerosis is postulated to be a Th1-type cell-mediated autoimmune disease. We investigated cytokine profiles in patients with progressive multiple sclerosis by using intracytoplasmic staining. We found increased IL-12 production by monocytes and increased IFN-gamma production by T cells...

'CM 88' - A multiple disease resistant chickpea mutant variety

International Nuclear Information System (INIS)

Haq, M.A.; Hassan, Mahmudul; Sadiq, M.

2001-01-01

Full text: Chickpea is the most important grain legume crop of Pakistan. Ascochyta blight (Ascochyta rabiei) and Fusarium wilt (Fusarium oxysporum F. sp cicer) are most serious diseases, having the potential to devastate a crop. A multiple disease resistant and high yielding mutant CM 88 has been developed through 100 Gy gamma irradiation treatment of variety 'C 727'. This was once a widely grown and popular variety, which lost its resistance to Ascochyta and was replaced. The selection of mutants was performed in the M2 generation grown in the Ascochyta blight nursery and sixteen mutants were selected. In the subsequent generations CM 88 proved resistant to both Ascochyta blight and Fusarium wilt, and exhibited superiority in agronomic characteristics. CM 88 was also tested for many years in the various yield trials on research stations and farmers fields throughout the country. In these trials it out yielded both the parent and standard varieties. The mutant CM 88 has been approved by the Punjab Seed Council on 27 October 1994 for general cultivation in the Punjab Province, especially the Thal area which accounts for more than 70% of the area under chickpea cultivation. (author)

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

Science.gov (United States)

Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

2018-04-18

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Internal tremor in Parkinson's disease, multiple sclerosis, and essential tremor.

Science.gov (United States)

Cochrane, Graham D; Rizvi, Syed; Abrantes, Ana; Crabtree, Brigid; Cahill, Jonathan; Friedman, Joseph H

2015-10-01

Internal tremor (IT) is a poorly recognized symptom that has been described in Parkinson's disease (PD). Described as a feeling of tremor in the extremities or trunk without actual movement, ITs are not debilitating but can be bothersome to patients. The origin of the sensation is unknown., and ITs may be prevalent in other diseases than PD. The present study sought to expand knowledge about IT by confirming their presence in PD, and determining their prevalence in Multiple Sclerosis (MS), and Essential Tremor (ET). A survey was developed in order to determine the prevalence of IT in PD, MS, and ET and to learn what associations with various disease characteristics were present. The survey was administered to 89 consecutive PD, 70 MS, and 11 ET patients. ITs were found to be a prevalent symptom in all three disorders (32.6% of PD, 35.9% of MS, and 54.5% of ET subjects reported experiencing ITs). ITs were found to be associated both with the subjects' perceived levels of anxiety and the presence of visible tremors. ITs appear to be a common symptom in all three disorders studied. These results need to be confirmed and compared to appropriate control populations. Copyright © 2015. Published by Elsevier Ltd.

Characterization of annual disease progression of multiple sclerosis patients: A population-based study

DEFF Research Database (Denmark)

Freilich, Jonatan; Manouchehrinia, Ali; Trusheim, Mark

2017-01-01

Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching...... the milestone. To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition...... from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect...

Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

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Anu Batra

2014-01-01

Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

2012-01-01

the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

One For All? Hitting multiple Alzheimer’s Disease targets with one drug

Directory of Open Access Journals (Sweden)

Rebecca Ellen Hughes

2016-04-01

Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

[Being cared for and caring: living with multiple chronic diseases (Leila)-a qualitative study about APN contributions to integrated care].

Science.gov (United States)

Müller-Staub, Maria; Zigan, Nicole; Händler-Schuster, Daniela; Probst, Sebastian; Monego, Renate; Imhof, Lorenz

2015-04-01

Living with multiple chronic diseases is complex and leads to enhanced care needs. To foster integrated care a project called "Living with chronic disease" (Leila) was initiated. The aim was to develop an Advanced Practice Nursing (APN) service in collaboration with medical centers for persons who are living with multiple chronic diseases. The following research questions were addressed: 1. What are patients' experiences, referring physicians and APNs with the Leila-Service? 2. How are referral processes performed? 3. How do the involved groups experience collaboration and APN role development? A qualitative approach according grounded theory of Corbin and Strauss was used to explore the experiences with the Leila project and the interaction of the persons involved. 38 interviews were conducted with patients who are living with multiple chronic diseases, their APN's and the referring physicians. The findings revealed "Being cared for and caring" as main category. The data demonstrated how patients responded to their involvement into care and that they were taken as serious partners in the care process. The category "organizing everyday life" describes how patients learned to cope with the consequences of living with multiple chronic diseases. "Using all resources" as another category demonstrates how capabilities and strengths were adopted. The results of the cooperation- and allocation processes showed that the APN recognition and APN role performance have to be negotiated. Prospective APN-services for this patient population should be integrated along with physician networks and other service providers including community health nursing.

The neutrophil-to-lymphocyte ratio as disease actvity marker in multiple sclerosis and optic neuritis

DEFF Research Database (Denmark)

Bisgaard, A K; Pihl-Jensen, G; Frederiksen, J L

2017-01-01

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). The neutrophil-to-lymphocyte ratio (NLR) has been identified as a disease activity marker in several diseases. We aim to evaluate the significance of the NLR in the different subtypes of MS......, optic neuritis (ON) and in relation to disease activity and Expanded Disability Status Scale (EDSS). METHODS: We included 378 patients and 813 healthy controls (HC) from The Nordic Reference Interval Project 2000 (NORIP). Complete blood count, demographic and clinical data from patients were evaluated...... between NLR and time of blood sampling. Logistic regression models were constructed for EDSS ≥ 4.0 as outcome. RESULTS: The NLR was significantly higher (p higher NLR (p

Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted?

OpenAIRE

Liu, Patricia; Waheed, Sana; Boujelbane, Lamya; Maursetter, Laura J.

2016-01-01

Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occu...

[Application of R-based multiple seasonal ARIMA model, in predicting the incidence of hand, foot and mouth disease in Shaanxi province].

Science.gov (United States)

Liu, F; Zhu, N; Qiu, L; Wang, J J; Wang, W H

2016-08-10

To apply the ' auto-regressive integrated moving average product seasonal model' in predicting the number of hand, foot and mouth disease in Shaanxi province. In Shaanxi province, the trend of hand, foot and mouth disease was analyzed and tested, under the use of R software, between January 2009 and June 2015. Multiple seasonal ARIMA model was then fitted under time series to predict the number of hand, foot and mouth disease in 2016 and 2017. Seasonal effect was seen in hand, foot and mouth disease in Shaanxi province. A multiple seasonal ARIMA (2,1,0)×(1,1,0)12 was established, with the equation as (1 -B)(1 -B12)Ln (Xt) =((1-1.000B)/(1-0.532B-0.363B(2))*(1-0.644B12-0.454B12(2)))*Epsilont. The mean of absolute error and the relative error were 531.535 and 0.114, respectively when compared to the simulated number of patients from Jun to Dec in 2015. RESULTS under the prediction of multiple seasonal ARIMA model showed that the numbers of patients in both 2016 and 2017 were similar to that of 2015 in Shaanxi province. Multiple seasonal ARIMA (2,1,0)×(1,1,0)12 model could be used to successfully predict the incidence of hand, foot and mouth disease in Shaanxi province.

Health-Related Quality of Life in Patients with Multiple Sclerosis : Impact of Disease-Modifying Drugs

NARCIS (Netherlands)

Jongen, Peter Joseph

Multiple sclerosis (MS) has a profound impact on health-related quality of life (HRQoL), a comprehensive subjective measure of the patient's health status. Assessment of HRQoL informs on the potential advantages and disadvantages of disease-modifying drugs (DMDs) beyond their effects on

The importance of studying sex differences in disease: The example of multiple sclerosis.

Science.gov (United States)

Golden, Lisa C; Voskuhl, Rhonda

2017-01-02

To date, scientific research has often focused on one sex, with assumptions that study of the other sex would yield similar results. However, many diseases affect males and females differently. The sex of a patient can affect the risk for both disease susceptibility and progression. Such differences can be brought to the laboratory bench to be investigated, potentially bringing new treatments back to the clinic. This method of research, known as a "bedside to bench to bedside" approach, has been applied to studying sex differences in multiple sclerosis (MS). Females have greater susceptibly to MS, while males have worse disease progression. These two characteristics of the disease are influenced by the immune system and the nervous system, respectively. Thus, sex differences in each system must be studied. Personalized medicine has been at the forefront of research recently, and studying sex differences in disease fits with this initiative. This review will discuss the known sex differences in MS and highlight how investigating them can lead to new insights and potential treatments for both men and women. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiple Bowen's disease and epithelioid malignant peripheral nerve sheath tumor in a patient who experienced chronic arsenic poisoning

Directory of Open Access Journals (Sweden)

Ching-En Chen

2017-01-01

Full Text Available The Southwest coastal plain of Taiwan is an endemic area of arsenic contamination. Residents who lived there before the 1970s and who used raw groundwater for drinking have a higher risk of arsenic poisoning. In 1968, Tseng et al. described Blackfoot disease as a peripheral vascular disease caused by chronic exposure to arsenic, thereby introducing the concept of arsenic-induced systemic illness in Taiwan. Multiple Bowen's disease (BD is one of the characteristic consequences of chronic arsenic poisoning and it usually presents as cutaneous carcinoma in situ. Multiple BD can also be associated with squamous cell carcinoma and basal cell carcinoma of the skin, as well as lung, liver, gastrointestinal, and bladder cancers. We encountered a 79-year-old male from Yun-Lin, a county in Southwest Taiwan, who presented with a progressing tumor in his right anterior chest wall. In addition, numerous keratoses and scaly skin lesions were noted on his trunk and extremities, some of which were combined with erosions. The patient was diagnosed with chronic arsenic poisoning with multiple BD and the huge tumor was confirmed as an epithelioid malignant peripheral nerve sheath tumor.

T regulatory cells are markers of disease activity in multiple sclerosis patients.

Directory of Open Access Journals (Sweden)

Dacia Dalla Libera

Full Text Available FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS, an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.

Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.

Directory of Open Access Journals (Sweden)

Cathy J Jensen

Full Text Available Recent association studies in multiple sclerosis (MS have identified and replicated several single nucleotide polymorphism (SNP susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.

Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

Science.gov (United States)

Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

2016-04-18

We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis.

Science.gov (United States)

Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

2017-01-01

Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis.

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

Science.gov (United States)

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

Directory of Open Access Journals (Sweden)

Jun eWang

2014-03-01

Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

Perceptual Measures of Speech from Individuals with Parkinson's Disease and Multiple Sclerosis: Intelligibility and beyond

Science.gov (United States)

Sussman, Joan E.; Tjaden, Kris

2012-01-01

Purpose: The primary purpose of this study was to compare percent correct word and sentence intelligibility scores for individuals with multiple sclerosis (MS) and Parkinson's disease (PD) with scaled estimates of speech severity obtained for a reading passage. Method: Speech samples for 78 talkers were judged, including 30 speakers with MS, 16…

A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.

Science.gov (United States)

Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman

2013-06-01

To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

Implications of multiple risk factors for delineation of disease control zones: Case study on foot-and-mouth disease occurrence in Uganda

DEFF Research Database (Denmark)

Chrisostom, Ayebazibwe; Okurut, Ademun Anna Rose; Tjørnehøj, Kirsten

2013-01-01

strategies to promote disease control and livestock trade in endemic countries was to introduce the concept of disease-free zones within which specific sanitary and market standards have to be met. In Africa, it is only Namibia, Botswana and South Africa that have ever had FMD free OIE-declared zones......, water, animal products, utensils and livestock-human contacts. Like other developing countries, animal production and marketing are heavily constrained by limited access to lucrative international markets because of failure to meet the required standards by the World Trade Organization. One of the major....... In pursuit of possibilities of beef export to EU and other markets within Africa by the year 2020, Uganda delineated two disease control zones (DCZs) in areas with large livestock populations and as a consequence high risk for FMD, thus requiring high capital investment. This paper highlights the multiple...

Influence of Multiple Infection and Relatedness on Virulence: Disease Dynamics in an Experimental Plant Population and Its Castrating Parasite

Science.gov (United States)

Buono, Lorenza; López-Villavicencio, Manuela; Shykoff, Jacqui A.; Snirc, Alodie; Giraud, Tatiana

2014-01-01

The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration. PMID:24892951

Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners.

Science.gov (United States)

Roman, Cortnee; Menning, Kara

2017-10-01

This review discusses the role of the nurse practitioner (NP) in evaluating the clinical effects, potential side effects, and monitoring requirements for treatment options in multiple sclerosis (MS) and provides guidance on how to help patients understand these issues. A literature search was conducted on PubMed to identify publications on monitoring and disease management of MS patients. Additional resources included drug information web sites and package inserts. NPs play an active role in the management of MS patients via effective monitoring and communication throughout the patient's treatment regimen and disease course. In the shared decision-making model of MS treatment, NPs ensure that patients understand the implications of their disease-modifying therapies (DMTs). As patients move through treatments during the course of their disease, the importance of this role increases, and it is critical that NPs follow the guidelines in each medication's product label and take into account any potential lingering effects of prior medications. It is critical for NPs to promote patient adherence, to ensure that patients understand treatment side effects and monitoring requirements, and to take sequencing and reversibility implications of DMTs into account when making clinical decisions. ©2017 American Association of Nurse Practitioners.

Bladder Diseases - Multiple Languages

Science.gov (United States)

... PDF Health Information Translations Spanish (español) Expand Section Bladder Diseases: MedlinePlus Health Topic - English Enfermedades de la vejiga: Tema de salud de MedlinePlus - español (Spanish) National ...

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving s......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

DEFF Research Database (Denmark)

Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

2011-01-01

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

Science.gov (United States)

Leiguarda, R; Merello, M; Balej, J; Starkstein, S; Nogues, M; Marsden, C D

2000-07-01

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

Science.gov (United States)

Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

2015-01-01

Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Science.gov (United States)

Disanto, Giulio; Berlanga, Antonio J.; Handel, Adam E.; Para, Andrea E.; Burrell, Amy M.; Fries, Anastasia; Handunnetthi, Lahiru; De Luca, Gabriele C.; Morahan, Julia M.

2011-01-01

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research. PMID:21197462

Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

Science.gov (United States)

Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

2016-01-01

MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

Directory of Open Access Journals (Sweden)

Hongbo Shi

Full Text Available MicroRNAs (miRNAs play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

Comparison of Intelligibility Measures for Adults with Parkinson's Disease, Adults with Multiple Sclerosis, and Healthy Controls

Science.gov (United States)

Stipancic, Kaila L.; Tjaden, Kris; Wilding, Gregory

2016-01-01

Purpose: This study obtained judgments of sentence intelligibility using orthographic transcription for comparison with previously reported intelligibility judgments obtained using a visual analog scale (VAS) for individuals with Parkinson's disease and multiple sclerosis and healthy controls (K. Tjaden, J. E. Sussman, & G. E. Wilding, 2014).…

One-Year Outcomes of an Integrated Multiple Sclerosis Disease Management Program.

Science.gov (United States)

Groeneweg, Marti; Forrester, Sara H; Arnold, Beth; Palazzo, Lorella; Zhu, Weiwei; Yoon, Paul; Scearce, Tim

2018-05-01

Multiple sclerosis (MS) is associated with high total health care cost, the majority of which is attributable to medications. Patients with MS are less likely to experience relapses, emergency department (ED) visits, and hospitalizations when they are adherent to disease-modifying treatments. Disease management programs are hypothesized to improve medication adherence thereby improving clinical and economic outcomes. To evaluate the clinical and economic effects of a specialty pharmacy and chronic disease management program for patients with MS from a health plan perspective. This study was a retrospective analysis using prescription drug claims, medical claims, and electronic medical record information (2013-2015) 1 year before and after enrollment in the disease management program for members with 24 months of continuous health plan coverage. Medication adherence was calculated using proportion of days covered (PDC). Relapse rate was defined as an MS outpatient visit associated with a corticosteroid dispense within 7 days of the visit or an MS hospitalization. Disease progression was assessed using the Modified Expanded Disability Status Scale (mEDSS). Resource use included outpatient visits, ED visits, and hospitalizations. Cost information was collected as health plan-paid amount and was reported in 2013 U.S. dollars. The analysis included 377 patients (mean age 55 years, 76.4% female). After enrollment in the program, 78.7% of the study group had a PDC of ≥ 0.80 compared with 70.0% before enrollment (P management for patients with MS can increase the proportion of patients adherent to medication. The increase in health plan spend on MS medications is not offset by savings in health care resource utilization. This study was funded by Kaiser Permanente Washington Health Research Institute and Kaiser Permanente Washington Pharmacy Administration. The authors have no disclosures to report.

Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

Science.gov (United States)

Maher, Pamela

2017-01-01

It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

Science.gov (United States)

Waldron, James S; Hetts, Steven W; Armstrong-Wells, Jennifer; Dowd, Christopher F; Fullerton, Heather J; Gupta, Nalin; Lawton, Michael T

2009-11-01

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

Demyelination versus remyelination in progressive multiple sclerosis

DEFF Research Database (Denmark)

Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis

Directory of Open Access Journals (Sweden)

Mario A. Moscarello

2013-03-01

Multiple sclerosis (MS is the most common CNS-demyelinating disease of humans, showing clinical and pathological heterogeneity and a general resistance to therapy. We first discovered that abnormal myelin hypercitrullination, even in normal-appearing white matter, by peptidylarginine deiminases (PADs correlates strongly with disease severity and might have an important role in MS progression. Hypercitrullination is known to promote focal demyelination through reduced myelin compaction. Here we report that 2-chloroacetamidine (2CA, a small-molecule, PAD active-site inhibitor, dramatically attenuates disease at any stage in independent neurodegenerative as well as autoimmune MS mouse models. 2CA reduced PAD activity and protein citrullination to pre-disease status. In the autoimmune models, disease induction uniformly induced spontaneous hypercitrullination with citrulline+ epitopes targeted frequently. 2CA rapidly suppressed T cell autoreactivity, clearing brain and spinal cord infiltrates, through selective removal of newly activated T cells. 2CA essentially prevented disease when administered before disease onset or before autoimmune induction, making hypercitrullination, and specifically PAD enzymes, a therapeutic target in MS models and thus possibly in MS.

Interferon Treatment of Multiple Sclerosis

OpenAIRE

Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

2012-01-01

Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

Directory of Open Access Journals (Sweden)

Lucy Matthews

Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

Bilateral multiple cystic kidney disease and renal cortical abscess in a Boerboel

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A. M. Kitshoffa

2011-04-01

Full Text Available Cystic renal disease is rare in dogs and although infected renal cysts have been reported in humans, no report could be found in dogs. A 58 kg, 5-year-old, castrated, male Boerboel presented with weight loss, pyrexia, lethargy and vomiting, 20 months after an incident of haematuria was reported. The initial ultrasonographic diagnosis was bilateral multiple renal cysts of unknown aetiology. The cysts had significantly increased in size over the 20-month period and some contained echogenic specks which could be related to infection, normal cellular debris or haemorrhage. In both kidneys the renal contours were distorted (the left more than the right. The abnormal shape of the left kidney was largely due to multiple cysts and a large crescent-shaped septate mass on the cranial pole of the kidney. Aspirates of the septate mass were performed (left kidney and the cytology and culture were indicative of an abscess. It is suggested that the previous incident of haematuria provided a portal of entry for bacteria into the cysts resulting in renal cortical abscess formation.

Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

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Yao Qin

2017-01-01

Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.

Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

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Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

2008-06-15

We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

Established and novel disease-modifying treatments in multiple sclerosis.

Science.gov (United States)

Cross, A H; Naismith, R T

2014-04-01

Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e

Quantification of whole-body bradykinesia in Parkinson's disease participants using multiple inertial sensors.

Science.gov (United States)

Memar, Sara; Delrobaei, Mehdi; Pieterman, Marcus; McIsaac, Kenneth; Jog, Mandar

2018-04-15

Bradykinesia (slowness of movement) is a common motor symptom of Parkinson's disease (PD) that can severely affect quality of life for those living with the disease. Assessment and treatment of PD motor symptoms largely depends on clinical scales such as the Unified Parkinson's Disease Rating Scale (UPDRS). However, such clinical scales rely on the visual assessment by a human observer, naturally resulting in inter-rater variability. Although previous studies have developed objective means for measuring bradykinesia in PD patients, their evaluation was restricted by the type of movement and number of joints assessed. These studies failed to provide a more comprehensive, whole-body evaluation capable of measuring multiple joints simultaneously. This study utilizes wearable inertial measurement units (IMUs) to quantify whole-body movements, providing novel bradykinesia indices for walking (WBI) and standing up from a chair (sit-to-stand; SBI). The proposed bradykinesia indices include the joint angles at both upper and lower limbs and trunk motion to compute a complete, objective score for whole body bradykinesia. Thirty PD and 11 age-matched healthy control participants were recruited for the study. The participants performed two standard walking tasks that involved multiple body joints in the upper and lower limbs. The WBI and SBI successfully identified differences between control and PD participants. The indices also effectively identified differences within the PD population, distinguishing participants assessed with (ON) and without (OFF) levodopa; the gold-standard of treatment for PD. The goal of this study is to provide health professionals with an objective score for whole body bradykinesia by simultaneously measuring the upper and lower extremities along with truncal movement. This method demonstrates potential to be used in conjunction with current clinical standards for motor symptom assessment, and may also be promising for the remote assessment of PD

Homocyst(e)ine and risk of cardiovascular disease in the multiple risk factor intervention trial.

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Evans, R W; Shaten, B J; Hempel, J D; Cutler, J A; Kuller, L H

2000-01-01

A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for upto 20 years, were analysed for homocyst(e)ine. Cases involved non-fatal myocardial infractions, identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease, monitored through 1990. The non-fatal myocardial infarction occurred within 7 years of sample collection, whereas the majority of coronary heart disease deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: myocardial infarction cases, 12.6 micromol/L; myocardial infarction controls, 13.1 micromol/L; coronary heart disease death cases, 12.8 micromol/L; and coronary heart disease controls, 12.7 micromol/L. Odds ratios versus quartile 1 for coronary heart disease deaths and myocardial infarctions combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase (C-reactive) protein. These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.

Bayesian modeling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard.

Science.gov (United States)

Jafarzadeh, S Reza; Johnson, Wesley O; Gardner, Ian A

2016-03-15

The area under the receiver operating characteristic (ROC) curve (AUC) is used as a performance metric for quantitative tests. Although multiple biomarkers may be available for diagnostic or screening purposes, diagnostic accuracy is often assessed individually rather than in combination. In this paper, we consider the interesting problem of combining multiple biomarkers for use in a single diagnostic criterion with the goal of improving the diagnostic accuracy above that of an individual biomarker. The diagnostic criterion created from multiple biomarkers is based on the predictive probability of disease, conditional on given multiple biomarker outcomes. If the computed predictive probability exceeds a specified cutoff, the corresponding subject is allocated as 'diseased'. This defines a standard diagnostic criterion that has its own ROC curve, namely, the combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is used to compare the predictive criterion based on multiple biomarkers to one based on fewer biomarkers. A multivariate random-effects model is proposed for modeling multiple normally distributed dependent scores. Bayesian methods for estimating ROC curves and corresponding (marginal) AUCs are developed when a perfect reference standard is not available. In addition, cAUCs are computed to compare the accuracy of different combinations of biomarkers for diagnosis. The methods are evaluated using simulations and are applied to data for Johne's disease (paratuberculosis) in cattle. Copyright © 2015 John Wiley & Sons, Ltd.

Abnormal pain perception in patients with Multiple System Atrophy.

Science.gov (United States)

Ory-Magne, F; Pellaprat, J; Harroch, E; Galitzsky, M; Rousseau, V; Pavy-Le Traon, A; Rascol, O; Gerdelat, A; Brefel-Courbon, C

2018-03-01

Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognosis of the individual course of disease--steps in developing a decision support tool for Multiple Sclerosis.

Science.gov (United States)

Daumer, M; Neuhaus, A; Lederer, C; Scholz, M; Wolinsky, J S; Heiderhoff, M

2007-05-08

Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient. For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials. This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.

Prognosis of the individual course of disease - steps in developing a decision support tool for Multiple Sclerosis

Science.gov (United States)

Daumer, M; Neuhaus, A; Lederer, C; Scholz, M; Wolinsky, JS; Heiderhoff, M

2007-01-01

Background Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient. Results For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials. Conclusion This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist. PMID:17488517

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, ...

Digital dashboard design using multiple data streams for disease surveillance with influenza surveillance as an example.

Science.gov (United States)

Cheng, Calvin K Y; Ip, Dennis K M; Cowling, Benjamin J; Ho, Lai Ming; Leung, Gabriel M; Lau, Eric H Y

2011-10-14

Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.

Type D, anxiety and depression in association with quality of life in patients with Parkinson's disease and patients with multiple sclerosis

NARCIS (Netherlands)

Dubayova, Tatiana; Krokavcova, Martina; Nagyova, Iveta; Rosenberger, Jaroslav; Gdovinova, Zuzana; Middel, Berrie; Groothoff, Johan W.; van Dijk, Jitse P.

The present study examines the role of Type D personality, anxiety and depression in quality of life (QoL) in patients with two chronic neurological diseases-Parkinson's disease (PD) and multiple sclerosis (MS). This cross-sectional study included 142 PD patients (73 % males; mean age 67.6 +/- A 9.2

[Future challenges in multiple sclerosis].

Science.gov (United States)

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Multiple Virus Infections and the Characteristics of Chronic Bee Paralysis Virus in Diseased Honey Bees (Apis Mellifera L. in China

Directory of Open Access Journals (Sweden)

Wu Yan Y.

2015-12-01

Full Text Available China has the largest number of managed honey bee colonies globally, but there is currently no data on viral infection in diseased A. mellifera L. colonies in China. In particular, there is a lack of data on chronic bee paralysis virus (CBPV in Chinese honey bee colonies. Consequently, the present study investigated the occurrence and frequency of several widespread honey bee viruses in diseased Chinese apiaries, and we used the reverse transcription-polymerase chain reaction (RT-PCR assay. Described was the relationship between the presence of CBPV and diseased colonies (with at least one of the following symptoms: depopulation, paralysis, dark body colorings and hairless, or a mass of dead bees on the ground surrounding the beehives. Phylogenetic analyses of CBPV were employed. The prevalence of multiple infections of honey bee viruses in diseased Chinese apiaries was 100%, and the prevalence of infections with even five and six viruses were higher than expected. The incidence of CBPV in diseased colonies was significantly higher than that in apparently healthy colonies in Chinese A. mellifera aparies, and CBPV isolates from China can be separated into Chinese-Japanese clade 1 and 2. The results indicate that beekeeping in China may be threatened by colony decline due to the high prevalence of multiple viruses with CBPV.

Mutant lines of currant tomato, valuable germplasm with multiple disease resistance

International Nuclear Information System (INIS)

Govorova, G.F.; Khrustaleva, V.V.; Shcherbakov, V.K.

1987-01-01

Studies were carried out for two years on eight mutant lines of currant tomato at the Krymsk Experimental Breeding Station of the N.I. Vavilov All-Union Scientific Research Institute of Plant-Growing (VIR). The station is situated in an area of commercial field tomato growing (Krasnodar region). The mutant lines of currant tomato (VIR specimen No. k-4053) were obtained through chronic gamma-irradiation. A disease resistance evaluation of the mutants was carried out for Verticillium wilt (Verticillium albo-atrum Rein. and Berth.), for black bacterial spotting (Xanthomonas vesicatoria Dows.), for tobacco mosaic virus Nicotiana 1 Smith), for streak virus (Nicotiana 1), for the combination TMV with X and Y potato viruses, for cucumber virus (Cucumis 1), and also for top rot. Fifty plants of each mutant line were evaluated and checks were made three times in each season. A comparison of the currant tomato mutants with the standard tomato varieties demonstrates the better resistance shown by the mutant germplasm to the main pathogens. The degree to which some currant tomato mutants were affected by Verticillium was lower than that of the most VerticiIlium-resistant samples of tomato evaluated between 1975 and 1981. The mutants of currant tomato should therefore be of interest as germplasm in breeding tomatoes for improved multiple disease resistance

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

Science.gov (United States)

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

Multiple systemic embolism in infective endocarditis underlying in Barlow's disease.

Science.gov (United States)

Yu, Ziqing; Fan, Bing; Wu, Hongyi; Wang, Xiangfei; Li, Chenguang; Xu, Rende; Su, Yangang; Ge, Junbo

2016-08-11

Systemic embolism, especially septic embolism, is a severe complication of infective endocarditis (IE). However, concurrent embolism to the brain, coronary arteries, and spleen is very rare. Because of the risk of hemorrhage or visceral rupture, anticoagulants are recommended only if an indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is controversial, but theoretically, this therapy has the potential to prevent and treat thrombosis and embolism in IE. Unfortunately, clinical trial results have been inconclusive. We describe a previously healthy 50-year-old man who presented with dysarthria secondary to bacterial endocarditis with multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy contributed to the multiple emboli. Emergency splenectomy was performed, with subsequent mitral valve repair. Pathological examination confirmed mucoid degeneration and mitral valve prolapse (Barlow's disease) as the underlying etiology of the endocardial lesion. Continuous antibiotics were prescribed, postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the onset of his illness showed no severe regurgitation, and there was no respiratory distress, fever, or lethargy during follow-up. Although antibiotic use in IE carries a risk of septic embolism, these drugs have bactericidal and antithrombotic benefits. It is important to consider that negative blood culture and symptom resolution do not confirm complete elimination of bacteria. However, vegetation size and Staphylococcus aureus infection accurately predict embolization. It is also important to consider that bacteria can be segregated from the microbicide when embedded in platelets and fibrin. Therefore, antimicrobial therapy with concurrent antiplatelet therapy should be considered carefully.

ɑ-Synuclein strains and seeding in Parkinson's disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences.

Science.gov (United States)

Peelaerts, W; Bousset, L; Baekelandt, V; Melki, R

2018-04-27

Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis.

'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

Directory of Open Access Journals (Sweden)

Nathali Kaushansky

Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

Genetic variations in multiple myeloma I

DEFF Research Database (Denmark)

Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

2012-01-01

Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variab......Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

Prognosis of the individual course of disease - steps in developing a decision support tool for Multiple Sclerosis

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Scholz M

2007-05-01

Full Text Available Abstract Background Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR developed an "online analytical processing (OLAP" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient. Results For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005 contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6 are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials. Conclusion This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.

Management of sleep disorders in Parkinson's disease and multiple system atrophy.

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Videnovic, Aleksandar

2017-05-01

Parkinson's disease (PD) and multiple system atrophy (MSA) are disorders associated with α synuclein-related neurodegeneration. Nonmotor symptoms are common hallmarks of these disorders, and disturbances of the sleep-wake cycle are among the most common nonmotor symptoms. It is only recently that sleep disturbances have received the attention of the medical and research community. Significant progress has been made in understanding the pathophysiology of sleep and wake disruption in alphasynucleinopathies during the past few decades. Despite these advancements, treatment options are limited and frequently associated with problematic side effects. Further studies that center on the development of novel treatment approaches are very much needed. In this article, the author discusses the current state of the management of disturbed sleep and alertness in PD and MSA. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

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Farrington, C. Paddy; Noufaily, Angela; Andrews, Nick J.; Charlett, Andre

2016-01-01

A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace. PMID:27513749

Multiple Sclerosis

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Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

Vowel Acoustics in Parkinson's Disease and Multiple Sclerosis: Comparison of Clear, Loud, and Slow Speaking Conditions

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Tjaden, Kris; Lam, Jennifer; Wilding, Greg

2013-01-01

Purpose: The impact of clear speech, increased vocal intensity, and rate reduction on acoustic characteristics of vowels was compared in speakers with Parkinson's disease (PD), speakers with multiple sclerosis (MS), and healthy controls. Method: Speakers read sentences in habitual, clear, loud, and slow conditions. Variations in clarity,…

Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease

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Sun, Zhanfang; Jia, Dandan; Shi, Yuting; Hou, Xuan; Yang, Xiaosu; Guo, Jifeng; Li, Nan; Wang, Junling; Sun, Qiying; Zhang, Hainan; Lei, Lifang; Shen, Lu; Yan, Xinxiang; Xia, Kun; Jiang, Hong; Tang, Beisha

2016-01-01

Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID:26867507

Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update; Bildgebung des multiplen Myeloms und verwandter monoklonaler Plasmazellerkrankungen. Ein Update

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Weber, Marc-Andre [Universitaetsklinikum, Heidelberg (Germany). Abt. Diagnostische und Interventionelle Radiologie; Delorme, Stefan [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie; Hillengass, Jens [Universitaetsklinikum, Heidelberg (Germany). Sektion Multiples Myelom

2014-09-15

Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

Multiple sclerosis: general features and pharmacologic approach; Esclerosis multiple: aspectos generales y abordaje farmacologico

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Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio [Instituto de Farmacia y Alimentos, Universidad de La Habana, La Habana (Cuba)

2009-07-01

Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

Multiple Thymoma with Myasthenia Gravis

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Dong Hyun Seo

2017-02-01

Full Text Available The actual incidence of multiple thymoma is unknown and rarely reported because it remains controversial whether the cases represent a disease of multicentric origin or a disease resulting from intrathymic metastasis. In this case, a patient underwent total thymectomy for multiple thymoma with myasthenia gravis via bilateral video-assisted thoracic surgery. A well-encapsulated multinodular cystic mass, measuring 57 mm×50 mm×22 mm in the right lobe of the thymus, and a well-encapsulated mass, measuring 32 mm×15 mm×14 mm in the left lobe, were found. Both tumors were type B2 thymoma. Few cases of multiple thymoma with myasthenia gravis have ever been reported in the literature. We report a case of synchronous multiple thymoma associated with myasthenia gravis.

Multiple Sclerosis and Vitamin D

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... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT ... caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided ...

Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

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Zettl, U K; Schreiber, H; Bauer-Steinhusen, U; Glaser, T; Hechenbichler, K; Hecker, M

2017-08-01

Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

99M-TC MIBI-an indicator of active disease in multiple myeloma

International Nuclear Information System (INIS)

Raluca Mititelu; Serban Ghita; Catalin Mazilu; George Marinescu

2004-01-01

Purpose: to evaluate the role of 99mTc-MIBI in the assessment of bone marrow involvement in patients with multiple myeloma and to demonstrate how different patterns of 99mTc-MIBI uptake are reflecting the activity of the disease. Material and method: 27 patients with documented MM were studied, 14M, 13 F, median age 62 years, range 31 - 78. 7 MPI (myocardial perfusion imaging) patients served as controle. Diagnosis and staging of the disease were based on standard criteria: 5 patients in stage I, 7 in stage II, 15 in stage III. The disease activity was determined by clinical and biological assessment and the aspect of bone marrow biopsy. 17 patients had active disease (2 patients in stage I, 4 in stage II, 11 in stage III), 10 patients had not' clinical and biological criteria of active disease. All patients included in the group of active disease underwent radiological examination, 99mTc-MDP whole-body scan and 99mTc-MIBI whole-body scan. MRI was performed in 5 patients with active disease (2 in stage I, 1 in stage II, 2 in stage lib - for evaluation of spine involvement. In the other group (patients with clinical and biological criteria of non-active disease), due to high cost of investigations, we performed whole-body 99mTc-MIBI scan, as the oncologist referred us the patient for monitoring therapeutic response. Whole-body 99mTc-MIBI scans were obtained 20 rain after iv injection of 740 MBq 99mTc-MIBI, in anterior and posterior views, with a dual-head gamma camera Philips -Axis. Results: In the group of patients with active disease (17 patients) we found three different patterns of pathologic 99mTc-MIBI uptake: focal uptake in different sites in 9 patients, diffuse uptake in 4, both focal and diffuse uptake in 3; no pathologic uptake was seen in 1 patient (probably due to overexpression of Pglycoprotein). In the other group, with non-active disease criteria (10 patients), we found normal aspect of 99mTc-MIBI uptake in 8 patients; 2 patients had diffuse increased

Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

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Shroff, Geeta

2016-12-13

BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

Exploration of machine learning techniques in predicting multiple sclerosis disease course.

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Yijun Zhao

Full Text Available To explore the value of machine learning methods for predicting multiple sclerosis disease course.1693 CLIMB study patients were classified as increased EDSS≥1.5 (worsening or not (non-worsening at up to five years after baseline visit. Support vector machines (SVM were used to build the classifier, and compared to logistic regression (LR using demographic, clinical and MRI data obtained at years one and two to predict EDSS at five years follow-up.Baseline data alone provided little predictive value. Clinical observation for one year improved overall SVM sensitivity to 62% and specificity to 65% in predicting worsening cases. The addition of one year MRI data improved sensitivity to 71% and specificity to 68%. Use of non-uniform misclassification costs in the SVM model, weighting towards increased sensitivity, improved predictions (up to 86%. Sensitivity, specificity, and overall accuracy improved minimally with additional follow-up data. Predictions improved within specific groups defined by baseline EDSS. LR performed more poorly than SVM in most cases. Race, family history of MS, and brain parenchymal fraction, ranked highly as predictors of the non-worsening group. Brain T2 lesion volume ranked highly as predictive of the worsening group.SVM incorporating short-term clinical and brain MRI data, class imbalance corrective measures, and classification costs may be a promising means to predict MS disease course, and for selection of patients suitable for more aggressive treatment regimens.

Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

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Denis Bernardi Bichuetti

2013-05-01

Full Text Available Although neuromyelitis optica (NMO is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS, few studies comparing both conditions in a single center have been done. Methods: Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007. Results: Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062 with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013 and progression index (0.9 versus 0.6, p≪0.0001, with more patients reaching expanded disability status scale (EDSS 6.0 (39 versus 17%, p=0.0036. The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

Multiple giant succular and fusiform right and left coronary artery aneurysms after early and adequate treatment of atypical kawasaki disease with unusual presentation.

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Mostafa Behjati-Ardakani

2014-06-01

Full Text Available The major complication of Kawasaki disease is coronary artery dilatation and aneurysm. It occurs in approximately 15-25% of untreated children with Kawasaki Disease. Early diagnosis and treatment with Intravenous immune globulin (IVIG and aspirin (ASA can reduce the incidence of coronary artery abnormality to 2%-5%. We report one case of Atypical Kawasaki Disease with Multiple giant coronary artery aneurysms despite early adequate treatment with IVIG and ASA.

Comparison of Multiple Chronic Obstructive Pulmonary Disease (COPD) Indices in Chinese COPD Patients.

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Zhang, Jinsong; Miller, Anastasia; Li, Yongxia; Lan, Qinqin; Zhang, Ning; Chai, Yanling; Hai, Bing

2018-04-01

Chronic obstructive pulmonary disease (COPD) is a serious chronic condition with a global impact. Symptoms of COPD include progressive dyspnea, breathlessness, cough, and sputum production, which have a considerable impact on the lives of patients. In addition to the human cost of living with COPD and the resulting death, COPD entails a huge economic burden on the Chinese population, with patients spending up to one-third of the average family income on COPD management in some regions is clinically beneficial to adopt preventable measures via prudent COPD care utilization, monetary costs, and hospitalizations. Toward this end, this study compared the relative effectiveness of six indices in predicting patient healthcare utilization, cost of care, and patient health outcome. The six assessment systems evaluated included the three multidimensional Body mass index, Obstruction, Dyspnea, Exercise capacity index, Dyspnea, Obstruction, Smoking, Exacerbation (DOSE) index, and COPD Assessment Test index, or the unidimensional measures that best predict the future of patient healthcare utilization, cost of care, and patient health outcome among Chinese COPD patients. Multiple linear regression models were created for each healthcare utilization, cost, and outcome including a single COPD index and the same group of demographic variables for each of the outcomes. We conclude that the DOSE index facilitates the prediction of patient healthcare utilization, disease expenditure, and negative clinical outcomes. Our study indicates that the DOSE index has a potential role beyond clinical predictions. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

[Current description of multiple sclerosis].

Science.gov (United States)

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Diagnostic performance of whole-body MRI for the detection of persistent or relapsing disease in multiple myeloma after stem cell transplantation

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Bannas, Peter; Hentschel, Hannah B.; Bley, Thorsten A.; Derlin, Thorsten; Yamamura, Jin; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Treszl, Andras; Eulenburg, Christine [University Medical Center Hamburg-Eppendorf, Department of Medical Biometry and Epidemiology, Hamburg (Germany); Stuebig, Thomas; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

2012-09-15

To compare the diagnostic performance of whole-body MRI (WBMRI) with haematological parameters for detecting persistent or relapsing disease in patients with multiple myeloma after stem cell transplantation. Sixty-six WBMRI acquisitions were performed in 33 patients with multiple myeloma at two time points after stem cell transplantation. Extent of disease and inter-test dynamics of intra- and extramedullary myeloma manifestations were compared (kappa statistics) with Uniform Response Criteria, comprising haematological parameters. Using data from 66 sequential WBMRI acquisitions in 33 patients, 10 patients (30.3 %) were classified as having progressive disease and 23 (69.7 %) as being in remission. Eight (80 %) of the ten patients with progressive disease revealed intramedullary lesions, and two patients (20 %) had intra- and extramedullary lesions. WBMRI and laboratory tests were concordant in 26/33 (78.8 %) patients. We found an agreement of 51.2 %, 95 % confidence interval 19.8 %-82.6 %, between results from WBMRI and haematological parameters. WBMRI had a sensitivity of 63.6 %, specificity of 86.4 %, PPV of 70.0 %, NPV of 82.6 % and accuracy of 78.8 % for detection of remission. WBMRI allows the detection and exact localisation of intra- and extramedullary myeloma manifestations after stem cell transplantation, but shows only moderate agreement with routinely performed laboratory tests for determination of remission. (orig.)

The Danish Multiple Sclerosis Treatment Register

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Magyari M

2016-10-01

Full Text Available Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion: The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. Keywords: multiple sclerosis, epidemiology, immunomodulatory treatment, neutralizing antibodies, observational studies, registry research, disease modifying therapy

Fatal case of Herbaspirillum seropedicae bacteremia secondary to pneumonia in an end-stage renal disease patient with multiple myeloma.

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Suwantarat, Nuntra; Adams, La'Tonzia L; Romagnoli, Mark; Carroll, Karen C

2015-08-01

Herbaspirillum spp. are rare causes of human infections associated primarily with bacteremia in cancer patients. We report the first fatal case of bacteremia secondary to pneumonia caused by Herbaspirillum seropedicae in a 65-year-old man with end-stage renal disease and multiple myeloma. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiple modes of impulsivity in Parkinson's disease.

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Cristina Nombela

Full Text Available Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I-III and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1 tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2 tests of motor inhibitory control, and the self-report behavioural approach system, (3 time estimation and delay aversion, and (4 reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2 and (3. The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and

Multiple sclerosis research

International Nuclear Information System (INIS)

Battaglia, M.A.

1990-01-01

This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture

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Ji-Yeon Song

2017-09-01

Full Text Available Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs, is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI, only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.

A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture.

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Song, Ji-Yeon; Mun, Sue-Jean; Sung, Soon-Ki; Hwang, Jae-Yeon; Baik, Seung-Kug; Kim, Jee Yeon; Cheon, Chong-Kun; Kim, Su-Young; Kim, Yoo-Mi

2017-09-01

Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI), only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.

Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs.

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Amato, Maria Pia; Portaccio, Emilio

2015-03-01

In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

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Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; Rodrigo, Luis; Nieto, Antonio; Cardeña, Carlos; Alcain, Guillermo; Díaz-Rubio, Manuel; de la Concha, Emilio G.; Fernandez, Oscar; Arroyo, Rafael

2010-01-01

Background A functional polymorphism located at −1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions. Methodology Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93–1.17)]. Conclusion The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions. PMID:20634952

Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in Whole Human Blood.

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Suneetha, A; Rajeswari, Raja K

2016-02-01

As a polytherapy treatment, multiple sclerosis disease demands prescriptions with more than one drug. Polytherapy is sometimes rational for drug combinations chosen to minimize adverse effects. Estimation of drugs that are concomitantly administered in polytherapy is acceptable as it shortens the analytical timepoints and also the usage of biological matrices. In clinical phase trials, the withdrawal of biofluids is a critical issue for each analysis. Estimating all the coadminsitered drugs in a single shot will be more effective and economical for pharmaceuticals. A single, simple, rapid and sensitive high-performance liquid chromatography assay method has been developed with UV detection and fully validated for the quantification of 14 drugs (at random combinations) used in the treatment of multiple sclerosis disease. The set of combinations was based on prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 × 3.9 mm, 5 µm) column. The analytes were extracted from 50 µL aliquots of whole human blood with protein precipitation using acetonitrile. All the drugs were sufficiently stable during storage for 24 h at room temperature and for 23 days at 2-8°C. The percentage recoveries of all drugs were between 90 and 115%, with RSD values <10.6%. This method has been shown to be reproducible and sensitive and can be applied to clinical samples from pharmacokinetic studies and also a useful tool in studying the drug interaction studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cerebrovascular and hypertensive diseases as multiple causes of death in Brazil from 2004 to 2013.

Science.gov (United States)

Villela, P B; Klein, C H; Oliveira, G M M

2018-06-02

The proportion of deaths attributed to hypertensive diseases (HYPDs) was only 50% of that registered for cerebrovascular diseases (CBVDs) in 2013 in Brazil. This article aims to evaluate mortality related to HYPDs and CBVDs as multiple causes of death, in Brazil from 2004 to 2013. Analysis of historical series of secondary data obtained from Brazilian official registries. Data about the deaths were obtained from the Mortality Information System of the Brazilian Ministry of Health, available on the DATASUS website. CBVDs and HYPDs were evaluated according to their mentions as the underlying cause of death or entry in any line of the death certificates (DCs), according to their International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. When CBVDs were the underlying causes of death, HYPDs were mentioned in 40.9% of the DCs. When HYPDs were the underlying causes of death, CBVDs were mentioned in only 5.0%. When CBVDs were mentioned without HYPDs, they were selected as the underlying cause of death 74.4% of the time. When HYPDs were mentioned in DCs without CBVDs, HYPDs were selected 30.0% of the time. In 2004, the frequency of any mention of HYPDs relative to the frequency of HYPDs cited as underlying causes increased fourfold and was followed by a plateau until 2013. In contrast, the frequency of any mention of CBVDs relative to the frequency of CBVDs as underlying causes decreased in the same period. Because this study was based on DC records, it was limited by the way these documents were completed, which may have included lack of record of the causes related to the sequence that culminated in death. When deaths related to HYPDs were evaluated as multiple causes of death, they were mentioned up to four times more often than when they were selected as underlying causes of death. This reinforces the need for better control of hypertension to prevent deaths. Copyright © 2018 The Royal Society for Public Health. Published by

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce...... in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.......About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity...

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

Science.gov (United States)

Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study

DEFF Research Database (Denmark)

Tsakiris, D.J.; Stel, V.S.; Finne, P.

2010-01-01

Background. Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes...... causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. Results. Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986...

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

OpenAIRE

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on bra...

Treatment of Multiple Sclerosis

OpenAIRE

Bošnjak-Pašić, Marija; Vidrih, Branka; Miškov, Snježana; Demarin, Vida

2009-01-01

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system, characterized by multifocal inflammatory destruction of myelin, axonal damage and loss of oligodendrocytes. The disease is carried through two stages: inflammatory and degenerative. The most common form of disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The treatment of MS is divided into: treatment of the acute phase of illness, prevention of new relapses and di...

Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease : more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

NARCIS (Netherlands)

Heeg, M; Klein, JP; Krikke, AP

1998-01-01

A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal

Right ventricular ejection fraction during exercise in normal subjects and in coronary artery disease patients: assessment by multiple-gated equilibrium scintigraphy

International Nuclear Information System (INIS)

Maddahi, J.; Berman, D.S.; Matsuoka, D.T.; Waxman, A.D.; Forrester, J.S.; Swan, H.J.C.

1980-01-01

The response of right ventricular ejection fraction (RVEF) during exercise and its relationship to the location and extent of coronary artery disease are not fully understood. We have recently developed and validated a new method for scintigraphic evaluation of RVEF using rapid multiple-gated equilibrium scintigraphy and multiple right ventricular regions of interest. The technique has been applied during upright bicycle exercise in 10 normal subjects and 20 patients with coronary artery disease. Resting RVEF was not significantly different between the groups (0.49 +- 0.04 vs 0.47 +- 0.09, respectively, mean +- SD). In all 10 normal subjects RVEF rose (0.49 +- 0.04 to 0.66 +- 0.08, p < 0.01) at peak exercise. At peak exercise in coronary artery disease patients, the group RVEF remained unchanged (0.47 +- 0.09 to 0.50 +- 0.11, p = NS), but the individual responses varied. In the coronary artery disease patients, the relationship between RVEF response to exercise and exercise left ventricular function, septal motion and right coronary artery stenosis were studied. Significant statistical association was found only between exercise RVEF and right coronary artery stenosis. RVEF rose during exercise in seven of seven patients without right coronary artery stenosis (0.42 +- 0.06 to 0.58 +- 0.08, p = 0.001) and was unchanged or fell in 12 of 13 patients with right coronary artery stenosis (0.50 +- 0.09 to 0.45 +- 0.10, p = NS). We conclude that (1) in normal subjects RVEF increases during upright exercise and (2) although RVEF at rest is not necessarily affected by coronary artery disease, failure of RVEF to increase during exercise, in the absence of chronic obstructive pulmonary disease or valvular heart disease, may be related to the presence of significant right coronary artery stenosis

Right ventricular ejection fraction during exercise in normal subjects and in coronary artery disease patients: assessment by multiple-gated equilibrium scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Maddahi, J.; Berman, D.S.; Matsuoka, D.T.; Waxman, A.D.; Forrester, J.S.; Swan, H.J.C.

1980-07-01

The response of right ventricular ejection fraction (RVEF) during exercise and its relationship to the location and extent of coronary artery disease are not fully understood. We have recently developed and validated a new method for scintigraphic evaluation of RVEF using rapid multiple-gated equilibrium scintigraphy and multiple right ventricular regions of interest. The technique has been applied during upright bicycle exercise in 10 normal subjects and 20 patients with coronary artery disease. Resting RVEF was not significantly different between the groups (0.49 +- 0.04 vs 0.47 +- 0.09, respectively, mean +- SD). In all 10 normal subjects RVEF rose (0.49 +- 0.04 to 0.66 +- 0.08, p < 0.01) at peak exercise. At peak exercise in coronary artery disease patients, the group RVEF remained unchanged (0.47 +- 0.09 to 0.50 +- 0.11, p = NS), but the individual responses varied. In the coronary artery disease patients, the relationship between RVEF response to exercise and exercise left ventricular function, septal motion and right coronary artery stenosis were studied. Significant statistical association was found only between exercise RVEF and right coronary artery stenosis. RVEF rose during exercise in seven of seven patients without right coronary artery stenosis (0.42 +- 0.06 to 0.58 +- 0.08, p = 0.001) and was unchanged or fell in 12 of 13 patients with right coronary artery stenosis (0.50 +- 0.09 to 0.45 +- 0.10, p = NS). We conclude that (1) in normal subjects RVEF increases during upright exercise and (2) although RVEF at rest is not necessarily affected by coronary artery disease, failure of RVEF to increase during exercise, in the absence of chronic obstructive pulmonary disease or valvular heart disease, may be related to the presence of significant right coronary artery stenosis.

Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

Science.gov (United States)

Eltayeb, Sana; Sunnemark, Dan; Berg, Anna-Lena; Nordvall, Gunnar; Malmberg, Asa; Lassmann, Hans; Wallström, Erik; Olsson, Tomas; Ericsson-Dahlstrand, Anders

2003-09-01

We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

Effects of multiple training modalities in patients with Alzheimer’s disease: a pilot study

Directory of Open Access Journals (Sweden)

Tai SY

2016-11-01

Full Text Available Shu-Yu Tai,1–4 Chia-Ling Hsu,5 Shu-Wan Huang,5 Tzu-Chiao Ma,6,7 Wen-Chien Hsieh,8,9 Yuan-Han Yang5,7,10,11 1Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 2Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 3Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 4Research Center for Environmental Medicine, Kaohsiung Medical University, 5Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 6Graduate Institute of Oral Health Sciences, Kaohsiung Medical University, 7Mentality Protection Center, Fo Guang Shan Compassion Foundation, 8Department of Social Work, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 9Department of Sociology and Social Work, Kaohsiung Medical University, 10Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 11Department of and Master’s Program in Neurology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan Objective: This pilot study investigated the effects of multiple training modalities on cognition, neuropsychiatric symptoms, caregivers’ burden, and quality of life in patients with Alzheimer’s disease (AD.Patients and methods: This intervention study was conducted in 24 patients with AD aged ≥65 years with a Clinical Dementia Rating (CDR score of 0.5–1. The patients were assigned to receive multiple training modalities (1 hour for each training: Tai Chi, calligraphy, and drawing over a 6-week period in either the experimental group (n=14 or the comparison group (n=10. A series of neuropsychological tests – namely the Traditional Chinese version Mini-Mental Status Examination, Cognitive Assessment Screening Instrument (CASI, Neuropsychiatric Inventory and the Neuropsychiatric Inventory Caregiver Distress Scale, and the Clinical Dementia

Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

Science.gov (United States)

Armah, Frederick Ato; Quansah, Reginald; Luginaah, Isaac; Chuenpagdee, Ratana; Hambati, Herbert; Campbell, Gwyn

2015-01-01

In the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania. We also assessed the collective (compositional and contextual) factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural) factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks. NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

Self-report fatigue questionnaires in multiple sclerosis, Parkinson’s disease and stroke: a systematic review of measurement properties

OpenAIRE

Elbers, Roy G.; Rietberg, Marc B.; van Wegen, Erwin E. H.; Verhoef, John; Kramer, Sharon F.; Terwee, Caroline B.; Kwakkel, Gert

2011-01-01

Purpose To critically appraise, compare and summarize the measurement properties of self-report fatigue questionnaires validated in patients with multiple sclerosis (MS), Parkinson’s disease (PD) or stroke. Methods MEDLINE, EMBASE, PsycINFO, CINAHL and SPORTdiscus were searched. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of studies. A qualitative data synthesis was performed to rate the mea...

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

Science.gov (United States)

Deleu, Dirk; Mesraoua, Boulenouar; Canibaño, Beatriz; Melikyan, Gayane; Al Hail, Hassan; El-Sheikh, Lubna; Ali, Musab; Al Hussein, Hassan; Ibrahim, Faiza; Hanssens, Yolande

2018-06-18

The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

Gastroesophageal reflux disease and eosinophilic esophagitis in infants and children. A study of esophageal pH, multiple intraluminal impedance and endoscopic ultrasound

DEFF Research Database (Denmark)

Dalby, Kasper; Nielsen, Rasmus; Kruse-Andersen, Søren

2010-01-01

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) in childhood share aspects of symptomatology. In order to characterize EE and GERD in infants and children with symptoms of GERD we performed a prospective investigation including prolonged esophageal pH measurement, multiple...

Multiple sclerosis and other white matter diseases

International Nuclear Information System (INIS)

Zimmerman, R.A.

1991-01-01

The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)

Progression of regional grey matter atrophy in multiple sclerosis.

Science.gov (United States)

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple

Progression of regional grey matter atrophy in multiple sclerosis

Science.gov (United States)

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

Science.gov (United States)

Pehlivan, Münevver; Kürtüncü, Murat; Tüzün, Erdem; Shugaiv, Erkingül; Mutlu, Melike; Eraksoy, Mefküre; Akman-Demir, Gülşen

2011-07-01

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis. Copyright © 2011 Elsevier GmbH. All rights reserved.

Primary progressive multiple sclerosis in the Polish population

Directory of Open Access Journals (Sweden)

Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

Directory of Open Access Journals (Sweden)

Caroline Vieira Spessotto

2016-08-01

Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

An autopsy case of multiple myeloma with veno-occlusive disease of the liver induced by ionizing radiation

International Nuclear Information System (INIS)

Ueno, Hironori; Inagaki, Yasutaka; Yonei, Yoshikazu; Ozawa, Yukako; Atsukawa, Kazuhiro; Tsukada, Nobuhiro; Miyamoto, Kei; Suzuki, Osamu; Kiryu, Yasuyoshi

1995-01-01

An autopsy case of multiple myeloma which accompanied radiation-induced veno-occlusion of the liver is presented. A 62-year-old woman with a chief complaint of low back pain was diagnosed as having multiple myeloma. Approximately one year later, the patient was treated with chemotherapy, consisting of VCR, MCNU, ADR, PSL, and CPA, and X-irradiation of 30 Gy to the bilateral trunk for medically intractable rib pain. The irradiation field included the entire liver. Six months later, she was admitted to the hospital due to abdominal distention and massive amounts of ascites. Various examinations failed to make a qualitative diagnosis. Postmortem examination revealed fibrotic occlusion of the central vein which is typical for veno-occlusion disease of the liver. This finding was restricted to the area that was not shielded, irrespective of anatomical structure, strongly suggesting radiation-induced veno-occlusion of the liver. (N.K.)

Chemokine receptor CCR5 in interferon-treated multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

2007-01-01

To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

Directory of Open Access Journals (Sweden)

Frederick Ato Armah

Full Text Available In the past decade, research on neglected tropical diseases (NTDs has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.We also assessed the collective (compositional and contextual factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks.NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis.

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Feucht, Nikolaus; Maier, Mathias; Lepennetier, Gildas; Pettenkofer, Moritz; Wetzlmair, Carmen; Daltrozzo, Tanja; Scherm, Pauline; Zimmer, Claus; Hoshi, Muna-Miriam; Hemmer, Bernhard; Korn, Thomas; Knier, Benjamin

2018-01-01

Patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) may show alterations of retinal layer architecture as measured by optical coherence tomography. Little is known about changes in the retinal vascular network during MS. To characterize retinal vessel structures in patients with MS and CIS and to test for associations with MS disease activity. In all, 42 patients with MS or CIS and 50 healthy controls underwent retinal optical coherence tomography angiography (OCT-A) with analysis of the superficial and deep vascular plexuses and the choriocapillaries. We tested OCT-A parameters for associations with retinal layer volumes, history of optic neuritis (ON), and the retrospective disease activity. Inner retinal layer volumes correlated positively with the density of both the superficial and deep vascular plexuses. Eyes of MS/CIS patients with a history of ON revealed reduced vessel densities of the superficial and deep vascular plexuses as compared to healthy controls. Higher choriocapillary vessel densities were associated with ongoing inflammatory disease activity during 24 months prior to OCT-A examination in MS and CIS patients. Optic neuritis is associated with rarefaction of the superficial and deep retinal vessels. Alterations of the choriocapillaries might be linked to disease activity in MS.

Sexual habits before multiple sclerosis: a national case-control study

DEFF Research Database (Denmark)

Lidegaard, O.; Svendsen, Anne Louise; Lidegaard, Øjvind

2008-01-01

The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease.......The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease....

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

International Nuclear Information System (INIS)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

1988-01-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

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Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

1988-04-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease.

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Xiong, Huaqi; Chen, Yongxiong; Yi, Yajun; Tsuchiya, Karen; Moeckel, Gilbert; Cheung, Joseph; Liang, Dan; Tham, Kyi; Xu, Xiaohu; Chen, Xing-Zhen; Pei, York; Zhao, Zhizhuang Jeo; Wu, Guanqing

2002-07-01

Autosomal recessive polycystic kidney disease (ARPKD) is a common hereditary renal cystic disease in infants and children. By genetic linkage analyses, the gene responsible for this disease, termed polycystic kidney and hepatic disease 1 (PKHD1), was mapped on human chromosome 6p21.1-p12, and has been further localized to a 1-cM genetic interval flanked by the D6S1714/D6S243 (telomeric) and D6S1024 (centromeric) markers. We recently identified a novel gene in this genetic interval from kidney cDNA, using cloning strategies. The gene PKHD1 (PKHD1-tentative) encodes a novel 3396-amino-acid protein with no apparent homology with any known proteins. We named its gene product "tigmin" because it contains multiple TIG domains, which usually are seen in proteins containing immunoglobulin-like folds. PKHD1 encodes an 11.6-kb transcript and is composed of 61 exons spanning an approximately 365-kb genomic region on chromosome 6p12-p11.2 adjacent to the marker D6S1714. Northern blot analyses demonstrated that the gene has discrete bands with one peak signal at approximately 11 kb, indicating that PKHD1 is likely to have multiple alternative transcripts. PKHD1 is highly expressed in adult and infant kidneys and weakly expressed in liver in northern blot analysis. This expression pattern parallels the tissue involvement observed in ARPKD. In situ hybridization analysis further revealed that the expression of PKHD1 in the kidney is mainly localized to the epithelial cells of the collecting duct, the specific tubular segment involved in cyst formation in ARPKD. These features of PKHD1 make it a strong positional candidate gene for ARPKD.

Imaging and neuropsychologic study of Alzheimer's disease and multiple infarct dementia

International Nuclear Information System (INIS)

Fujii, Tsutomu; Fukatsu, Ryo; Takabatake, Naohiko; Takahashi, Sadaichiro; Morita, Kazuo; Akino, Minoru.

1987-01-01

Iodine-123 single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) were undertaken in 8 patients with Alzheimer's disease (AD) and 7 patients with multiple infarct dementia (MID). Imaging features and their relationship to neuropsychologic findings were examined. The group of AD patients had markedly decreased activity in the bilateral parietal-occipital areas on SPECT and relatively marked atrophy in the corresponding area and thinning in the posterior part of callosal stem on MRI. The group of MID patients had a widespread and inhomogeneously decreased activity in the frontal lobe and mottled decrease of activity in the other cortical areas on SPECT. Neuropsychologic symptoms steming from the parietal-occipital area, which is considered as an causative area for AD, were frequently observed in the AD group, as opposed to the lack of these symptoms in the MID group. In both AD and MID groups, there was a good correlation between the areas with decreased activity on SPECT and atrophy on MRI. These imaging appearances were correlated with the occurrence of neuropsychologic symptoms as well. The importance of the parietal-occipital lobe that is likely responsible for the pathogenesis of dementia for AD is emphasized. (Namekawa, K.)

Mining gene expression data of multiple sclerosis.

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Pi Guo

Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

Proton density differences in signal characteristics of multiple sclerosis plaques versus white matter lesions of small vessel disease and vasculitis on high-field strength MR images

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Peyster, R.G.; Siegal, T.L.

1990-01-01

This paper determines if variations in signal intensity characteristics on multi-spin-echo images obtained with a high-field-strength magnet can be useful in differentiating demyelinating plaques of multiple sclerosis from other pathologic white matter processes due to small vessel disease and vasculities. Using the first of two multi-spin-echo images obtained with a General Electric 1.5-T magnet, the investigators compared signal intensity characteristics in 30 patients with a firm clinical diagnosis of multiple sclerosis versus a control group of 30 patients with a known clinical history of small-vessel disease and vasculitis are isodense to gray matter on proton-density images

Multiple sclerosis: general features and pharmacologic approach

International Nuclear Information System (INIS)

Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

2009-01-01

Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

Psychosocial predictors of patient adherence to disease-modifying therapies for multiple sclerosis

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Alosaimi FD

2017-03-01

Full Text Available Fahad D Alosaimi,1 Alaa AlMulhem,2 Hanan AlShalan,2 Mohammad Alqazlan,3 Abdulgader Aldaif,4 Matthew Kowgier,5 Janooshsheya Balasundaram,6 Sanjeev Sockalingam6,7 1Department of Psychiatry, 2College of Medicine, King Saud University, 3Department of Mental Health, King Faisal Specialist Hospital and Research Centre, 4Department of Neurology, King Saud University, Riyadh, Saudi Arabia; 5Dalla Lana School of Public Health, University of Toronto, 6Centre for Mental Health, University Health Network, 7Department of Psychiatry, University of Toronto, Toronto, ON, Canada Objectives: Our aim was to identify the impact of psychosocial predictors, specifically relationship style, depressive symptoms, anxiety symptoms, cognitive impairment, and culture-specific disease beliefs, on treatment adherence for multiple sclerosis (MS patients.Methods: In this cross-sectional observational study, patients from two MS clinics in Saudi Arabia completed self-reported questionnaires focused on MS treatment adherence, physical symptom burden, relationship style, cultural beliefs, depressive symptoms, anxiety, and cognitive impairment.Results: A total of 163 MS patients participated, 81.6% of them were female, and the mean age of the patients was 31.6 years. Mean patient-reported adherence to their MS treatment regimen was 79.47%±25.26%. Multivariate linear regression analysis only identified patients’ belief that their MS was due to “supernatural” forces as being significantly negatively associated with MS medication adherence.Conclusion: This study demonstrates the importance of cultural interpretations to MS medication adherence in comparison to psychosocial factors. Education and family involvement in the treatment planning may address this issue and warrant further research. Keywords: multiple sclerosis, adherence, depression, attachment style, culture

Breeding of Yangfumai No.5 with multiple disease resistance

International Nuclear Information System (INIS)

He Zhentian; Chen Xiulan; Zhang Rong; Wang Jianhua; Wang Jinrong

2013-01-01

To control the damage of wheat yellow mosaic disease and powdery mildew, new wheat cultivar with high-yield, disease-resistant was bred. Yangfumai 9311 with yellow mosaic disease resistant was used as donor parent to backcross with recurrent parent Yangmai 11, and combined with conventional breeding techniques and irradiation methods, a new wheat variety Yangfumai No.5 was developed and registered in 2011. Yangfumai No.5 with resistance of yellow mosaic disease and powdery mildew is suitable to grow in the Yangtze River region. (authors)

Magnetic resonance imaging in the diagnostics of multiple sclerosis

International Nuclear Information System (INIS)

Larsen, J.P.; Tjoerstad, K.; Kaass, B.; Oedegaard, H.

1987-01-01

Multiple sclerosis is an important and frequent neurological disease and the diagnosis might be difficult. The clinical criteria of multiple sclerosis and the role of laboratory examinations in the diagnosis of the disease are discussed. In particular the help offered by the magnetic resonance imaging method is the subject of this paper. Three patients are reported and discussed

Triple-orifice valve repair in severe Barlow disease with multiple-jet mitral regurgitation: report of mid-term experience.

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Fucci, Carlo; Faggiano, Pompilio; Nardi, Matilde; D'Aloia, Antonio; Coletti, Giuseppe; De Cicco, Giuseppe; Latini, Leonardo; Vizzardi, Enrico; Lorusso, Roberto

2013-09-10

Barlow disease represents a surgical challenge for mitral valve repair (MR) in the presence of mitral insufficiency (MI) with multiple regurgitant jets. We hereby present our mid-term experience using a modified edge-to-edge technique to address this peculiar MI. From March 2003 till December 2010, 25 consecutive patients (mean age 54 ± 7 years, 14 males) affected by severe Barlow disease with multiple regurgitant jets were submitted to MR. Preoperative transesophageal echo (TEE) in all the cases showed at least 2 regurgitant jets, involving one or both leaflets in more than one segment. In all the patients, a triple orifice valve (TOV) repair with annuloplasty was performed. Intra-operative TEE and postoperative transthoracic echocardiography (TTE) were carried out to evaluate results of the TOV repair. There was no in-hospital death and one late death (non-cardiac related). At intra-operative TEE, the three orifices showed a mean total valve area of 2.9 ± 0.1cm(2) (range 2.5-3.3 cm(2)) with no residual regurgitation (2 cases of trivial MI) and no sign of valve stenosis (mean transvalvular gradient 4.6 ± 1.5 mmHg). At follow up (mean 38 ± 22 months), TTE showed favourable MR and no recurrence of significant MI (6 cases of trivial and 1 of mild MI). Stress TTE was performed in 5 cases showing persistent effective valve function (2 cases of trivial MI at peak exercise). All the patients showed significant NYHA functional class improvement. This report indicates that the TOV technique is effective in correcting complex Barlow mitral valves with multiple jets. Further studies are required to confirm long-term applicability and durability in more numerous clinical cases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation

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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.

Multiple sclerosis and herpesvirus interaction

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Guilherme Sciascia do Olival

2013-09-01

Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

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Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

Rasch analysis of the Multiple Sclerosis Impact Scale (MSIS-29)

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Ramp, Melina; Khan, Fary; Misajon, Rose Anne; Pallant, Julie F

2009-01-01

Abstract Background Multiple Sclerosis (MS) is a degenerative neurological disease that causes impairments, including spasticity, pain, fatigue, and bladder dysfunction, which negatively impact on quality of life. The Multiple Sclerosis Impact Scale (MSIS-29) is a disease-specific health-related quality of life (HRQoL) instrument, developed using the patient's perspective on disease impact. It consists of two subscales assessing the physical (MSIS-29-PHYS) and psychological (MSIS-29-PSYCH) im...

Rehabilitation and multiple sclerosis

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Dalgas, Ulrik

2011-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

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Amanda Worker

Full Text Available Parkinson's disease (PD, Multiple System Atrophy (MSA and Progressive Supranuclear Palsy (PSP are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features.High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0. Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group.Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology.These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients.

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

Multiple myeloma: 45 cases

International Nuclear Information System (INIS)

Yang, Hee Chul; Suh, Jin Suck; Park, Chang Yun

1990-01-01

We evaluated 45 cases of multiple myelomas retrospectively confirmed in Severance Hospital from the period of 1983-1989. In order to assess the radiologic features of the multiple myeloma and to assist in possible early diagnosis and treatment. The result were as follows: 1. IgG(41%) was the most common immunoglobulin type secreted followed by light chain(36%). IgA(19%) and IgD(2%). Two percent of the patients had non-secretory type. 89% of patients were in their stage III of the disease. 2. Among the 45 patients, 96% had abnormal plain radiographic findings with average number of 4.5 lesions. Common sites were the spine, rib, skull, pelvis, and humerus in descending orders. The findings were localized or diffuse osteolytic bone destruction(85%). osteoporosis(49%), pathologic fracture and endosteal scalloping(55%). Osteoporosis was more prominent in stage III than stage II. 3. Both plain X-ray and radioisotope study was available for comparison in 28 patients. Concordance between the two studies were 44%, lesions detected only on plain X-ray film were 51%, and lesions detected only on the radioisotope were 5%. The plain radiography was able to detect only 54% of bone lesions confirmed by bone marrow biopsy. With the above results, accurate evaluation of bone lesions in multiple myeloma may be difficult with radiologic studies only. But familiarity with these radiologic findings of the this disease entity is necessary for early suspicion of the disease, thus for early diagnosis and treatment

Rehabilitation in multiple sclerosis.

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Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

2017-07-01

The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

Treatment of Cognitive Impairment in Multiple Sclerosis

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Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

2004-01-01

Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

Genetic association of multiple sclerosis with the marker rs391745 near the endogenous retroviral locus HERV-Fc1: analysis of disease subtypes

DEFF Research Database (Denmark)

Hansen, Bettina; Oturai, Annette Bang; Harbo, Hanne F

2011-01-01

We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients......-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS....

Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

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Lu Zhang

2012-01-01

Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

The primary cilium as a multiple cellular signaling scaffold in development and disease

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Hyuk Wan Ko*

2012-08-01

Full Text Available Primary cilia, single hair-like appendage on the surface of themost mammalian cells, were once considered to be vestigialcellular organelles for a past century because of their tinystructure and unknown function. Although they lack ancestralmotility function of cilia or flagella, they share common groundwith multiciliated motile cilia and flagella on internal structuresuch as microtubule based nine outer doublets nucleated from thebase of mother centrioles called basal body. Making cilia,ciliogenesis, in cells depends on the cell cycle stage due to reuseof centrioles for cell division forming mitotic spindle pole (Mphase and assembling cilia from basal body (starting G1 phaseand maintaining most of interphase. Ciliary assembly requiredtwo conflicting processes such as assembly and disassembly andbalance between these two processes determines the length ofcilia. Both process required highly conserved transport system tosupply needed substance to grow tip of cilia and bring ciliaryturnover product back to the base of cilia using motor protein,kinesin and dynein, and transport protein complex, IFT particles.Disruption of ciliary structure or function causes multiple humandisorder called ciliopathies affecting disease of diverse ciliatedtissues ranging from eye, kidney, respiratory tract and brain.Recent explosion of research on the primary cilia and theirinvolvement on animal development and disease attracts scientificinterest on how extensively the function of cilia related to specificcell physiology and signaling pathway. In this review, I introducegeneral features of primary cilia and recent progress inunderstanding of the ciliary length control and signaling pathwaystransduced through primary cilia in vertebrates.

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

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Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

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

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

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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.

The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis.

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Wickström, Anne; Fagerström, Maria; Wickström, Lucas; Granåsen, Gabriel; Dahle, Charlotte; Vrethem, Magnus; Sundström, Peter

2017-07-01

Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population ( p work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population ( p = 0.042). Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

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Levitt DG

2014-09-01

Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB and unconjugated bilirubin (UB. While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis, and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert's, Dubin–Johnson, Crigler–Najjar, Rotor syndromes. Novel aspects of this review include: 1 quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2 detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3 discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4 pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5 role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6 insights concerning the clinical interpretation of bilirubin measurements.Keywords: liver, conjugation, diazo, albumin, Rotor

Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients.

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Rydbirk, Rasmus; Elfving, Betina; Andersen, Mille Dahl; Langbøl, Mia Aggergaard; Folke, Jonas; Winge, Kristian; Pakkenberg, Bente; Brudek, Tomasz; Aznar, Susana

2017-10-01

Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which are the main inflammatory signalling molecules, have been identified in blood and cerebrospinal fluid of PD patients, but studies investigating the human brain levels are scarce. It is documented that neurotrophins, necessary for survival of brain cells and known to interact with cytokines, are altered in the basal ganglia of PD patients. In regards to MSA, no major study has investigated brain cytokine or neurotrophin protein expression. Here, we measured protein levels of 18 cytokines (IL-2, 4-8, 10, 12, 13, 17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1α and 1β, TNF-α) and 5 neurotrophins (BDNF, GDNF, bFGF, PDGF-BB, VEGF) in the dorsomedial prefrontal cortex in brains of MSA and PD patients and control subjects. We found altered expression of IL-2, IL-13, and G-CSF, but no differences in neurotrophin levels. Further, in MSA patients we identified increased mRNA levels of GSK3β that is involved in neuroinflammatory pathways. Lastly, we identified increased expression of the neurodegenerative marker S100B, but not CRP, in PD and MSA patients, indicating local rather than systemic inflammation. Supporting this, in both diseases we observed increased MHC class II + and CD45 + positive cells, and low numbers of infiltrating CD3 + cells. In conclusion, we identified neuroinflammatory responses in PD and MSA which seems more widespread in the brain than neurotrophic changes. Copyright © 2017 Elsevier Inc. All rights reserved.

Midkine and multiple sclerosis

OpenAIRE

Takeuchi, Hideyuki

2014-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4+CD25+FoxP3+ regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the d...

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

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Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Role of T cell – glial cell interactions in creating and amplifying Central Nervous System inflammation and Multiple Sclerosis disease symptoms

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Eric S. Huseby

2015-08-01

Full Text Available Multiple Sclerosis (MS is an inflammatory disease of the Central Nervous System (CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought of as a T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified gray matter lesions in MS patients, suggesting that CNS antigens other than myelin proteins may be involved during the MS disease process. We have recently found that T cells targeting astrocyte-specific antigens can drive unique aspects of inflammatory CNS autoimmunity, including the targeting of gray matter and white matter of the brain and inducing heterogeneous clinical disease courses. In addition to being a target of T cells, astrocytes play a critical role in propagating the inflammatory response within the CNS through cytokine induced NF-ΚB signaling. Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell – glial cell interactions and its contributions to CNS autoimmunity.

An architecture model for multiple disease management information systems.

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Chen, Lichin; Yu, Hui-Chu; Li, Hao-Chun; Wang, Yi-Van; Chen, Huang-Jen; Wang, I-Ching; Wang, Chiou-Shiang; Peng, Hui-Yu; Hsu, Yu-Ling; Chen, Chi-Huang; Chuang, Lee-Ming; Lee, Hung-Chang; Chung, Yufang; Lai, Feipei

2013-04-01

Disease management is a program which attempts to overcome the fragmentation of healthcare system and improve the quality of care. Many studies have proven the effectiveness of disease management. However, the case managers were spending the majority of time in documentation, coordinating the members of the care team. They need a tool to support them with daily practice and optimizing the inefficient workflow. Several discussions have indicated that information technology plays an important role in the era of disease management. Whereas applications have been developed, it is inefficient to develop information system for each disease management program individually. The aim of this research is to support the work of disease management, reform the inefficient workflow, and propose an architecture model that enhance on the reusability and time saving of information system development. The proposed architecture model had been successfully implemented into two disease management information system, and the result was evaluated through reusability analysis, time consumed analysis, pre- and post-implement workflow analysis, and user questionnaire survey. The reusability of the proposed model was high, less than half of the time was consumed, and the workflow had been improved. The overall user aspect is positive. The supportiveness during daily workflow is high. The system empowers the case managers with better information and leads to better decision making.

Therapeutic molecules for multiple human diseases identified from pigeon pea (Cajanus cajan L. Millsp. through GC–MS and molecular docking

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Deepu Mathew

2017-12-01

Full Text Available Molecular mechanism behind the therapeutic potential of pigeon pea over the human diseases such as rheumatoid arthritis, breast cancer, type II diabetes, malaria, measles and sickle cell disease were revealed through docking of GC–MS identified phyto-compound ligands with candidate disease proteins. Of the 242 ligands, three dimensional structures of 47 compounds had to be drawn using ChemSketch and the remaining structures were retrieved from PubChem and docked with the active sites of candidate proteins. The molecules identified through docking were further subjected to ADMET analysis and promising drug candidates were identified for each disease. This paper presents a precise account of the chemoprofile of pigeon pea leaves, stems and seeds, interaction of these molecules with target proteins and suggests 26 highly potential molecules which are drug candidates for multiple human diseases. Pigeon pea seeds are especially proven as invaluable source for therapeutic molecules. Keywords: Breast cancer, Drug discovery, Herbal medicine, In silico, Malaria, Measles, Phyto-compounds, Rheumatoid arthritis, Sickle cell disease, Type II diabetes

Multiple sclerosis - etiology and diagnostic potential.

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Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Multiple sclerosis - etiology and diagnostic potential

Directory of Open Access Journals (Sweden)

Joanna Kamińska

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

[Multiple sclerosis in literature, cinema and television].

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Collado-Vazquez, S; Carrillo, J M; Cano-de-la-Cuerda, R

2016-12-16

Today, the care of patients with multiple sclerosis and those around them represents a clinical and therapeutic challenge for healthcare professionals. The aim of this study is to analyse the appearance of multiple sclerosis in literature, cinema and television, and to reflect upon the image it has in these media. Several representative works that have addressed multiple sclerosis were reviewed, and many of them were seen to offer a very true-to-life vision of the disease. Likewise, a review was also conducted of the most relevant films and TV series that, on occasions, offer the general public a close look at the impact of the disease on patients or relatives, although they are sometimes somewhat exaggerated for the sake of increased dramatic effect and offer a slightly distorted view of reality. Literature largely reflects the real epidemiology, the symptoms and development of the disease, while less attention seems to be given to the diagnostic and therapeutic options open to patients. Cinema and television have offered a correct image but sometimes with the addition of more dramatic effects. It is important for literature, cinema and television to offer a realistic view of this neurological disease so as to make it better known among the public and to help lessen the stigma attached to it.

Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.

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Learmonth, Yvonne C; Motl, Robert W; Sandroff, Brian M; Pula, John H; Cadavid, Diego

2013-04-25

The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days. There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 &ρ = .647, respectively) and Cerebellar (ρ = .501 &ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 &ρ = .805, respectively), MSWS-12 scores (ρ = .801 &ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 &ρ = -.717, respectively). This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

[Psychological distress of children with progressive diseases and multiple disabilities: A crossed analysis].

Science.gov (United States)

Perifano, A; Scelles, R

2015-09-01

In this paper, we present the results of research conducted on the psychological distress of lysosomal-disease-affected children. Lysosomal diseases are rare genetic diseases most often leading to severe disabilities, both psychological and physiological. As frequently reported by their relatives, affected children experience nervous breakdowns, which are sometimes treated with antidepressant prescriptions. However, mental impairment as well physical disabilities can prevent children from making their pain noticed and identified by their relatives. This raises a new research question: when disabilities are severe, how should the psychological distress of affected children be identified? Recent studies on the care of children with multiple disabilities (San Salavadour 2000; Scelles 2003; Camelio 2006; Pautrel, 2009) have used the children's family and caregivers to access their feelings, considered to be translators of children's feelings because they understand their nonverbal language (Camelio, 2006). Using this methodology, four parents from the French not-for-profit association called "VML" (Vaincre les maladies lysosomales) and four professionals were involved in semi-structured interviews. The goal of these interviews was to identify signs of possible psychological suffering, the context in which those signs were expressed, the meaning and the value attributed to it by the family and caregivers, and the reaction as well as an evaluation of that reaction. Thirteen children were involved, 12 of whom were described as having shown signs of psychological distress. Six lysosomal diseases were represented. Two types of signs were reported: active signs (e.g., agitation, screaming, crying) and passive signs (e.g., no communication, withdrawal, lack of facial expression). Most of the time, passive signs were interpreted by the family and caregivers as evidence of deep psychological distress. The meanings of both types of sign were the following: fear, anxiety

Gait Characteristics in Adolescents With Multiple Sclerosis.

Science.gov (United States)

Kalron, Alon; Frid, Lior; Menascu, Shay

2017-03-01

Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple sclerosis and positive lyme serology

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Marco Aurélio Lana-Peixoto

1994-12-01

Full Text Available As Lyme neuroborreliosis (LNB may clinically mimick multiple sclerosis (MS the presence of antibodies to Borrelia burgdorferi in serum of patients with a MS-like disease in non-edemic areas for Lyme disease may be troublesome. We report the case of a 45-year-old white female with the diagnosis of relapsing/ remitting form of MS due to a 15-year history of optic neuritis and recurrent episodes of motor and sensation disturbance in the upper right limb and in both lower extremites associated with bladder dysfunction. A magnetic resonance imaging of the brain revealed multiple high intensity periventricular white matter lesions. The patient had been exposed to ticks but did not recall the presence of erythema migrans. ELISA for Lyme disease was positive in two different laboratories and the positive serology was confirmed by Western blotting. No convincing reponse followed treatment with ceftriaxone. Although it is clear that the patient had been infect by Borrelia burgdorferi the relationship of this spirochetal infection with the neurological disease could not be ascertained.

Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

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Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

2013-10-01

Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P treatment gaps of ≥ 60 days (44.8% vs 55.3%, P treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men

International Nuclear Information System (INIS)

Hung, J.; Chaitman, B.R.; Lam, J.; Lesperance, J.; Dupras, G.; Fines, P.; Cherkaoui, O.; Robert, P.; Bourassa, M.G.

1985-01-01

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy

Multiple sclerosis: a geographical hypothesis.

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Carlyle, I P

1997-12-01

Multiple sclerosis remains a rare neurological disease of unknown aetiology, with a unique distribution, both geographically and historically. Rare in equatorial regions, it becomes increasingly common in higher latitudes; historically, it was first clinically recognized in the early nineteenth century. A hypothesis, based on geographical reasoning, is here proposed: that the disease is the result of a specific vitamin deficiency. Different individuals suffer the deficiency in separate and often unique ways. Evidence to support the hypothesis exists in cultural considerations, in the global distribution of the disease, and in its historical prevalence.

Guidelines for supportive care in multiple myeloma 2011.

Science.gov (United States)

Snowden, John A; Ahmedzai, Sam H; Ashcroft, John; D'Sa, Shirley; Littlewood, Timothy; Low, Eric; Lucraft, Helen; Maclean, Rhona; Feyler, Sylvia; Pratt, Guy; Bird, Jennifer M

2011-07-01

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011. © 2011 Blackwell Publishing Ltd.

Quantifying cause-related mortality by weighting multiple causes of death

Science.gov (United States)

Moreno-Betancur, Margarita; Lamarche-Vadel, Agathe; Rey, Grégoire

2016-01-01

Abstract Objective To investigate a new approach to calculating cause-related standardized mortality rates that involves assigning weights to each cause of death reported on death certificates. Methods We derived cause-related standardized mortality rates from death certificate data for France in 2010 using: (i) the classic method, which considered only the underlying cause of death; and (ii) three novel multiple-cause-of-death weighting methods, which assigned weights to multiple causes of death mentioned on death certificates: the first two multiple-cause-of-death methods assigned non-zero weights to all causes mentioned and the third assigned non-zero weights to only the underlying cause and other contributing causes that were not part of the main morbid process. As the sum of the weights for each death certificate was 1, each death had an equal influence on mortality estimates and the total number of deaths was unchanged. Mortality rates derived using the different methods were compared. Findings On average, 3.4 causes per death were listed on each certificate. The standardized mortality rate calculated using the third multiple-cause-of-death weighting method was more than 20% higher than that calculated using the classic method for five disease categories: skin diseases, mental disorders, endocrine and nutritional diseases, blood diseases and genitourinary diseases. Moreover, this method highlighted the mortality burden associated with certain diseases in specific age groups. Conclusion A multiple-cause-of-death weighting approach to calculating cause-related standardized mortality rates from death certificate data identified conditions that contributed more to mortality than indicated by the classic method. This new approach holds promise for identifying underrecognized contributors to mortality. PMID:27994280

The Geomagnetic Field and Correlations with Multiple Sclerosis: A Possible Etiology of Disease

Science.gov (United States)

Wade, Brett

Multiple sclerosis (MS) is a complex autoimmune disease that results in a demyelinating process of the central nervous system. It is the most common, progressive, neurological disease affecting young adults, and there is no cure. A curious feature of MS is its distinct global prevalence with high rates of occurrence between 40 and 60 degrees latitude. While genetics may partially explain this phenomenon, studies have shown that the influence of genetics is modest. Many non-genetic variables, such as viruses, vitamin D, smoking, diet, hormones, etc., have been shown to be related to the expression of MS but none of these variables have been determined to be necessarily strong enough to exclude other factors. The geomagnetic field, which is a non-uniform, three dimensional entity which protects all living things from ionizing radiation, is suggested in this research to be related to global MS prevalence. This study hypothesized that either the total field, the vertical field, or the horizontal field strength of the geomagnetic field will be correlated with MS. Using secondary sources of prevalence studies (N=131) and geomagnetic data, the results supported all three hypotheses with the strongest correlation being an inverse relationship between the horizontal field and MS (r = -.607). The explanation for the inverse relationship being most strongly correlated with MS prevalence is explained by the fact that the horizontal aspect of the geomagnetic field has a protective effect from incoming cosmic radiation. Chronic exposure to high levels of background radiation can have deleterious health effects. This research suggests that living in areas of a weak horizontal field increases a person's exposure to ionizing radiation and therefore increases the risk for developing MS. While it was not the intention of this research, it became clear that an explanation which explained the results of this research and also attempted to unify the mechanisms of all non

A Pictorial Review on Extraosseous Manifestations of Multiple Myelomas

International Nuclear Information System (INIS)

Seo, Jung Min; Lee, Kyung Soo; Yi, Chin A; Kim, Seong Hyun; Park, Byung Kwan; Han, Boo Kyung; Kim, Hyung Jin

2011-01-01

Extraosseous involvement of multiple myelomas can be seen clinically or radiologically in approximately 10-20% of patients at the time of initial diagnosis and may develop in an additional 15% of patients over the course of the disease. The condition can arise in any tissue of the body and its presence has been associated with more aggressive disease, a guarded prognosis, or high-dose chemotherapy. Imaging findings of extraosseous multiple myelomas are diverse. They usually show high enhancement on contrast-medium enhanced CT scans, exhibit iso-signal intensity on both T1- and T2- weighted images, and variable 18F-fluorine deoxyglucose (FDG) uptake at PET. The disease may simulate an infectious condition since it may be concurrent with underlying multiple myelomas per se or it may occur during myeloma treatment including stem cell transplantation.

Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.

Directory of Open Access Journals (Sweden)

Anat Achiron

Full Text Available BACKGROUND/AIMS: Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years. METHODS: 1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD and severe cognitive impairment as below 2SD for age and education matched healthy population norms. RESULTS: Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p=0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p=0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p=0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years. CONCLUSIONS: The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

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Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1994-09-01

Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

Science.gov (United States)

Saiz, A; Mora, S; Blanco, J

2015-05-01

Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Olfactory bulb and olfactory sulcus depths are associated with disease duration and attack frequency in multiple sclerosis patients.

Science.gov (United States)

Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

2015-11-15

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease that progresses to axonal loss and demyelinization. Olfactory dysfunction in patients with MS has been reported frequently. We were interested in the associations of olfactory bulb (OB) and olfactory sulcus depth (OSD) with disease duration and attack frequency. We included 25 patients with MS and 30 age- and sex-matched controls in this study. The Expanded Disability Status Scale, Beck Depression Inventory, and Mini Mental State Examination were applied. OB, OSD, and magnetic resonance imaging plaque numbers were calculated. OB volume and OSD in patients with MS were significantly lower than those in the control group (right and left OB: p<0.001; right OSD: p=0.001; and left OSD: p=0.039). Disease duration was negatively correlated with right and left OB volume (right OB: r=-0.434, p=0.030 and left OB: r=-0.518, p=0.008). Attack frequency was negatively correlated with left OB volume and left OSD (left OB: r=-0.428, p=0.033 and left OSD: r=-0.431, p=0.032). The OB and OSD were atrophied significantly in patients with MS, and this was correlated with disease duration and attack frequency. The left side tended to be dominant. Copyright © 2015 Elsevier B.V. All rights reserved.

Disease spread across multiple scales in a spatial hierarchy: effect of host spatial structure and of inoculum quantity and distribution.

Science.gov (United States)

Gosme, Marie; Lucas, Philippe

2009-07-01

Spatial patterns of both the host and the disease influence disease spread and crop losses. Therefore, the manipulation of these patterns might help improve control strategies. Considering disease spread across multiple scales in a spatial hierarchy allows one to capture important features of epidemics developing in space without using explicitly spatialized variables. Thus, if the system under study is composed of roots, plants, and planting hills, the effect of host spatial pattern can be studied by varying the number of plants per planting hill. A simulation model based on hierarchy theory was used to simulate the effects of large versus small planting hills, low versus high level of initial infections, and aggregated versus uniform distribution of initial infections. The results showed that aggregating the initially infected plants always resulted in slower epidemics than spreading out the initial infections uniformly. Simulation results also showed that, in most cases, disease epidemics were slower in the case of large host aggregates (100 plants/hill) than with smaller aggregates (25 plants/hill), except when the initially infected plants were both numerous and spread out uniformly. The optimal strategy for disease control depends on several factors, including initial conditions. More importantly, the model offers a framework to account for the interplay between the spatial characteristics of the system, rates of infection, and aggregation of the disease.

Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

DEFF Research Database (Denmark)

Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

2018-01-01

Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

Multiple familial trichoepithelioma: a rare cutaneous tumour

International Nuclear Information System (INIS)

Arfan-ul-Bari; Simeen-ber-Rehman

2004-01-01

Multiple familial trichoepithelioma (MFT) is a rare autosomal dominant skin disease that presents as many small tumours predominantly on the face. We report a case of multiple familial trichoepithelioma occurring in three members of a family. They were diagnosed simultaneously. Only one was treated with medium depth chemical peeling with partial response. (author)

Seizures in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Uyttenboogaart, Maarten; Polman, Susan; De Keyser, Jacques

Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the

Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

Directory of Open Access Journals (Sweden)

Crawford A

2014-08-01

Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

Body fluid markers to monitor multiple sclerosis: The assays and the challenges

NARCIS (Netherlands)

Laman, J.D.; Thompson, E.J.; Kappos, L.

1998-01-01

The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis

Clinical outcome of Crohn's disease according to the Vienna classification: disease location is a useful predictor of disease course

NARCIS (Netherlands)

Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

2006-01-01

OBJECTIVES: Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

Clinical outcome of Crohn's disease according to the Vienna classification : disease location is a useful predictor of disease course

NARCIS (Netherlands)

Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

Objectives Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

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Mithu Storoni

2015-01-01

Full Text Available Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.

Predictive value of testing for multiple genetic variants in multifactorial diseases: implications for the discourse on ethical, legal and social issues

Directory of Open Access Journals (Sweden)

A. Cecile J.W. Janssens

2006-12-01

Full Text Available Multifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is expected to lead to individualized medicine, in which the prevention and treatment strategies are personalized on the basis of the results of predictive genetic tests. This great optimism is counterbalanced by concerns about the ethical, legal, and social implications of genomic medicine, such as the protection of privacy and autonomy, stigmatization, discrimination, and the psychological burden of genetic testing. These concerns are translated from genetic testing in monogenic disorders, but this translation may not be appropriate. Multiple genetic testing (genomic profiling has essential differences from genetic testing in monogenic disorders. The differences lie in the lower predictive value of the test results, the pleiotropic effects of susceptibility genes, and the low inheritance of genomic profiles. For these reasons, genomic profiling may be more similar to nongenetic tests than to predictive tests for monogenic diseases. Therefore, ethical, legal, and social issues that apply to predictive genetic testing for monogenic diseases may not be relevant for the prediction of multifactorial disorders in genomic medicine.

Acute form of multiple sclerosis in a child simulation encephalitis

International Nuclear Information System (INIS)

Niagolova, S.; Karapasheva, V.; Nikolova, M.

2007-01-01

Multiple sclerosis (MS) is considered the most common demyelinating process involving the CNS. Although usually considered an adult disease multiple sclerosis can begin to manifest during childhood. The clinical presentation of the disease in early childhood can range from paraesthesias to dramatic presentations, suggesting diffuse encephalopathy with cerebral oedema, meningismus and impaired consciousness. Multiple sclerosis is usually characterized by a typical relapsing-remitting clinical course. But there are acute, clinically fulminant forms with atypical. neurologic symptoms and death in months. MRI has become increasingly relevant in the diagnosis of multiple sclerosis in the past years. Yet, the specificity is limited. Atypical forms of MS and other diseases of CNS may show similar patterns on MRI. We report a case of 7 years old boy with clinically fulminant Marburg type of multiple sclerosis that ended with death in two months. The patient was a diagnostic problem despite the certain degree of clinical and radiological suspicion. The postmortem diagnosis is based on pathomorphologic changes (gross pathologic and microscopic features) in CNS.The present case is of clinical, radiological and pathomorphologic interest because of its early onset in childhood, unusual clinical course and acute progression. Awareness of the MRI features of multiple sclerosis and MS-variants (subtypes) may help in such atypical presentations in childhood. (authors)

Vaccines in Multiple Sclerosis.

Science.gov (United States)

Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

2016-04-01

Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Focus on Longitudinal Assessment of Donor Chimerism, Extramedullary Disease, and High-Risk Cytogenetic Features.

Science.gov (United States)

Rasche, Leo; Röllig, Christoph; Stuhler, Gernot; Danhof, Sophia; Mielke, Stephan; Grigoleit, Goetz Ulrich; Dissen, Lea; Schemmel, Lea; Middeke, Jan Moritz; Rücker, Viktoria; Schreder, Martin; Schetelig, Johannes; Bornhäuser, Martin; Einsele, Hermann; Thiede, Christian; Knop, Stefan

2016-11-01

Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study. Outcome variables were studied in univariate and multivariable analyses. Available were 2.324 DC samples (median, 12 per patient). Loss of full DC was associated with shorter progression-free survival (PFS) (HR, 1.7; 95% CI, 1.1 to 2.6) but did not impact overall survival. Two-thirds of patients with International Myeloma Working Group-defined relapses still displayed a full DC in peripheral blood or bone marrow. Extramedullary manifestations were observed in 33% of patients, accounting for the discrepancy between DC analysis and the actual disease status. In multivariable analysis, the 2 most relevant variables for an unfavorable PFS were progressive disease before allo-SCT (HR, 3.0; 95% CI, 1.5 to 5.9) and allo-SCT at least the second relapse (HR, 2.8; 95% CI, 1.5 to 4.9), whereas for overall survival progressive disease or partial response before allo-SCT had the strongest negative effects (HR, 4.2; 95% CI, 1.9 to 9, and HR, 2.0; 95% CI, 1.0 to 3.8, respectively). Adverse cytogenetics such as del17p, t(4,14) or amp(1q21) were not associated with shorter survival after allo-SCT. Extensive DC sampling beyond robust engraftment does not appear to provide additional information helpful for disease management in most patients and is challenged by a significant incidence of extramedullary disease. In our

Multiple sclerosis care: an integrated disease-management model.

Science.gov (United States)

Burks, J

1998-04-01

A disease-management model must be integrated, comprehensive, individual patient focused and outcome driven. In addition to high quality care, the successful model must reduce variations in care and costs. MS specialists need to be intimately involved in the long-term care of MS patients, while not neglecting primary care issues. A nurse care manager is the "glue" between the managed care company, health care providers and the patient/family. Disease management focuses on education and prevention, and can be cost effective as well as patient specific. To implement a successful program, managed care companies and health care providers must work together.

A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

Science.gov (United States)

Colpitts, Sara L; Kasper, Eli J; Keever, Abigail; Liljenberg, Caleb; Kirby, Trevor; Magori, Krisztian; Kasper, Lloyd H; Ochoa-Repáraz, Javier

2017-11-02

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.

Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis?

DEFF Research Database (Denmark)

Dalgas, Ulrik; Stenager, Egon

2012-01-01

studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally......, (4) longitudinal exercise studies applying the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression by clinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reported data...... (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients...

Cell-based therapeutic strategies for multiple sclerosis.

Science.gov (United States)

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

MR in the diagnosis and monitoring of multiple sclerosis: An overview

International Nuclear Information System (INIS)

Rovira, Alex; Leon, Adelaida

2008-01-01

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

MR in the diagnosis and monitoring of multiple sclerosis: An overview

Energy Technology Data Exchange (ETDEWEB)

Rovira, Alex [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)], E-mail: alex.rovira@idi-cat.org; Leon, Adelaida [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)

2008-09-15

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

Type 1 diabetes and multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, N.M.; Westergaard, T.; Frisch, M.

2006-01-01

BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil....... OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish...

Defining active progressive multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

2017-01-01

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

Descriptive epidemiology of chronic liver disease in northeastern Italy: an analysis of multiple causes of death.

Science.gov (United States)

Fedeli, Ugo; Schievano, Elena; Lisiero, Manola; Avossa, Francesco; Mastrangelo, Giuseppe; Saugo, Mario

2013-10-10

The analysis of multiple causes of death data has been applied in the United States to examine the population burden of chronic liver disease (CLD) and to assess time trends of alcohol-related and hepatitis C virus (HCV)-related CLD mortality. The aim of this study was to assess the mortality for CLD by etiology in the Veneto Region (northeastern Italy). Using the 2008-2010 regional archive of mortality, all causes registered on death certificates were extracted and different descriptive epidemiological measures were computed for HCV-related, alcohol-related, and overall CLD-related mortality. The crude mortality rate of all CLD was close to 40 per 100,000 residents. In middle ages (35 to 74 years) CLD was mentioned in about 10% and 6% of all deaths in males and females, respectively. Etiology was unspecified in about half of CLD deaths. In females and males, respectively, HCV was mentioned in 44% and 21% and alcohol in 11% and 26% of overall CLD deaths. A bimodal distribution with age was observed for HCV-related proportional mortality among females, reflecting the available seroprevalence data. Multiple causes of death analyses can provide useful insights into the burden of CLD mortality according to etiology among different population subgroups.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

Directory of Open Access Journals (Sweden)

Georgios Koutsis

2015-01-01

Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

Science.gov (United States)

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

[Current therapy of multiple sclerosis].

Science.gov (United States)

Antonio García Merino, J

2014-12-01

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

Science.gov (United States)

Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

2016-03-01

Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

Directory of Open Access Journals (Sweden)

Nabeela Nathoo

2014-01-01

Full Text Available There are exciting new advances in multiple sclerosis (MS resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

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

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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

From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

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Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

Chromosomal radiosensitivity in patients with multiple sclerosis

International Nuclear Information System (INIS)

Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domínguez, Inmaculada

2013-01-01

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Chromosomal radiosensitivity in patients with multiple sclerosis

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Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: idomin@us.es [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)

2013-09-15

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Multiple sclerosis: current immunological aspects

Directory of Open Access Journals (Sweden)

Carlos Cuevas-García

2017-02-01

Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

Global N-acetylaspartate concentration in benign and non-benign multiple sclerosis patients of long disease duration

International Nuclear Information System (INIS)

Achtnichts, Lutz; Gonen, Oded; Rigotti, Daniel J.; Babb, James S.; Naegelin, Yvonne; Penner, Iris-Katharina; Bendfeldt, Kerstin; Hirsch, Jochen; Amann, Michael; Kappos, Ludwig; Gass, Achim

2013-01-01

Background and objective: To examine whether clinically benign multiple sclerosis patients (BMS) show similar losses of their global N-acetylaspartate (NAA) neuronal marker relative to more clinically disabled patients of similar disease duration. Methods: The whole-brain NAA concentration (WBNAA) was acquired with whole-head non-localizing proton MR spectroscopy. Fractional brain parenchymal volume (fBPV), T 2 and T 1 lesion loads, were obtained from the MRI in: (i) 24 BMS patients: 23.1 ± 7.2 years disease duration, median Expanded Disability Status Scale (EDSS) score of 2.0 (range: 0–3); (ii) 26 non-benign MS patients (non-BMS), 24.5 ± 7.4 years disease duration, median EDSS of 4.0 (range: 3.5–6.5); (iii) 15 healthy controls. Results: Controls’ 12.4 ± 2.3 mM WBNAA was significantly higher than the BMS's and non-BMS's 10.5 ± 2.4 and 9.9 ± 2.1 mM (both p < 0.02), but the difference between the patients’ groups was not (p > 0.4). Likewise, the controls’ 81.2 ± 4.5% fBPV exceeded the BMS and non-BMS's 77.0 ± 5.8% and 76.3 ± 8.6% (p < 0.03), which were also not different from one another (p > 0.7). BMS patients’ T 1 -hypointense lesion load, 2.1 ± 2.2 cm 3 , was not significantly different than the non-BMS's 4.1 ± 5.4 cm 3 (p > 0.08) and T 2 -hyperintense loads: 6.0 ± 5.7 cm 3 and 8.7 ± 7.8 cm 3 , were also not different (p > 0.1). Conclusions: WBNAA differentiates normal controls from MS patients but does not distinguish BMS from more disabled MS patients of similar disease duration. Nevertheless, all MS patients who remain RR for 15+ years suffered WBNAA loss similar to the average RR MS population at fourfold shorter disease duration suggesting relative global neuronal sparing or leveling-off of the neurodegeneration rate

Multiple myeloma: diagnosis and treatment.

Science.gov (United States)

Nau, Konrad C; Lewis, William D

2008-10-01

Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections

Using impedance cardiography to detect subclinical cardiovascular disease in women with multiple risk factors: a pilot study.

Science.gov (United States)

Demarzo, Arthur P

2009-01-01

Early detection of cardiovascular disease (CVD) could initiate appropriate treatment and prevent progression. This study used impedance cardiography (ICG) waveform analysis with postural change to detect functional CVD in women older than 40 years with no history of CVD and >or=2 of the following risk factors: cigarette smoking, poor diet, physical inactivity, central adiposity, family history of premature CVD, hypertension, and dyslipidemia. A study group of 32 women underwent ICG in standing and supine positions. An age-matched control group had 20 women with an active lifestyle, no risk factors, and no history of CVD. All women in the control group had normal ICG data. All women in the study group had some abnormal ICG data, with 28 (87.5%) having multiple ICG abnormalities. ICG data indicated that 13 (40.6%) had ventricular dysfunction, 14 (43.8%) had high vascular resistive load, and 30 (93.8%) had elevated vascular pulsatile load. The data suggest that subclinical CVD, detectable by ICG, is prevalent in women older than 40 years with multiple risk factors. Abnormal ICG results could expedite the initiation of customized treatment as part of a preventive approach to CVD. (c) 2009 Wiley Periodicals, Inc.

Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

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Andreas Keller

Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

Neuromyelitis optica and multiple sclerosis

DEFF Research Database (Denmark)

Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.

2015-01-01

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel...

Epstein-Barr virus and disease activity in multiple sclerosis

NARCIS (Netherlands)

D. Buljevac (Dragan); H.Z. Flach (Zwenneke); J. Groen (Jan); P.A. van Doorn (Pieter); F.G.A. van der Meché (Frans); R.Q. Hintzen (Rogier); W.C.J. Hop (Wim); A.D.M.E. Osterhaus (Albert); G.J.J. van Doornum (Gerard)

2005-01-01

textabstractOBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study

A newborn with multiple fractures

International Nuclear Information System (INIS)

Kantorova, E.; Kratky, L.; Nevsimal, I.; Marik, K.; Kozlowski, K.

2008-01-01

Sometimes newborns with multiple fractures are diagnosed as osteogenesis imperfecta in spite of absence of radiographic findings supporting this diagnosis. A newborn with multiple fractures was diagnosed as osteogenesis imperfecta. Analysis of the structure of the long bones, pattern of fractures and poorly developed muscles suggested the diagnosis of fetal akinesia deformation syndrome. This was confirmed by pregnancy history and clinical findings. Multiple fractures in a newborn may present with diagnostic radiographic features as in osteogenesis imperfecta, or as in lethal gracile bone dysplasias or achondrogenesis type IA. If those features are absent, other diseases should be considered. Radiographs should be compared with pregnancy history and clinical findings in the newborn. (authors)

Multiple sclerose : epidemiologie en kwaliteit van leven

NARCIS (Netherlands)

Zwanikken, Cornelis Petrus

1997-01-01

Multiple Sclerosis (MS) is a chronic disease of the brain and the spinal cord. The cause of MS is unknown. MS usually starts in young adulthood. In the course of the disease progression of neurological handicap and increase of impairments in daily life is common. In this study there were two aims.

Multiple endocrine diseases in cats: 15 cases (1997-2008).

Science.gov (United States)

Blois, Shauna L; Dickie, Erica L; Kruth, Stephen A; Allen, Dana G

2010-08-01

The objective of this retrospective study was to characterize a population of cats from a tertiary care center diagnosed with multiple endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Medical records of 15 cats diagnosed with more than one endocrine disorder were reviewed. The majority of cats were domestic shorthairs, and the mean age at the time of diagnosis of the first disorder was 10.3 years. The most common combination of disorders was diabetes mellitus and hyperthyroidism. Two cats had concurrent diabetes mellitus and hyperadrenocorticism, one cat had concurrent central diabetes insipidus and diabetes mellitus. A mean of 25.7 months elapsed between diagnoses of the first and second endocrine disorder, but this was variable. This study suggests the occurrence of multiple endocrine disorders is uncommon in cats. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Effect of 12-Week Pilates Trainning on EDSS in Women Suffering fromMultiple Sclerosis

OpenAIRE

Z Shanazari; SM Marandi; S Samie

2013-01-01

Abstract Background & aim: Multiple sclerosis is a debilitating disease that strikes the immune system. Multiple sclerosis is a chronic disease which debilitates the nervous system. The study was evaluated the effects of Pilates exercise on women with physical disabilities suffering from multiple sclerosis for 12 weeks .The aim of this study was to investigating the effects of Pilates trainning on EDSS of women suffering from Multiple Sclerosis (MS) for 12 weeks. Methods: In the pres...

Interesting images: Multiple coronary artery aneurysms.

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Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

Science.gov (United States)

Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

2014-01-01

Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

Human genetics of infectious diseases: a unified theory

OpenAIRE

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predispos...

Will the real multiple sclerosis please stand up?

NARCIS (Netherlands)

Stys, P.K.; Zamponi, G.W.; van Minnen, J.; Geurts, J.J.G.

2012-01-01

Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing - remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a

Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Sandra Hellberg

2016-09-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

Nuclear magnetic resonance relaxation in multiple sclerosis

DEFF Research Database (Denmark)

Larsson, H B; Barker, G J; MacKay, A

1998-01-01

OBJECTIVES: The theory of relaxation processes and their measurements are described. An overview is presented of the literature on relaxation time measurements in the normal and the developing brain, in experimental diseases in animals, and in patients with multiple sclerosis. RESULTS...... AND CONCLUSION: Relaxation time measurements provide insight into development of multiple sclerosis plaques, especially the occurrence of oedema, demyelination, and gliosis. There is also evidence that normal appearing white matter in patients with multiple sclerosis is affected. What is now needed are fast...

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

Science.gov (United States)

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

Science.gov (United States)

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

Multiple plasmid-borne virulence genes of Clavibacter michiganensis ssp. capsici critical for disease development in pepper.

Science.gov (United States)

Hwang, In Sun; Oh, Eom-Ji; Kim, Donghyuk; Oh, Chang-Sik

2018-02-01

Clavibacter michiganensis ssp. capsici is a Gram-positive plant-pathogenic bacterium causing bacterial canker disease in pepper. Virulence genes and mechanisms of C. michiganensis ssp. capsici in pepper have not yet been studied. To identify virulence genes of C. michiganensis ssp. capsici, comparative genome analyses with C. michiganensis ssp. capsici and its related C. michiganensis subspecies, and functional analysis of its putative virulence genes during infection were performed. The C. michiganensis ssp. capsici type strain PF008 carries one chromosome (3.056 Mb) and two plasmids (39 kb pCM1 Cmc and 145 kb pCM2 Cmc ). The genome analyses showed that this bacterium lacks a chromosomal pathogenicity island and celA gene that are important for disease development by C. michiganensis ssp. michiganensis in tomato, but carries most putative virulence genes in both plasmids. Virulence of pCM1 Cmc -cured C. michiganensis ssp. capsici was greatly reduced compared with the wild-type strain in pepper. The complementation analysis with pCM1 Cmc -located putative virulence genes showed that at least five genes, chpE, chpG, ppaA1, ppaB1 and pelA1, encoding serine proteases or pectate lyase contribute to disease development in pepper. In conclusion, C. michiganensis ssp. capsici has a unique genome structure, and its multiple plasmid-borne genes play critical roles in virulence in pepper, either separately or together. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Genetics Home Reference: multiple epiphyseal dysplasia

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... Hamel BC, Spranger J, Zabel B, Cohn DH, Cole WG, Hecht JT, Superti-Furga A. Recessive multiple ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.

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Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

2016-01-01

Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Siobhan Simpson

2016-01-01

Full Text Available Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM, yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

Future directions of multiple behavior change research.

Science.gov (United States)

Geller, Karly; Lippke, Sonia; Nigg, Claudio R

2017-02-01

Non-communicable diseases (i.e., chronic diseases including cardiovascular disease, cancer, chronic respiratory disease, diabetes and obesity) result in 36 million deaths each year. Individuals' habitual participation in a single health-risk behaviors substantially contribute to morbidity and mortality (e.g., tobacco use, daily fast food intake, etc.); however, more concerning is the impact of typically co-occurring or clustering of multiple health-risk behaviors. This burden can be minimized through successful cessation of health-risk behaviors and adoption of healthy behaviors; namely healthy lifestyle adoption or multiple health behavior change (MHBC). MHBC is a developing field and future research recommendations are provided to advance MHBC research. A valid measure of MHBC (i.e., lifestyle) is warranted to provide the needed basis for MHBC investigations and evaluations. MHBC is thought to occur through shared co-variation of underlying motivating mechanisms, but how these relationships influence behavior remains unclear. A better understanding of the relationship between behaviors and the related motivating mechanisms (and potential cross-relationship of influences) is needed. Future research should also aim to improve lifestyles through understanding how to change multiple health behaviors. Finally, MHBC research should target the development of sustainable interventions which result in lasting effects (e.g., capacity, systems, policy and environmental changes), with dissemination considered during development. Focusing MHBC research in these areas will increase our understanding and maximize the impact on the health of populations.

Zinc in multiple sclerosis

DEFF Research Database (Denmark)

Bredholt, Mikkel; Fredriksen, Jette Lautrup

2016-01-01

In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS...

Disease: H01030 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available with anterior horn cell disease (LAAHD) is a condition with fetal akinesia deformation sequence (FADS), multiple contract...eletal disease; Neurodegenerative disease GLE1 [HSA:2733] [KO:K18723] ... Lethal congenital contract

Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant?

Science.gov (United States)

Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-10-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia.

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

DEFF Research Database (Denmark)

Bonora, E.; Lamb, J.A.; Barnby, G.

2005-01-01

in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect......Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants...

Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

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Raed Alroughani

2016-01-01

Full Text Available The burden of multiple sclerosis (MS in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs, which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

Multiple Spontaneous Cerebral Microbleeds and Leukoencephalopathy in PSEN1-Associated Familial Alzheimer's Disease: Mirror of Cerebral Amyloid Angiopathy?

Science.gov (United States)

Floris, Gianluca; Di Stefano, Francesca; Cherchi, Maria Valeria; Costa, Gianna; Marrosu, Francesco; Marrosu, Maria Giovanna

2015-01-01

Cerebral microbleeds (CMB) might reflect specific underlying vascular pathologies like cerebral amyloid angiopathy (CAA). In the present study we report the gradient-echo MRI pattern of two siblings with P284S PSEN1 mutation. T2* gradient-echo images of the two subjects demonstrated multiple microbleeds in lobar regions. The role and causes of CMB in sporadic Alzheimer's disease (AD) patients have not been clearly established and useful contributions could derive from familial AD studies. Furthermore, since CAA is a potential risk factor for developing adverse events in AD immunization trials, the identification in vivo of CAA through non-invasive MRI methods could be useful to monitoring side effects.

Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

Science.gov (United States)

Kindred, John H; Li, Kaigang; Ketelhut, Nathaniel B; Proessl, Felix; Fling, Brett W; Honce, Justin M; Shaffer, William R; Rudroff, Thorsten

2017-08-01

Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis. The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (PCannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunomodulation of multiple myeloma.

Science.gov (United States)

Tohnya, Tanyifor M; Figg, William D

2004-11-01

Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

Celiac Disease

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Manoochehr Karjoo

2014-08-01

Full Text Available Celiac disease also known as gluten-sensitive enteropathy is characterized by intestinal mucosal damage and malabsorption from dietary intake of wheat, rye or barley. Symptoms may appear with introduction of cereal in the first 3 years of life. A second peak in symptoms occurs in adults during the third or forth decade and even as late as eight decade of life. The prevalence of this disease is approximately 1 in 250 adults. The disease is more prevalent in Ireland as high as 1 in 120 adults. The disorder occurs in Arab, Hispanics, Israeli Jews, Iranian and European but is rare in Chinese and African American. To have celiac disease the patient should have the celiac disease genetic markers as HLA DQ 2 and HLA DQ 8. Patient with celiac disease may have 95 per cent for DQ 2 and the rest is by DQ 8. Someone may have the genetic marker and never develops the disease. In general 50 percent with markers may develop celiac disease. To develop the disease the gene needs to become activated. This may happen with a viral or bacterial infection, a surgery, delivery, accident, or psychological stress. After activation of gene cause the tight junction to opens with the release of Zonulin This results in passage of gluten through the tight junction and formation of multiple antibodies and autoimmune disease. This also allows entrance of other proteins and development of multiple food allergies. As a result is shortening, flattening of intestinal villi resulting in food, vitamins and minerals malabsorption.

Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

Science.gov (United States)

Bourne, Theresa; Waltz, Michael; Casper, T C; Kavak, K; Aaen, G; Belman, A; Benson, L; Candee, M; Chitnis, T; Graves, J; Greenberg, B; Gorman, M; Harris, Y; Krupp, L; Lotze, T; Mar, S; Ness, J; Olsen, C; Roalstad, S; Rodriguez, M; Rose, J; Rubin, J; Schreiner, T; Tillema, J M; Kahn, I; Waldman, A; Barcellos, L; Waubant, E; Weinstock-Guttman, B

2017-04-15

Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies. Copyright © 2017 Elsevier B.V. All rights reserved.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

Science.gov (United States)

Fominykh, Vera; Shevtsova, Tatyana; Arzumanian, Narine; Brylev, Lev

2017-10-01

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

Science.gov (United States)

Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

The diagnosis of multiple sclerosis

International Nuclear Information System (INIS)

Sanders, E.A.C.M.

1982-01-01

This thesis describes recently developed research methods for the diagnosis of multiple sclerosis. In Chapter X the use of the CT-scan in the detection of hemispheral or cerebellar lesions is discussed. In chapter XIII the results of the application of all methods to a group of 89 patients with definite, probable or possible multiple sclerosis and to a group of 25 purely optic neuritis patients are presented. With the aid of the CT-scan, hypo- or hyperdense areas in the white matter of the cerebral hemispheres were found in 52% of the 114 patients. Most reports ascribe these lesions to demyelinating cerebral plaques. The CT-scan showed no cerebellar or brainstem lesions. The CT-scan is independent of the duration of, and degree of incapacitation due to, the disease and can be helpful in giving a definite diagnosis in an early stage of the disease. The CT-scan will always play an important role for the differential diagnosis. (Auth.)

[Special cases of multiple sclerosis].

Science.gov (United States)

Mendibe Bilbao, Mar

2014-12-01

Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

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Georgios Koutsis

2014-01-01

Full Text Available Introduction. Spinocerebellar ataxia 17 (SCA 17 is a rare autosomal dominant cerebellar ataxia (ADCA caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

Global N-acetylaspartate concentration in benign and non-benign multiple sclerosis patients of long disease duration

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Achtnichts, Lutz [Departments of Neurology and Neuroradiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Gonen, Oded, E-mail: oded.gonen@nyumc.org [Department of Radiology, New York University School of Medicine, 660 First Avenue, 4th Floor, New York, NY 10016 (United States); Rigotti, Daniel J.; Babb, James S. [Department of Radiology, New York University School of Medicine, 660 First Avenue, 4th Floor, New York, NY 10016 (United States); Naegelin, Yvonne [Departments of Neurology and Neuroradiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Penner, Iris-Katharina; Bendfeldt, Kerstin [Department of Cognitive Psychology and Methodology, University of Basel, Missionsstrasse 60/62, 4055 Basel (Switzerland); Hirsch, Jochen; Amann, Michael; Kappos, Ludwig [Departments of Neurology and Neuroradiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Gass, Achim [Departments of Neurology and Neuroradiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Dept. of Neurology, Universitaetsmedizin Mannheim, University of Heidelberg (Germany)

2013-12-01

Background and objective: To examine whether clinically benign multiple sclerosis patients (BMS) show similar losses of their global N-acetylaspartate (NAA) neuronal marker relative to more clinically disabled patients of similar disease duration. Methods: The whole-brain NAA concentration (WBNAA) was acquired with whole-head non-localizing proton MR spectroscopy. Fractional brain parenchymal volume (fBPV), T{sub 2} and T{sub 1} lesion loads, were obtained from the MRI in: (i) 24 BMS patients: 23.1 ± 7.2 years disease duration, median Expanded Disability Status Scale (EDSS) score of 2.0 (range: 0–3); (ii) 26 non-benign MS patients (non-BMS), 24.5 ± 7.4 years disease duration, median EDSS of 4.0 (range: 3.5–6.5); (iii) 15 healthy controls. Results: Controls’ 12.4 ± 2.3 mM WBNAA was significantly higher than the BMS's and non-BMS's 10.5 ± 2.4 and 9.9 ± 2.1 mM (both p < 0.02), but the difference between the patients’ groups was not (p > 0.4). Likewise, the controls’ 81.2 ± 4.5% fBPV exceeded the BMS and non-BMS's 77.0 ± 5.8% and 76.3 ± 8.6% (p < 0.03), which were also not different from one another (p > 0.7). BMS patients’ T{sub 1}-hypointense lesion load, 2.1 ± 2.2 cm{sup 3}, was not significantly different than the non-BMS's 4.1 ± 5.4 cm{sup 3} (p > 0.08) and T{sub 2}-hyperintense loads: 6.0 ± 5.7 cm{sup 3} and 8.7 ± 7.8 cm{sup 3}, were also not different (p > 0.1). Conclusions: WBNAA differentiates normal controls from MS patients but does not distinguish BMS from more disabled MS patients of similar disease duration. Nevertheless, all MS patients who remain RR for 15+ years suffered WBNAA loss similar to the average RR MS population at fourfold shorter disease duration suggesting relative global neuronal sparing or leveling-off of the neurodegeneration rate.

[N-methyl 11C]meta-Hydroxyephedrine positron emission tomography in Parkinson's disease and multiple system atrophy

International Nuclear Information System (INIS)

Berding, Georg; Hoff, Joerg van den; Meyer, Geerd J.; Knapp, Wolfram H.; Schrader, Christoph H.; Peschel, Thomas; Kolbe, Hans; Dengler, Reinhard

2003-01-01

Orthostatic hypotension (OH) can be present in idiopathic Parkinson's disease (IPD) as well as in atypical parkinsonian syndromes such as multiple system atrophy (MSA). According to clinical tests of sympathetic nerve function and histopathological data, OH is caused by primarily postganglionic sympathetic dysfunction in IPD and by predominantly central and preganglionic degeneration in MSA. It has been proposed that this concept of a different underlying pathogenesis for OH should be applied in the differential diagnosis of parkinsonian disorders, in the form of measurements of sympathetic myocardial innervation. In this pilot study, myocardial imaging with [N-methyl 11 C]meta-hydroxyephedrine ( 11 C-HED) and positron emission tomography (PET) was used as a quantitative tool to evaluate the feasibility of such an approach. Seven patients were included in the study. Two had MSA and OH, three had probable IPD and OH (duration of disease, >3 years), one had probable IPD without OH (disease duration, 3 years) and one had possible IPD without OH (disease duration, 2 years). Ratios of maximal 11 C-HED uptake in the myocardium to that in the liver at 5 and 40 min post injection (p.i.) and - based on kinetic modelling - tracer influx rates K 1 were calculated. Compared with MSA patients (n=2), IPD patients with OH (n=3) showed definitely lower uptake ratios at both 5 min p.i. (0.39-0.57 vs 0.78-0.79) and 40 min p.i. (0.21-0.60 vs 0.89-1.06), as well as lower K 1 values (0.198-0.359 vs 0.384-0.450 min -1 ). The patient with probable IPD without OH showed intermediate values (uptake ratio at 5 min: 0.65; uptake ratio at 40 min: 0.87; K 1 =0.363). In the patient with possible IPD, values (uptake ratio at 5 min: 0.96; uptake ratio at 40 min: 1.04; K 1 =0.400) did not differ from those observed in MSA. These results support the hypothesis that measurement of myocardial innervation may contribute to the differential diagnosis of parkinsonian disorders and suggest a need for

Clinicopathological features of plasmablastic multiple myeloma

DEFF Research Database (Denmark)

Møller, Hanne E H; Preiss, Birgitte S; Pedersen, Per

2015-01-01

Multiple myeloma (MM) is a common malignant hematological disease displaying considerable heterogeneity. Historical data indicate a prognostic significance of plasmablastic morphology, proliferation, and adverse cytogenetics, but there is little knowledge on the degree of interdependency......, which indicates that plasmablastic morphology reflects advanced and highly proliferative disease. However, plasmablastic morphology did not correlate with established adverse prognostic cytogenetics identified by FISH, for example, t(4;14), t(14;16) and del(17p)....

Can multiple sclerosis as a cognitive disorder influence patients? dreams?

OpenAIRE

Moghadasi, Abdorreza Naser; Owji, Mahsa

2013-01-01

Dream should be considered as a kind of cognitive ability that is formed parallel to other cognitive capabilities like language. On the other hand, multiple sclerosis (MS) is a complex disease that can involve different aspects of our cognition. Therefore, MS may influence patients’ dreams. In fact, we do not know what the importance of dream is in MS, but further studies may introduce dream and dreaming as a sign of improvement or progression in MS disease.Multiple sclerosis (MS) is a diseas...

Multiple primary cancer

International Nuclear Information System (INIS)

Jung, Gyu Sik; Lee, Ouk; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duck

1989-01-01

It is rare for one human being to be afflicted with more than one cancer. However with further advances in therapeutic regimens, histopathologic observation, diagnostic modalities, and increased curiosity, there are increasing number of case reports of multiple primary cancer. The present study evaluates 25 histologically confirmed cases of multiple primary cancer from 1974 to 1988 at Kosin Medical Center. The most frequent site of the first primary cancer in male was stomach and in female, uterine cervix. The first primary cancer in female occurred in endocrine-related organs (breast, uterus and thyroid) in 63.6 percent. Synchronous cancers are diagnosed simultaneously or within an interval of about six months and synchronous cancers were 16 out of 25 cases. Metachronous cancers are diagnosed at interval of more than six months. There were 9 metachronous cancers and average interval between the first and second primary cancer was 22.8 months. The incidence of multiple primary cancer was 0.11 percent. The average age was 51.9 years at the time of the first primary cancer (53.1 years in male and 50.3 years in female). CT scan was most helpful in early detection of multiple primary cancers facilitating biopsy and surgery. Multiple primary cancers are beyond the medical curiosity. Early diagnosis of the disease and careful follow-up study, based on an awareness of the possibility of second cancers, will substantially increase the survival of these patients

Multiple mechanisms of transmission of the Caribbean coral disease white plague

Science.gov (United States)

Clemens, E.; Brandt, M. E.

2015-12-01

White plague is one of the most devastating coral diseases in the Caribbean, and yet important aspects of its epidemiology, including how the disease transmits, remain unknown. This study tested potential mechanisms and rates of transmission of white plague in a laboratory setting. Transmission mechanisms including the transport of water, contact with macroalgae, and predation via corallivorous worms and snails were tested on the host species Orbicella annularis. Two of the tested mechanisms were shown to transmit disease: water transport and the corallivorous snail Coralliophila abbreviata. Between these transmission mechanisms, transport of water between a diseased coral and a healthy coral resulted in disease incidence significantly more frequently in exposed healthy corals. Transmission via water transport also occurred more quickly and was associated with higher rates of tissue loss (up to 3.5 cm d-1) than with the corallivorous snail treatment. In addition, water that was in contact with diseased corals but was filtered with a 0.22-μm filter prior to being introduced to apparently healthy corals also resulted in the transmission of disease signs, but at a much lower rate than when water was not filtered. This study has provided important information on the transmission potential of Caribbean white plague disease and highlights the need for a greater understanding of how these processes operate in the natural environment.

Designing multiple ligands - medicinal chemistry strategies and challenges.

Science.gov (United States)

Morphy, Richard; Rankovic, Zoran

2009-01-01

It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.

Abbreviation modalities of nitrogen multiple-breath washout tests in school children with obstructed lung disease

DEFF Research Database (Denmark)

Green, Kent; Ejlertsen, Jacob S; Madsen, Astrid

2016-01-01

, the lung clearance index, calculated as lung volume turnovers required to reach 2.5% of the starting N2 concentration (LCI2.5 ). METHODS: Cross-sectional study of triplicate N2 MBW measurements obtained in cystic fibrosis (CF) patients (N = 60), primary ciliary dyskinesia (PCD) patients (N = 28......RATIONALE: Nitrogen multiple-breath washout (N2 MBW) is a promising tool for assessing early lung damage in children with chronic obstructive pulmonary disease, but it can be a time-consuming procedure. We compared alternative test-shortening endpoints with the most commonly reported N2 MBW outcome...... MBW runs in each session. N2 MBW endpoints were analyzed as z-scores calculated from healthy controls. RESULTS: In PCD, Cn@TO6 and LCI2.5 exhibited similar values (mean [95%CI] difference: 0.33 [-0.24; 0.90] z-scores), reducing the test duration by one-third (5.4 min; 95%CI: 4.0; 6.8). All other...

The genetics of multiple sclerosis: review of current and emerging candidates

Directory of Open Access Journals (Sweden)

Muñoz-Culla M

2013-08-01

Full Text Available Maider Muñoz-Culla,1,2 Haritz Irizar,1,2 David Otaegui1,2 1Multiple Sclerosis Unit, Instituto Biodonostia, San Sebastián, Spain; 2Red Española de Esclerosis Múltiple (REEM, Barcelona, Spain Abstract: Multiple sclerosis (MS is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. Keywords: multiple sclerosis, genetics, gene expression, microRNA

Respiratory muscle training for multiple sclerosis

NARCIS (Netherlands)

Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.

2017-01-01

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and

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

Curability of Multiple Myeloma

Directory of Open Access Journals (Sweden)

Raymond Alexanian

2012-01-01

Full Text Available Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987–1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12–22 years. These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.

Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at thyroid

International Nuclear Information System (INIS)

Matsui, Hideaki; Udaka, Fukashi; Oda, Masaya; Tamura, Akiko; Kubori, Tamotsu; Nishinaka, Kazuto; Kameyama, Masakuni

2005-01-01

Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. The objective of this study was to compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p<0.0001) and multiple system atrophy (p=0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p=0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p=0.010). Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid. (author)

Serum galectin-1 in patients with multiple myeloma

DEFF Research Database (Denmark)

Andersen, Morten Nørgaard; Ludvigsen, Maja; Abildgaard, Niels

2017-01-01

with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma...

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

Science.gov (United States)

Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

Science.gov (United States)

Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

2018-03-01

Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage

DEFF Research Database (Denmark)

Owens, Trevor

2003-01-01

progression correlate with axonal damage, and that brain atrophy resulting from axonal loss is a feature of early multiple sclerosis, and is not restricted to the secondary progressive forms of the disease. Inflammatory mediators (CD8 T cells and antibodies) are implicated in axonal damage, and treatment...... cells for oligodendrocytes. SUMMARY: Oligodendrocyte precursors are abundant in multiple sclerosis lesions, but fail to remyelinate. Oligodendrocyte growth and regeneration are probably compromised by the action of growth inhibitory signals and lack of growth stimuli. Inflammatory cells and mediators......PURPOSE OF REVIEW: The demyelinating disease multiple sclerosis has an autoimmune inflammatory component, which has dominated the description of multiple sclerosis. A degenerative component to multiple sclerosis was always apparent, but was underappreciated until recently. Recent work has brought...

Epidemiological study of multiple sclerosis in La Rioja.

Science.gov (United States)

Bártulos Iglesias, M; Marzo Sola, M E; Estrella Ruiz, L A; Bravo Anguiano, Y

2015-01-01

Multiple sclerosis is a demyelinating disease that causes severe disability in younger patients. Many epidemiology studies have confirmed a variable prevalence. The objective of this study was to analyse the prevalence of this disease in La Rioja (Spain), using such variables as age and sex; type of progression, initial form of the disease, EDSS and number of relapses; disease-modifying treatment and reasons for treatment withdrawal; personal and family history of cancer; and incidence and mortality. Analysis of patients in La Rioja diagnosed with MS (according to Poser criteria or the 2005 McDonald criteria) during a 10-year period (2001-2011). Data were collected from hospital records, multiple sclerosis associations, and personal records kept by neurologists. The MS prevalence rate in La Rioja is 65 patients/100 000 inhabitants with an incidence rate of 3.5 cases/100 000 residents per year. Relapsing-remitting MS is present in 67.6% of the patient total. Mean age of onset is 20-29 years (range, 12 to 70). Most EDSS scores were mostly ≤ 2. Untreated MS cases account for 47.6% of the total and the most commonly used therapy is interferon. We detected 4 haematological tumours and 7 families with multiple members affected by MS. Prevalence and incidence are similar to those found in other regions Spain. The average age at onset age for primary progressive MS is slightly higher than in other papers (40-49 years). In families with multiple patients, MS may be more aggressive. Disability in these patients remains very severe. We require more epidemiology studies with a variety of data gathering methods to support findings for prevalence obtained in different provinces. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

A qualitative study assessing patient perspectives in the process of decision-making on disease modifying therapies (DMT's) in multiple sclerosis (MS).

Science.gov (United States)

Ceuninck van Capelle, Archibald de; Meide, Hanneke van der; Vosman, Frans J H; Visser, Leo H

2017-01-01

Physicians commonly advise patients to begin disease modifying therapies (DMT's) shortly after the establishment of a diagnosis of Multiple Sclerosis (MS) to prevent further relapses and disease progression. However, little is known about the meaning for patients going through the process of the diagnosis of MS and of making decisions on DMT's in early MS. To explore the patient perspective on using DMT's for MS. Methods: Ten participants with a recent (approach. The analysis revealed the following themes: (1) Constant confrontation with the disease, (2) Managing inevitable decline, (3) Hope of delaying the progression of the disease, and, (4) The importance of social support. The themes show that patients associate the recommendation to begin DMT's (especially injectable DMT's) with views about their bodies as well as their hopes about the future. Both considering and adhering to treatment are experienced by patients as not only matters of individual and rational deliberation, but also as activities that are lived within a web of relationships with relatives and friends. From the patient perspective, the use of DMT's is not a purely rational and individual experience. More attention to the use of DMT's as relational and lived phenomena will improve the understanding of the process of decision-making for DMT's in MS.

Demographic, genetic, and environmental factors that modify disease course.

Science.gov (United States)

Marrie, Ruth Ann

2011-05-01

As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously. Copyright © 2011 Elsevier Inc. All rights reserved.

Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina.

Science.gov (United States)

Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge

2014-01-01

Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6-1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders.

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity i...

Prevalence of multiple sclerosis in Denmark 1950-2005

DEFF Research Database (Denmark)

Bentzen, Joan; Meulengracht Flachs, Esben; Stenager, Egon

2010-01-01

Multiple sclerosis is an inflammatory disease of the central nervous system of unknown aetiology. Its prevalence varies by ethnicity and place: persons of northern European descent are at increased risk while persons living at lower latitudes appear to be protected against the disease. The Danish...... Multiple Sclerosis Registry is a national registry established in 1956 after a population-based survey which receives information from numerous sources. It is considered to be more than 90% complete, with a validity of 94%. Using data from the Registry, we calculated prevalences per 100,000 inhabitants....... The standardized prevalence of multiple sclerosis increased from 58.8 (95% confidence interval: 54.9-62.7) in 1950 to 154.5 per 100,000 (95% confidence interval: 148.8-160.2) in 2005, and the female to male ratio increased from 1.31 in 1950 to 2.02 in 2005. The increase in prevalence is due to both increased...

Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

International Nuclear Information System (INIS)

Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

2014-01-01

Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

Energy Technology Data Exchange (ETDEWEB)

Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

2014-03-15

Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

Integrating Multiple On-line Knowledge Bases for Disease-Lab Test Relation Extraction.

Science.gov (United States)

Zhang, Yaoyun; Soysal, Ergin; Moon, Sungrim; Wang, Jingqi; Tao, Cui; Xu, Hua

2015-01-01

A computable knowledge base containing relations between diseases and lab tests would be a great resource for many biomedical informatics applications. This paper describes our initial step towards establishing a comprehensive knowledge base of disease and lab tests relations utilizing three public on-line resources. LabTestsOnline, MedlinePlus and Wikipedia are integrated to create a freely available, computable disease-lab test knowledgebase. Disease and lab test concepts are identified using MetaMap and relations between diseases and lab tests are determined based on source-specific rules. Experimental results demonstrate a high precision for relation extraction, with Wikipedia achieving the highest precision of 87%. Combining the three sources reached a recall of 51.40%, when compared with a subset of disease-lab test relations extracted from a reference book. Moreover, we found additional disease-lab test relations from on-line resources, indicating they are complementary to existing reference books for building a comprehensive disease and lab test relation knowledge base.

Devic's Disease (Neuromyelitis optical)

International Nuclear Information System (INIS)

Pinzon, Alfredo; Echeverry, Tatiana; Rodriguez, Aida Bibiana

2010-01-01

We present a case report about a young woman initially treated as having multiple sclerosis, who relapsed with serious visual impairment. Devic's disease is a demyelinating disorder that presents as transverse myelitis associated with optic neuritis, typically bilateral. Multiple sclerosis is in fact the main differential diagnosis

Pervasive sharing of genetic effects in autoimmune disease.

Directory of Open Access Journals (Sweden)

Chris Cotsapas

2011-08-01

Full Text Available Genome-wide association (GWA studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs and risk of common autoimmune and inflammatory (immune-mediated diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44% immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA<0.01. We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

Directory of Open Access Journals (Sweden)

Marta Sofia Mendes Oliveira

2015-09-01

Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

New management algorithms in multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg

2014-01-01

complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

Multiple Unerupted Permanent Teeth Associated with Noonan ...

African Journals Online (AJOL)

[2] Oral findings in patients with NS include a high arched palate ... the atypical dental anomalies such as multiple unerupted permanent ... clinical features in a child with NS. .... Disabilities, Centers for Disease Control and Prevention (CDC).

Registers of multiple sclerosis in Denmark

DEFF Research Database (Denmark)

Koch-Henriksen, N; Magyari, M; Laursen, B

2015-01-01

between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have......There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS....

in silico identification of genetic variants in glucocerebrosidase (GBA gene involved in Gaucher’s disease using multiple software tools.

Directory of Open Access Journals (Sweden)

Madhumathi eManickam

2014-05-01

Full Text Available Gaucher’s disease is an autosomal recessive disorder caused by the deficiency of glucocerebrosidase, a lysosomal enzyme that catalysis the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Polymorphisms in GBA gene have been associated with the development of Gaucher disease. We hypothesize that prediction of SNPs using multiple state of the art software tools will help in increasing the confidence in identification of SNPs involved in Gaucher's disease. Enzyme replacement therapy is the only option for GD. Our goal is to use several state of art SNP algorithms to predict/address harmful SNPs using comparative studies. In this study seven different algorithms (SIFT, MutPred, nsSNP Analyzer, PANTHER, PMUT, PROVEAN and SNPs&GO were used to predict the harmful polymorphisms. Among the 7 programs, SIFT found 47 nsSNPs as deleterious, MutPred found 46 nsSNPs as harmful. nsSNP Analyzer program found 43 out of 47 nsSNPs are disease causing SNPs whereas PANTHER found 32 out of 47 as highly deleterious, 22 out of 47 are classified as pathological mutations by PMUT, 44 out of 47 were predicted to be deleterious by PROVEAN server, all 47 shows the disease related mutations by SNPs&GO. Twenty two nsSNPs were commonly predicted by all the seven different algorithms. The common 22 targeted mutations are F251L, C342G, W312C, P415R, R463C, D127V, A309V, G46E, G202E, P391L, Y363C, Y205C, W378C, I402T, S366R, F397S, Y418C, P401L, G195E, W184R, R48W and T43R.

Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains

DEFF Research Database (Denmark)

Brudek, Tomasz; Winge, Kristian; Rasmussen, Nadja Bredo

2016-01-01

Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease-specific transcript......Together with Parkinson's disease (PD) and dementia with Lewy bodies, multiple system atrophy (MSA) is a member of a diverse group of neurodegenerative disorders termed α-synucleinopathies. Previously, it has been shown that α-synuclein, parkin, and synphilin-1 display disease......-specific transcription patterns in frontal cortex in PD, dementia with Lewy bodies, and MSA, and thus may mediate the development of α-synucleinopathies. In this study, the differential expression of α-synuclein isoforms on transcriptional and translational levels was ascertained in MSA patients in comparison with PD......-synuclein in the brain. We report differential expression of α-synuclein, parkin, and synphilin-1 isoforms in multiple system atrophy (MSA) versus Parkinson's disease and normal control brains. We have focused on brain regions that are severely affected by α-synuclein pathology and neurodegeneration in MSA. The reported...

A Promising Approach to Integrally Evaluate the Disease Outcome of Cerebral Ischemic Rats Based on Multiple-Biomarker Crosstalk

Directory of Open Access Journals (Sweden)

Guimei Ran

2017-01-01

Full Text Available Purpose. The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. Methods. Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100β, HIF-1α, IL-1β, PGI2, TXA2, and GSH-Px. The levels or activities of these biomarkers in plasma were detected before and after ischemia. Concurrently, neurological deficit scores and cerebral infarct volumes were assessed. Based on a mathematic model, network balance maps and three integral disruption parameters (k, φ, and u of the simplified crosstalk network were achieved. Results. The levels or activities of the related biomarkers and neurological deficit scores were significantly impacted by cerebral ischemia. The balance maps intuitively displayed the network disruption, and the integral disruption parameters quantitatively depicted the disruption state of the simplified network after cerebral ischemia. The integral disruption parameter u values correlated significantly with neurological deficit scores and infarct volumes. Conclusion. Our results indicate that the approach based on crosstalk network may provide a new promising way to integrally evaluate the outcome of cerebral ischemia.

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases.

Science.gov (United States)

Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo; Aggarwal, Bharat B

2017-06-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

Science.gov (United States)

Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo

2016-01-01

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638428

Outcome measures in inflammatory rheumatic diseases.

NARCIS (Netherlands)

Fransen, J.; Riel, P.L.C.M. van

2009-01-01

Inflammatory rheumatic diseases are generally multifaceted disorders and, therefore, measurement of multiple outcomes is relevant to most of these diseases. Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Outcome measurement will

Induced multiple disease resistance in wheat

International Nuclear Information System (INIS)

Borojevic, K.; Worland, A.J.

1990-01-01

Full text: The existence of genes suppressing resistance to leaf rust, stem rust and yellow rust in hexaploid wheat has been suggested. If such genes are deleted or inactivated, a more resistant variety may be obtained. In mutant lines of the wheat variety San Pastore, selected after treatment with 20,000 rad of gamma-rays, resistance to leaf rust, yellow rust, stem rust, and to some extent to Erysiphe graminis was determined. The mutants responded to infection by producing necrotic flecks in the presence of high level of disease inoculum. Similar flecks develop under stress condition. It is likely that the mother variety San Pastore carries genes for resistance which are masked by suppressor genes. Irradiation inactivates suppressors so that resistance genes which were previously masked are expressed. The first results of monosomic analysis indicate that chromosomes of groups 4 and 5 or possibly 7 may be critical for expression of resistance in the mutant lines. (author)

NCI collaborates with Multiple Myeloma Research Foundation

Science.gov (United States)

The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

A model for diagnosing and explaining multiple disorders.

Science.gov (United States)

Jamieson, P W

1991-08-01

The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.

Clustering of autoimmune diseases in patients with rosacea

DEFF Research Database (Denmark)

Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar Hilmar

2016-01-01

BACKGROUND: Rosacea is a common inflammatory skin condition that shares genetic risk loci with autoimmune diseases such as type 1 diabetes mellitus (T1DM) and celiac disease. A recent genomewide association study identified 90 genetic regions associated with T1DM, celiac disease, multiple sclerosis......, and/or rheumatoid arthritis, respectively. However, a possible association with rosacea was not investigated. OBJECTIVE: We evaluated the association between rosacea and T1DM, celiac disease, multiple sclerosis, and rheumatoid arthritis, respectively. METHODS: We performed a population-based case...... and socioeconomic status, patients with rosacea had significantly increased ORs for T1DM (OR 2.59, 95% CI 1.41-4.73), celiac disease (OR 2.03, 95% CI 1.35-3.07), multiple sclerosis (OR 1.65, 95% CI 1.20-2.28), and rheumatoid arthritis (OR 2.14, 95% CI 1.82-2.52). The association was mainly observed in women...

Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

Science.gov (United States)

Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

2013-08-01

Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

Whole body MR in patients with multiple myeloma

International Nuclear Information System (INIS)

Piekarek, A.; Sosnowski, P.; Nowicki, A.; Komarnicki, M.

2009-01-01

Background: Multiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration. Aim: Whole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions. Ma terial and methods: MR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznan in the years 2005 - 2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36 -48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), infiltrative, mixed and 'salt and pepper' type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification. Results: Four main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and 'salt and pepper' type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging. Conclusions: WB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma. (authors)

Differential diagnoses of the appearance of multiple sclerosis on MR tomography

International Nuclear Information System (INIS)

Gowin, W.; Mariss, G.

1986-01-01

Magnetic resonance imaging (MRI) has the advantage of high sensitivity compared to other diagnostic imaging techniques in focal pathological lesions of the brain in multiple sclerosis patients. However, the specificity of this examination method is limited. Diseases of the central nervous system due to other, different causes could produce a similar magnetic resonance image. Clinically examined cases of malignant and toxic affections of the brain caused by inflammatory, degenerative, traumatic and vascular diseases are presented and compared with the changes occurring in multiple sclerosis. (orig.) [de

Top 10 Research Questions Related to Physical Activity and Multiple Sclerosis

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Motl, Robert W.; Learmonth, Yvonne C.; Pilutti, Lara A.; Gappmaier, Eduard; Coote, Susan

2015-01-01

An estimated 2.5 million people worldwide are living with multiple sclerosis (MS), and this disease may be increasing in prevalence. MS is a disease of the central nervous system that is associated with heterogeneous symptoms and functional consequences, and the current first-line disease-modifying therapies often become ineffective later in the…

Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

DEFF Research Database (Denmark)

Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

2017-01-01

The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

Antigen-specific therapies in multiple sclerosis

NARCIS (Netherlands)

Noort, J.M. van

1998-01-01

Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is

Recent advances in understanding multiple myeloma [version 1; referees: 4 approved

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Binod Dhakal

2016-08-01

Full Text Available There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

Amyloid PET in pseudotumoral multiple sclerosis.

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Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Cortés-Martínez, Ana; Pytel, Vanesa; Moreno-Ramos, Teresa; Oreja-Guevara, Celia; Carreras, José Luis; Matías-Guiu, Jorge

2017-07-01

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18 F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. 18 F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Patient perceptions of multiple sclerosis and its treatment

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de Seze J, Borgel F, Brudon F

2012-04-01

Full Text Available Jérôme de Seze1, Florent Borgel2, Frédérique Brudon31Department of Neurology CHRU de Strasbourg, Strasbourg, 2Medical Center, Grenoble, 3Clinique du Tonkin, Villeurbanne, FranceBackground: In order to improve the treatment outcome in multiple sclerosis, it is important to document the factors that influence adherence to therapy. The purpose of this study was to determine patient perceptions and awareness of multiple sclerosis and its treatment, treatment adherence, and impact on quality of life and daily living.Methods: This was a cross-sectional observational study performed in France. Each participating neurologist included the first three patients with relapsing-remitting multiple sclerosis who consulted after the start of the study. Data on clinical features were collected from a physician questionnaire and on disease and treatment perception and on quality of life from a patient autoquestionnaire.Results: A total of 175 neurologists entered 202 patients in the study. The mean duration of disease was 8.0 ± 7.0 years, and immunomodulatory treatment had been administered for a mean duration of 3.0 ± 2.0 years. A total of 166 patients (82.2% were treated with interferon-ß preparations and 36 patients (17.8% with glatiramer acetate. Eighty-five patients (42.1% reported missing their injections from time to time and 36 patients (17.8% reported “drug holidays”. The most frequently given reason for nonadherence was forgetfulness (38.7% of cases. Eighty-six patients (42.6% and 70 patients (34.7% claimed to be well informed about their disease and treatment, respectively. Adherence was significantly higher in well informed patients (P = 0.035. The majority of patients (176 patients, 87.1% intended continuing their current treatment and 49.5% considered that their current treatment might reduce relapses. The most frequently reported side effect was muscle pain (124 patients, 61.4%.Conclusion: Patient understanding of treatment for disease

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.

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Kishore Malyavantham

Full Text Available To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC, relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS, 128 secondary progressive MS (SP-MS, 33 primary progressive MS (PP-MS and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b, respectively. Antibodies against CSF114(Glc, KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

Medicinal Plants with Multiple Effects on Cardiovascular Diseases: A Systematic Review.

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Rouhi-Boroujeni, Hojjat; Heidarian, Esfandiar; Rouhi-Boroujeni, Hamid; Deris, Fatemeh; Rafieian-Kopaei, Mahmoud

2017-01-01

Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases. Copyright© Bentham Science Publishers; For any

Survey of diagnostic and treatment practices for multiple sclerosis in Europe

DEFF Research Database (Denmark)

Fernández, O; Delvecchio, M; Edan, G

2017-01-01

BACKGROUND AND PURPOSE: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice...... syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. RESULTS: Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat...... a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. CONCLUSIONS...

Progresive diseases study using Markov´s multiple stage models

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René Iral Palomino, Esp estadística

2005-12-01

Full Text Available Risk factors and their degree of association with a progressive disease,such as Alzheimerís disease or liver cancer, can be identifi edby using epidemiological models; some examples of these modelsinclude logistic and Poisson regression, log-linear, linear regression,and mixed models. Using models that take into account not onlythe different health status that a person could experience betweenvisits but also his/her characteristics (i.e. age, gender, genetic traits,etc. seems to be reasonable and justifi ed. In this paper we discussa methodology to estimate the effect of covariates that could beassociated with a disease when its progression or regression canbe idealized by means of a multi-state model that incorporates thelongitudinal nature of data. This method is based on the Markovproperty and it is illustrated using simulated data about Alzheimerísdisease. Finally, the merits and limitations of this method are discussed.

Fundamentals in the management of multiple myeloma.

Science.gov (United States)

Fadilah, S A W

2010-09-01

Progress in our understanding of multiple myeloma and its treatment has resulted in a more tailored approach to patient management, with different therapeutics regimens for different patient populations. The decision to initiate therapy depends primarily on the presence of symptoms which has to balance the chance of tumor clearance and against the risks of treatment related mortality. Selection of appropriate initial treatment should be based primarily on patient's characteristics (biologic age, co-morbidities), the disease characteristics (tumor burden and genetic risk profile) and the expected toxicity profile of the different regimens. When treatment begins, in younger transplant eligible patients the goal is to achieve high quality responses with intensive therapies as the quality of response appears to be important surrogates for long-term outcome. In the majority of myeloma patients in whom intensive treatment is not an option due to advanced age and co-morbidities, treatment should emphasize on optimal disease control to obtain symptomatic relief and to maintain a satisfactory quality of life. The introduction of novel agents has substantially changed the treatment paradigm of this otherwise incurable disease. The utilization of these drugs has moved from relapse setting to the front line setting and has benefited all patient groups. Because of these rapid developments and many treatment options we need good quality clinical studies to guide clinical practice in the management of patients with multiple myeloma. This review presents an update on current concepts of diagnosis and treatment of patients with multiple myeloma and provides recommendations on tailored therapies with particular reference to the local practice. The information presented herein may be used by the health care providers caring for myeloma patients as a guideline to counsel patients to understand their disease and the treatment better.

The emergence of designed multiple ligands for neurodegenerative disorders.

Science.gov (United States)

Geldenhuys, Werner J; Youdim, Moussa B H; Carroll, Richard T; Van der Schyf, Cornelis J

2011-09-01

The incidence of neurodegenerative diseases has seen a constant increase in the global population, and is likely to be the result of extended life expectancy brought about by better health care. Despite this increase in the incidence of neurodegenerative diseases, there has been a dearth in the introduction of new disease-modifying therapies that are approved to prevent or delay the onset of these diseases, or reverse the degenerative processes in brain. Mounting evidence in the peer-reviewed literature shows that the etiopathology of these diseases is extremely complex and heterogeneous, resulting in significant comorbidity and therefore unlikely to be mitigated by any drug acting on a single pathway or target. A recent trend in drug design and discovery is the rational design or serendipitous discovery of novel drug entities with the ability to address multiple drug targets that form part of the complex pathophysiology of a particular disease state. In this review we discuss the rationale for developing such multifunctional drugs (also called designed multiple ligands or DMLs), and why these drug candidates seem to offer better outcomes in many cases compared to single-targeted drugs in pre-clinical studies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Examples are drawn from the literature of drug candidates that have already reached the market, some unsuccessful attempts, and others that are still in the drug development pipeline. Copyright © 2011. Published by Elsevier Ltd.

[Multiple gestation epidemiology--15 years survey].

Science.gov (United States)

Rodrigues, Carla T; Branco, Miguel R; Ferreira, Isabel D; Nordeste, Ana; Fonseca, Margarida; Taborda, Adelaide; Silva, Isabel S; Almeida, Maria do Céu

2005-01-01

Between January of 1987 and December of 2001 were born 1243 twins related to 609 multiple pregnancies, in Maternidade Bissaya-Barreto. Data were grouped in periods of three years and several parameters were studied. The rate of multiple gestation has increased probably due to the contribution of the assisted conception techniques, and to the increase of the number of multiple fetal pregnancies (two or more) and to the increase of the mother age. These more frequent obstetric problems were preterm birth, gestational hypertension and abnormal sonographic data of fetal growth. The average age of delivery was 34 weeks and the birth weight has decreased. The most important factors for neonatal morbidity were hyaline membranous disease, intraventricular haemorrhage and the twin-twin transfusion syndrome. The neonatal mortality decreased in the last studied period.

Human genetics of infectious diseases: a unified theory

Science.gov (United States)

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

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

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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.

Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

International Nuclear Information System (INIS)

Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico; Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio; Russo, Camilla; Feriozzi, Sandro; Veroux, Massimiliano; Battaglia, Yuri; Concolino, Daniela; Pieruzzi, Federico; Tuttolomondo, Antonino; Caronia, Aurelio; Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo

2017-01-01

Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

Comorbidity Influences Multiple Aspects of Well-Being of Patients with Ischemic Heart Disease

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Shervin Assari

2013-12-01

Full Text Available Background: Comorbidity is prevalent among patients with Ischemic Heart Disease (IHD and may influence patients’ subjective and objective domains of well-being. Objectives: We aimed to investigate the associations between comorbidity and different measures of well-being (i.e. health related quality of life, psychological distress, sleep quality, and dyadic adjustment among patients with IHD. Methods: In this cross-sectional study, 796 outpatients with documented IHD were enrolled from an outpatient cardiology clinic in 2006. Comorbidity (Ifudu index, quality of life (SF36, psychological distress (Hospital Anxiety Depression Scale; HADS, sleep quality (Pittsburg Sleep Quality Index; PSQI, and dyadic adjustment quality (Revised Dyadic Adjustment Scale; RDAS were measured. Associations between comorbidity and different measures of well-being were determined. Results: Significant correlations were found between comorbidity score and all measures of well-being. Comorbidity score was correlated with physical quality of life (r = -0.471, P < 0.001, mental quality of life (r = -0.447, P < 0.001, psychological distress (r = 0.344, P < 0.001, sleep quality (r = 0.358, P < 0.001, and dyadic adjustment (r = -0.201, P < 0.001. Conclusions: This study showed a consistent pattern of associations between somatic comorbidities and multiple aspects of well-being among patients with IHD. Findings may increase cardiologists’ interest to identify and treat somatic conditions among IHD patients.

Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

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Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

2017-06-15

Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

Associations of Systemic Diseases with Intermediate Uveitis.

Science.gov (United States)

Shoughy, Samir S; Kozak, Igor; Tabbara, Khalid F

2016-01-01

To determine the associations of systemic diseases with intermediate uveitis. The medical records of 50 consecutive cases with intermediate uveitis referred to The Eye Center in Riyadh, Saudi Arabia, were reviewed. Age- and sex-matched patients without uveitis served as controls. Patients had complete ophthalmic and medical examinations. There were 27 male and 23 female patients. Mean age was 29 years with a range of 5-62 years. Overall, 21 cases (42%) had systemic disorders associated with intermediate uveitis and 29 cases (58%) had no associated systemic disease. A total of 11 patients (22%) had asthma, 4 (8%) had multiple sclerosis, 3 (6%) had presumed ocular tuberculosis, 1 (2%) had inflammatory bowel disease, 1 (2%) had non-Hodgkin lymphoma and 1 (2%) had sarcoidosis. Evidence of systemic disease was found in 50 (5%) of the 1,000 control subjects. Bronchial asthma was found in 37 patients (3.7 %), multiple sclerosis in 9 patients (0.9%), inflammatory bowel disease in 3 patients (0.3%), and tuberculosis in 1 patient (0.1%). None of the control patients had sarcoidosis or lymphoma. There were statistically significant associations between intermediate uveitis and bronchial asthma (p = 0.0001), multiple sclerosis (p = 0.003) and tuberculosis (p = 0.0005). Bronchial asthma and multiple sclerosis were the most frequently encountered systemic diseases associated with intermediate uveitis in our patient population. Patients with intermediate uveitis should undergo careful history-taking and investigations to rule out associated systemic illness.

Intact protein analysis of ubiquitin in cerebrospinal fluid by multiple reaction monitoring reveals differences in Alzheimer's disease and frontotemporal lobar degeneration.

Science.gov (United States)

Oeckl, Patrick; Steinacker, Petra; von Arnim, Christine A F; Straub, Sarah; Nagl, Magdalena; Feneberg, Emily; Weishaupt, Jochen H; Ludolph, Albert C; Otto, Markus

2014-11-07

The impairment of the ubiquitin-proteasome system (UPS) is thought to be an early event in neurodegeneration, and monitoring UPS alterations might serve as a disease biomarker. Our aim was to establish an alternate method to antibody-based assays for the selective measurement of free monoubiquitin in cerebrospinal fluid (CSF). Free monoubiquitin was measured with liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MS/MS) in CSF of patients with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), behavioral variant of frontotemporal dementia (bvFTD), Creutzfeldt-Jakob disease (CJD), Parkinson's disease (PD), primary progressive aphasia (PPA), and progressive supranuclear palsy (PSP). The LC-MS/MS method showed excellent intra- and interassay precision (4.4-7.4% and 4.9-10.3%) and accuracy (100-107% and 100-106%). CSF ubiquitin concentration was increased compared with that of controls (33.0 ± 9.7 ng/mL) in AD (47.5 ± 13.1 ng/mL, p < 0.05) and CJD patients (171.5 ± 103.5 ng/mL, p < 0.001) but not in other neurodegenerative diseases. Receiver operating characteristic curve (ROC) analysis of AD vs control patients revealed an area under the curve (AUC) of 0.832, and the specificity and sensitivity were 75 and 75%, respectively. ROC analysis of AD and FTLD patients yielded an AUC of 0.776, and the specificity and sensitivity were 53 and 100%, respectively. In conclusion, our LC-MS/MS method may facilitate ubiquitin determination to a broader community and might help to discriminate AD, CJD, and FTLD patients.

Prevalence of benign tumors among patients with multiple sclerosis

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Aryan Rafiee Zadeh

2015-10-01

Full Text Available Multiple sclerosis (MS, an inflammatory autoimmune disease, affects almost 1% of world’s population in which myelin sheaths of neurons are targeted by immune cells. Association of different factors and diseases with MS provides new insights into possible pathogenesis and treatment for this disease. In this regard, we investigated the association of benign tumors with MS disease by studying total Isfehan multiple sclerosis (TIMS records for MS patients registered in Isfahan Multiple Sclerosis Society (IMSS who had developed any kind of benign tumors whether before MS diagnosis or after it. This study was performed in Isfahan province, third large province of Iran, with 4,815,863 populations located 1590 meters above sea level between latitudes 30 and 34 degrees north of the equator, and longitude 49-55 east. Among 4950 registered patients, 28 patients were discovered to have three types of benign tumors; pituitary adenoma in 22, meningioma in 5 and lipoma in 1 patient. The incidence rate of developing pituitary adenoma and meningioma were higher than in general population (OR 95%CI: 1.110; range: 0.731-1.685 and 1.035; range: 0.431-2.487 respectively but these findings were not statistically significant (p= 0.624 for pituitary adenoma and p= 0.939 for meningioma. But the incidence rate for lipoma was lower among MS patients (OR 95%CI: 0.020; range: 0.003-0.143 which was statistically significant (p <0.001.

Multiple myeloma of the jaw: A case report

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Shubhasini A Raghavan

2014-01-01

Full Text Available Multiple myeloma is a systemic B-cell lymphoproliferative disease that causes osteolytic lesions in the vertebra, ribs, pelvic bone, skull and jaw. Rarely jaw lesions are seen as the first sign in multiple myeloma. This is a case report with follow up of a 57-year-old female patient, previously treated for osteoporosis, who presented with a swelling of the jaw. On radiographic examination, she was found to have osteolytic lesions in the mandible and skull bones. These conventional aids led to the diagnosis of multiple myeloma thereby proving that the osteoporotic lesions were a part of the spectrum of multiple myeloma. The patient underwent chemotherapy and is currently on follow-up. This case report emphasizes the importance of early diagnosis of multiple myeloma in the jaw using readily available technologies and illustrates the contribution that oral assessment can provide.

Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer's Disease: Future Early Diagnostic Biomarkers?

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Bagattini, Chiara; Mazza, Veronica; Panizza, Laura; Ferrari, Clarissa; Bonomini, Cristina; Brignani, Debora

2017-01-01

The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis.

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Zongqi Xia

2010-11-01

Full Text Available Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS. We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer's Disease (AD influence brain volume and cognition in MS patients.MS subjects were genotyped for five single nucleotide polymorphisms (snps associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF measurements obtained from Magnetic Resonance Imaging (MRI data and cognitive function using the Symbol Digit Modalities Test (SDMT. Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD age at enrollment of 41 (±10 years were followed for 44 (±28 months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708G is associated with a smaller average brain volume (P=0.0047 at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P=0.0088. Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P=0.0089 at the last MRI visit.Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.

Lenalidomide in relapsed and refractory multiple myeloma disease: feasibility and benefits of long-term treatment.

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Zago, Manola; Oehrlein, Katharina; Rendl, Corinna; Hahn-Ast, Corinna; Kanz, Lothar; Weisel, Katja

2014-12-01

Lenalidomide in combination with dexamethasone is an effective and well-established treatment of relapsed or refractory multiple myeloma (rrMM) disease. Due to the scarcity of reports assessing benefit and risk of long-term lenalidomide treatment in non-selected rrMM patients, we retrospectively analysed the long-term outcome in patients with rrMM treated with lenalidomide and dexamethasone. Sixty-seven patients (pts) who were treated with lenalidomide/dexamethasone for rrMM in the approved indication from 2007 to 2011 were included in this retrospective, single-centre analysis. Kaplan-Meier survival estimates were compared between total population, patients on lenalidomide for more than 12 months (mo) and patients discontinuing therapy earlier than 12 months. Median overall survival (OS) of the total patient population was 33.2 mo. OS of pts treated beyond 12 mo was 42.9 mo compared to 20.2 mo (p = 0.027) for pts stopping lenalidomide earlier than 12 mo for other reasons than progression disease (PD). OS of pts >12 mo on lenalidomide treatment did not significantly differ between pts who had received previous autologous transplantation, allogeneic transplantation or conventional therapy. Main non-hematologic toxicities were infections of grade 3/4 in 25 % and thrombembolic events of all grades in 18 % of patients. To the best of our knowledge, this is the first report on feasibility and efficacy of long-term lenalidomide treatment in a non-selected patient cohort. OS of pts >12 mo on lenalidomide is superior when compared to pts discontinued earlier for reasons other than PD. Our data confirm the current use of lenalidomide as a continuous long-term treatment strategy.

A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

DEFF Research Database (Denmark)

Jagodic, Maja; Colacios, Celine; Nohra, Rita

2009-01-01

Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

Multiple trauma in children: critical care overview.

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Wetzel, Randall C; Burns, R Cartland

2002-11-01

Multiple trauma is more than the sum of the injuries. Management not only of the physiologic injury but also of the pathophysiologic responses, along with integration of the child's emotional and developmental needs and the child's family, forms the basis of trauma care. Multiple trauma in children also elicits profound psychological responses from the healthcare providers involved with these children. This overview will address the pathophysiology of multiple trauma in children and the general principles of trauma management by an integrated trauma team. Trauma is a systemic disease. Multiple trauma stimulates the release of multiple inflammatory mediators. A lethal triad of hypothermia, acidosis, and coagulopathy is the direct result of trauma and secondary injury from the systemic response to trauma. Controlling and responding to the secondary pathophysiologic sequelae of trauma is the cornerstone of trauma management in the multiply injured, critically ill child. Damage control surgery is a new, rational approach to the child with multiple trauma. The selection of children for damage control surgery depends on the severity of injury. Major abdominal vascular injuries and multiple visceral injuries are best considered for this approach. The effective management of childhood multiple trauma requires a combined team approach, consideration of the child and family, an organized trauma system, and an effective quality assurance and improvement mechanism.

Ollier disease

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Jüppner Harald

2006-09-01

Full Text Available Abstract Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease (WHO terminology. The estimated prevalence of Ollier disease is 1/100,000. Clinical manifestations often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery. Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier disease and Maffucci syndrome have only occurred in isolated patients and not familial. It remains uncertain whether the disorder is caused by a single gene defect or by combinations of (germ-line and/or somatic mutations. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. There is no medical treatment for enchondromatosis. Surgery is indicated in case of complications (pathological fractures, growth defect, malignant transformation. The prognosis for Ollier disease is difficult to assess. As is generally the case, forms with an early onset appear more severe. Enchondromas in Ollier disease present a risk of malignant transformation of enchondromas into chondrosarcomas.

Gene features selection for three-class disease classification via multiple orthogonal partial least square discriminant analysis and S-plot using microarray data.

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Yang, Mingxing; Li, Xiumin; Li, Zhibin; Ou, Zhimin; Liu, Ming; Liu, Suhuan; Li, Xuejun; Yang, Shuyu

2013-01-01

DNA microarray analysis is characterized by obtaining a large number of gene variables from a small number of observations. Cluster analysis is widely used to analyze DNA microarray data to make classification and diagnosis of disease. Because there are so many irrelevant and insignificant genes in a dataset, a feature selection approach must be employed in data analysis. The performance of cluster analysis of this high-throughput data depends on whether the feature selection approach chooses the most relevant genes associated with disease classes. Here we proposed a new method using multiple Orthogonal Partial Least Squares-Discriminant Analysis (mOPLS-DA) models and S-plots to select the most relevant genes to conduct three-class disease classification and prediction. We tested our method using Golub's leukemia microarray data. For three classes with subtypes, we proposed hierarchical orthogonal partial least squares-discriminant analysis (OPLS-DA) models and S-plots to select features for two main classes and their subtypes. For three classes in parallel, we employed three OPLS-DA models and S-plots to choose marker genes for each class. The power of feature selection to classify and predict three-class disease was evaluated using cluster analysis. Further, the general performance of our method was tested using four public datasets and compared with those of four other feature selection methods. The results revealed that our method effectively selected the most relevant features for disease classification and prediction, and its performance was better than that of the other methods.

Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction

NARCIS (Netherlands)

Poll-The, B. T.; Saudubray, J. M.; Ogier, H.; Schutgens, R. B.; Wanders, R. J.; Schrakamp, G.; van den Bosch, H.; Trijbels, J. M.; Poulos, A.; Moser, H. W.

1986-01-01

Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid

Freedom poverty: a new tool to identify the multiple disadvantages affecting those with CVD.

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Callander, Emily J; Schofield, Deborah J; Shrestha, Rupendra N

2013-06-20

It is recognised that CVD affects an individual's financial situation, placing them in income poverty. However, recent developments in poverty measurement practice recognises other forms of disadvantage other than low income, such as poor health and insufficient education also affect living standards. Using the Freedom Poverty Measure, the multiple forms of disadvantage experienced by those with no health condition, heart disease, other diseases of the circulatory system, and all other health conditions was assessed using data on the adult Australian population contained in the 2003 Survey of Disability, Ageing and Carers. 24% of those with heart disease and 23% of those with other diseases of the circulatory system were in freedom poverty, suffering from multiple forms of disadvantage. Those with heart disease and those with other diseases of the circulatory system were around three times more likely to be in freedom poverty (OR 3.02, 95% CI: 2.29-3.99, p<.0001; OR 2.78, 95% CI: 1.94-3.98, p<.0001) than those with no health condition. Recognising the multiple forms of disadvantage suffered by those with CVD provides a clearer picture of their living standards than just looking at their income alone and the high proportion of individuals with CVD that are suffering from multiple forms of disadvantage should make them a target for policy makers wishing to improve living standards. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Radionuclide assessment of Gaucher's disease

International Nuclear Information System (INIS)

Cheng, T.H.; Holman, B.L.

1978-01-01

Gaucher's disease involves multiple organs and may present with variable severity. The scintigraphic appearance of the reticuloendothelial system and bone are described in three patients with Gaucher's disease. Scintigraphic abnormalities reflected the severity of organ involvement and correlated well with the patients' clinical status. Scintigraphy appears useful for the evaluation and followup of patients with Gaucher's disease

Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

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Jan-Patrick Stellmann

Full Text Available New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS--the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.To analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.A systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC and the Hamburg MS patient database (HAPIMS was pooled for a retrospective validation of these predictors on the annualized EDSS change.The systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.None of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

Axonal loss in the multiple sclerosis spinal cord revisited.

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Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Biggins, J.A.; Taylor, A.; Caspary, E.A.

1978-01-01

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

Doença óssea em Mieloma Múltiplo Bone disease in Multiple Myeloma

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Vania T. M. Hungria

2007-03-01

Full Text Available As principais manifestações clínicas do mieloma múltiplo estão relacionadas à destruição óssea. Esta doença óssea pode levar a fraturas patológicas, compressão da medula espinhal, hipercalcemia e dor, sendo uma das principais causas de morbidade e mortalidade. Estas complicações resultam do desequilíbrio da reabsorção e formação óssea, decorrente do aumento da atividade osteoclástica. Este aumento é mediado pela liberação de fatores ativadores dos osteoclastos, que são produzidos no microambiente da medula óssea por células tumorais e não tumorais. Os bisfosfonatos são inibidores específicos da atividade osteoclástica e são eficazes no tratamento da hipercalcemia associada às neoplasias malignas e podem reduzir o aparecimento de complicações esqueléticas. Estudos recentes identificaram novas moléculas como o receptor de ativação nuclear kappa B (RANK, seu ligante (RANKL, osteoprotegerina (OPG, e a proteína inflamatória dos macrófagos-1alfa, que estão envolvidas na ativação e diferenciação dos osteoclastos, enquanto que a proteína dikkopf-1 inibe a formação óssea osteoblástica. Estas novas moléculas parecem não só interferir na biologia da destruição óssea do mieloma, mas também com a sobrevida e crescimento tumoral, sendo novos alvos para o desenvolvimento de drogas antimieloma. Estudos recentes com anticorpo monoclonal anti-RANKL são promissores. O tratamento da doença óssea do mieloma múltiplo inclui principalmente o uso de bisfosfonatos, radioterapia e procedimentos cirúrgicos.The major clinical manifestation of multiple myeloma is related to osteolytic bone destruction. Bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain, and is a major cause of morbidity and mortality. These complications result from asynchronous bone turnover wherein increased osteoclastic bone resorption is not accompanied by a comparable increase in bone formation

Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

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Timon E. Adolph

2017-07-01

Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

Cognitive Impairment in Multiple Sclerosis

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Farnaz Etesam

2014-01-01

Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

Science.gov (United States)

Timmermann, Lars; Jain, Roshini; Chen, Lilly; Maarouf, Mohamed; Barbe, Michael T; Allert, Niels; Brücke, Thomas; Kaiser, Iris; Beirer, Sebastian; Sejio, Fernando; Suarez, Esther; Lozano, Beatriz; Haegelen, Claire; Vérin, Marc; Porta, Mauro; Servello, Domenico; Gill, Steven; Whone, Alan; Van Dyck, Nic; Alesch, Francois

2015-07-01

High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure

A rare presentation of multiple endocrine neoplasia (MEN type 2A syndrome

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Elroy Patrick Weledji

2016-02-01

Full Text Available Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease.

Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.

Science.gov (United States)

Lazzarino, Giacomo; Amorini, Angela M; Petzold, Axel; Gasperini, Claudio; Ruggieri, Serena; Quartuccio, Maria Esmeralda; Lazzarino, Giuseppe; Di Stasio, Enrico; Tavazzi, Barbara

2017-11-01

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

Two Siblings Followed Up for Hereditary Multiple Exostoses

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Meltem Erol

2014-06-01

Full Text Available Hereditary multiple exostoses is an autosomal dominant disease with abnormal bone formation especially at the long bones. Osteochondromas, which occur in the course of the disease, can cause growth disturbances in affected children. Due to pressure effects of osteochondromas, compression of vessels, nerves and tendons, restriction of joint motion, and neurologic compromise as well as painful local symptoms can be seen. Here, we aimed to present two siblings who had generalized pain and swelling in different parts of the body. We detected multiple osteochondromas in different parts of their bodies, especially at the long bones. Our patients had painful local symptoms. There was no growth retardation, but the presence of many osteochondromas led us to contemplate that it was serious form of the disease. Their father had lesser number of osteochondromas. In this paper, we aimed to emphasize the necessity of close follow-up for the risk of malignant transformation of osteochondromas. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 116-9

Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

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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.

Multiple coil closure of isolated aortopulmonary collateral

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Padhi Sumanta

2010-01-01

Full Text Available A 7-month-old girl was diagnosed to have large aortopulmonary collateral during evaluation for congestive heart failure. There was no other evidence of cardiopulmonary disease. The collateral was successfully closed with multiple coils delivered sequentially. We describe the issues associated during closure of the aortopulmonary collateral in this case. To the best of our knowledge, this is the first reported case of large aortopulmonary collateral presenting with heart failure in an otherwise structurally normal heart that was closed successfully with multiple coils delivered sequentially.

Disease processes as hybrid dynamical systems

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Pietro Liò

2012-08-01

Full Text Available We investigate the use of hybrid techniques in complex processes of infectious diseases. Since predictive disease models in biomedicine require a multiscale approach for understanding the molecule-cell-tissue-organ-body interactions, heterogeneous methodologies are often employed for describing the different biological scales. Hybrid models provide effective means for complex disease modelling where the action and dosage of a drug or a therapy could be meaningfully investigated: the infection dynamics can be classically described in a continuous fashion, while the scheduling of multiple treatment discretely. We define an algebraic language for specifying general disease processes and multiple treatments, from which a semantics in terms of hybrid dynamical system can be derived. Then, the application of control-theoretic tools is proposed in order to compute the optimal scheduling of multiple therapies. The potentialities of our approach are shown in the case study of the SIR epidemic model and we discuss its applicability on osteomyelitis, a bacterial infection affecting the bone remodelling system in a specific and multiscale manner. We report that formal languages are helpful in giving a general homogeneous formulation for the different scales involved in a multiscale disease process; and that the combination of hybrid modelling and control theory provides solid grounds for computational medicine.

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

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Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple

Multiple systems atrophy: Differentiation and findings by Magnetic resonance

International Nuclear Information System (INIS)

Vargas Velez, Sergio Alberto; Alzate Betancur, Catalina Maria

2006-01-01

Multiple system atrophy (MSA) is a neuro degenerative disorder of undetermined cause, characterized clinically by Parkinson's, autonomic, cerebellar or pyramidal sing and symptoms. lts differentiation from Parkinson's disease may be difficult, mainly in the early stages owing to overlapping features. Magnetic resonance imaging has demonstrated usefulness in MSA diagnosis and in differentiation with Parkinson's disease. One case with magnetic resonance findings is described

Safety and Efficacy of Fingolimod in Treatment-Naïve Multiple Sclerosis Patients

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James J. Marriott

2011-01-01

Full Text Available Fingolimod was recently approved for use in the United States after two phase III trials confirmed its effectiveness in reducing disease activity in relapsing-remitting multiple sclerosis. These positive results, coupled with the important fact that this is the first oral disease-modifying therapy, has lead to considerable enthusiasm amongst physicians and patients. However, fingolimod is associated with rare but serious adverse events. In addition, unlike conventional disease-modifying therapies, cardiopulmonary, ophthalmological and dermatological safety monitoring unfamiliar to both neurologists and patients is required before and during treatment. This paper will discuss these issues from the perspective of using fingolimod as a first-line disease-modifying therapy in treatment-Naïve relapsing-remitting multiple sclerosis patients

Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

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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...

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

Univariate and multiple linear regression analyses for 23 single nucleotide polymorphisms in 14 genes predisposing to chronic glomerular diseases and IgA nephropathy in Han Chinese.

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Wang, Hui; Sui, Weiguo; Xue, Wen; Wu, Junyong; Chen, Jiejing; Dai, Yong

2014-09-01

Immunoglobulin A nephropathy (IgAN) is a complex trait regulated by the interaction among multiple physiologic regulatory systems and probably involving numerous genes, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of IgAN nephropathy is based on multiple genes with minor effects. To learn the association between 23 single nucleotide polymorphisms (SNPs) in 14 genes predisposing to chronic glomerular diseases and IgAN in Han males, the 23 SNPs genotypes of 21 Han males were detected and analyzed with a BaiO gene chip, and their associations were analyzed with univariate analysis and multiple linear regression analysis. Analysis showed that CTLA4 rs231726 and CR2 rs1048971 revealed a significant association with IgAN. These findings support the multi-gene nature of the etiology of IgAN and propose a potential gene-gene interactive model for future studies.

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

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Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease.

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Dunn, Shannon E; Gunde, Eva; Lee, Hyunwoo

2015-01-01

It is well known that a number of autoimmune diseases including multiple sclerosis (MS) predominantly affect women and there has been much attention directed toward understanding why this is the case. Past research has revealed a number of sex differences in autoimmune responses that can account for the female bias in MS. However, much less is known about why the incidence of MS has increased exclusively in women over the past half century. The recency of this increase suggests that changing environmental or lifestyle factors are interacting with biological sex to increase MS risk predominantly in females. Indeed, a number of recent studies have identified sex-specific differences in the effect of environmental factors on MS incidence. The first part of this chapter will overview this evidence and will discuss the possible scenarios of how the environment may be interacting with autoimmune mechanisms to contribute to the preferential rise in MS incidence in women. Despite the strong female bias in MS incidence, culminating evidence from natural history studies, and imaging and pathology studies suggests that males who develop MS may exhibit a more rapid decline in disability and cognitive functioning than women. Very little is known about the biological basis of this more rapid deterioration, but some insights have been provided by studies in rodent models of demyelination/remyelination. The second part of this chapter will overview the evidence that males with relapsing-onset MS undergo a more rapid progression of disease than females and will discuss potential biological mechanisms that account for this sex difference.

Connexins and Disease

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Delmar, Mario; Laird, Dale W; Naus, Christian C

2017-01-01

Inherited or acquired alterations in the structure and function of connexin proteins have long been associated with disease. In the present work, we review current knowledge on the role of connexins in diseases associated with the heart, nervous system, cochlea, and skin, as well as cancer...... of connexins are fundamental components in the pathophysiology of multiple connexin related disorders, many of them highly debilitating and life threatening. Improved understanding of connexin biology has the potential to advance our understanding of mechanisms, diagnosis, and treatment of disease....

Multiple self-healing squamous epithelioma of Ferguson-Smith

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Broesby-Olsen, Sigurd; Bygum, Anette; Gerdes, Anne-Marie

2008-01-01

Multiple self-healing squamous epithelioma of Ferguson-Smith (MSSE) is a rare autosomal dominantly inherited disease, almost exclusively reported in patients of Scottish origin, with recurrent, histologically malignant tumours that undergo spontaneous regression. We report clinical observations...

Fibronectin aggregation in multiple sclerosis lesions impairs remyelination

NARCIS (Netherlands)

Stoffels, J.M.J.; de Jonge, J.C.; Stancic, M.; Nomden, A.; van Strien, M.E.; Ma, D.; Siskova, Z.; Maier, O.; Ffrench-Constant, C.; Franklin, R.J.M.; Hoekstra, D.; Zhao, C.; Baron, W.

2013-01-01

Remyelination following central nervous system demyelination is essential to prevent axon degeneration. However, remyelination ultimately fails in demyelinating diseases such as multiple sclerosis. This failure of remyelination is likely mediated by many factors, including changes in the

Fibronectin aggregation in multiple sclerosis lesions impairs remyelination

NARCIS (Netherlands)

Stoffels, Josephine M. J.; de Jonge, Jenny C.; Stancic, Mirjana; Nomden, Anita; van Strien, Miriam E.; Ma, Dan; Siskova, Zuzana; Maier, Olaf; Ffrench-Constant, Charles; Franklin, Robin J. M.; Hoekstra, Dick; Zhao, Chao; Baron, Wia

Remyelination following central nervous system demyelination is essential to prevent axon degeneration. However, remyelination ultimately fails in demyelinating diseases such as multiple sclerosis. This failure of remyelination is likely mediated by many factors, including changes in the

Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

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Necla Keskin

2013-08-01

Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

Multiple Kernel Learning with Random Effects for Predicting Longitudinal Outcomes and Data Integration

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Chen, Tianle; Zeng, Donglin

2015-01-01

Summary Predicting disease risk and progression is one of the main goals in many clinical research studies. Cohort studies on the natural history and etiology of chronic diseases span years and data are collected at multiple visits. Although kernel-based statistical learning methods are proven to be powerful for a wide range of disease prediction problems, these methods are only well studied for independent data but not for longitudinal data. It is thus important to develop time-sensitive prediction rules that make use of the longitudinal nature of the data. In this paper, we develop a novel statistical learning method for longitudinal data by introducing subject-specific short-term and long-term latent effects through a designed kernel to account for within-subject correlation of longitudinal measurements. Since the presence of multiple sources of data is increasingly common, we embed our method in a multiple kernel learning framework and propose a regularized multiple kernel statistical learning with random effects to construct effective nonparametric prediction rules. Our method allows easy integration of various heterogeneous data sources and takes advantage of correlation among longitudinal measures to increase prediction power. We use different kernels for each data source taking advantage of the distinctive feature of each data modality, and then optimally combine data across modalities. We apply the developed methods to two large epidemiological studies, one on Huntington's disease and the other on Alzheimer's Disease (Alzheimer's Disease Neuroimaging Initiative, ADNI) where we explore a unique opportunity to combine imaging and genetic data to study prediction of mild cognitive impairment, and show a substantial gain in performance while accounting for the longitudinal aspect of the data. PMID:26177419

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study.

Directory of Open Access Journals (Sweden)

Amanda Worker

Full Text Available Although often clinically indistinguishable in the early stages, Parkinson's disease (PD, Multiple System Atrophy (MSA and Progressive Supranuclear Palsy (PSP have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI data to compare differences in fractional anisotropy (FA and mean diffusivity (MD between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients

Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

DEFF Research Database (Denmark)

Fu, Jing; Li, Shirong; Feng, Rentian

2016-01-01

Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets...

MYO9B polymorphisms in multiple sclerosis

DEFF Research Database (Denmark)

Kemppinen, A.; Suvela, M.; Tienari, P.J.

2009-01-01

Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

Skeletal surveys in multiple myeloma

International Nuclear Information System (INIS)

Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

1986-01-01

Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

Depression and anxiety in multiple system atrophy.

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Zhang, L-Y; Cao, B; Zou, Y-T; Wei, Q-Q; Ou, R-W; Zhao, B; Wu, Y; Shang, H-F

2018-01-01

It has been noticed that the patients with multiple system atrophy (MSA) can accompany with depression and anxiety. This study aimed to establish the incidence and determinants of depression and anxiety symptoms in Chinese MSA patients. A total of 237 MSA patients were enrolled in the study. Neuropsychological assessment was performed using Hamilton Depression Rating Scale-24 items and Hamilton Anxiety Rating Scale. We found that 62.0% and 71.7% patients had at least mild depression and anxiety symptoms, respectively. The severity of depression of MSA patients was associated with lower educational years (P=.024), longer disease duration (Panxiety was associated with increased disease duration (Panxiety were female gender, longer disease duration, and disease severity. Depression and anxiety symptoms are common in patients with MSA. Neurologists should pay attention to depression and anxiety in patients with MSA, especially in female patients and those with longer disease duration and severe disease condition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of information system in multiple sclerosis management.

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