CD21+ (B2 antigen+) cell decrement and CD4+CD29+ (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis.

PubMed

Gambi, D; Porrini, A M; Giampietro, A; Macor, S

1991-08-01

Two-color flow cytometric analysis on peripheral blood lymphocytes of 35 untreated multiple sclerosis (MS) patients, 17 other medical disease (OMD) patients and 14 healthy control (HC) subjects was performed to evaluate the levels of different T and B cell subpopulations. In MS patients we observed an increase in CD4+CD29+ helper-inducer cells but this increase was not related to the different phases of the disease. We hypothesize that this change is related to the reduction of CD21+ cells expressing B2 antigen, a 140 kDa molecule disappearing after B cell activation. An increased level of CD4+CD45RA- (helper-inducer-like cells) and a reduction of CD4+CD29- (suppressor-inducer-like cells) were also present in our patients. These findings demonstrate an immune 'disequilibrium' in MS, which is linked with an increased level of CD25+ cells expressing the interleukin-2 (IL-2) receptor. IL-2, besides being a T cell growth factor, is also a B cell growth factor. These data let us hypothesize that an activation of the immune response is present in MS.

Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.

PubMed

Sadarzanska-Terzieva, Behidhe; Tzvetanov, Plamen; Hegde, Vishwajit; Al-Hashel, Jasem Y; Rousseff, Rossen Т; Haralanov, Lubomir; Stamenov, Boyko; Atanassova, Milena; Marinova, Iveta; Marinova, Anna; Rousseva, Adelaida

2015-06-01

To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS). Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies. Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008). High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

PubMed Central

Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

2017-01-01

Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness. PMID:28103257

Epidemiological study of multiple sclerosis in La Rioja.

PubMed

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.

Prevalence and predictors of depression in Iranian patients with multiple sclerosis: a population-based study.

PubMed

Seyed Saadat, Seyed Mohammad; Hosseininezhad, Mozaffar; Bakhshayesh, Babak; Seyed Saadat, Seyedeh Nastaran; Nabizadeh, Seyedeh Parand

2014-05-01

Depression is a frequent symptom in multiple sclerosis (MS) which has a negative impact on quality of life and cognitive status. The purpose of this study was to determine the prevalence and associated factors of depression, and status of antidepressant use in Iranian MS patients. One-hundred and sixty patients with definite MS were included. Demographic and clinical characteristics were recorded. Fatigue and depression were evaluated using the fatigue severity scale and Beck depression inventory-II. Cognitive performance and disability were examined by mini-mental status examination and expanded disability status scale. Multiple logistic regressions were used to determine the associated factors of depression and antidepressant use. The prevalence of depression and severe depression was 59.4 and 18.1 %, respectively. However, only 21.1 % of patients were on antidepressant treatment, while the prevalence of unrecognized/untreated depression was found to be as high as 44.1 %. Multivariable analysis showed that fatigue (P < 0.0001, OR = 5.98, 95 % CI = 2.9-12.3) and older age (P = 0.027, OR = 2.24, 95 % CI = 1.09-4.6) were associated with depression in MS patient. A significant association was found between fatigue and antidepressant use (P = 0.001, OR = 6.81, 95 % CI = 2.26-20.48). Our findings demonstrate that depression is significantly associated with fatigue and older age, regardless of other factors. Moreover, despite the high prevalence of depression in MS, most patients do not receive adequate treatment.

Association between serum uric acid, metabolic syndrome and microalbuminuria in previously untreated essential hypertensive patients.

PubMed

Rodilla, Enrique; Pérez-Lahiguera, Francisco; Costa, José A; González, Carmen; Miralles, Amparo; Moral, Desamparados; Pascual, José María

2009-01-17

The aim of the study was to assess the association of serum uric acid levels with microalbuminuria -urinary albumin excretion (UAE)> or = 30mg/24h-. Cross-sectional study in 429 (220 women) hypertensive, non diabetic, never treated patients (mean age: 47 years) with glomerular filtration rate > or =60ml/min/1.73m(2). The prevalence of microalbuminuria was 20.5%; 18% had hyperuricemia and 47% fulfilled the criteria for metabolic syndrome (MS). Baseline UAE correlated in the unvaried analysis to diastolic blood pressure, waist circumference, high-density lipoprotein cholesterol and uric acid. In multiple linear regression models, only MS (beta=0.113; p=0.03), and serum uric acid values (beta=0.04; p=0.05) were independently associated with logUAE, after adjustment for age and sex. Hyperuricemia (serum uric acid level > or =7.0mg/dl for men and > or =6.5mg/dl for women; odds ratio=2.18; 95% confidence interval, 1.21-3.92; p=0.010), and MS (odds ratio=2.16; 95% confidence interval, 1.32-3.53; p=0.002) were independently associated with a higher risk of microalbuminuria in multiple logistic regression analyses. The prevalence of microalbuminuria was 45.8% in patients with coexistent MS and hyperuricemia, as compared to 13.6% in hypertensive patients without it (p<0.001). In patients with concomitant MS and hyperuricemia the probability of being microalbuminuric was 3.7 times higher than in patients without those factors. Serum uric acid level is associated with microalbuminuria. Coexistence of MS and hyperuricemia in hypertensive patients increases almost 4 times the odds of being microalbuminuric.

Left atrial appendage function in prediction of paroxysmal atrial fibrilation in patients with untreated hypertension.

PubMed

Tenekecioglu, Erhan; Agca, Fahriye Vatansever; Karaagac, Kemal; Ozluk, Ozlem Arican; Peker, Tezcan; Kuzeytemiz, Mustafa; Senturk, Muhammed; Yılmaz, Mustafa

2014-01-01

Abstract The onset of AF results in a significant increase in mortality rates and morbidity in hypertensive patients and this rhythm disorder exposes patients to a significantly increased risk of cerebral or peripheral embolisms. Tissue Doppler imaging was found to be useful in early detection of myocardial dysfunction in several diseases. It was shown that tissue Doppler analysis of the walls of the left atrial appendage (LAA) can give accurate information about the function of the LAA in hypertensive patients. In this study, we aimed to investigate and identify the specific predictive parameters for the onset of AF in patients with hypertension with tissue Doppler imaging of LAA. We studied age and sex matched 57 untreated hypertensive patients with paroxysmal atrial fibrillation (PAF) and 27 untreated hypertensive subjects without PAF. With transthoracic echocardiography, diastolic mitral A-velocity and LA maximal volume index which reflects reservoir function of left atrium was measured, with transesophageal echocardiography, LAA emptying velocity (LAA-PW D2) and tissue Doppler contracting velocity of LAA (LAA-TDI-D2) were measured. LA maximal volume index of the groups (22.28 ± 3.59 mL/m(2) in Group 1 versus 20.37 ± 3.97 mL/m(2) in Group 2, p = 0.07) and diastolic mitral A-velocity [0.93 (0.59-1.84) m/s in patients with PAF versus 0.90 (0.62-1.76) m/s in patients without PAF, p = 0.26] was not significantly different between study groups, during TEE, LAA-PW D2 (0.31 ± 0.04 m/s in Group 1 versus 0.33 ± 0.03 m/s in Group 2, p = 0.034) and LAA-TDI-D2 (0.18 ± 0.04 m/s in Group 1 versus 0.21 ± 0.05 m/s in Group 2, p = 0.014) were significantly decreased in Group 1. In this study, we found that in hypertensive PAF patients despite normal global LA functions, LAA contracting function was deteriorated. Tissue Doppler analysis of LAA is clinically usefull approach to detect the risk of developing PAF in hypertensives.

Identification of polar, ionic, and highly water soluble organic pollutants in untreated industrial wastewaters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castillo, M.; Alonso, M.C.; Riu, J.

1999-04-15

This paper presents a generic protocol for the determination of polar, ionic, and highly water soluble organic pollutants on untreated industrial wastewaters involving the use of two different solid-phase extraction (SPE) methodologies followed by liquid chromatography-mass spectrometry (LC-MS). Untreated industrial wastewaters might contain natural and synthetic dissolved organic compounds with total organic carbon (TOC) values varying between 100 and 3000 mg/L. All polar, ionic and highly water soluble compounds comprising more than 95% of the organic content and with major contribution to the total toxicity of the sample cannot be analyzed by conventional gas chromatography-mass spectrometry (GC-MS), and LC-MS ismore » a good alternative. In this work two extraction procedures were used to obtain fractionated extracts of the nonionic polar compounds: a polymeric Isolute ENV + SPE cartridge for the preconcentration of anionic analytes and a sequential solid-phase extraction (SSPE) method percolating the samples first in octadecylsilica cartridge in series with the polymeric Lichrolut EN cartridge. Average recoveries ranging from 72% to 103% were obtained for a variety of 23 different analytes. Determination of nonionic pollutants was accomplished by reverse-phase liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS), while anionic compounds were analyzed by ion pair chromatography-electrospray-mass spectrometry (IP-ESI-MS) and LC-ESI-MS. This protocol was applied to a pilot survey of textile and tannery wastewaters leading to the identification and quantification of 33 organic pollutants.« less

[Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

PubMed

Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

2013-08-01

In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study

PubMed Central

2011-01-01

Background The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy. Methods A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥ 18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables. Results Patients were followed for an average of 35.7 ± 17.5 months after their index diagnosis. Forty-three percent (n = 4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3 ± 9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6 ± 14.6 months, and 16.5% had treatment gaps in excess of 60 days. Conclusions Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity. PMID:21974973

Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis

PubMed Central

Lugaresi, Alessandra; di Ioia, Maria; Travaglini, Daniela; Pietrolongo, Erika; Pucci, Eugenio; Onofrj, Marco

2013-01-01

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics. There is no single best treatment strategy, but therapy has to be tailored to the patient. This is a time-consuming task, rich in complexity, and influenced by the attitude towards risk on the parts of both the patient and the clinical team. The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for. PMID:23836975

Determination of Phenylalanine and Tyrosine by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

Peat, Judy; Garg, Uttam

2016-01-01

Hyperphenylalaninemia/phenylketonuria (PKU) is one of the most common inborn errors of amino acid metabolism affecting about 1:15,000 infants in the United States. PKU is an autosomal recessive disorder that if untreated results in mental retardation. The most common cause of PKU is deficiency of the enzyme phenylalanine hydroxylase that converts phenylalanine to tyrosine. Tyrosine deficiency results in impaired synthesis of catecholamines and thyroxine. Less commonly, it can result from defects in the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor for the enzyme phenylalanine hydroxylase. Increased phenylalanine and decreased tyrosine in blood are used in the diagnosis and follow-up of patients with PKU. LC/MS/MS method is described for the quantification of phenylalanine and tyrosine.

Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients.

PubMed

Raϊch-Regué, Dàlia; Grau-López, Laia; Naranjo-Gómez, Mar; Ramo-Tello, Cristina; Pujol-Borrell, Ricardo; Martínez-Cáceres, Eva; Borràs, Francesc E

2012-03-01

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Current therapies decrease the frequency of relapses and limit, to some extent, but do not prevent disease progression. Hence, new therapeutic approaches that modify the natural course of MSneed to be identified. Tolerance induction to self-antigens using monocyte-derived dendritic cells (MDDCs) is a promising therapeutic strategy in autoimmunity. In this work, we sought to generate and characterize tolerogenic MDDCs (tolDCs) from relapsing-remitting (RR) MSpatients, loaded with myelin peptides as specific antigen, with the aim of developing immunotherapeutics for MS. MDDCs were generated from both healthy-blood donors and RR-MSpatients, and MDDCmaturation was induced with a proinflammatory cytokine cocktail in the absence or presence of 1α,25-dihydroxyvitamin-D(3) , a tolerogenicity-inducing agent. tolDCs were generated from monocytes of RR-MSpatients as efficiently as from monocytes of healthy subjects. The RR-MStolDCs expressed a stable semimature phenotype and an antiinflammatory profile as compared with untreated MDDCs. Importantly, myelin peptide-loaded tolDCs induced stable antigen-specific hyporesponsiveness in myelin-reactive T cells from RR-MS patients. These results suggest that myelin peptide-loaded tolDCs may be a powerful tool for inducing myelin-specific tolerance in RR-MS patients. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Untargeted LC-MS/MS Profiling of Cell Culture Media Formulations for Evaluation of High Temperature Short Time Treatment Effects.

PubMed

Floris, Patrick; McGillicuddy, Nicola; Albrecht, Simone; Morrissey, Brian; Kaisermayer, Christian; Lindeberg, Anna; Bones, Jonathan

2017-09-19

An untargeted LC-MS/MS platform was implemented for monitoring variations in CHO cell culture media upon exposure to high temperature short time (HTST) treatment, a commonly used viral clearance upstream strategy. Chemically defined (CD) and hydrolysate-supplemented media formulations were not visibly altered by the treatment. The absence of solute precipitation effects during media treatment and very modest shifts in pH values observed indicated sufficient compatibility of the formulations evaluated with the HTST-processing conditions. Unsupervised chemometric analysis of LC-MS/MS data, however, revealed clear separation of HTST-treated samples from untreated counterparts as observed from analysis of principal components and hierarchical clustering sample grouping. An increased presence of Maillard products in HTST-treated formulations contributed to the observed differences which included organic acids, observed particularly in chemically defined formulations, and furans, pyridines, pyrazines, and pyrrolidines which were determined in hydrolysate-supplemented formulations. The presence of Maillard products in media did not affect cell culture performance with similar growth and viability profiles observed for CHO-K1 and CHO-DP12 cells when cultured using both HTST-treated and untreated media formulations.

Ethnic differences in the degree of morning blood pressure surge and in its determinants between Japanese and European hypertensive subjects: data from the ARTEMIS study.

PubMed

Hoshide, Satoshi; Kario, Kazuomi; de la Sierra, Alejandro; Bilo, Grzegorz; Schillaci, Giuseppe; Banegas, José Ramón; Gorostidi, Manuel; Segura, Julian; Lombardi, Carolina; Omboni, Stefano; Ruilope, Luis; Mancia, Giuseppe; Parati, Gianfranco

2015-10-01

Morning blood pressure (BP) surge has been reported to be a prognostic factor for cardiovascular events. Its determinants are still poorly defined, however. In particular, it is not clear whether ethnic differences play a role in determining morning surge (MS) size. Aim of our study was to explore whether differences exist in the size of MS between Japanese and Western European hypertensive patients. We included 2887 untreated hypertensive patients (age 62.3±8.8 years) from a European ambulatory BP monitoring database and 811 hypertensive patients from a Japanese database (Jichi Medical School Ambulatory Blood Pressure Monitoring WAVE1, age 72.3±9.8 years) following the same inclusion criteria. Their 24-hour ambulatory BP monitoring recordings were analyzed focusing on MS. Sleep-trough MS was defined as the difference between mean systolic BP during the 2 hours after awakening and mean systolic BP during the 1-hour night period that included the lowest sleep BP level. The sleep-trough MS was higher in Japanese than in European hypertensive patients after adjusting for age and 24-hour mean BP levels (40.1 [95% confidence interval 39.0-41.2] versus 23.0 [22.4-23.5] mm Hg; P<0.001). This difference remained significant after accounting for differences in night-time BP dipping. Age was independently associated with MS in the Japanese database, but not in the European subjects. Our results for the first time show the occurrence of substantial ethnic differences in the degree of MS. These findings may help in understanding the role of ethnic factors in cardiovascular risk assessment and in identifying possible ethnicity-related differences in the most effective measures to be implemented for prevention of BP-related cardiovascular events. © 2015 American Heart Association, Inc.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

PubMed

Vriz, Olga; Favretto, Serena; Jaroch, Joanna; Wojciech, Rychard; Bossone, Eduardo; Driussi, Caterina; Antonini-Canterin, Francesco; Palatini, Paolo; Loboz-Grudzien, Krystyna

2017-01-01

To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W 1 ) and late systole (W 2 ). A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVβ) and the interval between the R wave on ECG and the first peak of WI (R-W 1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W 1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s 3 , P =.001) and W 2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s 3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W 1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s 3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W 1 . Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W 1 values, as compared with normotensive subjects, but no differences in LV diastolic function. © 2016 by the American Institute of Ultrasound in Medicine.

Rapid screening for lipid storage disorders using biochemical markers. Expert center data and review of the literature.

PubMed

Voorink-Moret, M; Goorden, S M I; van Kuilenburg, A B P; Wijburg, F A; Ghauharali-van der Vlugt, J M M; Beers-Stet, F S; Zoetekouw, A; Kulik, W; Hollak, C E M; Vaz, F M

2018-02-01

In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74). In addition, the oxysterols cholestane-3β,5α,6β-triol and 7-ketocholesterol were measured in a subset of these patients (n=36) as well as chitotriosidase activity (n=43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3β,5α,6β-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly elevated in all other lipid storage disorders. Review of the literature identified 44 publications. Most findings were in line with our cohort. Several moderate elevations of biochemical markers were found across a wide range of other, mainly inherited metabolic, diseases. Measurement in plasma of LysoSLs and oxysterols by UPLC-MS/MS in combination with activity of chitotriosidase provides a useful first tier screening of patients suspected of lipid storage disease. The LysoSM-509/LysoSM ratio is a promising parameter in Niemann-Pick disease type C. Further studies in larger groups of untreated patients and controls are needed to improve the specificity of the findings. Copyright © 2018 Elsevier Inc. All rights reserved.

Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

PubMed

Tortorella, C; Romano, R; Direnzo, V; Taurisano, P; Zoccolella, S; Iaffaldano, P; Fazio, L; Viterbo, R; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

2013-08-01

Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

A randomized side-by-side study comparing alexandrite laser at different pulse durations for port wine stains.

PubMed

Carlsen, Berit C; Wenande, Emily; Erlendsson, Andres M; Faurschou, Annesofie; Dierickx, Christine; Haedersdal, Merete

2017-01-01

Pulsed dye laser (PDL) represents the gold-standard treatment for port wine stains (PWS). However, approximately 20% of patients are poor responders and yield unsatisfactory end-results. The Alexandrite (Alex) laser may be a therapeutic alternative for selected PWS subgroups, but optimal laser parameters are not known. The aim of this study was to assess clinical PWS clearance and safety of Alex laser at a range of pulse durations. Sixteen individuals (14 previously PDL-treated) with deep red (n = 4), purple macular (n = 5) and purple hypertrophic (n = 7) PWS were included. Four side-by-side test areas were marked within each lesion. Three test areas were randomized to Alex laser at pulse durations of 3, 5, or 10 ms (8 mm spot, DCD 60/40), while the fourth was untreated. The lowest effective fluence to create purpura within the entire test spot was titrated and applied to intervention areas. Standardized clinical photographs were taken prior to, immediately after laser exposure and at 6-8 weeks follow up. Clinical PWS clearance and laser-related side effects were assessed using clinical photos. Alex laser at 3, 5, and 10 ms pulse durations demonstrated significant clearance compared to untreated controls (P < 0.001). Three milli second pulse duration exhibited improved clearance versus 5 ms (P = 0.016) and 10 ms (P = 0.004), while no difference between five and 10 ms was shown (P = 0.063). Though not significant, good responders (>50% clearance) were more likely to have purple hypertrophic PWS (5/7) compared to purple macular (2/5) and deep red lesions (1/4). Eight laser-exposed test areas (17%) developed hypopigmented atrophic scarring. Side effects tended to be more frequently observed with 5 ms (n = 4) and 10 ms (n = 3) versus 3 ms pulse duration (n = 1). Correspondingly, 3 ms was associated with a superior (n = 6) or comparable (n = 10) overall cosmetic appearance for all individuals. Alex laser at 3 ms pulse duration offers superior clinical clearance and safety compared to 5 and 10 ms, and seems best suited for purple hypertrophic PWS. Treatment should be restricted to experienced personnel due to a particularly narrow therapeutic window. Lasers Surg. Med. 49:97-103, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Development of protein biomarkers in cerebrospinal fluid for secondary progressive multiple sclerosis using selected reaction monitoring mass spectrometry (SRM-MS)

PubMed Central

2012-01-01

Background Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). It involves damage to the myelin sheath surrounding axons and to the axons themselves. MS most often presents with a series of relapses and remissions but then evolves over a variable period of time into a slowly progressive form of neurological dysfunction termed secondary progressive MS (SPMS). The reasons for this change in clinical presentation are unclear. The absence of a diagnostic marker means that there is a lag time of several years before the diagnosis of SPMS can be established. At the same time, understanding the mechanisms that underlie SPMS is critical to the development of rational therapies for this untreatable stage of the disease. Results Using high performance liquid chromatography-coupled mass spectrometry (HPLC); we have established a highly specific and sensitive selected reaction monitoring (SRM) assay. Our multiplexed SRM assay has facilitated the simultaneous detection of surrogate peptides originating from 26 proteins present in cerebrospinal fluid (CSF). Protein levels in CSF were generally ~200-fold lower than that in human sera. A limit of detection (LOD) was determined to be as low as one femtomol. We processed and analysed CSF samples from a total of 22 patients with SPMS, 7 patients with SPMS treated with lamotrigine, 12 patients with non-inflammatory neurological disorders (NIND) and 10 healthy controls (HC) for the levels of these 26 selected potential protein biomarkers. Our SRM data found one protein showing significant difference between SPMS and HC, three proteins differing between SPMS and NIND, two proteins between NIND and HC, and 11 protein biomarkers showing significant difference between a lamotrigine-treated and untreated SPMS group. Principal component analysis (PCA) revealed that these 26 proteins were correlated, and could be represented by four principal components. Overall, we established an efficient platform to develop and verify protein biomarkers in CSF, which can be easily adapted to other proteins of interest related to neurodegenerative diseases. Conclusions A highly specific and sensitive multiplex SRM-MS assay was established for development and verification of CSF protein biomarkers in SPMS. Five proteins were found to be expressed significantly differently between the three cohorts, SPMS, NIND and HC and 11 proteins associated with lamotrigine treatment, which we expect will further our current understanding of SPMS disease pathology and/or therapeutic intervention. PMID:22846148

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

PubMed Central

Petkau, J; Reingold, SC; Held, U; Cutter, GR; Fleming, TR; Hughes, MD; Miller, DH; McFarland, HF; Wolinsky, JS

2009-01-01

Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy. PMID:18535021

A validated UHPLC-MS/MS method to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses.

PubMed

Decloedt, Anneleen; Bailly-Chouriberry, Ludovic; Vanden Bussche, Julie; Garcia, Patrice; Popot, Marie-Agnes; Bonnaire, Yves; Vanhaecke, Lynn

2015-06-01

Doping control is a main priority for regulatory bodies of both the horse racing industry and the equestrian sports. Urine and blood samples are screened for the presence of hundreds of forbidden substances including anabolic-androgenic steroids (AASs). Based on the suspected endogenous origin of some AASs, with β-boldenone as the most illicit candidate, this study aimed to improve the knowledge of the naturally present AAS in horse urine. To this extent, a novel ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated according to the Association of Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving the power of this new method. Low limits of detection (0.2 ng/mL), good reproducibility (percentage of standard deviation (%RSD) < 10%), high recovery (94.6 to 117.1%), selectivity and specificity, and a linear response (confirmed with R(2) > 0.99 and lack-of-fit analysis) were obtained for all included AASs. With this method, urine samples of 105 guaranteed untreated horses (47 geldings, 53 mares, and 5 stallions serving as a control) were screened for β-boldenone and five related natural steroids: androstadienedione (ADD), androstenedione (AED), alpha-testosterone (αT), beta-testosterone (βT), and progesterone (P). Progesterone, β-testosterone, and α-testosterone were detected in more than half of the horses at low concentrations (<2 ng/mL). Occasionally, not only testosterone and progesterone but also low concentrations of AED, ADD, and boldenone (Bol) were found (0.5-5 ng/mL). Graphical Abstract A sensitive, new and fully validated UHPLC-MS/MS method has been developed that is able to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses (mares and geldings).

Metam sodium reduces viability and infectivity of Eimeria oocysts.

PubMed

Fetterer, R H; Jenkins, M C; Miska, K B; Cain, G D

2010-06-01

Metam sodium (MS, sodium N-methyldithiocarbamate) is a widely used soil pesticide. Fumigation or chemical sterilization of poultry litter containing infectious oocysts could be an effective strategy to block the transmission of avian coccidia. In the current study, the effect of MS on the viability and infectivity of ocysts was investigated. The development of isolated, unsporulated oocysts of both Eimeria tenella and Eimeria maxima was inhibited, in a dose-related manner (IC(50) 8 to 14 microg/ml), by exposure to aqueous MS. Most treated oocysts failed to develop beyond early stages of sporulation. To determine the effect of MS on infectivity, isolated oocysts of E. tenella , Eimeria acervulina , and E. maxima were exposed for 24 hr to aqueous concentrations of MS ranging from 0 to 1,000 microg/ml. Treated oocysts were inoculated into chickens, and parameters of coccidiosis infection were compared to chickens inoculated with equal numbers of untreated oocysts. In a dose-related manner, MS significantly reduced the infectivity of oocysts with maximum effect observed at a dose of 300 microg/ml. When a mixture of oocysts containing 3 coccidian species was exposed to 300 microg/ml MS, from 0 to 24 hr, infectivity of oocysts was significantly reduced after a minimum of 12 hr of exposure. Treatment of aqueous slurries of litter samples obtained from commercial poultry houses, with 300 microg/ml MS for 24 hr, prevented the sporulation of eimerian oocysts in the litter samples relative to untreated control samples. The results indicate that MS could be used to reduce coccidial contamination of poultry litter.

Association of target organ damage with 24-hour systolic and diastolic blood pressure levels and hypertension subtypes in untreated Chinese.

PubMed

Wei, Fang-Fei; Li, Yan; Zhang, Lu; Xu, Ting-Yan; Ding, Feng-Hua; Staessen, Jan A; Wang, Ji-Guang

2014-02-01

The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure <130/<80 mm Hg. Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P≤0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic blood pressure were +3.31/-0.36 g/m(2) (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/-0.05 m/s (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m(2) (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/-0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.

Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice using AAV9 gene therapy.

PubMed

Keeler, Allison M; Conlon, Thomas; Walter, Glenn; Zeng, Huadong; Shaffer, Scott A; Dungtao, Fu; Erger, Kirsten; Cossette, Travis; Tang, Qiushi; Mueller, Christian; Flotte, Terence R

2012-06-01

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 × 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids in treated animals. Correction was not observed in liver tissue extracts, but cardiac muscle extracts showed significant reduction of long-chain metabolites. Disease-specific phenotypes were characterized, including thermoregulation and maintenance of euglycemia after a fasting cold challenge. Internal body temperatures of untreated VLCAD(-/-) mice dropped below 20 °C and the mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated VLCAD(-/-) mice and the wild-type controls maintained body temperatures. rAAV9-treated VLCAD(-/-) mice maintained euglycemia, whereas untreated VLCAD(-/-) mice suffered hypoglycemia following a fasting cold challenge. These promising results suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in humans.

Boldenone, testosterone and 1,4-androstadiene-3,17-dione determination in faeces from horses, untreated and after administration of androsta-1,4-diene-3,17-dione (boldione).

PubMed

Popot, M A; Boyer, S; Menaut, L; Garcia, P; Bonnaire, Y; Lesage, D

2008-06-01

Faeces, which could be a potential alternative medium for doping control, have been used for the detection of 1,4-androstadiene-3,17-dione administration to the horse. Semi-quantitative analyses of 1,4-androstadiene-3,17-dione, testosterone, 17alpha- and 17beta-boldenone have been conducted in pre- and post-administration faeces, and in controls (untreated stallions, geldings and mares). Sample preparation comprised diethyl ether extraction, lipid removal, HPLC purification and derivatisation. 1,4-Androstadiene-3,17-dione, testosterone, 17alpha- and 17beta-boldenone were analysed by GC-EI/MS/MS. Quantitative limits of detection were 0.1 ng/g for 1,4-androstadiene-3,17-dione, and 0.025 ng/g for testosterone, 17alpha- and 17beta-testosterone. In post-administration samples from geldings and mares, peak levels of 1,4-androstadiene-3,17-dione, 17alpha-, 17beta-boldenone and testosterone were attained 24 h after administration. In untreated geldings and mares (in di- or anoestrus), 17alpha- and 17beta-boldenone and testosterone were not detected. Faeces from females in oestrus had detectable levels of boldenone isomers and testosterone. 1,4-Androstadiene-3,17-dione was undetectable in faeces collected from untreated horses, but the presence of this androgen was recently reported in faeces from untreated swine and it would therefore be advisable to check for its possible presence in a larger number of individual faecal samples. Copyright (c) 2008 John Wiley & Sons, Ltd.

Untreated head and neck cancer in Korea: a national cohort study.

PubMed

Choi, Hyo Geun; Park, Bumjung; Ahn, Soon-Hyun

2017-03-01

Few studies have analyzed the survival of patients with untreated head and neck cancer. The objective of this study is to assess the survival rates of untreated head and neck cancer patients and to determine why the patients were not treated. Using data from a national patient sample cohort (1,025,340 cases) from the Korean Health Insurance Review and Assessment Service, 605 patients with diagnoses of head and neck cancer (lip and oral cavity, oropharynx, hypopharynx, and laryngeal cancer) between 2003 and 2013 were evaluated. Cox proportional hazards modeling and multiple logistic regression analysis were performed. Of the considered cases of head and neck cancer, 32.2% were untreated. The median survival rate of untreated groups was 9 months. The untreated group showed poorer survival than the treatment groups. Old age [adjusted odds ratio (AOR) = 1.37, 95% confidence internal (CI) 1.25-1.49, P < 0.001] and low income (AOR = 0.94, 95% CI 0.89-1.00, P = 0.028) were related to not receiving treatment. Many head and neck cancers go untreated. Clinicians should focus on untreated patients and seek to understand the reasons for their lack of treatment.

Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases.

PubMed

Mehta, Gautam U; Malekzadeh, Parisa; Shelton, Thomas; White, Donald E; Butman, John A; Yang, James C; Kammula, Udai S; Goff, Stephanie L; Rosenberg, Steven A; Sherry, Richard M

2018-06-01

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed. Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. Intracranial objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%, respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site of initial tumor progression (61%) in patients with untreated brain metastases. Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease. Melanoma brain metastases likely require local therapy despite the systemic effect of ACT.

Oxaliplatin in patients with metastatic colorectal cancer: efficacy and pharmacokinetics parameters.

PubMed

Burz, C; Berindan-Neagoe, I; Balacescu, O; Todor, N; Pelau, D; Floares, C; Kacso, G; Tanaselia, C; Ursu, M; Vlase, L; Leucuta, S E; Cristea, V; Irimie, A

2010-01-01

The aim of this study was to investigate the efficiency of the FOLFOX-4 regimen and to evaluate the pharmacokinetics of oxaliplatin in untreated patients with metastatic colorectal cancer. 43 patients were enrolled in the study. Patients received oxaliplatin 85 mg/m(2) as 2-h i.v. infusion, on day 1, and bolus 5-fluorouracil (5FU) 400 mg/m(2) plus leucovorin (LV) 200 mg/m(2) followed by 5FU 600 mg/m(2) as 22-h infusion on day 1 and 2, every 2 weeks. The pharmacokinetics of oxaliplatin evaluated in 4 patients was performed in blood, plasma and ultrafiltered plasma (UFT) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The overall response rate and the median time to progression (TTP) were 53.49% and 7.1 months, respectively. Grade 3-4 toxic effects were observed in 11 (25.5%) patients. Grade 3 neuropathy was observed in 13.95% of the cases. In univariate analysis only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was correlated with response. No correlation was found between grade 3-4 adverse events and the patient characteristics. The area under the time-concentration curve (AUC) in UFT was 4.8 + or - 0.72 standard deviation (SD) microg h/ml and the total clearance 30.17 + or - 7.75 l/min. The values for volume of distribution and the maximum concentration were 567 + or - 20 liters and 0.38 + or - 0.17 ug/ml, respectively. FOLFOX-4 was an effective regimen with good tolerability in previously untreated metastatic colorectal cancer patients. The pharmacokinetics of oxaliplatin was triphasic with a short initial distribution phase and a long terminal elimination phase.

[Vasovagal syncope and increased baroreceptor activity: evidence for increased sensibility of the baroreflex and its rapid reversal with acute administration of metoprolol].

PubMed

Pucciarelli, G; De Vecchis, R; Ebraio, F; Corigliano, G G

1997-07-01

In 17 patients suffering from recurrent episodes of vasovagal syncope as well as in 21 healthy subjects without clinical episodes of presyncope or syncope, we evaluated the reflex decrease in heart rate evoked by the phenilephrine test. In the syncopal patients, the measurements were taken 4-12 hours after the clinical appearance of syncope. We divided the syncopal patients as follows: 9 patients, undergoing pharmacological treatment, and 8 untreated patients (drug free arm). In the pharmacological arm of the study, an alternate, randomized administration of metoprolol (150 mg twice daily for 2 days) and verapamil (80 mg every 6 hours for 2 days) was provided. Therefore, in the pharmacological arm as well as in drug free patients, we tested again the baroreflex sensitivity, by means of iv phenilephrine bolus, 3 and 7 days after the clinical appearance of the syncopal event. The baroreflex sensitivity values were significantly higher in the syncopal group compared to the control group (21 +/- 5 vs 13 +/- 4.5 ms/mm Hg; p < 0.01). Of the two tested drugs, only the metoprolol produced a fast (day 3) decrease in baroreflex sensitivity. On the basis of measurements taken after 7 days, we noted a pattern of widespread reduction in baroreflex sensitivity values, found in both treated and untreated patients. In conclusion, patients with vasovagal syncope exhibited a more pronounced maximal parasympathetic activation compared to the control group. The high baroreflex sensitivity values were soon (day 3) reduced by metoprolol, but not by verapamil therapy; a spontaneous normalization in baroreflex sensitivity values was found 7 days after the clinical episode, regardless of therapy.

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

PubMed

Deniz, Ferhat; Kepez, Alper; Ay, Seyit Ahmet; Ergogan, Okan; Baskoy, Kamil; Guncıkan, Mustafa Nuri; Dogan, Zekeriya; Yonem, Arif

2015-11-01

There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

Impact of seasonality and air pollutants on carotid-femoral pulse wave velocity and wave reflection in hypertensive patients

PubMed Central

Stea, Francesco; Massetti, Luciano; Taddei, Stefano; Ghiadoni, Lorenzo; Modesti, Pietro Amedeo

2017-01-01

Objective The effects of seasonality on blood pressure (BP) and cardiovascular (CV) events are well established, while the influence of seasonality and other environmental factors on arterial stiffness and wave reflection has never been analyzed. This study evaluated whether seasonality (daily number of hours of light) and acute variations in outdoor temperature and air pollutants may affect carotid-femoral pulse wave velocity (PWV) and pressure augmentation. Design and method 731 hypertensive patients (30–88 years, 417 treated) were enrolled in a cross-sectional study during a 5-year period. PWV, central BP, Augmentation Index (AIx) and Augmentation Pressure (AP) were measured in a temperature-controlled (22–24°C) room. Data of the local office of the National Climatic Data Observatory were used to estimate meteorological conditions and air pollutants (PM10, O3, CO, N2O) exposure on the same day. Results PWV (mean value 8.5±1.8 m/s) was related to age (r = 0.467, p<0.001), body mass index (r = 0.132, p<0.001), central systolic (r = 0.414, p<0.001) and diastolic BP (r = 0.093, p = 0.013), daylight hours (r = -0.176, p<0.001), mean outdoor temperature (r = -0.082, p = 0.027), O3 (r = -0.135, p<0.001), CO (r = 0.096, p = 0.012), N2O (r = 0.087, p = 0.022). In multiple linear regression analysis, adjusted for confounders, PWV remained independently associated only with daylight hours (β = -0.170; 95% CI: -0.273 to -0.067, p = 0.001). No significant correlation was found between pressure augmentation and daylight hours, mean temperature or air pollutants. The relationship was stronger in untreated patients and women. Furthermore, a positive, independent association between O3 levels and PWV emerged in untreated patients (β: 0.018; p = 0.029; CI: 0.002 to 0.034) and in women (β: 0.027; p = 0.004; CI: 0.009 to 0.045). Conclusions PWV showed a marked seasonality in hypertensive patients. Environmental O3 levels may acutely reduce arterial stiffness in hypertensive women and in untreated patients. PMID:28231259

Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

ClinicalTrials.gov

2018-03-30

Anaplastic Astrocytoma; Brain Stem Glioma; Childhood Mixed Glioma; Fibrillary Astrocytoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

ClinicalTrials.gov

2017-06-16

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis.

PubMed

Touil, Hanane; Kobert, Antonia; Lebeurrier, Nathalie; Rieger, Aja; Saikali, Philippe; Lambert, Caroline; Fawaz, Lama; Moore, Craig S; Prat, Alexandre; Gommerman, Jennifer; Antel, Jack P; Itoyama, Yasuto; Nakashima, Ichiro; Bar-Or, Amit

2018-04-19

The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease. B cells are known to persist in the inflamed MS CNS and are more recently described as concentrated in meningeal immune-cell aggregates, adjacent to the subpial cortical injury which has been associated with progressive disease. How B cells are fostered within the MS CNS and how they may contribute locally to the propagation of CNS-compartmentalized inflammation remain to be elucidated. We considered whether activated human astrocytes might contribute to B cell survival and function through soluble factors. B cells from healthy controls (HC) and untreated MS patients were exposed to primary human astrocytes that were either maintained under basal culture conditions (non-activated) or pre-activated with standard inflammatory signals. B cell exposure to astrocytes included direct co-culture, co-culture in transwells, or exposure to astrocyte-conditioned medium. Following the different exposures, B cell survival and expression of T cell co-stimulatory molecules were assessed by flow cytometry, as was the ability of differentially exposed B cells to induce activation of allogeneic T cells. Secreted factors from both non-activated and activated human astrocytes robustly supported human B cell survival. Soluble products of pre-activated astrocytes also induced B cell upregulation of antigen-presenting cell machinery, and these B cells, in turn, were more efficient activators of T cells. Astrocyte-soluble factors could support survival and activation of B cell subsets implicated in MS, including memory B cells from patients with both relapsing and progressive forms of disease. Our findings point to a potential mechanism whereby activated astrocytes in the inflamed MS CNS not only promote a B cell fostering environment, but also actively support the ability of B cells to contribute to the propagation of CNS-compartmentalized inflammation, now thought to play key roles in progressive disease.

Use of ultra-high-pressure liquid chromatography-quadrupole time-of-flight MS to discover the presence of pesticide metabolites in food samples.

PubMed

Hernández, Félix; Grimalt, Susana; Pozo, Oscar J; Sancho, Juan V

2009-07-01

In this paper we illustrate the use of two different methodologies to investigate the presence of pesticide metabolites in parent pesticide-positive food samples, using ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. First, a common fragmentation pathway between the parent pesticide and its metabolites has been considered to search for metabolites in two positive market samples (imazalil in lemon, chlorpyrifos in grape). Secondly, olive oil samples from field residue trials were used for automated application of comparative software (MetaboLynx), which was used with treated and untreated samples to search for expected and unexpected metabolites of phosmet. One of the main objectives when using these approaches was to avoid the tedious manual searching for potential metabolites within the huge amount of information contained in the total ion chromatogram acquired by TOF MS. The common fragmentation approach applied to TOF MS full-acquisition data, considering an enhanced fragmentation in the collision cell, has allowed the discovery of two metabolites of imazalil (1-[2-(2,4-dichlorophenyl)-2-hydroxyethyl]-1H-imidazole and 1-[2-(2,4-dichlorophenyl)-2-oxoethyl]-1H-imidazole) in a lemon positive sample, as well as another two metabolites of chlorpyrifos (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) in a grape positive sample. Moreover, MetaboLynx application to TOF MS data, without promoting fragmentation, from treated and untreated olive oil samples has been helpful in detecting the metabolite phosmet-oxon. In both strategies, every metabolite detected by TOF MS was confirmed using QTOF and/or triple quadrupole instruments. Accurate masses given by TOF MS together with the valuable information on product ions given by QTOF MS/MS experiments were crucial for the unambiguous identification of metabolites.

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ClinicalTrials.gov

2018-06-19

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Brain Stem Glioma; Childhood Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Gliosarcoma

Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure

PubMed Central

Hintsala, Heidi E.; Kiviniemi, Antti M.; Tulppo, Mikko P.; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J. K.; Ikäheimo, Tiina M.

2016-01-01

Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55–65 years) who underwent a whole-body cold exposure (−10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04–0.15 Hz) and high frequency (0.15–0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg2, compared with hypertensive group [0 (−13, 20) mmHg2]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension. PMID:27313543

A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi).

PubMed

Taylor, Andrew J; Paris, Daniel H; Newton, Paul N

2015-01-01

Scrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease's non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes. A literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0-70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9-19)). Results show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies.

A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

PubMed Central

Earl, H. M.; Rudd, R. M.; Spiro, S. G.; Ash, C. M.; James, L. E.; Law, C. S.; Tobias, J. S.; Harper, P. G.; Geddes, D. M.; Eraut, D.

1991-01-01

In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy. PMID:1654983

Succinylacetone as Primary Marker to Detect Tyrosinemia Type I in Newborns and its Measurement by Newborn Screening Programs

PubMed Central

De Jesús, Víctor R.; Adam, Barbara W.; Mandel, Daniel; Cuthbert, Carla D.; Matern, Dietrich

2015-01-01

Tyrosinemia type I (TYR I) is caused by autosomal recessive fumarylacetoacetate hydrolase deficiency and is characterized by development of severe liver disease in infancy and neurologic crises. If left untreated, most patients die of liver failure in the first years of life. Intervention with medication is effective when initiated during the first month of life. This improvement in the treatment of TYR I patients influenced the decision to include TYR I in the US Secretary of the Department of Health and Human Services’ (HHS) Recommended Uniform Screening Panel. However, while tyrosine is routinely measured in newborn screening (NBS) by tandem mass spectrometry (MS/MS), elevated tyrosine levels are not specific to TYR I. To improve the specificity of NBS for TYR I, several assays were developed to measure succinylacetone (SUAC) in dried blood spots (DBS). SUAC is a pathognomonic marker of TYR I, and its detection by NBS MS/MS is possible. This review of the current status of NBS for TYR I in the US is the result of discussions at the HHS Secretary’s (Discretionary) Advisory Committee on Heritable Disorders in Newborns and Children about the inconsistent implementation of effective NBS for TYR I in the US. We sought to understand the different TYR I screening practices in US NBS programs. Results indicate that 50 out of 51 NBS programs in the US screen for TYR I, and a successful SUAC performance evaluation scheme is available from the Centers for Disease Control and Prevention. Programmatic and methodological barriers were identified that prevent widespread adoption of SUAC measurements in NBS laboratories. However, since SUAC detection is currently the best approach to NBS for TYR I, a further delay of the addition of SUAC measurement into NBS procedures is discouraged. SUAC measurement should improve both the false positive and false negative rate in NBS for TYR I thereby yielding the desired benefits for affected patients at no expense to the overall population served. PMID:25066104

Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis.

PubMed

Tortorella, C; Direnzo, V; Taurisano, P; Romano, R; Ruggieri, M; Zoccolella, S; Mastrapasqua, M; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

2015-04-01

Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected). Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index. Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS. © The Author(s), 2014.

Spatial investigation of the elemental distribution in Wilson's disease liver after d-penicillamine treatment by LA-ICP-MS.

PubMed

Hachmöller, Oliver; Zibert, Andree; Zischka, Hans; Sperling, Michael; Groba, Sara Reinartz; Grünewald, Inga; Wardelmann, Eva; Schmidt, Hartmut H-J; Karst, Uwe

2017-12-01

At present, the copper chelator d-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10μm) laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method was applied. Untreated LPP -/- rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA-ICP-MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Multicenter performance evaluation of a second generation cortisol assay.

PubMed

Vogeser, Michael; Kratzsch, Jürgen; Ju Bae, Yoon; Bruegel, Mathias; Ceglarek, Uta; Fiers, Tom; Gaudl, Alexander; Kurka, Hedwig; Milczynski, Christoph; Prat Knoll, Cristina; Suhr, Anna C; Teupser, Daniel; Zahn, Ingrid; Ostlund, Richard E

2017-05-01

Untreated disorders of the adrenocortical system, such as Cushing's or Addison's disease, can be fatal, and accurate quantification of a patient's cortisol levels is vital for diagnosis. The objective of this study was to assess the analytical performance of a new fully-automated Elecsys® Cortisol II assay (second generation) to measure cortisol levels in serum and saliva. Four European investigational sites assessed the intermediate precision and reproducibility of the Cortisol II assay (Roche Diagnostics) under routine conditions. Method comparisons of the Cortisol II assay vs. liquid chromatography-tandem mass spectrometry (LC-MS/MS), the gold standard for cortisol measurement, were performed. Cortisol reference ranges from three US sites were determined using samples from self-reported healthy individuals. The coefficients of variation (CVs) for repeatability, intermediate precision, and reproducibility for serum samples were ≤2.6%, ≤5.8%, and ≤9.5%, respectively, and for saliva were ≤4.4% and ≤10.9%, and ≤11.4%, respectively. Agreement between the Cortisol II assay and LC-MS/MS in serum samples was close, with a slope of 1.02 and an intercept of 4.473 nmol/L. Reference range samples were collected from healthy individuals (n=300) and serum morning cortisol concentrations (5-95th percentile) were 166.1-507 nmol/L and afternoon concentrations were 73.8-291 nmol/L. Morning, afternoon, and midnight saliva concentrations (95th percentile) were 20.3, 6.94, and 7.56 nmol/L, respectively. The Cortisol II assay had good precision over the entire measuring range and had excellent agreement with LC-MS/MS. This test was found suitable for routine diagnostic application and will be valuable for the diagnosis of adrenocortical diseases.

Causes of anorexia in untreated hyperthyroidism: a prospective study

PubMed Central

Dai, W.; Meng, X.

2000-01-01

Seventeen consecutive patients (mean (SD) 46 (11) years) with untreated hyperthyroidism and anorexia and 29 patients (35 (9) years) with untreated hyperthyroidism without anorexia were studied. The study was conducted at the thyroid clinic of the PUMC Hospital, Beijing, China from March to August 1997. The patients' ages, serum free calcium, liver function and emotional state, specifically the level of anxiety (using the self anxiety scale, Chinese version), were compared before and/or after antithyroid drug treatment in the two groups. This prospective study suggested that the causes of anorexia in untreated hyperthyroidism are complicated. Older age, abnormal liver function, and the level of anxiety are significantly related to anorexia in untreated hyperthyroidism, but hypercalcaemia was not confirmed to be related to anorexia in the study.


Keywords: hypercalcaemia; hyperthyroidism; anorexia; anxiety PMID:10775283

Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.

PubMed

Anesten, Birgitta; Yilmaz, Aylin; Hagberg, Lars; Zetterberg, Henrik; Nilsson, Staffan; Brew, Bruce J; Fuchs, Dietmar; Price, Richard W; Gisslén, Magnus

2016-12-01

Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined. BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART). The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis. BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.

Peripheral lymphocyte subsets in chronic hepatitis C: Effects of 12 weeks of antiviral treatment with interferon-alpha plus ribavirin.

PubMed

Oliveira, Isabela S; Carvalho, Lucas P; Schinoni, Maria Isabel; Paraná, Raymundo; Atta, Ajax M; Atta, Maria Luiza B Sousa

2016-02-01

Chronic infection with hepatitis C virus (HCV) causes a quantitative and functional alteration in innate and adaptative immunity. In the present work, we determined by flow-cytometry the profile of blood lymphocyte of untreated HCV patients and in subjects of this group that achieved or not an early virologic response at 12-weeks of treatment with interferon-α plus ribavirin. Twenty-six untreated HCV patients and 20 control healthy individuals were enrolled in the study. Untreated HCV patients had a higher proportion of B cell and a lower proportion of CD8(+) T cell and NK cells than healthy individuals did, but the proportions of CD4(+) T cells and Treg cells (CD4(+)CD25(+)Foxp3(+)) were similar in these patients and controls. Untreated HCV patients presenting cryoglobulinemia had a lower proportion of Treg cells and a lower Treg/NK cell ratio when compared with those without cryoglobulins. Nineteen out of 26 untreated HCV patients remained in the study and were treated with Interferon-α plus ribavirin. At 12-weeks of treatment, 10 of them achieved early virologic response (EVR), whereas 9 were non-responders (NR). EVR patients differed from NR patients in the increase of their proportion of NK cells at 12 weeks of treatment. In conclusion, untreated HCV patients exhibit an altered profile of blood lymphocyte subsets, including a reduction in the proportion of CD4(+)CD25(+)FoxP3(+)T regulatory cells in patients that present cryoglobulinemia. An early virological response at 12-weeks of treatment with IFN-α plus ribavirin seems to be associated a significant improvement in the proportion of NK cells of HCV treated patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System

ClinicalTrials.gov

2018-05-16

Medulloblastoma; Pineoblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified; Untreated Childhood Medulloblastoma; Untreated Childhood Pineoblastoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study.

PubMed

Child, Christopher J; Conroy, Daniel; Zimmermann, Alan G; Woodmansee, Whitney W; Erfurth, Eva Marie; Robison, Leslie L

2015-06-01

Speculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP). Incident neoplasms during HypoCCS were evaluated in 8418 GH-treated vs 1268 untreated patients for primary malignancies, 3668 GH-treated vs 720 untreated patients with PA history, and 956 GH-treated vs 102 untreated patients with CP history. Using population cancer rates, standardised incidence ratios (SIRs) were calculated for all primary cancers, breast, prostate, and colorectal cancers. Neoplasm rates in GH-treated vs untreated patients were analysed after propensity score adjustment of baseline treatment group imbalances. During mean follow-up of 4.8 years, 225 primary cancers were identified in GH-treated patients, with SIR of 0.82 (95% CI 0.71-0.93). SIRs (95% CI) for GH-treated patients were 0.59 (0.36-0.90) for breast, 0.80 (0.57-1.10) for prostate, and 0.62 (0.38-0.96) for colorectal cancers. Cancer risk was not statistically different between GH-treated and untreated patients (relative risk (RR)=1.00 (95% CI 0.70-1.41), P=0.98). Adjusted RR for recurrence was 0.91 (0.68-1.22), P=0.53 for PA and 1.32 (0.53-3.31), P=0.55 for CP. There was no increased risk for all-site cancers: breast, prostate or colorectal primary cancers in GH-treated patients during HypoCCS. GH treatment did not increase the risk of PA and CP recurrences. © 2015 European Society of Endocrinology.

Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

PubMed

Jessen Krut, Jan; Mellberg, Tomas; Price, Richard W; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.

Determination of naturally occurring formaldehyde levels in sap and wood tissue of maple trees using gas chromatgraphy/mass spectrometry.

PubMed

Lagacé, Luc; Gaudy, Réjean; Perez-Locas, Carolina; Sadiki, Mustapha

2012-01-01

The occurrence of formaldehyde in sap and wood tissue of treated and untreated maple sugar trees was investigated using GC/MS. Samples were collected at different periods of the 2009 season and at different locations in Quebec, Canada. The natural concentration of formaldehyde found in untreated samples varied according to periods and locations and ranged from below the LOQ to 1.82 mg/kg for sap samples and from 2.39 to 8.92 mg/kg of fresh tissue for wood samples. Late season samples tended to have higher concentrations of formaldehyde. Samples of sap and wood tissue from tapholes treated with solutions of formaldehyde showed increased concentrations of formaldehyde for many days after treatment and were clearly distinct from untreated samples. These results will be useful to elaborate new inspection procedures for sugarbushes to control the illegal use of formaldehyde.

Neuroprotective effects of placenta-derived mesenchymal stromal cells in a rat model of experimental autoimmune encephalomyelitis.

PubMed

Selim, Assmaa O; Selim, Sally A; Shalaby, Sally M; Mosaad, Hala; Saber, Taisir

2016-09-01

Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stromal cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS. A preparation of MSCs derived from full-term human placenta (PDMSCs) is a new approach in the treatment of patients with MS. This study aimed to rule out the possible therapy by PDMSCs in experimental autoimmune encephalomyelitis (EAE), a rat model of MS. Thirty-five female Wistar rats were classified into the following groups: I, control; II, EAE untreated; III and IV, EAE treated with phosphate-buffered saline (PBS) at 9 and 16 days post-immunization (dpi), respectively; V and VI, EAE treated with PDMSCs at 9 and 16 dpi, respectively. Intravenous administration of PDMSCs at 9 or 16 dpi significantly ameliorated the disease course, decreasing brain inflammation and degenerating neurons. A reduction of axonal damage as well as an increase of oligodendrocyte precursors were recorded. Moreover, there was an engraftment of the PDMSCs into the brain tissue. Human brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin 3 (NTF3) were significantly expressed in brains of rats treated by PDMSCs. Human PDMSCs have demonstrated striking therapeutic effects when delivered at the onset or at the peak of the disease. PDMSCs have direct neurotrophic support after their engraftment within the lesion through expression of the neurotrophins. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Blood–brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV

PubMed Central

Yilmaz, Aylin; Hagberg, Lars; Zetterberg, Henrik; Nilsson, Staffan; Brew, Bruce J.; Fuchs, Dietmar; Price, Richard W.; Gisslén, Magnus

2016-01-01

Objective: Although blood–brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined. Methods: BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART). Results: The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis. Conclusions: BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals. PMID:27868081

Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

PubMed

Ito, Shoko; Fujiwara, Shin-Ichiro; Mashima, Kiyomi; Umino, Kento; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

2017-05-01

The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

Health services determinants of the duration of untreated psychosis among African-American first-episode patients.

PubMed

Compton, Michael T; Ramsay, Claire E; Shim, Ruth S; Goulding, Sandra M; Gordon, Tynessa L; Weiss, Paul S; Druss, Benjamin G

2009-11-01

The duration of untreated psychosis is associated with poor outcomes in multiple domains in the early course of nonaffective psychotic disorders, although relatively little is known about determinants of this critical period, particularly health services-level determinants. This study examined three hypothesized predictors of duration of untreated psychosis (lack of insurance, financial problems, and broader barriers) among urban, socioeconomically disadvantaged African Americans, while controlling for the effects of three patient-level predictors (mode of onset of psychosis, living with family versus alone or with others before hospitalization, and living above versus below the federally defined poverty level). Analyses included data from 42 patient-family member dyads from a larger sample of 109 patients with a first episode of nonaffective psychosis. The duration of untreated psychosis and all other variables were measured in a rigorous, standardized fashion in a study designed specifically to examine determinants of treatment delay. Survival analyses and Cox regression assessed the effects of the independent predictors on time from onset of psychosis to hospital admission for initial evaluation and treatment. The median duration of untreated psychosis was 24.5 weeks. When the analyses controlled for the three patient-level covariates, patients without health insurance, with financial problems, or with barriers to seeking help had a significantly longer duration of untreated psychosis. Health services-related factors, such as lack of insurance, are predictive of longer treatment delay. Efforts to eliminate uninsurance and underinsurance, as well as minimize barriers to treatment, would be beneficial for improving the prognosis of young patients with emerging nonaffective psychotic disorders.

Low-Level detections of halogenated volatile organic compounds in groundwater: Use in vulnerability assessments

USGS Publications Warehouse

Plummer, Niel; Busenberg, E.; Eberts, S.M.; Bexfield, L.M.; Brown, C.J.; Fahlquist, L.S.; Katz, B.G.; Landon, M.K.

2008-01-01

Concentrations of halogenated volatile organic compounds (VOCs) were determined by gas chromatography (GC) with an electron-capture detector (GC-ECD) and by gas chromatography with mass spectrometry (GC-MS) in 109 groundwater samples from five study areas in the United States. In each case, the untreated water sample was used for drinking-water purposes or was from a monitoring well in an area near a drinking-water source. The minimum detection levels (MDLs) for 25 VOCs that were identified in GC-ECD chromatograms, typically, were two to more than four orders of magnitude below the GC-MS MDLs. At least six halogenated VOCs were detected in all of the water samples analyzed by GC-ECD, although one or more VOCs were detected in only 43% of the water samples analyzed by GC-MS. In nearly all of the samples, VOC concentrations were very low and presented no known health risk. Most of the low-level VOC detections indicated post-1940s recharge, or mixtures of recharge that contained a fraction of post-1940s water. Concentrations of selected halogenated VOCs in groundwater from natural and anthropogenic atmospheric sources were estimated and used to recognize water samples that are being impacted by nonatmospheric sources. A classification is presented to perform vulnerability assessments at the scale of individual wells using the number of halogenated VOC detections and total dissolved VOC concentrations in samples of untreated drinking water. The low-level VOC detections are useful in vulnerability assessments, particularly for samples in which no VOCs are detected by GC-MS analysis.

Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod.

PubMed

Nakhaei-Nejad, Maryam; Barilla, David; Lee, Chieh-Hsin; Blevins, Gregg; Giuliani, Fabrizio

2018-03-01

Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia. All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N. This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis.

Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod

PubMed Central

Nakhaei-Nejad, Maryam; Barilla, David; Lee, Chieh-Hsin; Blevins, Gregg

2017-01-01

Objective: Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Methods: Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia. Results: All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N. Conclusions: This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis. PMID:29296636

Glucocorticoid receptors in bronchial epithelial cells in asthma.

PubMed

Vachier, I; Chiappara, G; Vignola, A M; Gagliardo, R; Altieri, E; Térouanne, B; Vic, P; Bousquet, J; Godard, P; Chanez, P

1998-09-01

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Excess Mortality in Treated and Untreated Hyperthyroidism Is Related to Cumulative Periods of Low Serum TSH.

PubMed

Lillevang-Johansen, Mads; Abrahamsen, Bo; Jørgensen, Henrik Løvendahl; Brix, Thomas Heiberg; Hegedüs, Laszlo

2017-07-01

Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of antithyroid treatment on mortality, especially in subclinical hyperthyroidism, remains unclarified. We investigated the association between hyperthyroidism and mortality in both treated and untreated hyperthyroid individuals. Register-based cohort study of 235,547 individuals who had at least one serum thyroid-stimulating hormone (TSH) measurement in the period 1995 to 2011 (7.3 years median follow-up). Hyperthyroidism was defined as at least two measurements of low serum TSH. Mortality rates for treated and untreated hyperthyroid subjects compared with euthyroid controls were calculated using multivariate Cox regression analyses, controlling for age, sex, and comorbidities. Cumulative periods of decreased serum TSH were analyzed as a time-dependent covariate. Hazard ratio (HR) for mortality was increased in untreated [1.23; 95% confidence interval (CI), 1.12 to 1.37; P < 0.001], but not in treated, hyperthyroid patients. When including cumulative periods of TSH in the Cox regression analyses, HR for mortality per every 6 months of decreased TSH was 1.11 (95% CI, 1.09 to 1.13; P < 0.0001) in untreated hyperthyroid patients (n = 1137) and 1.13 (95% CI, 1.11 to 1.15; P < 0.0001) in treated patients (n = 1656). This corresponds to a 184% and 239% increase in mortality after 5 years of decreased TSH in untreated and treated hyperthyroidism, respectively. Mortality is increased in hyperthyroidism. Cumulative periods of decreased TSH increased mortality in both treated and untreated hyperthyroidism, implying that excess mortality may not be driven by lack of therapy, but rather inability to keep patients euthyroid. Meticulous follow-up during treatment to maintain biochemical euthyroidism may be warranted. Copyright © 2017 by the Endocrine Society

Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

ClinicalTrials.gov

2017-07-18

Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

PubMed Central

Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use. PMID:24523921

Alterations in Pain Responses in Treated and Untreated Patients with Restless Legs Syndrome: Associations with Sleep Disruption

PubMed Central

Edwards, Robert R; Quartana, Phillip J.; Allen, Richard P; Greenbaum, Seth; Earley, Christopher J; Smith, Michael T

2011-01-01

Objective There has been recent interest in characterizing potential abnormalities of pain processing in patients with sleep disorders such as Restless Legs Syndrome (RLS). The aim of this study was to evaluate psychophysical responses to noxious heat and pressure stimuli in both treated and untreated RLS patients, compared to matched controls. Methods This study is a cross-sectional group comparison of RLS patients with matched controls. A total of 31 patients (15 treated, 16 untreated) with a confirmed diagnosis of RLS were compared to 18 controls with no history of RLS or related sleep disorders. Results RLS patients (both treated and untreated) demonstrated reduced pain thresholds and reported greater clinical pain relative to controls. Moreover, RLS patients demonstrated enhanced temporal summation of heat pain (p< .05), which may reflect aberrant central nervous system facilitation of pain transmission. Both treated and untreated RLS patients reported disrupted sleep relative to controls, and mediation analyses suggested that the reduced pain thresholds in RLS were attributable to sleep disturbance. However, the effect of RLS on the magnitude of temporal summation of heat pain was independent of sleep disturbance. Conclusions These findings suggest that central nervous system pain processing may be amplified in RLS, perhaps partially as a consequence of sleep disruption. RLS patients, even those whose symptoms are managed pharmacologically, may be at elevated long-term risk for the development or maintenance of persistent pain conditions. Further studies in larger samples could help to improve the prospects for pain management in RLS patients. PMID:21570347

The AMIGO Clinical Study: Attrition Rates Among Military Beneficiaries Undergoing Intensive Group Outpatient Pre-Diabetes Care

DTIC Science & Technology

2013-11-11

or lactating  Patients with untreated hypothyroidism or previously diagnosed Cushing’s syndrome  Patients currently taking metformin or...screening  Age គ years old  Women who are currently (or within past 6-weeks) pregnant or lactating  Patients with untreated hypothyroidism or

Label-free LC-MS analysis of HER2+ breast cancer cell line response to HER2 inhibitor treatment.

PubMed

Di Luca, Alessio; Henry, Michael; Meleady, Paula; O'Connor, Robert

2015-08-04

Human epidermal growth-factor receptor (HER)-2 is overexpressed in 25 % of breast-cancers and is associated with an aggressive form of the disease with significantly shortened disease free and overall survival. In recent years, the use of HER2-targeted therapies, monoclonal-antibodies and small molecule tyrosine-kinase inhibitors has significantly improved the clinical outcome for HER2-positive breast-cancer patients. However, only a fraction of HER2-amplified patients will respond to therapy and the use of these treatments is often limited by tumour drug insensitivity or resistance and drug toxicities. Currently there is no way to identify likely responders or rational combinations with the potential to improve HER2-focussed treatment outcome. In order to further understand the molecular mechanisms of treatment-response with HER2-inhibitors, we used a highly-optimised and reproducible quantitative label-free LC-MS strategy to characterize the proteomes of HER2-overexpressing breast-cancer cell-lines (SKBR3, BT474 and HCC1954) in response to drug-treatment with HER2-inhibitors (lapatinib, neratinib or afatinib). Following 12 ours treatment with different HER2-inhibitors in the BT474 cell-line; compared to the untreated cells, 16 proteins changed significantly in abundance following lapatinib treatment (1 μM), 21 proteins changed significantly following neratinib treatment (150 nM) and 38 proteins changed significantly following afatinib treatment (150 nM). Whereas following 24 hours treatment with neratinib (200 nM) 46 proteins changed significantly in abundance in the HCC1954 cell-line and 23 proteins in the SKBR3 cell-line compared to the untreated cells. Analysing the data we found that, proteins like trifunctional-enzyme subunit-alpha, mitochondrial; heterogeneous nuclear ribonucleoprotein-R and lamina-associated polypeptide 2, isoform alpha were up-regulated whereas heat shock cognate 71 kDa protein was down-regulated in 3 or more comparisons. This proteomic study highlights several proteins that are closely associated with early HER2-inhibitor response and will provide a valuable resource for further investigation of ways to improve efficacy of breast-cancer treatment.

Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry.

PubMed

Almeida, Antonio M; Bedrosian, Camille; Cole, Alexander; Muus, Petra; Schrezenmeier, Hubert; Szer, Jeff; Rosse, Wendell F

2017-09-01

Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA). Three populations from the International PNH Registry were studied: (i) non-transfused, untreated; (ii) non-transfused, eculizumab-treated and (iii) transfused, eculizumab-treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non-transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy (FACIT)-Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 Fatigue scores from baseline to last available assessment. The study population included (i) 144 non-transfused, untreated patients; (ii) 45 non-transfused, eculizumab-treated patients and (iii) 105 transfused, eculizumab-treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non-transfused, treated patients had greater absolute reduction in LDH (-1318.8 vs -39.4; P < 0.001) and greater percentage reduction in LDH (-69.9 vs -1.6%; P < 0.001). Clinically meaningful improvements in FACIT-Fatigue (73.7 vs 24.6%, respectively) and in EORTC-QLQ-C30 (84.2 vs 33.3%, respectively) were observed. Non-transfused, treated patients with HDA had significantly reduced LDH levels (P < 0.001) and clinically meaningful improvements in FACIT-Fatigue (P = 0.003) and EORTC-QLQ-C30 (P = 0.020) versus untreated patients. Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history. © 2017 Royal Australasian College of Physicians.

77 FR 34064 - Notice of Lodging of the Consent Decree under the Clean Water Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... Permit; (3) Arecibo violates its Small MS4 General Permit by discharging sewage and sewage sludge not...; and failing to properly operate and maintain its system; and (4) discharges untreated sewage from its... public has or may have come into contact with the sewage. The proposed Consent Decree addresses the...

Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue.

PubMed

Gottschall, Heike; Schmöcker, Christoph; Hartmann, Dirk; Rohwer, Nadine; Rund, Katharina; Kutzner, Laura; Nolte, Fabian; Ostermann, Annika I; Schebb, Nils Helge; Weylandt, Karsten H

2018-05-01

Eicosanoids, including prostaglandins (PGs) and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid, particularly PGE 2 , formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n = 27) had significantly lower tissue eicosanoid levels of most COX-derived metabolites than untreated individuals (n = 31). In contrast, COX-derived lipid metabolites tended to be higher in patients with statin treatment (n = 7) as compared with those not receiving statins (n = 24). This effect was not discernible in subjects treated with ASA and statins (n = 11): Individuals treated with both drugs showed a pronounced suppression of COX-derived eicosanoids in colon tissue, even compared with subjects treated with ASA alone. Our data from a routine clinical setting support the hypothesis that ASA and statins could inhibit CRC development via lipid mediator modification. Further studies should directly investigate the effect of dual ASA and statin treatment on colon tumorigenesis in humans. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

Health Services Determinants of the Duration of Untreated Psychosis Among African-American First-Episode Patients

PubMed Central

Compton, Michael T.; Ramsay, Claire E.; Shim, Ruth S.; Goulding, Sandra M.; Gordon, Tynessa L.; Weiss, Paul S.; Druss, Benjamin G.

2018-01-01

Objective The duration of untreated psychosis is associated with poor outcomes in multiple domains in the early course of nonaffective psychotic disorders, although relatively little is known about determinants of this critical period, particularly health services–level determinants. This study examined three hypothesized predictors of duration of untreated psychosis (lack of insurance, financial problems, and broader barriers) among urban, socioeconomically disadvantaged African Americans, while controlling for the effects of three patient-level predictors (mode of onset of psychosis, living with family versus alone or with others before hospitalization, and living above versus below the federally defined poverty level). Methods Analyses included data from 42 patient–family member dyads from a larger sample of 109 patients with a first episode of nonaffective psychosis. The duration of untreated psychosis and all other variables were measured in a rigorous, standardized fashion in a study designed specifically to examine determinants of treatment delay. Survival analyses and Cox regression assessed the effects of the independent predictors on time from onset of psychosis to hospital admission for initial evaluation and treatment. Results The median duration of untreated psychosis was 24.5 weeks. When the analyses controlled for the three patient-level covariates, patients without health insurance, with financial problems, or with barriers to seeking help had a significantly longer duration of untreated psychosis. Conclusions Health services–related factors, such as lack of insurance, are predictive of longer treatment delay. Efforts to eliminate uninsurance and underinsurance, as well as minimize barriers to treatment, would be beneficial for improving the prognosis of young patients with emerging nonaffective psychotic disorders. (Psychiatric Services 60:1489–1494, 2009) PMID:19880467

Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

PubMed Central

Schuurhuis, J M; Span, L F R; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

2016-01-01

Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. Methods: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. Results: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. Conclusions: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID:27002936

Troxerutin abrogates mitochondrial oxidative stress and myocardial apoptosis in mice fed calorie-rich diet.

PubMed

Geetha, Rajagopalan; Sathiya Priya, Chandrasekaran; Anuradha, Carani Venkatraman

2017-12-25

Mitochondrial oxidative stress plays a major role in the pathogenesis of myocardial apoptosis in metabolic syndrome (MS) patients. In this study, we investigated the effect of troxerutin (TX), an antioxidant on mitochondrial oxidative stress and apoptotic markers in heart of mice fed fat and fructose-rich diet. Adult male Mus musculus mice were fed either control diet or high fat, high fructose diet (HFFD) for 60 days to induce MS. Mice from each dietary group were divided into two on the 16th day and were either treated or untreated with TX (150 mg/kg bw, p.o) for the next 45 days. At the end of the study, mitochondrial reactive oxygen species (ROS) generation, oxidative stress markers, levels of intracellular calcium, cardiolipin content, cytochrome c release and apoptotic markers were examined in the myocardium. HFFD-feeding resulted in diminution of antioxidants and increased ROS production, lipid peroxidation and oxidatively modified adducts of 8-OHG, 4-HNE and 3-NT. Further increase in Ca 2+ levels, low levels of calcium transporters and decrease in cardiolipin content were noted. Changes in the mitochondrial structure were observed by electron microscopy. Furthermore, cytochrome c release, increase in proapoptotic proteins (APAF-1, BAX, caspases-9 and-3) and decrease in antiapoptotic protein (BCL-2) in HFFD-fed mice suggest myocardial apoptosis. These changes were significantly restored by TX supplementation. TX administration effectively attenuated cardiac apoptosis and exerted a protective role by increasing antioxidant potential and by improving mitochondrial function. Thus, TX could be a promising therapeutic candidate for treating cardiac disease in MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of manuka honey on the expression of universal stress protein A in meticillin-resistant Staphylococcus aureus.

PubMed

Jenkins, Rowena; Burton, Neil; Cooper, Rose

2011-04-01

Staphylococcus aureus is an important pathogen that can cause many problems, from impetigo to endocarditis. With its continued resistance to multiple antibiotics, S. aureus remains a serious health threat. Honey has been used to eradicate meticillin-resistant S. aureus (MRSA) strains from wounds, but its mode of action is not yet understood. Proteomics provides a potent group of techniques that can be used to analyse differences in protein expression between untreated bacterial cells and those treated with inhibitory concentrations of manuka honey. In this study, two-dimensional (2D) electrophoresis was combined with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) to determine the identities of proteins whose levels of expression were changed at least two-fold following treatment with manuka honey. Protein extracts were obtained from cells grown in tryptone soy broth (with or without manuka honey) by mechanical disruption and were separated on 2D polyacrylamide gels. A protein was isolated in gels prepared from untreated cell extract that was absent from gels made using honey-treated cell extract. Using MALDI-TOF MS, the protein was identified as universal stress protein A (UspA). Downregulation of this protein was confirmed by real-time polymerase chain reaction (PCR), which showed a 16-fold downregulation in honey-treated cells compared with untreated samples. This protein is involved in the stress stamina response and its downregulation could help to explain the inhibition of MRSA by manuka honey. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Impairment of attention networks in patients with untreated hyperthyroidism.

PubMed

Yuan, Lili; Tian, Yanghua; Zhang, Fangfang; Dai, Fang; Luo, Li; Fan, Jin; Wang, Kai

2014-06-27

Attention disorders are common symptoms in patients with untreated hyperthyroidism. Nevertheless, it is unknown whether they represent a global attention deficit or selective impairment of attention networks. Thirty-seven patients with hyperthyroidism were recruited and underwent the Attention Network Test (ANT), which provided measures of three independent attention networks (alerting, orienting and executive control), before being treated with methimazole. This study demonstrated that patients with untreated hyperthyroidism had significant deficits in the alerting and executive control networks. Interestingly, a significant positive association was also found between T4 level and the value of the executive network in patients with hyperthyroidism. These results suggest that the patients with hyperthyroidism may not just exist a specific impairment of attention networks, and there was some relationship between the level of T4, not T3 or TSH, and the value of the executive control network in patients with hyperthyroidism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

ClinicalTrials.gov

2017-01-30

Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

PubMed

Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

Split-season herbaceous weed control for full-season seedling performance

Treesearch

Jimmie L. Yeiser; Andrew W. Ezell

2010-01-01

Results from four loblolly pine (Pinus taeda L.) sites, one in each of MS and TX in 2001 and again in 2002, are presented. Twelve herbicide treatments and an untreated check were tested. Herbicide treatments were applied early (mid-March), late (mid-May), both timings, or not at all to achieve, early- late-, full-season, or no weed control. When...

Mechanochemical depolymerization of inulin.

PubMed

Xing, Haoran; Yaylayan, Varoujan A

2018-05-02

Although chemical reactions driven by mechanical force is emerging as a promising tool in the field of physical sciences, its applications in the area of food sciences are not reported. In this paper, we propose ball milling as an efficient tool for the controlled generation of fructooligosaccharide (FOS) mixtures from inulin with a degree of polymerization (dp) ranging between 4 and 7. The addition of catalytic amounts of AlCl 3 together with ball milling (30 min, at 30 Hz) generated mixtures rich in dehydrated disaccharides such as di-D-fructose dianhydrides. Based on anion exchange chromatography in conjunction with ESI/qTOF/MS/MS analysis, catalysis increased the overall content of mono-, di-, and tri-saccharides by around 30 fold compared to un-catalyzed milling. In addition, dialysis results of the untreated and treated samples have indicated that under catalysis the percent of depolymerization (dp < 12) reached 73.4% from the starting value of 27.6% in the untreated sample. Both processes resulted in mixtures of prebiotic value. The use of mechanical energy may be suitable for a fast, cost-efficient and green conversion of inulin to value-added food ingredients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Relationship between increased arterial stiffness and other markers of target organ damage.

PubMed

Rodilla, Enrique; Costa, José Antonio; Pérez-Lahiguera, Francisco; González, Carmen; Pascual, José María

2010-04-24

The purpose of the present study was to assess the relationship of arterial stiffness with other markers of target organ damage, and the clinical factors related to it. Cross-sectional study that included 208 (115 men) never treated hypertensive, non-diabetic patients (mean age, 49+/-12 years). In addition to a full clinical study, 24h ambulatory blood pressure (BP), and determination of left ventricular hypertrophy (LVH) and microalbuminuria were performed. Clinical arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) obtained with applanation tonometry (SphygmoCor-System). PWV was 8.3 (7.3-9.9)m/s (median, interquartile range). Stepwise regression analysis revealed that age (beta=0.086, p<0.001), 24-h pulse pressure (beta=0.058, p<0.001), and low-density lipoprotein (LDL) cholesterol (beta=0.009, p<0.013) were independent determinants of PWV. PWV>12m/s (indicating target organ lesion) was present in only 16 (7.7%) patients, less frequent than LVH (28% of the patients) and microalbuminuria (16%). However, of the 16 patients with elevated PWV, 10 (62%) had neither LVH or microalbuminuria. In a logistic multivariate regression analysis the factors related to elevated PWV were age > or =45 in man and > or =55 in women (OR: 23.8, 95% CI: 2.7-195.5; p=0.004), LDL cholesterol > or =160mg/dl (OR: 10.6, 95% CI: 2.6-42.7; p=0.001) and increased 24-h pulse pressure > or =55mmHg (OR: 3.9, 95% CI: 1.2-12.9; p=0.03). In untreated middle age hypertensives arterial stiffness assessed by PWV is less frequent than LVH or microalbuminuria. PWV is mainly related to age, LDL cholesterol, and pulse pressure values. 2009 Elsevier España, S.L. All rights reserved.

The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis.

PubMed

Chang, Vi-Sion; Okechukwu, Patrick N; Teo, Swee-Sen

2017-03-01

The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC 50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was found significantly higher than the experimental group and the normal group. In conclusion, K. alvarezii extract might able to slow down the growth rate of the tumour cells, therefore, identification of an active compound of inhibition growth rate of the tumour cells can be positively carried out in the future. Copyright © 2016. Published by Elsevier Masson SAS.

Arterial Destiffening in Previously Untreated Mild Hypertensives After 1 Year of Routine Clinical Management.

PubMed

Rodilla, Enrique; Millasseau, Sandrine; Costa, Jose Antonio; Pascual, Jose Maria

2017-05-01

Arterial stiffness, measured with pulse wave velocity (PWV), is now classified as a marker of target organ damage (TOD) alongside left ventricular hypertrophy and moderately increased albuminuria. Interventional studies on treated hypertensive patients have shown that PWV could be improved. Our aim was to assess changes in arterial stiffness after 1 year of routine clinical practice in never-treated hypertensive patients. We studied 356 never-treated patients with suspected hypertension. After standard clinical assessment during which presence of TOD was evaluated, hypertension diagnosis was confirmed in 231 subjects who subsequently received standard routine care. Both hypertensive and the 125 controls came back for a follow-up visit after 1 year. Hypertensive patients were slightly older (46 ± 12 vs. 50 ± 12 years, P < 0.001), with higher mean arterial pressure (MAP)-adjusted PWV compared to controls (8.6 ± 2.0 vs. 8.0 ± 1.7 m/s, P < 0.001) and 47% of them presented 1 or more TOD. After 1 year of treatment, MAP was similar in both groups (94.9 vs. 96.2 mm Hg; P = ns), but adjusted PWV remained significantly higher in the hypertensive patients (7.8 ± 1.4 vs. 8.3 ± 1.7 m/s, P = 0.004). The prevalence of elevated PWV was reduced from 20% to 12%. All antihypertensive drugs achieved the same blood pressure (BP) and PWV reduction with the exception of vasodilating beta-blockers which gave slightly better results probably due to heart rate reduction. BP reduction in newly diagnosed hypertensive patients improves arterial stiffness within a year of real-life clinical practice. Patients with the highest PWV and the largest reduction of BP "destiffened" the most whatever antihypertensive class was used. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

PubMed Central

Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

2011-01-01

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

Laron syndrome (primary growth hormone insensitivity): a unique model to explore the effect of insulin-like growth factor 1 deficiency on human hair.

PubMed

Lurie, R; Ben-Amitai, D; Laron, Z

2004-01-01

Classical Laron syndrome is a recessive disease of primary insulin-like growth factor 1 (IGF-1) deficiency and primary growth hormone insensitivity. Affected children have, among other defects, sparse hair growth and frontal recessions. The hair is thin and easy to pluck. Young adults have various degrees of alopecia, more pronounced in males. The aim of the present study was to investigate the effect of primary IGF-1 deficiency on hair structure. The study sample included 11 patients with Laron syndrome--5 children (2 untreated) and 6 adults (5 untreated). Hairs were examined by light and electron microscopy. The most significant structured defect, pili torti et canaliculi, was found in 2 young, untreated patients. Grooving, tapered hair and trichorrhexis nodosa were found in the remainder. IGF-1-treated patients had either none or significantly fewer pathological changes compared to the untreated patients. This is the first documentation of the role of primary IGF-1 deficiency on hair structure in human beings. Copyright 2004 S. Karger AG, Basel

Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

PubMed Central

Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

2016-01-01

Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

MR Fingerprinting of Adult Brain Tumors: Initial Experience.

PubMed

Badve, C; Yu, A; Dastmalchian, S; Rogers, M; Ma, D; Jiang, Y; Margevicius, S; Pahwa, S; Lu, Z; Schluchter, M; Sunshine, J; Griswold, M; Sloan, A; Gulani, V

2017-03-01

MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69-1.00; P < .0001). MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting-based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. © 2017 by American Journal of Neuroradiology.

The influence of fipronil on Reticulitermes flavipes (Isoptera: Rhinotermitidae) feeding beyond treated plots

Treesearch

Thomas Shelton

2013-01-01

A small-plot field trial was conducted to examine the area of influence of fipronil at incremental distances away from treated plots on the Harrison Experimental Forest near Saucier, MS. Small treated (water and fipronil) plots were surrounded by untreated wooden boards in an eight-point radial pattern, and examined for evidence of termite feeding every 60 d for 1 yr...

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

PubMed

Brunetti, G; Papadia, F; Tummolo, A; Fischetto, R; Nicastro, F; Piacente, L; Ventura, A; Mori, G; Oranger, A; Gigante, I; Colucci, S; Ciccarelli, M; Grano, M; Cavallo, L; Delvecchio, M; Faienza, M F

2016-07-01

In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients.

Coagulation profile of Sudanese children with homozygous sickle cell disease and the effect of treatment with omega-3 fatty acid on the coagulation parameters.

PubMed

Awoda, Shiekh; Daak, Ahmed A; Husain, Nazik Elmalaika; Ghebremeskel, Kebreab; Elbashir, Mustafa I

2017-01-01

It has been reported that patients with SCD do have an abnormal coagulation profile. Coagulopathy is thought to be one of the key factors that contribute to the vaso-occlusive crisis that characterises sickle cell disease (SCD). In this study, we investigated whether Sudanese sickle cell patients have an abnormal coagulation profile. In addition, the effect of treatment with either omega-3 fatty acids or hydroxyurea on coagulation profile was assessed. Homozygous SCD patients untreated ( n  = 52), omega-3 treated ( n  = 44), hydroxyurea (HU) treated ( n  = 8) and healthy (HbAA) controls ( n  = 52) matched for age (4-20 years), gender and socioeconomic status were enrolled. Patients on omega-3 fatty acids, according to age, received one to four capsules containing 277.8 mg DHA and 39.0 mg eicosapentnoic. Patients on Hydroxyurea were in on dosage more than 20 mg/kg/day. The steady state levels of the coagulation parameters and the effect of the treatments with either HU or omega-3 fatty acids on markers of coagulation were investigated. Compared to the healthy controls, treated and untreated HbSS patients had lower hemoglobin, plasma Protein C, proteins S and higher white blood cell count (WBC), platelets count (PLTs) and plasma D-dimer levels,( p  < 0.05). In comparison to untreated HbSS, treatment with neither omega-3 nor HU had effect on the WBC, plasma proteins C and S, ( p  > 0.05). HU treated group had a lower PLTs count compared to HbSS untreated group ( p  < 0.5). The prothrombin and activated partial thromboplastin times and international normalized ratio (INR) of untreated patients are significantly higher than n-3 treated, HU-treated patients and health controls, ( p  < 0.05). Patients treated with omega-3 had lowered D-dimer levels in comparison to HU-treated and untreated HbSS patients, ( p  < 0.001). This study provides evidence that Sudanes patients have abnormal coagulation profile and treatment with either HU or omega-3 fatty acids might partially ameliorate SCD-associated chronic coagulopathic state.

Immediate loading of implants placed in patients with untreated periodontal disease: a 5-year prospective cohort study.

PubMed

Maló, Paulo; Nobre, Miguel de Araújo; Lopes, Armando; Ferro, Ana; Gravito, Inês

2014-01-01

To report the 5-year outcome of immediately loaded dental implants in patients with untreated periodontal disease. This prospective cohort study included 103 consecutive patients (51 females and 52 males) with an average age of 52 years (range: 22 to 80 years) who were rehabilitated with 380 implants supporting 145 prostheses in both jaws (40 single; 33 partial and 72 complete rehabilitations). The implants were inserted in patients with active and untreated periodontitis. The patients did not receive any previous periodontal treatment before implant surgery, except for an oral hygiene session immediately before the implant surgery. In maintenance (every 6 months) patients received periodontal treatment as needed. Outcome measures were: prostheses failures; implant failures; complications; and marginal bone level changes. Fifteen patients dropped out of the study (14.6%). Two patients lost two implants (FDI positions nos.12 and 42), rendering a cumulative survival rate of 97.9% and 99.4% at 5 years of followup using the patient and implant as unit of analysis, respectively. The average (standard deviation) marginal bone resorption was 0.71 mm (0.42 mm) at 5 years. Mechanical complications occurred in 14 patients, consisting of prostheses fractures (10 provisional prostheses and 4 definitive prostheses). Thirteen implants (3.9%) in 13 patients (14.8%) presented peri-implant pathology. Within the limitations of this study, it is possible to conclude that the rehabilitation of patients with untreated periodontitis using immediately loaded dental implants is feasible in the medium-term, when periodontal therapy is provided after rehabilitation and the patients are regularly maintained.

The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

PubMed Central

Tanuma, Yasushi

2017-01-01

Objectives The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice. Methods A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined. Results The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years. Conclusions 35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment. Trial Registration This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910). PMID:28694823

Reasons for Schizophrenia Patients Remaining out of Treatment: Results from a Prospective Study in a Rural South Indian Community.

PubMed

Kumar, Channaveerachari Naveen; Thirthalli, Jagadisha; Suresha, Kudumallige Krishnappa; Venkatesh, Basappa K; Kishorekumar, Kengeri V; Arunachala, Udupi; Gangadhar, Bangalore N

2016-01-01

A few studies have examined the factors associated with schizophrenia patients remaining untreated in India. We identified 184 schizophrenia patients in a rural community, offered the treatment with antipsychotics and followed them up in their Primary Health Centers for 1-year. Twenty-nine (15.8%) patients remained untreated at both the baseline and 1-year follow-up despite our best attempts to keep them under the treatment umbrella. They were interviewed in detail regarding the reasons for remaining untreated. This group was compared with another group of patients (n = 69) who had stopped the treatment at baseline but were successfully brought under the treatment umbrella throughout the 1-year follow-up period. The reasons for remaining untreated were (n; %): (a) Unsatisfactory improvement with previous treatment attempts (19; 65.5%), (b) poor bond between the patients and the families (6; 20.7%), (c) active symptoms not allowing any treatment efforts from the family members (6; 20.7%), (d) magico-religious beliefs about the illness and its treatment (4; 13.8%), (e) poor social support (3; 10.3%), (f) adverse effects of the medications (2; 6.9%), and (g) perception of recovery and cure (1; 3.4%). For many patients, a constellation of these reasons was responsible for them remaining untreated. In contrast, the common reasons for those who restarted medications to have stopped the treatment at some time were the lack of awareness, the need to continue medications (47; 68.1%), and the financial constraints (28; 40.6%). The predominant reason for schizophrenia patients not remaining on the treatment in this rural community was the families' lack of faith in antipsychotic treatment. Provision of comprehensive treatment package including medical, psychosocial and rehabilitative services, and sensitizing the community about benefits of the treatment may help in ensuring that all patients with psychosis receive the best care.

Progression of Treated versus Untreated Liver Imaging Reporting and Data System Category 4 Masses after Transcatheter Arterial Embolization Therapy.

PubMed

Ronald, James; Gupta, Rajan T; Marin, Daniele; Wang, Qi; Durocher, Nicholas S; Suhocki, Paul V; Kim, Charles Y

2018-05-01

To compare outcomes of treated vs untreated Liver Imaging Reporting and Data System category 4 (LR-4) masses after transcatheter arterial embolization. In 167 patients undergoing embolization for HCC from January 2005 to December 2012, LR-4 masses were retrospectively identified on CT and MR imaging examinations performed before embolization. In 149 patients undergoing embolization from January 2013 to December 2016, masses prospectively classified as LR-4 were identified. In total, there were 81 LR-4 masses in 62 patients (16 women; mean age 62 y; range 29-83 y). Procedures were reviewed to determine whether LR-4 masses were within or outside the liver volume that received embolization during treatment of dominant masses. Time to progression to LR-5 and by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was estimated for treated vs untreated LR-4 masses using the Kaplan-Meier method and compared using the log rank test. LR-4 masses averaged 1.8 cm; 88%, 60%, 14%, and 14% demonstrated arterial phase hyperenhancement, washout, a capsule, and growth. Of LR-4 masses, 62 were within the liver volume that received embolization and considered treated, and 19 were outside and considered untreated. Response rates according to mRECIST were 37% vs 21% for treated vs untreated masses (P = .27). The 6- and 12-month rates of progression to LR-5 were 7% and 26% for treated masses vs 27% and 75% for untreated masses (P = .001). According to mRECIST, 7% and 27% of treated masses progressed vs 30% and 65% of untreated masses (P = .001). LR-4 masses that receive embolization in the setting of dominant masses elsewhere show lower rates of progression compared with untreated masses. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study.

PubMed

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.

Prevalence of thyroid dysfunction in untreated cancer patients: a cross-sectional study.

PubMed

Dişel, Umut; Beşen, Ayberk; Karadeniz, Cemile; Mertsoylu, Hüseyin; Sezer, Ahmet; Köse, Fatih; TanerSümbül, Ahmet; Gürkut, Ozlem; Muallaoğlu, Sadik; Abali, Hüseyin; Ozyilkan, Ozgür

2012-12-01

The relationship between thyroid disease and cancer (and cancer therapies) has been under investigation for years. Factors that increase the risk for thyroid disease include iodine deficiency, autoimmune disorders, old age, and pregnancy. The screening policy for thyroid disease in the healthy population is not precisely defined, and the frequency of thyroid dysfunction in untreated cancer patients has not been investigated in any great detail. This study was designed to compare the prevalence of thyroid dysfunction in 457 untreated cancer patients at the time of initial diagnosis to that of 373 age- and sex-matched subjects who were healthy and cancer-free (control group). Thyroid dysfunction was found in 29.5 % (135/457) of the cancer patients, while only 15.4 % (56/373) of the control group had thyroid dysfunction (p = 0.0001). The most prevalent abnormality was euthyroid sick syndrome (14.0 %, 64/457). Overt and subclinical hyperthyroidism and overt hypothyroidism were observed more frequently in cancer patients than the control group, and these differences were all statistically significant. Thyroid dysfunction was more frequent in patients with poor performance scores and those over the age of 50 years. These data indicate that alterations in thyroid hormone metabolism are twice as common in patients with untreated cancer than in control subjects. Those alterations may lead to delayed diagnosis, suboptimal treatment, and a poorer prognosis. In all, this study suggests that screening with thyroid function tests is strongly recommended in all newly diagnosed cancer patients.

Hand size and growth in untreated and IGF-I treated patients with Laron syndrome.

PubMed

Konen, O; Silbergeld, A; Lilos, P; Kornreich, L; Laron, Z

2009-03-01

We have previously reported on the linear growth, growth of the head circumference and foot length in untreated and IGF-I treated patients with Laron syndrome (LS) (primary GH insensitivity). To assess the size and growth of the hands in patients with LS from early childhood to adult age. Ten IGF-I treated children with LS (4 M, 6 F) and 24 untreated patients (10 M, 14 F) were studied. Measurements of palm length were made on available standardized hand X-rays from infancy to adult age. The measurements were compared to normal references and SD values were calculated for each measurement. The growth of the hand was compared to the concomitant height of the body. Hand SDS in untreated patients with LS decreased with age, from a mean of -2.8 +/- 0.7 (age 1-3 years) to -7.3 +/- 0.8 (age 13-15 years) and to -9.0 +/- 3.9 (age 40-50 years). During 9 years of IGF-I treatment the hand size deficit SDS did not improve in contradistinction to the height SDS which decreased from -6.2 +/- 1.2 to -3.9 +/- 0.5. Congenital IGF-I deficiency, as in Laron syndrome, profoundly affects the size and growth of the hand as part of its growth retardation characteristics, resulting in acromicria.

Duration of Untreated Psychosis Is Associated with More Negative Schizophrenia Symptoms after Acute Treatment for First-Episode Psychosis

ERIC Educational Resources Information Center

Grano, Niklas; Lindsberg, Jenni; Karjalainen, Marjaana; Gronroos, Peter; Blomberg, Ari-Pekka

2010-01-01

Evidence of association between duration of untreated psychosis (DUP) and negative symptoms of schizophrenia in first-episode psychosis (FEP) patients is inconsistent in the recent literature. In the present study, DUP, schizophrenia symptoms, duration of medication, and diagnosis were obtained from hospital archives in a sample of FEP patients.…

Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy.

PubMed

Sato, Atsushi; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Minegishi, Masayoshi; Iinuma, Kazuie; Imaizumi, Masue

2006-12-01

Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n = 12) or single prophylaxis (n = 5), or left untreated (n = 7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy.

Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-02-22

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Pre- Versus Posttransplant Treatment of Hepatitis C Virus With Direct-Acting Antivirals in Liver Transplant Recipients: More Issues to be Solved.

PubMed

Abdelqader, Abdelhai; Kabacam, Gokhan; Woreta, Tinsay A; Hamilton, James P; Luu, Harry; Al Khalloufi, Kawtar; Saberi, Behnam; Philosophe, Benjamin; Cameron, Andrew M; Gurakar, Ahmet

2017-02-01

Our goal was to investigate wait times related to hepatitis C virus treatment with direct acting antivirals before versus after liver transplant at a single center as well as wait times for insurance approval for preemptive treatment with these agents after liver transplant. We retrospectively evaluated hepatitis C virus infections in transplant recipients of deceased liver donations in 2014 and 2015. Demographics, hepatocellular carcinoma incidence, Model for End-Stage Liver Disease scores, and transplant wait times were compared between patients treated before or after liver transplant. Wait times to approval of direct-acting antiviral treatment were evaluated in those untreated before transplant. During our study period, of 67 deceased-donor liver transplants, 21 patients received hepatitis C virus treatment pretransplant (treated group) and 46 patients were not treated pretransplant (untreated group). Twenty-five patients in the untreated group received hepatitis C virus-positive donations, with all in this group treated with direct-acting antivirals. We found no statistically significant differences regarding age, sex, race, donation after cardiac death, or incidence of hepatocellular carcinoma between groups. The treated group had a longer median wait time (287 vs 172 days; P = .02). Twelve of the 46 untreated patients (26.1%) developed biopsy-proven hepatitis C virus-related relapse (median 87 days; range, 55-383 days). Preemptive direct-acting antiviral therapy was initiated at a median of 81 days in the untreated group. Although treatment of hepatitis C virus before liver transplant is an attractive option to eliminate the risk of complications, it can limit the donor pool for recipients to uninfected donors, significantly increasing wait times in regions with large hepatitis C virus-positive donor pools. Allocation of Model for End-Stage Liver Disease score was not different between the treated and untreated groups. Insurance companies should revise their policies for rapid approval of preemptive direct-acting antiviral treatment after liver transplant.

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis

PubMed Central

Schmidt, André; Palaniyappan, Lena; Smieskova, Renata; Simon, Andor; Riecher-Rössler, Anita; Lang, Undine E.; Fusar-Poli, Paolo; McGuire, Philip; Borgwardt, Stefan J.

2016-01-01

Background Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. Methods We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. Results The model including reward-induced modulation of insula–ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula–ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula–ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. Limitations The modest sample size of untreated patients with FEP was a limitation of our study. Conclusion This study indicates that insula–ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction. PMID:26854756

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

PubMed

Carlioglu, Ayse; Kaygusuz, Ikbal; Karakurt, Feridun; Gumus, Ilknur Inegol; Uysal, Aysel; Kasapoglu, Benan; Armutcu, Ferah; Uysal, Sema; Keskin, Esra Aktepe; Koca, Cemile

2014-11-01

To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients. Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis. PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group. In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

Emotion, working memory, and cognitive control in patients with first-onset and previously untreated minor depressive disorders.

PubMed

Li, Mi; Lu, Shengfu; Wang, Gang; Feng, Lei; Fu, Bingbing; Zhong, Ning

2016-06-01

To explore working memory and the ability to process different emotional stimuli in patients with first-onset and untreated minor (mild or moderate) depression. Patients with first-onset and previously untreated minor depression, and healthy controls, were enrolled. Using a modified Sternberg working memory paradigm to investigate the combined effects of emotional stimuli with working memory, participants were exposed to experimental stimuli comprising pictures that represented positive, neutral and negative emotions. Working memory ability was measured using reaction time and accuracy, and emotion-processing ability was measured using pupil diameter. Out of 36 participants (18 patients with minor depression and 18 controls), there were no statistically significant between-group differences in response time and accuracy. Positive stimuli evoked changes in pupil diameter that were significantly smaller in patients with minor depression versus controls, but changes in pupil diameter evoked by negative stimuli were not significantly different between the two groups. Healthy subjects showed a stronger emotional response to positive emotional stimuli than patients with first onset and previously untreated minor depression, but there were no differences in response to negative emotions. There were no statistically significant between-group differences in terms of speed of cognitive response, but this may have been due to the relatively small samples sizes assessed. Studies with larger sample populations are required to further investigate these results. © The Author(s) 2016.

Beat-to-beat, reading-to-reading, and day-to-day blood pressure variability in relation to organ damage in untreated Chinese.

PubMed

Wei, Fang-Fei; Li, Yan; Zhang, Lu; Xu, Ting-Yan; Ding, Feng-Hua; Wang, Ji-Guang; Staessen, Jan A

2014-04-01

Whether target organ damage is associated with blood pressure (BP) variability independent of level remains debated. We assessed these associations from 10-minute beat-to-beat, 24-hour ambulatory, and 7-day home BP recordings in 256 untreated subjects referred to a hypertension clinic. BP variability indices were variability independent of the mean, maximum-minimum difference, and average real variability. Effect sizes (standardized β) were computed using multivariable regression models. In beat-to-beat recordings, left ventricular mass index (n=128) was not (P≥0.18) associated with systolic BP but increased with all 3 systolic variability indices (+2.97-3.53 g/m(2); P<0.04); the urinary albumin-to-creatinine ratio increased (P≤0.03) with systolic BP (+1.14-1.17 mg/mmol) and maximum-minimum difference (+1.18 mg/mmol); and pulse wave velocity increased with systolic BP (+0.69 m/s; P<0.001). In 24-hour recordings, all 3 indices of organ damage increased (P<0.03) with systolic BP, whereas the associations with BP variability were nonsignificant (P≥0.15) except for increases in pulse wave velocity (P<0.05) with variability independent of the mean (+0.16 m/s) and maximum-minimum difference (+0.17 m/s). In home recordings, the urinary albumin-to-creatinine ratio (+1.27-1.30 mg/mmol) and pulse wave velocity (+0.36-0.40 m/s) increased (P<0.05) with systolic BP, whereas all associations of target organ damage with the variability indices were nonsignificant (P≥0.07). In conclusion, while accounting for BP level, associations of target organ damage with BP variability were readily detectable in beat-to-beat recordings, least noticeable in home recordings, with 24-hour ambulatory monitoring being informative only for pulse wave velocity.

"What if I do nothing?" The natural history of operable cancer of the alimentary tract.

PubMed

Keshava, H B; Rosen, J E; DeLuzio, M R; Kim, A W; Detterbeck, F C; Boffa, D J

2017-04-01

"Natural history", or anticipated survival without treatment, is critical for patients weighing risks and benefits of cancer surgery. Current estimates concerning the natural history of cancer includes patients whose poor health precludes treatment; a cohort whose fate is likely distinctly worse than those eligible for surgery ("operable"). The study objective was to evaluate survival among patients recommended for cancer surgery but went untreated, to determine the natural history of "operable" alimentary tract cancer. The NCDB was queried for untreated patients with clinical stage I-III esophageal, gastric, colon, and rectal cancer diagnosed between 2003 and 2009. Untreated patients who were recommended for surgery were considered "operable," while patients coded as surgically ineligible for health reasons were "inoperable." 5-year survival of untreated, "operable" alimentary tract cancers varied by clinical stage: esophageal cI = 10.0%, cII = 9.8%, cIII = 4.6%; gastric cI = 9.2%, cII = 5.8%, cIII = 4.3%; colon cI = 18.4%, cII = 5.0%, cIII = 10.4; and rectal cI = 17.1%, cII = 14.0%, cIII = 19.9%. At every timepoint, stage-specific survival of "operable" patients was superior to inoperable patients (p < 0.05). Additionally, median survival among "operable" patients at least doubled "inoperable" patients for each tumor. Natural history of patients with "operable" alimentary tract cancer is superior to that of "inoperable" patients. Preoperative counseling should be refined to reflect this distinction. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

PubMed

Cowley, D S; Roy-Byrne, P P; Radant, A; Ritchie, J C; Greenblatt, D J; Nemeroff, C B; Hommer, D W

1995-04-01

The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

PubMed

Damiani, G R; Riva, D; Pellegrino, A; Gaetani, M; Tafuri, S; Turoli, D; Croce, P; Loverro, G

2016-01-01

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.

PubMed

Axelsson, Markus; Malmeström, Clas; Gunnarsson, Martin; Zetterberg, Henrik; Sundström, Peter; Lycke, Jan; Svenningsson, Anders

2014-01-01

In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

Feasibility of the silver-UV process for drinking water disinfection.

PubMed

Butkus, Michael A; Talbot, Mark; Labare, Michael P

2005-12-01

A synergistic effect between cationic silver and UV radiation (silver-UV disinfection) has been observed that can appreciably enhance inactivation of viruses. The purpose of this work was to assess the feasibility of this technique for drinking water disinfection and evaluate the effects of selected impurities, found in fresh water, and common parameters on inactivation of the coliphage MS-2 with the silver-UV process. Turbidity (kaolin), calcium hardness, carbonate alkalinity, and pH did not significantly degrade inactivation. Inactivation was reduced in the presence of chloride, at concentrations greater than 30 mg/L, and in water samples with UV-254 absorbance values greater than ca. 0.1 cm(-1). Inactivation of MS-2 with silver-UV disinfection was also reduced at high phosphate concentrations (above ca. 5 mM). Silver-UV inactivation of MS-2 increased with increases in temperature between 10 and 20 degrees C. Silver-UV inactivation of MS-2 was increased by greater than 1-log over UV alone, in two untreated fresh water sources, which indicates that silver-UV may be a viable treatment technology. An assessment of operation and management costs suggests that an increase in inactivation of MS-2 with silver-UV disinfection could be economically beneficial.

Enhanced activity of the purine nucleotide cycle of the exercising muscle in patients with hyperthyroidism.

PubMed

Fukui, H; Taniguchi , S; Ueta, Y; Yoshida, A; Ohtahara, A; Hisatome, I; Shigemasa, C

2001-05-01

Myopathy frequently develops in patients with hyperthyroidism, but its precise mechanism is not clearly understood. In this study we focused on the purine nucleotide cycle, which contributes to ATP balance in skeletal muscles. To investigate purine metabolism in muscles, we measured metabolites related to the purine nucleotide cycle using the semiischemic forearm test. We examined the following four groups: patients with untreated thyrotoxic Graves' disease (untreated group), patients with Graves' disease treated with methimazole (treated group), patients in remission (remission group), and healthy volunteers (control group). To trace the glycolytic process, we measured glycolytic metabolites (lactate and pyruvate) as well as purine metabolites (ammonia and hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and ammonia released were remarkably higher than those in the control group. Hypoxanthine release also increased in the untreated group, but the difference among the patient groups was not statistically significant. The accelerated purine catabolism did not improve after 3 months of treatment with methimazole, but it was completely normalized in the remission group. This indicated that long-term maintenance of thyroid function was necessary for purine catabolism to recover. We presume that an unbalanced ATP supply or conversion of muscle fiber type may account for the acceleration of the purine nucleotide cycle under thyrotoxicosis. Such acceleration of the purine nucleotide cycle is thought to be in part a protective mechanism against a rapid collapse of the ATP energy balance in exercising muscles of patients with hyperthyroidism.

Cochlear hearing loss in patients with Laron syndrome.

PubMed

Attias, Joseph; Zarchi, Omer; Nageris, Ben I; Laron, Zvi

2012-02-01

The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.

Cell-mediated immunity in Chagas' disease: Alterations induced by treatment with a trypanocidal drug (nifurtimox).

PubMed Central

Lelchuk, R; Cardoni, R L; Fuks, A S

1977-01-01

Peripheral leucocyte migration inhibition (LMI) with Trypanosoma cruzi-specific antigens, measured as a migration index (MI), was studied in chronic Chagas' disease patients. The MI of untreated patients with polymerized antigens from culture forms (epimastigotes) of T. cruzi was significantly lower than that of controls. In contrast, when chronic Chagas' patients were treated with nifurtimox, 10 mg/kg/day for 2 months, the MI was not different from control values. Treated and untreated patients had normal T- and B-lymphocyte markers, measured by the ability to form rosettes either with sheep erythrocytes (E-RFC) or with sheep erythrocytes--antibody--complement (EAC-RFC). In addition, the number of lymphocytes bearing surface membrane Ig (SMIg) was the same as that of controls. Non-specific functional assays, such as PHA-induced blastogenesis and antibody-dependent cell-mediated cytotoxicity (ADCC) to sensitized chicken erythrocytes were also normal, both in treated and untreated patients. Thus, nifurtimox produced a particularly effect on cell-mediated immunity, specially detectable using LMI. PMID:414867

Reasons and determinants for not receiving treatment for common mental disorders.

PubMed

van Beljouw, Ilse; Verhaak, Peter; Prins, Marijn; Cuijpers, Pim; Penninx, Brenda; Bensing, Jozien

2010-03-01

This study focused on patients in the general population whose anxiety or depressive disorder is untreated. It explored reasons for not receiving treatment and compared four groups of patients-three that did not receive treatment for different reasons (no problem perceived, no perceived need for care, and unmet need for care) and one that received treatment-regarding their predisposing, enabling, and need factors. Cross-sectional data were used for 743 primary care patients with current anxiety or depressive disorder from the Netherlands Study of Depression and Anxiety (NESDA). Diagnoses were confirmed with the Composite International Diagnostic Interview. Patients' perception of the presence of a mental problem, perceived need for care, service utilization, and reasons for not receiving treatment were assessed with the Perceived Need for Care Questionnaire. Forty-three percent of the respondents with a six-month anxiety or depression diagnosis did not receive treatment. Twenty-one percent of all respondents with depression or anxiety expressed a need for care but did not receive any. Preferring to manage the problem themselves was the most common reason for respondents to avoid seeking treatment. There were no significant differences in clinical need factors between treated patients and untreated patients with a perceived need for care. Compared with patients in the other two untreated groups, untreated patients with a perceived need for care were more hindered in regard to symptom severity, functional disability, and psychosocial functioning. General practitioners should pay considerable attention to patients whose need for care is unmet. Furthermore, findings support the implementation of patient empowerment in mental health care in order to contribute to easily accessible and patient-centered care.

Partner management for gonococcal and chlamydial infection: expansion of public health services to the private sector and expedited sex partner treatment through a partnership with commercial pharmacies.

PubMed

Golden, M R; Whittington, W L; Handsfield, H H; Malinski, C; Clark, A; Hughes, J P; Gorbach, P M; Holmes, K K

2001-11-01

Public health partner notification (PN) services currently affect only a small minority of patients with gonorrhea or chlamydial infection and new approaches to PN are needed. To expand PN for gonorrhea and chlamydial infection to private sector patients and to assess the feasibility of treating sex partners through commercial pharmacies. Selected patients were offered PN assistance and were randomly offered medication to deliver to their partners. Providers permitted the health department to contact 3613 (91%) of 3972 potentially eligible patients, and 1693 (67%) of 2531 successfully contacted patients consented to interview. Of these, 1095 (65%) reported at least one untreated partner. Most patients (90%) wished to notify partners themselves. Patients were more likely to have partners who had not yet been treated and to request PN assistance if they had more than one sex partner in the preceding 60 days or a partner they did not anticipate having sex with in the future. These two factors characterized 49% of all patients interviewed, 70% of those with a partner that was untreated 7 or more days after index patient treatment, and 83% of those accepting PN assistance. Among 458 randomly selected patients with untreated partners at time of study interview, 346 (76%) agreed to deliver treatment to a partner. Of these, most (266) chose to obtain medication for a partner at a pharmacy, of whom 223 (84%) successfully did so. A substantial minority of private sector patients have untreated partners more than 7 days after their own treatment; some need help with PN, but most will agree to deliver medication to partners themselves.

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

ClinicalTrials.gov

2018-06-25

B Acute Lymphoblastic Leukemia; Central Nervous System Leukemia; Ph-Like Acute Lymphoblastic Leukemia; Testicular Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis.

PubMed

Crofford, L J; Kalogeras, K T; Mastorakos, G; Magiakou, M A; Wells, J; Kanik, K S; Gold, P W; Chrousos, G P; Wilder, R L

1997-04-01

Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma Il-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains normal and apparently is insufficient to inhibit ongoing inflammation in early untreated RA patients.

CD20+ T cell numbers are decreased in untreated HIV-1 patients and recover after HAART.

PubMed

Förster, Friederike; Singla, Anuj; Arora, Sunil K; Schmidt, Reinhold E; Jacobs, Roland

2012-08-30

To elucidate if CD20(+) T cells are affected by HIV-1 infection and may have a prognostic value for the course of disease, numbers of CD20(+) T cells were determined in healthy controls, untreated and HAART-treated HIV-1 patients. Coexpression patterns of CD4, CD8, and CD38 were analysed on CD3(+)CD20(+) and CD3(+)CD20(-) T cells. We found a significant decrease of CD20(+) T cell numbers in untreated HIV-1 patients (1.4%) as compared to healthy controls (2.5%) which recovered under HAART (1.9%). Particularly, the CD8(+) T cell compartment was affected revealing significant differences between healthy controls (3.4%) and both treated (1.7%) and untreated (1.1%) patients. CD38 was expressed on a few CD20(+) T cells but preferentially on CD20(-) cells in all three groups. IFN-γ production was measured upon cell activation using PMA alone or in combination with ionomycin in order to assess functional capacities of the cells. PMA alone was much more effective in CD20(+) cells regardless of CD38 coexpression, indicating a supportive role of CD20 but not CD38 in T cell activation. Here we present data showing that CD3(+)CD20(+) T cells are decreased in untreated HIV-1 patients and normal numbers are restored under HAART. Expression of CD20 and CD38 is independently regulated on T cells. Contrary to CD38, CD20 can substitute ionophores for Ca(2+) flux in early T cell activation and also strongly amplify cell stimulation in the presence of Ca(2+) ionophores, indicating that CD20 contributes to T cell activation. Copyright © 2012 Elsevier B.V. All rights reserved.

Role of CXCR3/CXCL10 axis in immune cell recruitment into the small intestine in celiac disease.

PubMed

Bondar, Constanza; Araya, Romina E; Guzman, Luciana; Rua, Eduardo Cueto; Chopita, Nestor; Chirdo, Fernando G

2014-01-01

Lymphocytic infiltration in the lamina propria (LP), which is primarily composed of CD4(+) Th1 cells and plasma cells, and increased numbers of intraepithelial lymphocytes (IELs), is a characteristic finding in active celiac disease (CD). Signals for this selective cell recruitment have not been fully established. CXCR3 and its ligands, particularly CXCL10, have been suggested to be one of the most relevant pathways in the attraction of cells into inflamed tissues. In addition, CXCR3 is characteristically expressed by Th1 cells. The aim of this work was to investigate the participation of the chemokine CXCL10/CXCR3 axis in CD pathogenesis. A higher concentration of CXCL10 was found in the serum of untreated CD patients. The mRNA levels of CXCL10 and CXCL11 but not CXCL9 were significantly higher in duodenal biopsies from untreated CD patients compared with non-CD controls or treated patients. The results demonstrate that CXCL10 is abundantly produced in untreated CD and reduced in treated patients, and the expression of CXCL10 was found to be correlated with the IFNγ levels in the tissue. Plasma cells and enterocytes were identified as CXCL10-producing cells. Moreover, the CXCL10 expression in intestinal tissues was upregulated by poly I:C and IL-15. IELs, LP T lymphocytes, and plasma cells, which infiltrate the intestinal mucosa in untreated CD, express CXCR3. The CXCR3/CXCL10 signalling axis is overactivated in the small intestinal mucosa in untreated patients, and this finding explains the specific recruitment of the major cell populations that infiltrate the epithelium and the LP in CD.

Rebamipide Improves Chronic Inflammation in the Lesser Curvature of the Corpus after Helicobacter pylori Eradication: A Multicenter Study

PubMed Central

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369. PMID:26060821

Modest Improvement of Untreated Severe Sleep-Disordered Breathing in the Middle-Aged and Elderly

PubMed Central

Jeon, Hong Jun; Bang, Young Rong; Jeon, Soyeon; Lee, Tae Young; Park, Hye Youn

2017-01-01

Objective It has been reported that untreated sleep-disordered breathing (SDB) deteriorates over time, however this remains contentious. The aim of the present study is to evaluate the clinical course of SDB in middle-aged and older SDB patients, and to identify how relevant factors contribute to the change in SDB severity. Methods Baseline and follow-up polysomnographic data of 56 untreated SDB patients (mean age, 61.2±5.71) were obtained retrospectively and the mean interval was 62.4±22.0 months. Subgroup analysis was performed based on the baseline severity, and the factors associated with the course of SDB were analyzed. Results At the baseline, 13 subjects were simple snorers, 15 had mild to moderate SDB, and 28 were severe SDB patients. While there was no significant change in apnea-hypopnea index (AHI) as a whole, subgroup analysis showed decrease of AHI in severe SDB patients (43.9±10.6 to 35.6±20.0, p=0.009). The change in supine time percent and baseline AHI were associated with the change in AHI (β=0.387, p=0.003; β=-0.272, p=0.037). Conclusion Untreated SDB did not deteriorate over time with modest improvement in severe SDB. A proportion of severe SDB patients might expect decrease in SDB severity irrespective of changes in sleep position or body weight. PMID:29042892

Modest Improvement of Untreated Severe Sleep-Disordered Breathing in the Middle-Aged and Elderly.

PubMed

Jeon, Hong Jun; Bang, Young Rong; Jeon, Soyeon; Lee, Tae Young; Park, Hye Youn; Yoon, In-Young

2017-09-01

It has been reported that untreated sleep-disordered breathing (SDB) deteriorates over time, however this remains contentious. The aim of the present study is to evaluate the clinical course of SDB in middle-aged and older SDB patients, and to identify how relevant factors contribute to the change in SDB severity. Baseline and follow-up polysomnographic data of 56 untreated SDB patients (mean age, 61.2±5.71) were obtained retrospectively and the mean interval was 62.4±22.0 months. Subgroup analysis was performed based on the baseline severity, and the factors associated with the course of SDB were analyzed. At the baseline, 13 subjects were simple snorers, 15 had mild to moderate SDB, and 28 were severe SDB patients. While there was no significant change in apnea-hypopnea index (AHI) as a whole, subgroup analysis showed decrease of AHI in severe SDB patients (43.9±10.6 to 35.6±20.0, p=0.009). The change in supine time percent and baseline AHI were associated with the change in AHI (β=0.387, p=0.003; β=-0.272, p=0.037). Untreated SDB did not deteriorate over time with modest improvement in severe SDB. A proportion of severe SDB patients might expect decrease in SDB severity irrespective of changes in sleep position or body weight.

Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

ClinicalTrials.gov

2017-10-11

Brain Stem Glioma; Cerebral Astrocytoma; Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Spinal Cord Neoplasm; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebral Astrocytoma

A gender-related action of IFNbeta-therapy was found in multiple sclerosis.

PubMed

Contasta, Ida; Totaro, Rocco; Pellegrini, Patrizia; Del Beato, Tiziana; Carolei, Antonio; Berghella, Anna Maria

2012-11-14

Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in the regulation of T-helper (Th) cell network homeostasis. We focused on sexually dimorphic changes in the immune response in multiple sclerosis (MS) patients in order to ascertain how these alterations relate to the pathway regulation of the cytokine homeostasis and the Th cell networks. We studied antigen presenting cell (APC)-dependent T cell activation in groups of healthy subjects, in patients under interferon (IFN) β-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded disability status scale (EDSS) were used as biomarkers for T cell differentiation and neurological deficit. The data confirm our belief that sexual dimorphism in autoimmune diseases is the result of differing pathways that regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and IFNγ pathways in men. Given the increased susceptibility of women to MS and the significance of IL6 in the autoimmune process compared to IFNγ, it is logical to assume that IL6 pathways are in some way implicated in the prevalence of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are also involved in T regulatory (Treg) cell imbalance and an increase in neurological deficit in both men and women groups of MS patients, underlining the autoimmune etiology of multiple sclerosis. In further support of differing cytokine pathways in men and women, we noted that the efficacy of IFNβ-treatment in the re-establishment of Th-network balance and in the delaying of the neurological disability progression is linked to the IL6 pathway in women, but to the IFNγ pathway in men. Lastly, we also identified specific gender biomarkers for the use in therapy. The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment.

Factors Associated with Neurologists' Provision of MS Patient Care

PubMed Central

Halpern, Michael T.; Teixeira-Poit, Stephanie M.; Kane, Heather; Frost, Corey; Keating, Michael; Olmsted, Murrey

2014-01-01

Neurologists are central to providing quality care for individuals with MS. However, neurologist shortages may restrict access to care for MS patients. To examine factors influencing neurologists' provision of MS care, we surveyed 1,700 US neurologists to assess demographic/practice characteristics, training, and attitudes toward MS care. The study population consisted of 573 respondents: 87 (15.2%) MS subspecialists and 486 (84.8%) “other neurologists,” including subspecialists in other neurology areas (i.e., non-MS) and general neurologists. MS subspecialists indicating they “enjoy interacting with MS patients” had a significantly greater rate of MS patients seen per week. In separate analyses of the “other neurologists” group, the rate of MS patients seen was lower among neurologists in university-based groups or those practicing in major cities; female neurologists; and neurologists who indicated lack of sufficient knowledge regarding MS patient care. Rates of MS patients seen were significantly greater for other neurologists who agreed that MS care involved “ability to improve patient outcomes and quality of life”; “dynamic area with evolving treatment options”; and “enjoy interacting with MS patients.” Understanding factors influencing MS patient care by neurologists and developing policies for appropriate access to care is critical for optimal outcomes among this population. PMID:24949203

Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C.

PubMed

Petta, Salvatore; Cabibbo, Giuseppe; Enea, Marco; Macaluso, Fabio Salvatore; Plaia, Antonella; Bruno, Raffaele; Gasbarrini, Antonio; Bruno, Savino; Craxì, Antonio; Cammà, Calogero

2014-10-01

We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro, at 2013 value), life-years gained, quality-adjusted life year, and incremental cost-effectiveness ratio. The robustness of the results was evaluated by multivariable probabilistic sensitivity analyses. According to the baseline predictors of sustained virological response (genotype 1b, low viral load, fibrosis F0-F3, and body mass index) and the 1Log drop of HCV-RNA after the dual therapy lead-in period, boceprevir was cost-effective in different patient profiles. In untreated genotype 1b chronic hepatitis C patients, the cost-effectiveness of boceprevir-based triple therapy widely ranges according to different profiles of sustained virological response predictors, allowing optimization and personalization of triple therapy. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Metabolism of tilmicosin by rabbit liver microsomes and hepatocytes.

PubMed

Montesissa, C; Capolongo, F; Santi, A; Biancotto, G; Dacasto, M

2004-01-01

We investigated tilmicosin (TIM) metabolism, at 25, 50 or 100 microM, in cultures of primary hepatocytes from rabbits bred commercially for food and in liver microsomes prepared from both untreated and rifampicin (RIF)-treated rabbits. RIF is a well-known cytochrome P4503A (CYP 3A) inducer in rabbits and most macrolides are known to be substrates of CYP 3A. No peaks in addition to those of the cis and trans forms of TIM were observed by high performance liquid chromatography (HPLC) in extracts of microsomes from untreated rabbits. When TIM was incubated with induced microsomes, at least two peaks were found by HPLC and an additional peak, eluting at shorter retention time was isolated from hepatocytes incubated for 24h with the macrolide. The structures of the metabolites were then estimated by liquid chromatography-mass spectrometry (LC-MS) in concentrated extracts from induced microsomes. Five metabolites were separated and putatively identified: cis and trans demethylated tilmicosin, tilmicosin N-oxide and cis and trans tilmicosin epoxide. The overall amount of metabolites produced in vitro using livers of untreated and RIF treated rabbits was very low, has also been observed in vivo and in vitro in cattle, chickens and pigs.

A 10-year follow-up to determine the effect of YAG laser iridotomy on the natural history of pigment dispersion syndrome: a randomized clinical trial.

PubMed

Gandolfi, Stefano A; Ungaro, Nicola; Tardini, Maria Grazia; Ghirardini, Stella; Carta, Arturo; Mora, Paolo

2014-12-01

Prospective long-term analyses of the role of drug-induced mydriasis and laser peripheral iridotomy (LPI) are needed to identify and manage the eyes of patients with pigment dispersion syndrome (PDS) at risk for progressing to ocular hypertension. To assess the 10-year incidence of increased intraocular pressure (IOP) in the 2 eyes of patients with PDS, with 1 eye that underwent LPI and the other that did not. In a randomized clinical trial in the glaucoma research unit at the University Hospital of Parma, Italy, 72 patients with PDS underwent phenylephrine testing. Of these 72 patients, 29 (58 eyes) tested positive for succeeding IOP elevation, and 43 (59 eyes) tested negative. For the 29 high-risk patients (all in both eyes), one eye was randomly assigned to LPI, and the fellow eye was left untreated. For the 43 low-risk patients, the affected eyes were left untreated. An IOP elevation of 5 mm Hg or higher vs baseline (daily phasing) was considered to be a significant increase (ie, an event). In the high-risk group, 3 of 21 eyes that underwent LPI (14.3%) and 13 of 21 untreated eyes (61.9%) showed an increase in IOP of 5 mm Hg or higher during the follow-up period; 4 of 35 low-risk eyes (11.4%) showed a similar increase. Event-free mean (SD) time was 7.99 (0.43) years for high-risk treated eyes, 3.89 (0.68) years for high-risk untreated eyes, and 7.16 (0.23) years for low-risk eyes. The log-rank test showed the following: P < .001 for treated high-risk eyes vs untreated high-risk eyes, P = .74 for treated high-risk eyes vs low-risk eyes, and P < .001 for untreated high-risk eyes vs low-risk eyes. At the end of the 10-year follow-up, (1) approximately one-third of the whole PDS patient population showed an IOP increase of 5 mm Hg or higher in at least 1 eye; (2) phenylephrine testing identified eyes at high risk for developing IOP elevation; and (3) LPI, when performed on high-risk eyes, reduced the rate of IOP elevation to the same level as the low-risk eyes. clinicaltrials.gov Identifier: NCT01053416.

Selenium speciation profiles in biofortified sangiovese wine.

PubMed

Fontanella, Maria Chiara; D'Amato, Roberto; Regni, Luca; Proietti, Primo; Beone, Gian Maria; Businelli, Daniela

2017-09-01

Biofortification is an agronomic-based strategy, utilized by farmers, to produce selenium (Se)-enriched food products that may help reduce dietary deficiencies of Se occurring throughout susceptible regions of the world. The foliar exposure route application ensures a high efficiency of Se assimilation by the plant since it does not depend on root-to-shoot translocation. In this study we treated grapevines of Sangiovese variety in the pre-flowering period with sodium selenate (100mg Se L -1 ). Se content was measured in leaves, fruit at harvest time and in wine respectively in treated and not treated samples with ICP-MS. At harvest, a higher amount of Se in the treated leaves compared to untreated ones was found, 16.0±3.1mgkg -1 dry weight (dw) against 0.17±0.006mgkg -1 dw in the untreated ones. The treated grapes had a content of Se of 0.800±0.08mgkg -1 dw, while that untreated one 0.065±0.025mgkg -1 dw. Immediately after the malolactic fermentation, the wine obtained from treated and untreated vines had a Se content of 0.620±0.09mg Se L -1 and 0.024±0.010mg Se L -1 respectively. In our case the percentage of inorganic Se is 26% of the total Se in the untreated wine, while in Se enriched wine this percentage increase to 47.5% of the total Se. The Se(VI) was the inorganic chemical form more present in enriched wine, probably due to foliar application with selenate. Distributions of Se species suggested being careful to the choice of the enrichment solutions to promote a balanced distribution of different chemical forms, perhaps favouring the accumulation of organic forms. Copyright © 2016 Elsevier GmbH. All rights reserved.

Higher proportion of fast-twitch (type II) muscle fibres in idiopathic inflammatory myopathies - evident in chronic but not in untreated newly diagnosed patients.

PubMed

Loell, I; Helmers, S B; Dastmalchi, M; Alexanderson, H; Munters, L A; Nennesmo, I; Lindroos, E; Borg, K; Lundberg, I E; Esbjörnsson, M

2011-01-01

Polymyositis and dermatomyositis are idiopathic, inflammatory myopathies characterized by proximal muscle fatigue. Conventional immunosuppressive treatment gives a variable response. Biopsies from chronic patients display a low proportion type I and a high proportion of type II muscle fibres. This raised a suspicion that the low proportion of type I fibres might play a role in the muscle fatigue. To investigate whether the muscle fibre attributes evident in chronic myositis are characteristic for the polymyositis and dermatomyosistis diseases themselves. Muscle biopsies were obtained from thigh muscle from untreated patients (n = 18), treated responders (n = 14) and non-responders (n = 6) and from healthy controls (n = 11), respectively. For clinical evaluations, creatine kinase, functional index of myositis and cumulative dose of cortisone were established.   Chronic patients had a lower proportion of type I fibres and a higher proportion of type II fibres compared to untreated myositis patients and healthy controls. Fibre cross-sectional area (CSA) did not differ between patients and healthy individuals but all women had a 20% smaller type II fibre CSA compared to men. Untreated polymyositis and dermatomyositis patients and healthy controls have a different fibre type composition than chronic polymyositis and dermatomyositis patients. Fibre CSA did not differ between healthy controls or any of the patient groups. A low proportion of oxidative muscle fibres can therefore be excluded as a contributing factor causing muscle fatigue at disease onset and the gender difference should be taken into consideration when evaluating fibre CSA in myositis. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota.

PubMed

Deusch, Simon; Serrano-Villar, Sergio; Rojo, David; Martínez-Martínez, Mónica; Bargiela, Rafael; Vázquez-Castellanos, Jorge F; Sainz, Talía; Barbas, Coral; Moya, Andrés; Moreno, Santiago; Gosalbes, María J; Estrada, Vicente; Seifert, Jana; Ferrer, Manuel

2018-06-19

In a recent blinded randomized study, we found that in HIV-infected individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and that could provide additional functional information. A total of six healthy individuals, and 16 HIV-infected patients comprising viremic untreated patients (n = 5) and antiretroviral therapy-treated patients that are further divided into immunological responders (n = 7) and immunological nonresponders (n = 4) completed the 6-week course of prebiotic treatment, including six patients receiving a placebo. Alpha and beta diversity of potentially active and total gut microbiota was evaluated using shotgun proteomics and 16S rRNA gene sequencing. HIV infection decreased dormancy and increased alpha diversity of active bacteria in comparison with the healthy controls, whose richness was not further influenced by the prebiotic intervention. The effect of the prebiotics was most evident at the beta-diversity of active bacteria, particularly within viremic untreated patients. We found that the prebiotics did not only ameliorate dysbiosis of total bacteria in viremic untreated patients but also increased the abundance of active bacteria with strong immunomodulatory properties and amino acids metabolism, namely Bifidobacteriaceae, at similar levels to those in healthy individuals. This effect was attenuated in ART-treated individuals. The effect of prebiotics was greater among ART-naive HIV-infected individuals than in ART-treated patients and healthy controls. This highlights the importance of therapies aimed at manipulating the microbiome in this group of patients.

Clinical application of ghrelin for diabetic peripheral neuropathy.

PubMed

Ueno, Hiroaki; Shiiya, Tomomi; Nagamine, Kazuhiro; Tsuchimochi, Wakaba; Sakoda, Hideyuki; Shiomi, Kazutaka; Kangawa, Kenji; Nakazato, Masamitsu

2017-01-01

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and its progression significantly worsens the patient's quality of life. Although several drugs are available for DPN, all of these provide only symptomatic relief. We investigated the therapeutic effects of ghrelin for DPN, based on its various physiological functions. Seven patients with type 2 diabetes with typical clinical signs and symptoms of DPN were hospitalized. Synthetic human ghrelin (1.0 μg/kg) was administered intravenously for 14 days. Motor nerve conduction velocity (MCV) of the posterior tibial nerve improved significantly after the treatment, compared to that at baseline (35.1 ± 1.8 to 38.6 ± 1.8 m/s, p < 0.0001), while the MCV in six untreated patients did not change throughout hospitalization. The subjective symptoms assessed based on the total symptom score also significantly improved (15.6 ± 3.1 to 11.1 ± 2.2, p = 0.047). Although sensory nerve conduction velocity (SCV) of the sural nerve could not be detected in three patients at baseline, it was detected in two of the three patients after 14 days of ghrelin administration. Overall, SCV did not change significantly. Plasma glucose, but not serum C peptide, levels during a liquid meal tolerance test significantly improved after treatment. These results suggest that ghrelin may be a novel therapeutic option for DPN; however, a double-blind, placebo-controlled trial is needed in the future.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area.

PubMed

Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Nerbrand, Christina; Valdemarsson, Stig

2011-03-01

To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Patient survey study. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area

PubMed Central

Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Nerbrand, Christina; Valdemarsson, Stig

2011-01-01

Objective To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Design Patient survey study. Setting and subjects A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. Main outcome measures ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Results Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Conclusion Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted. PMID:21323498

High levels of anomalous self-experience are associated with longer duration of untreated psychosis.

PubMed

Haug, Elisabeth; Øie, Merete; Andreassen, Ole A; Bratlien, Unni; Nelson, Barnaby; Melle, Ingrid; Møller, Paul

2017-04-01

To investigate the relationship between anomalous self-experiences and duration of untreated psychosis in a sample of patients with first-episode schizophrenia spectrum disorders. Anomalous self-experiences were assessed by means of the Examination of Anomalous Self-Experience manual in 55 patients referred to their first adequate treatment for schizophrenia. Diagnoses, symptom severity, functioning and childhood trauma were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Premorbid Adjustment Scale, Social Functioning Scale and Childhood Trauma Questionnaire. Substance misuse was measured with the Drug Use Disorder Identification Test, and alcohol use was measured with the Alcohol Use Disorder Identification Test. Duration of untreated psychosis was measured in accordance with a standardized procedure. High levels of anomalous self-experiences are significantly associated with longer duration of untreated psychosis, an association which held after correcting for other variables associated with long duration of untreated psychosis. The field of early detection in psychosis is in need of additional clinical perspectives to make further progress. Improved understanding and assessment of anomalous self-experiences may help clinicians to detect these important phenomena and provide earlier help, and thus reduce treatment delay. © 2015 Wiley Publishing Asia Pty Ltd.

Co-morbidities increase the risk of disability pension among MS patients: a population-based nationwide cohort study.

PubMed

Tinghög, Petter; Björkenstam, Charlotte; Carstensen, John; Jansson, Catarina; Glaser, Anna; Hillert, Jan; Alexanderson, Kristina

2014-06-03

Multiple sclerosis (MS) is a chronic and often disabling disease. In 2005, 62% of the MS patients in Sweden aged 16-65 years were on disability pension. The objective of this study is to investigate whether the presence of common co-morbidities increase MS patients' risk for disability pension. This population-based cohort study included 4 519 MS patients and 4 972 174 non-MS patients who in 2005 were aged 17-64 years, lived in Sweden, and were not on disability pension. Patients with MS were identified in the nationwide in- and outpatient registers, while four different registers were used to construct three sets of measures of musculoskeletal, mental, and cardiovascular disorders. Time-dependent proportional hazard models with a five-year follow up were performed, adjusting for socio-demographic factors. All studied disorders were elevated among MS patients, regardless of type of measure used. MS patients with mental disorders had a higher risk for disability pension than MS patients with no such co-morbidities. Moreover, mental disorders had a synergistic influence on MS patients' risk for disability pension. These findings were also confirmed when conducting sensitivity analyses. Musculoskeletal disorders appeared to increase MS patients' risk for disability pension. The results with regard to musculoskeletal disorders' synergistic influence on disability pension were however inconclusive. Cardiovascular co-morbidity had no significant influence on MS-patients' risk for disability pension. Co-morbidities, especially mental disorders, significantly contribute to MS patients' risk of disability pension, a finding of relevance for MS management and treatment.

Effect of Psychiatric Intervention in Attempted Suicide: A Controlled Study

PubMed Central

Greer, Steven; Bagley, Christopher

1971-01-01

All patients presenting at the casualty department of King's College Hospital during the first six months of 1968 with deliberate self-poisoning or self-injury were followed up. Of 211 patients 204 (97%) were traced after a mean interval of 18 months (range one to two years). Despite official hospital policy, 22% had not been seen by a psychiatrist before discharge; these 44 untreated patients were compared with the remaining 160 who had received either brief (one or two interviews) or more prolonged psychiatric and social help. Subsequent suicidal attempts occurred significantly more often among untreated than among treated patients, prolonged treatment being associated with the best prognosis. The same trend was observed in respect of actual suicide, though the numbers were small and differences did not reach statistical significance. These findings held good when the untreated and treated groups were controlled for other variables which were found to be correlated with outcome. These results indicate that psychiatric intervention is associated with a significant reduction in subsequent suicidal behaviour. PMID:5100261

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pérez-Pimienta, Jose A.; Vargas-Tah, Alejandra; López-Ortega, Karla M.

Agave bagasse (AGB) has gained recognition as a drought-tolerant biofuel feedstock with high productivity in semiarid regions. A comparative analysis of ionic liquid (IL) and organosolv (OV) pretreatment technologies in AGB was performed using a sequential enzymatic saccharification and fermentation (SESF) strategy with cellulolytic enzymes and the ethanologenic Escherichia coli strain MS04. After pretreatment, 86% of xylan and 45% of lignin were removed from OV-AGB, whereas IL-AGB reduced lignin content by 28% and xylan by 50% when compared to the untreated biomass. High glucan ( > 90%) and xylan ( > 83%) conversion was obtained with both pretreated samples. Duringmore » the fermentation stage (48 h), 12.1 and 12.7 kg of ethanol were produced per 100 kg of untreated AGB for IL and OV, respectively. These comparative analyses showed the advantages of SESF using IL and OV in a biorefinery configuration where a better understanding of AGB recalcitrance is key for future applications.« less

Toxicological and chemical investigation of untreated municipal wastewater: Fraction- and species-specific toxicity.

PubMed

Hrubik, Jelena; Glisic, Branka; Tubic, Aleksandra; Ivancev-Tumbas, Ivana; Kovacevic, Radmila; Samardzija, Dragana; Andric, Nebojsa; Kaisarevic, Sonja

2016-05-01

Absence of a municipal wastewater (WW) treatment plant results in the untreated WW discharge into the recipient. The present study investigated toxic effects and chemical composition of water extracts and fractions from untreated WW and recipient Danube River (DR). Samples were prepared by solid-phase extraction and silica gel fractionation and screened for EROD activity and cytotoxicity using aquatic models, comprising of fish liver cells (PLHC-1) and a model of the early development of zebrafish embryos, while rat (H4IIE) and human (HepG2) hepatoma cells served as mammalian models. Polar fraction caused cytotoxicity and increased the EROD activity in PLHC-1 cells, and increased mortality and developmental abnormalities in developing zebrafish embryos. In H4IIE, polar fraction induced inhibition of cell growth and increased EROD activity, whereas HepG2 exerted low or no response to the exposure. Non-polar and medium-polar fractions were ineffective. Tentative identification by GC/MS showed that WW is characterized by the hydrocarbons, alkylphenols, plasticizers, and a certain number of benzene derivatives and organic acids. In DR, smaller number of organic compounds was identified and toxicity was less pronounced than in WW treatments. The present study revealed the potent toxic effect of polar fraction of untreated WW, with biological responses varying in sensitivity across organisms. Obtained results confirmed that fraction- and species-specific toxicity should be considered when assessing health risk of environmental pollution. Copyright © 2016 Elsevier Inc. All rights reserved.

Summary of studies on the blue-green autofluorescence and light transmission of the ocular lens

NASA Astrophysics Data System (ADS)

Van Best, Jaap A.; Kuppens, Esmeralda V.

1996-07-01

This paper reviews previous work done to demonstrate the clinical relevance of the measurement of blue-green autofluorescence and light transmission of the ocular lens. These can be determined quantitatively with fluorophotometry in a few seconds. Autofluorescence and transmission values are determined in healthy volunteers, in patients with insulin-dependent diabetes mellitus, and in patients with untreated glaucoma or untreated ocular hypertension. The lens autofluorescence of healthy volunteers increased linearly and transmission decreased exponentially with age. Each year of diabetes induced an increase of autofluorescence equal to one extra year of age. Untreated glaucoma or ocular hypertension had no significant effect on lens autofluorescence and transmission. Increased autofluorescence and decreased transmission values in comparison with values of a healthy population are proved to be indicative for an increased risk of developing cataract and the clinical usefulness of these measures is demonstrated. Diabetes is a risk factor for developing cataracts while untreated glaucoma or ocular hypertension is not.

Manganese-enhanced magnetic resonance microscopy of mineralization

USGS Publications Warehouse

Chesnick, I.E.; Todorov, T.I.; Centeno, J.A.; Newbury, D.E.; Small, J.A.; Potter, K.

2007-01-01

Paramagnetic manganese (II) can be employed as a calcium surrogate to sensitize magnetic resonance microscopy (MRM) to the processing of calcium during bone formation. At high doses, osteoblasts can take up sufficient quantities of manganese, resulting in marked changes in water proton T1, T2 and magnetization transfer ratio values compared to those for untreated cells. Accordingly, inductively coupled plasma mass spectrometry (ICP-MS) results confirm that the manganese content of treated cell pellets was 10-fold higher than that for untreated cell pellets. To establish that manganese is processed like calcium and deposited as bone, calvaria from the skull of embryonic chicks were grown in culture medium supplemented with 1 mM MnCl2 and 3 mM CaCl2. A banding pattern of high and low T2 values, consistent with mineral deposits with high and low levels of manganese, was observed radiating from the calvarial ridge. The results of ICP-MS studies confirm that manganese-treated calvaria take up increasing amounts of manganese with time in culture. Finally, elemental mapping studies with electron probe microanalysis confirmed local variations in the manganese content of bone newly deposited on the calvarial surface. This is the first reported use of manganese-enhanced MRM to study the process whereby calcium is taken up by osteoblasts cells and deposited as bone. ?? 2007 Elsevier Inc. All rights reserved.

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

PubMed

Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

2014-12-01

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Effects of topical steroids on tight junction proteins and spongiosis in esophageal epithelia of patients with eosinophilic esophagitis.

PubMed

Katzka, David A; Tadi, Ravikanth; Smyrk, Thomas C; Katarya, Eesha; Sharma, Anamay; Geno, Deborah M; Camilleri, Michael; Iyer, Prasad G; Alexander, Jeffrey A; Buttar, Navtej S

2014-11-01

The allergic response associated with eosinophilic esophagitis (EoE) occurs when food antigens permeate tight junction-mediated epithelial dilated intercellular spaces. We assessed whether levels of tight junction proteins correlate with the dilation of intercellular spaces (spongiosis) and the effects of topical steroids on these parameters. We assessed esophageal biopsy samples from 10 patients with active EoE treated with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease (controls) for degree of spongiosis. Immunohistochemical assays were used to determine the levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2, ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed blindly, with levels of tight junction proteins and degree of spongiosis rated on scales of 0 to 3. The mean degrees of spongiosis in untreated and treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6, 1.4, and 0.7, respectively. In biopsy specimens from patients treated with fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3 (P = .25 compared with untreated patients), respectively. The correlation between the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO-3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs ZO-3 staining). Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO-2) are detected in the esophageal mucosa of patients with EoE treated with steroids and individuals without esophageal disease. Without treatment, spongiosis increases, corresponding with reduced levels of filaggrin, ZO-3, and claudin-1. Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chromium in rivers impacted by tannery wastes determined by high performance liquid chromatography - inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Pereira de Abreu, M.-H.; Vignati, D.; Dominik, J.

2003-05-01

The total chromium concentrations by ICP-MS and HPLC-ICP-MS and the redox chromium species have been determined in rivers impacted by untreated wastes from tanneries at Fès (Morocco). The results obtained by two ICP-MS analysis methods showed significantly different chromium values at m/z 53. The higher values obtained with external calibration, can be attributed to matrix effects, especially ^{37}Cl ^{16}O at m/z 53. This is confirmed on the chromatograms by the presence of a peak at 100s with the anomalous ^{52}Cr/^{53}Cr isotopic ratio. The hexavalent chromium was not detected. Two trivalent chromium monomer species, Cr(OH)(H2O)5^{2+} and Cr(H2O)6^{3+}, were present in low concentrations. We suppose that the major part of chromium occurred as Cr(III) polymeric species which were not retained on the column. These Cr(III) forms are usually complexed with Cl^- or/and SO4^{2-}, used as tanning agents.

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

ClinicalTrials.gov

2013-06-13

Adult Malignant Mesenchymoma; Adult Rhabdomyosarcoma; Alveolar Childhood Rhabdomyosarcoma; Childhood Malignant Mesenchymoma; Embryonal Childhood Rhabdomyosarcoma; Embryonal-botryoid Childhood Rhabdomyosarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Previously Untreated Childhood Rhabdomyosarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma

The use of Endopep-MS to detect multiple subtypes of botulinum neurotoxins A, B, E, and F

NASA Astrophysics Data System (ADS)

Kalb, Suzanne R.; Smith, Theresa J.; Moura, Hercules; Hill, Karen; Lou, Jianlong; Geren, Isin N.; Garcia-Rodriguez, Consuelo; Marks, James D.; Smith, Leonard A.; Pirkle, James L.; Barr, John R.

2008-12-01

Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. Rapid determination of exposure to BoNT is an important public health goal. Previous work in our laboratory focused on the development of Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT A-G in buffer and BoNT A, B, E, and F in clinical samples. We introduce here the use of Endopep-MS to detect non-commercial subtypes of BoNT A, B, E, and F which have been associated with botulism outbreaks. We have now tested and successfully detected 15 of the 17 known subtypes of BoNT A, B, E, and F by Endopep-MS. Extraction of BoNT A and B from a complex mixture prior to analysis is accomplished by using monoclonal antibodies specific for the catalytically inactive heavy chain of the toxin. These antibodies have high-binding affinities and do not interfere with the catalytic activity of the light chain resulting in a lower limit of detection for BoNT A and B than previously reported. We also report for the first time limits of detection for BoNT A2, A3, B2, and bivalent B using Endopep-MS.

Interest in Providing Multiple Sclerosis Care and Subspecializing in Multiple Sclerosis Among Neurology Residents

PubMed Central

Teixeira-Poit, Stephanie; Kane, Heather L.; Frost, A. Corey; Keating, Michael; Olmsted, Murrey

2014-01-01

Background: Although detailed knowledge regarding treatment options for multiple sclerosis (MS) patients is largely limited to neurologists, shortages in the neurologist workforce, including MS subspecialists, are predicted. Thus, MS patients may have difficulties in gaining access to appropriate care. No systematic evaluation has yet been performed of the number of neurology residents planning to pursue MS subspecialization. This study identifies factors affecting interest in providing MS patient care or MS subspecialization among current neurology residents. Methods: We randomly selected half of all Accreditation Council of Graduate Medical Education–certified neurology residency programs in the continental United States to receive the neurology resident survey. Completed surveys were received from 218 residents. Results: Residents were significantly more likely to have increased interest in MS care when they participated in MS research, were interested in teaching, and indicated that the “ability to improve patient outcomes and quality of life” was a positive factor influencing their desire to provide MS patient care. Residents who were interested in providing MS care, interested in teaching, and indicated that “research opportunities” was a positive factor for providing MS patient care were significantly more likely to express interest in MS subspecialization. Conclusions: Increasing opportunities to interact with MS patients, learn about MS care, and participate in MS research may increase interest in MS care and subspecialization among neurology residents. Opportunities to educate residents regarding MS patient care may affect residents’ attitudes. PMID:24688352

Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

PubMed Central

2011-01-01

Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression. PMID:21831310

N-terminal pro-brain natriuretic peptide levels and abnormal geometric patterns of left ventricle in untreated hypertensive patients.

PubMed

Elbasan, Zafer; Gür, Mustafa; Sahin, Durmuş Yıldıray; Kırım, Sinan; Akyol, Selahattin; Kuloğlu, Osman; Koyunsever, Nermin Yıldız; Seker, Taner; Kıvrak, Ali; Caylı, Murat

2014-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts cardiovascular events and mortality in hypertensive patients. Relationship between NT-proBNP level and left ventricular (LV) hypertrophy is well known in hypertensive patients. However, the studies investigating relationship between LV geometric patterns and serum NT-proBNP level have conflicting results and are in a limited number. The goal of the present study is to investigate relation between NT-proBNP and abnormal LV geometric patterns in untreated hypertensive patients. Measurements were obtained from 273 patients with untreated essential hypertension (mean age = 51.7 ± 5.8 years) and 44 healthy control subjects (mean age; 51.3 ± 4.7). Four different geometric patterns (NG: normal geometry; CR: concentric remodelling; EH: eccentric hypertrophy; CH: concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness. NT-proBNP and other biochemical markers were measured in all subjects. The highest NT-proBNP levels were determined in the CH group compared with the control group and other geometric patterns (p < 0.05). NT-proBNP levels of all geometric patterns were higher than the control group (p < 0.05, for all). NT-proBNP levels were similar between CR and NG groups (p > 0.05). NT-proBNP was independently associated with LV geometry (β = 0.304, p = 0.003) and LVMI (β = 0.266, p = 0.007) in multiple linear regression analysis. Serum NT-proBNP level was independently associated with LVMI and LV geometry in untreated hypertensive patients with preserved ejection fraction.

LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients

PubMed Central

Duzkale, Hatice; Schweighofer, Carmen D.; Coombes, Kevin R.; Barron, Lynn L.; Ferrajoli, Alessandra; O'Brien, Susan; Wierda, William G.; Pfeifer, John; Majewski, Tadeusz; Czerniak, Bogdan A.; Jorgensen, Jeffrey L.; Medeiros, L. Jeffrey; Freireich, Emil J; Keating, Michael J.

2011-01-01

We previously identified LDOC1 as one of the most significantly differentially expressed genes in untreated chronic lymphocytic leukemia (CLL) patients with respect to the somatic mutation status of the immunoglobulin heavy-chain variable region genes. However, little is known about the normal function of LDOC1, its contribution to the pathophysiology of CLL, or its prognostic significance. In this study, we have investigated LDOC1 mRNA expression in a large cohort of untreated CLL patients, as well as in normal peripheral blood B-cell (NBC) subsets and primary B-cell lymphoma samples. We have confirmed that LDOC1 is dramatically down-regulated in mutated CLL cases compared with unmutated cases, and have identified a new splice variant, LDOC1S. We show that LDOC1 is expressed in NBC subsets (naive > memory), suggesting that it may play a role in normal B-cell development. It is also expressed in primary B-cell lymphoma samples, in which its expression is associated with somatic mutation status. In CLL, we show that high levels of LDOC1 correlate with biomarkers of poor prognosis, including cytogenetic markers, unmutated somatic mutation status, and ZAP70 expression. Finally, we demonstrate that LDOC1 mRNA expression is an excellent predictor of overall survival in untreated CLL patients. PMID:21310924

Initial study of transdermal oxybutynin for treating hyperhidrosis.

PubMed

Millán-Cayetano, José Francisco; Del Boz, Javier; Toledo-Pastrana, Tomas; Nieto-Guindo, Miriam; García-Montero, Pablo; de Troya-Martín, Magdalena

2017-06-01

Oral oxybutynin for treating hyperhidrosis is effective and safe. Its side-effects are mild but frequent so we consider whether transdermal oxybutynin (considered to have a better side-effect profile) could be an alternative for treating hyperhidrosis. During 2015, a prospective study was conducted. Epidemiological variables, effectiveness (using the Hyperhidrosis Disease Severity Scale) and tolerance to transdermal oxybutynin were compiled concerning two different groups (patients previously treated or untreated with oral oxybutynin), at baseline, and at 3 and 12 months. Seven previously treated and six previously untreated patients were included. Five patients in the first group discontinued the treatment within 3 months. Of the two remaining patients, one reported ineffectiveness and the other obtained an excellent response but discontinued due to local irritation. Among the untreated patients, two showed no response and four experienced improvement (three with "partial response" and one with "excellent response"). All patients discontinued treatment within 12 months. No major adverse effects were observed. The absence of active metabolites after transdermal oxybutynin could result in less effectiveness than oral oxybutynin, although it is usually well tolerated. In conclusion, transdermal oxybutynin could have low effectiveness for the treatment of hyperhidrosis in patients following intolerance to oral oxybutynin but could provide good results in patients who have never tried systemic drugs. © 2017 Japanese Dermatological Association.

Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis

PubMed Central

Rubin, Leah H.; Carter, C. Sue; Bishop, Jeffrey R.; Pournajafi-Nazarloo, Hossein; Harris, Margret S. H.; Hill, Scot K.; Reilly, James L.; Sweeney, John A.

2013-01-01

Background In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine-vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. Method Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. Results Patients demonstrated increased AVP levels compared to controls (p=0.01). Higher AVP levels were associated with greater positive symptoms (r=0.58, p=0.03) and worse verbal learning (r=−0.63, p=0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. Conclusion Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia. PMID:23465965

A Rare Case of an Adult with Untreated Bladder Exstrophy Presenting with Signet-Ring Cell Adenocarcinoma of Urinary Bladder.

PubMed

Savalia, Abhishek J; Kumar, Vikash; Kasat, Gaurav; Sawant, Ajit

2016-11-01

Untreated bladder exstrophy in an adult is rare, as the defect is obvious and primary reconstruction is usually done in infancy. There are less than 90 reported cases of primary adenocarcinoma in an untreated bladder exstrophy in literature and only two such case reports from India. Of these, only one case was of signet-ring cell type of mucinous adenocarcinoma. Here we report the second case of signet-ring cell adenocarcinoma in a 63 year old male with untreated bladder exstrophy (oldest patient in literature), to highlight the extreme rarity, yet distinct possibility and challenges faced in surgical management of such cases.

Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

PubMed Central

Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

2015-01-01

Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in increasing the risk of liver injury. PMID:26543313

Dietary Interventions in Multiple Sclerosis: Development and Pilot-Testing of an Evidence Based Patient Education Program

PubMed Central

Riemann-Lorenz, Karin; Eilers, Marlene; von Geldern, Gloria; Schulz, Karl-Heinz; Köpke, Sascha; Heesen, Christoph

2016-01-01

Background Dietary factors have been discussed to influence risk or disease course of multiple sclerosis (MS). Specific diets are widely used among patients with MS. Objective To design and pilot-test an evidence based patient education program on dietary factors in MS. Methods We performed a systematic literature search on the effectiveness of dietary interventions in MS. A web-based survey among 337 patients with MS and 136 healthy controls assessed knowledge, dietary habits and information needs. An interactive group education program was developed and pilot-tested. Results Fifteen randomised-controlled trials (RCTs) were included in the systematic review. Quality of evidence was low and no clear benefit could be seen. Patients with MS significantly more often adhered to a `Mediterranean Diet`(29.7% versus 14.0%, p<0.001) compared to controls. 143 (42%) of the patients with MS had tried special MS diets. Important information needs addressed effectiveness of MS diets (44%) and relation between nutrition and MS (43%). A pilot test of our newly developed patient education program with 13 participants showed excellent comprehensibility and the MS-specific content was judged as very important. However, the poor evidence base for dietary approaches in MS was perceived disappointing. Conclusions Development and pilot-testing of an evidence-based patient education program on nutrition and MS is feasible. Patient satisfaction with the program suffers from the lack of evidence. Further research should focus on generating evidence for the potential influence of lifestyle habits (diet, physical activity) on MS disease course thus meeting the needs of patients with MS. PMID:27764237

Dietary Interventions in Multiple Sclerosis: Development and Pilot-Testing of an Evidence Based Patient Education Program.

PubMed

Riemann-Lorenz, Karin; Eilers, Marlene; von Geldern, Gloria; Schulz, Karl-Heinz; Köpke, Sascha; Heesen, Christoph

2016-01-01

Dietary factors have been discussed to influence risk or disease course of multiple sclerosis (MS). Specific diets are widely used among patients with MS. To design and pilot-test an evidence based patient education program on dietary factors in MS. We performed a systematic literature search on the effectiveness of dietary interventions in MS. A web-based survey among 337 patients with MS and 136 healthy controls assessed knowledge, dietary habits and information needs. An interactive group education program was developed and pilot-tested. Fifteen randomised-controlled trials (RCTs) were included in the systematic review. Quality of evidence was low and no clear benefit could be seen. Patients with MS significantly more often adhered to a `Mediterranean Diet`(29.7% versus 14.0%, p<0.001) compared to controls. 143 (42%) of the patients with MS had tried special MS diets. Important information needs addressed effectiveness of MS diets (44%) and relation between nutrition and MS (43%). A pilot test of our newly developed patient education program with 13 participants showed excellent comprehensibility and the MS-specific content was judged as very important. However, the poor evidence base for dietary approaches in MS was perceived disappointing. Development and pilot-testing of an evidence-based patient education program on nutrition and MS is feasible. Patient satisfaction with the program suffers from the lack of evidence. Further research should focus on generating evidence for the potential influence of lifestyle habits (diet, physical activity) on MS disease course thus meeting the needs of patients with MS.

The Application of SILAC Mouse in Human Body Fluid Proteomics Analysis Reveals Protein Patterns Associated with IgA Nephropathy.

PubMed

Zhao, Shilin; Li, Rongxia; Cai, Xiaofan; Chen, Wanjia; Li, Qingrun; Xing, Tao; Zhu, Wenjie; Chen, Y Eugene; Zeng, Rong; Deng, Yueyi

2013-01-01

Body fluid proteome is the most informative proteome from a medical viewpoint. But the lack of accurate quantitation method for complicated body fluid limited its application in disease research and biomarker discovery. To address this problem, we introduced a novel strategy, in which SILAC-labeled mouse serum was used as internal standard for human serum and urine proteome analysis. The SILAC-labeled mouse serum was mixed with human serum and urine, and multidimensional separation coupled with tandem mass spectrometry (IEF-LC-MS/MS) analysis was performed. The shared peptides between two species were quantified by their SILAC pairs, and the human-only peptides were quantified by mouse peptides with coelution. The comparison for the results from two replicate experiments indicated the high repeatability of our strategy. Then the urine from Immunoglobulin A nephropathy patients treated and untreated was compared by this quantitation strategy. Fifty-three peptides were found to be significantly changed between two groups, including both known diagnostic markers for IgAN and novel candidates, such as Complement C3, Albumin, VDBP, ApoA,1 and IGFBP7. In conclusion, we have developed a practical and accurate quantitation strategy for comparison of complicated human body fluid proteome. The results from such strategy could provide potential disease-related biomarkers for evaluation of treatment.

Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2016-09-08

Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Serum Paraoxonase Activity and Malondialdehyde Serum Concentrations Remain Unaffected in Response to Hydroxyurea Therapy in β-Thalassemia Patients.

PubMed

Zohaib, Muhammad; Ansari, Saqib H; Hashim, Zehra; Shamsi, Tahir S; Zarina, Shamshad

2016-07-01

β-Thalassemia is the most common hereditary disorder characterized by reduced production of β-globin chains of hemoglobin A (HbA). In recent years, hydroxyurea (HU) has shown promising therapeutic benefits in patients with β-thalassemia by fetal hemoglobin augmentation. We have analyzed effects of hydroxyurea treatment on oxidative stress in β-thalassemia patients by assessing activities of paraoxonase (PON) and arylesterase along with malondialdehyde (MDA) and total reactive oxygen species (ROS) concentrations. Blood samples from 159 individuals including 56 HU-treated and 58 untreated β-thalassemia patients and 45 healthy controls were analyzed. PON activity was found to be highest in healthy individuals (177.76 ± 4.44 U/mL) as compared to treated (52.67 ± 3.65 U/mL) and untreated (55.11 ± 3.26 U/mL) patients. A similar trend was observed in the case of arylesterase activity in normal, β-thalassemia-treated, and untreated (210.0 ± 11.25 U/mL, 163.03 ± 9.04 U/mL, 139.77 ± 10.10 U/mL) subjects. Serum MDA concentrations (2.59 ± 0.09 nmol/mL, 2.45 ± 0.08 nmol/mL, and 1.15 ± 0.05 nmol/mL) and total ROS concentrations (3.73 ± 0.20 nmol/mL, 3.54 ± 0.23 nmol/mL, and 2.45 ± 0.14 nmol/mL) were significantly elevated in both groups (untreated and treated) as compared to healthy individuals (P < .01). Oxidative stress was found to be markedly elevated in β-thalassemia patients as compared to healthy controls. Insignificant differences were, however, observed in mean concentrations of PON1 paraoxonase and arylesterase activities, serum MDA concentration and total ROS concentrations between HU-treated and untreated patients. We propose that HU therapy alone seems to be ineffective in managing oxidative stress and is likely to offer a better clinical outcome when supplemented with efficient iron chelation therapy and antioxidants. © 2015, The American College of Clinical Pharmacology.

Reduced Dual-Task Performance in MS Patients Is Further Decreased by Muscle Fatigue.

PubMed

Wolkorte, Ria; Heersema, Dorothea J; Zijdewind, Inge

2015-06-01

Multiple sclerosis (MS) can be accompanied by motor, cognitive, and sensory impairments. Additionally, MS patients often report fatigue as one of their most debilitating symptoms. It is, therefore, expected that MS patients will have difficulties in performing cognitive-motor dual tasks (DTs), especially in a fatiguing condition. To determine whether MS patients are more challenged by a DT than controls in a fatiguing and less-fatiguing condition and whether DT performance is associated with perceived fatigue. A group of 19 MS patients and 19 age-, sex-, and education-matched controls performed a cognitive task (2-choice reaction time task) separately or concurrent with a low-force or a high-force motor task (index finger abduction at 10% or 30% maximal voluntary contraction). MS patients performed less well on a cognitive task than controls. Cognitive task performance under DT conditions decreased more for MS patients. Moreover, under high-force DT conditions, cognitive performance declined in both groups but to a larger degree for MS patients. Besides a decline in cognitive task performance, MS patients also showed a stronger decrease in motor performance under high-force DT conditions. DT costs were positively related to perceived fatigue as measured by questionnaires. Compared with controls, MS patients performed less well on DTs as demonstrated by a reduction in both cognitive and motor performances. This performance decrease was stronger under fatiguing conditions and was related to the sense of fatigue of MS patients. These data illustrate problems that MS patients may encounter in daily life because of their fatigue. © The Author(s) 2014.

Computerized cognitive testing in patients with type I Gaucher disease: effects of enzyme replacement and substrate reduction.

PubMed

Elstein, Deborah; Guedalia, Judith; Doniger, Glen M; Simon, Ely S; Antebi, Vered; Arnon, Yael; Zimran, Ari

2005-02-01

Because of concern for drug-induced cognitive dysfunction during clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher disease and because it has been suggested that some patients with type 1 Gaucher disease may develop neurocognitive impairment as part of the natural history, two different batteries of neuropsychological tests were devised to examine these issues. Using these tests, cognitive function was assessed in patients treated with miglustat, in patients receiving enzyme replacement (standard care for symptomatic patients), and in untreated (milder) patients. For this study, 55/60 patients exposed to miglustat in Israel participated in psychologist-administered testing; 36/55 participated in computerized testing. Of these, 31 enzyme-treated patients and 22 untreated patients participated in the psychologist-administered testing, and 15 enzyme-treated patients and 18 untreated patients participated in computerized testing. The psychologist-administered battery consisted of 18 standard neuropsychological subtests specific to executive and visuospatial functioning. The computerized battery (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping multiple cognitive domains. Between-group analyses for each modality compared cognitive performance. In the psychologist-administered testing, patients exposed to miglustat performed significantly less well than the other groups in 5/18 subtests. On the computerized tests, all patients performed comparably to normal controls. Scores in patients exposed to miglustat were higher than in untreated patients, particularly in visuospatial function, whereas enzyme-treated patients performed less well. However, with the exception of visuospatial function, these results were not statistically significant. It is unclear why different testing methods yielded discordant results. Any dysfunction suggested by the current study is apparently subtle and of doubtful clinical relevance given that cognitive status did not interfere with patients' daily intellectual function. The computerized battery has methodological advantages (e.g., language options, objectivity, brevity, and ease of use) that make it well-suited for longitudinal studies, for long-term surveillance of substrate reduction therapy as well as for comparisons with other lysosomal storage disorders and other chronic diseases. These preliminary findings should allay fears of cognitive dysfunction due to short-term miglustat therapy.

Is There Extra Cost of Institutional Care for MS Patients?

PubMed Central

Noyes, Katia; Bajorska, Alina; Weinstock-Guttman, Bianca

2013-01-01

Throughout life, patients with multiple sclerosis (MS) require increasing levels of support, rehabilitative services, and eventual skilled nursing facility (SNF) care. There are concerns that access to SNF care for MS patients is limited because of perceived higher costs of their care. This study compares costs of caring for an MS patient versus those of a typical SNF patient. We merged SNF cost report data with the 2001–2006 Nursing Home Minimum Data Set (MDS) to calculate percentage of MS residents-days and facility case-mix indices (CMIs). We estimated the average facility daily cost using hybrid cost functions, adjusted for facility ownership, average facility wages, CMI-adjusted number of SNF days, and percentage of MS residents-days. We describe specific characteristics of SNF with high and low MS volumes and examine any sources of variation in cost. MS patients were no longer more costly than typical SNF patients. A greater proportion of MS patients had no significant effect on facility daily costs (P = 0.26). MS patients were more likely to receive care in government-owned facilities (OR = 1.904) located in the Western (OR = 2.133) and Midwestern (OR = 1.3) parts of the USA (P < 0.05). Cost of SNF care is not a likely explanation for the perceived access barriers that MS patients face. PMID:24163769

Psychiatric diagnoses, medication and risk for disability pension in multiple sclerosis patients; a population-based register study.

PubMed

Brenner, Philip; Alexanderson, Kristina; Björkenstam, Charlotte; Hillert, Jan; Jokinen, Jussi; Mittendorfer-Rutz, Ellenor; Tinghög, Petter

2014-01-01

Psychiatric comorbidity is common among multiple sclerosis (MS) patients. The majority of MS patients of working ages are on disability pension. The aims of this study were to chart the prevalences of psychiatric diagnoses and medications among MS patients of working ages, and to investigate their association with the risk for future disability pension. This nationwide, population-based prospective cohort study includes 10,750 MS patients and 5,553,141 non-MS individuals who in 2005 were aged 17-64 years. Psychiatric diagnoses and medications were identified using nationwide registers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated adjusting for socio-demographics. Furthermore, a survival analysis with five-year follow-up was performed among the 4,571 MS patients not on disability pension in 2005, with psychiatric diagnoses and medication as risk factors, and disability pension as the outcome. Among MS patients, 35% had been prescribed psychiatric medication compared to 10% of non-MS individuals, adjusted OR 3.72 (95% CI 3.57 to 3.88). Ten percent of MS patients had received a psychiatric diagnosis, compared to 5.7% of non-MS individuals, OR 1.82 (95% CI 1.71 to 1.94). Serotonin reuptake inhibitors (SSRIs), were the most commonly prescribed drugs (17%) among MS patients, while depression (4.8%) was the most common psychiatric diagnosis. In the survival analysis, MS patients with any psychiatric diagnosis had a hazard ratio (HR) of 1.83 (95% CI 1.53 to 2.18) for disability pension compared to other MS patients. MS patients with any psychiatric drug prescription had a HR for disability pension of 2.09 (95% CI 1.84 to 2.33). Psychiatric diagnoses and medications are common among MS patients and adversely affect risk for disability pension. This highlights the importance of correct diagnosis and management of psychiatric comorbidity, in a clinical as well as in a societal perspective.

Celiac disease causing severe osteomalacia: an association still present in Morocco!

PubMed

Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

2014-01-01

Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.

Celiac disease causing severe osteomalacia: an association still present in Morocco!

PubMed Central

Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

2014-01-01

Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities. PMID:25667705

Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal.

PubMed

Cheraghlou, Shayan; Kuo, Phoebe; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

2018-03-01

Oral cavity cancer is the most common malignant disease of the head and neck. The natural course of the disease is poorly characterized and unavailable for patient consideration during initial treatment planning. Our primary objective was to outline this natural history, with a secondary aim of identifying predictors of treatment refusal. Retrospective review of adult patients with oral cavity cancer who refused surgery that was recommended by their physician in the National Cancer Database. Demographic, tumor, and survival variables were included in the analyses. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. Patients who were older, uninsured, had government insurance, or had more advanced disease were more likely to go untreated. Survival among untreated patients was poor, but there was a small proportion of patients surviving long term. Five-year survival rates ranged from 31.1% among early-stage patients to 12.6% among stage 4 patients. Although the natural course of oral cavity cancer carries a poor prognosis, there are a number of patients with longer-than-expected survival. The survival estimates may provide supplemental information for patients deciding whether to pursue treatment. In addition to age and extent of disease, system factors such as insurance status and facility case volume are associated with a patient's likelihood of refusing treatment. 4. Laryngoscope, 128:664-669, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies

PubMed Central

El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

2017-01-01

Background Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. Objectives To evaluate the efficacy and safety of ERT for AFD. Materials and methods For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. Results 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Conclusions Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended. PMID:28296917

Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

PubMed

El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

2017-01-01

Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta over agalsidase alfa or untreated patients. A linear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

PubMed

Hittelman, W N; Broussard, L C; McCredie, K

1979-11-01

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2014-03-20

Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

[The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)].

PubMed

Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine

2014-09-01

The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina.

PubMed

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.

Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-05-02

Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease?

PubMed

Erro, Roberto; Santangelo, Gabriella; Barone, Paolo; Picillo, Marina; Amboni, Marianna; Longo, Katia; Giordano, Flavio; Moccia, Marcello; Allocca, Roberto; Pellecchia, Maria Teresa; Vitale, Carmine

2014-12-01

Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored. We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation. We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up. This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI. © The Author(s) 2014.

Platelets in blood stored in untreated and siliconed glass bottles and plastic bags

PubMed Central

Kissmeyer-Nielsen, F.; Madsen, C. B.; Nedergaard, Jytte

1961-01-01

Platelet survival was determined using untreated and siliconed glass bottles and plastic bags (Fenwal) for collecting and storing blood. The platelets were tagged in vivo with P32 in six polycythaemic patients undergoing treatment with P32. The results showed that fresh ACD blood collected in untreated glass, siliconed glass, and plastic gave the same recovery of platelets in the recipients. The use of EDTA (Fenwal formula) as anticoagulant gave results inferior to those obtained with blood using ACD as anticoagulant. Even after storage up to 24 hours in untreated glass bottles (ordinary bank blood) a satisfactory recovery of platelets was observed. After storage for 72 hours the recovery was less but not negligible. PMID:14456481

Duration of untreated psychosis/illness and brain volume changes in early psychosis.

PubMed

Rapp, Charlotte; Canela, Carlos; Studerus, Erich; Walter, Anna; Aston, Jacqueline; Borgwardt, Stefan; Riecher-Rössler, Anita

2017-09-01

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a "toxic" effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms. Copyright © 2017. Published by Elsevier B.V.

Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh

PubMed Central

Tabassum, Shahina; Ullah Munshi, Saif; Hossain, Marufa; Imam, Akhter

2014-01-01

ABSTRACT Background and aim Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels. Materials and methods The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR. Results The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p < 0.01). Expression of PECAM-1 was positively correlated with serum ALT levels of both untreated (r = 0.580) and treated (r = 0.566) CHB patients. Moreover, in both untreated and treated groups, these gene expressions were positively correlated to serum HBV DNA load with the correlation coefficient r = 0.545 and r = 0.591 respectively. Conclusion PECAM-1 may be used as a biomarker for assessment of inflammatory activity as well as therapeutic response in CHB patients. How to cite this article: Sultana N, Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91. PMID:29699354

Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy.

PubMed

Cabrerizo, Javier; Livny, Eitan; Musa, Fayyaz U; Leeuwenburgh, Paulien; van Dijk, Korine; Melles, Gerrit R J

2014-10-01

The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED-affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. Compared with untreated FED-affected eyes, best spectacle-corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome.

EEG abnormalities and two year outcome in first episode psychosis.

PubMed

Manchanda, R; Norman, R; Malla, A; Harricharan, R; Takhar, J; Northcott, S

2005-03-01

This study examines the relationship of EEG to 2 year symptomatic outcome, duration of illness and untreated psychosis and gender. A total of 122 patients presenting for treatment of first episode psychosis had their baseline EEG classified by modified Mayo Clinic system criteria as normal, essentially normal or dysrhythmia. Positive and negative symptoms of psychoses were rated on entry and after 2 years of treatment. The socio-demographic variables and duration of illness and of untreated psychosis were also recorded. Patients with a normal EEG showed significantly more reduction in both positive and negative symptoms of psychoses over 2 years and were more likely to be in 'remission' as compared with the essentially normal or dysrhythmia group. The dysrhythmic group had significantly higher duration of illness than either the normal or essentially normal groups. There were no gender differences in the distribution of EEGs. An abnormal EEG in patients with first episode psychosis is associated with a poorer prognosis and a longer duration of untreated illness. Copyright (c) Blackwell Munksgaard 2005

Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

PubMed

Pornsriniyom, Darakul; Kim, Hu won; Bena, James; Andrews, Noah D; Moul, Douglas; Foldvary-Schaefer, Nancy

2014-08-01

Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term echocardiographic follow-up of untreated 2+ functional tricuspid regurgitation in patients undergoing mitral valve surgery†

PubMed Central

Kusajima, Kunio; Fujita, Tomoyuki; Hata, Hiroki; Shimahara, Yusuke; Miura, Sayaka; Kobayashi, Junjiro

2016-01-01

OBJECTIVES Concomitant tricuspid valve surgery with mitral valve surgery is recommended for patients with severe functional tricuspid regurgitation (TR). However, the treatment for 2+ TR (mild TR) remains controversial. Here, we evaluated the long-term results of untreated 2+ TR in patients undergoing mitral valve surgery. METHODS We retrospectively reviewed the records of 96 patients with untreated 2+ TR among 885 patients who underwent mitral valve surgery from 2003 to 2010. Exclusion criteria were tricuspid valve surgery (TVS), emergency surgery, primary TR and pacemaker lead through the tricuspid valve. We assessed survival and freedom from heart failure. The freedom from 3+ (moderate) or 4+ (severe) TR was investigated by echocardiographic data at pre- and postoperative week 1, then at 1, 3, 5, 7 and 10 postoperative years, which were compared with those in patients who had 2+ TR preoperatively and underwent concomitant TVS in the same period (n = 47). RESULTS The mean follow-up was 7.1 ± 2.7 years. There was no 30-day mortality. The survival rate was 97.5% at 5 years and 87.5% at 10 years. The independent risk factors for mortality were age (OR 1.2, P = 0.03) and left ventricular ejection fraction (OR 0.9, P = 0.03). Untreated 2+ TR improved transiently within the first postoperative year (P < 0.001), but progressed again in the mid- to long term. Freedom from ≥3+ TR was 64.2% at 5 years and 46.7% at 10 years, which was significantly lower than that from ≥3+ TR in patients who underwent concomitant TVS (P = 0.006). The independent risk factors for TR progression (≥3 + TR) were age (OR 1.1, P = 0.005), atrial fibrillation (OR 2.2, P = 0.04) and tricuspid annular diameter (TAD) index (mm/m2; OR 1.1, P = 0.02). Receiver operating characteristic curves showed that the optimal TAD index cut-off value was 21.0 for long-term survival [area under the curve (AUC) = 0.72] and 21.2 for TR progression (AUC = 0.64). CONCLUSIONS Although untreated, 2+ TR significantly improved after mitral valve surgery, it then progressed again in the mid- to long term. Therefore, concomitant TVS should be considered in patients with 2+ TR who have dilated tricuspid annulus or atrial fibrillation, if feasible. PMID:26993477

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

PubMed

Calabrese, Massimiliano; Gajofatto, Alberto; Gobbin, Francesca; Turri, Giulia; Richelli, Silvia; Matinella, Angela; Oliboni, Eugenio Simone; Benedetti, Maria Donata; Monaco, Salvatore

2015-04-01

Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs. © The Author(s), 2014.

Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

PubMed Central

Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

2012-01-01

Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

PubMed

Magnano, Laura; Montoto, Silvia; González-Barca, Eva; Briones, Javier; Sancho, Juan Manuel; Muntañola, Ana; Salar, Antonio; Besalduch, Joan; Escoda, Lourdes; Moreno, Carol; Domingo-Domenech, Eva; Estany, Cristina; Oriol, Albert; Altés, Albert; Pedro, Carmen; Gardella, Santiago; Asensio, Antoni; Vivancos, Pilar; Fernández de Sevilla, Alberto; Ribera, Josep María; Colomer, Dolors; Campo, Elias; López-Guillermo, Armando

2017-04-01

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Health-care disparities stemming from sexual orientation of Italian patients with Multiple Sclerosis: A cross-sectional web-based study.

PubMed

Lavorgna, Luigi; Moccia, Marcello; Russo, Antonio; Palladino, Raffaele; Riccio, Lucia; Lanzillo, Roberta; Brescia Morra, Vincenzo; Tedeschi, Gioacchino; Bonavita, Simona

2017-04-01

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=-0.449; p<0.001; 95%CI=-0.682 to -0.217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95%CI=1.011-4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status. Copyright © 2017. Published by Elsevier B.V.

Metabolic syndrome in patients with psoriasis: A comparative study.

PubMed

Lakshmi, Sristi; Nath, Amiya Kumar; Udayashankar, Carounanidy

2014-04-01

Psoriasis patients are at increased risk of developing the metabolic syndrome (MS). Proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6 that are increased in the psoriatic plaques are known to contribute to features of MS such as hypertension, dyslipidemia and insulin resistance. (1) To establish the frequency of MS in patients with psoriasis. (2) To study the risk factors associated with MS in psoriasis. A hospital based comparative study was conducted involving 40 adult patients with psoriasis and 40 age- and sex-matched controls. All participants were evaluated for components of MS. Both groups included 31 males and 9 females. The mean age of the cases and controls were 49.95 years and 49.35 years, respectively. Psoriasis patients with MS had a statistically significant higher mean age (56.31 ± 11.36 years) compared with those without MS (46.89 ± 11.51 years). MS was present in 13 out of 40 (32.5%) patients with psoriasis and 12 out of 40 (30%) controls; this difference was not statistically significant. Higher age and female gender correlated with the presence of MS in psoriasis patients. The presence of MS in psoriasis patients was statistically independent of psoriasis area severity index score, body surface area involvement or psoriatic arthropathy. Our results suggest that there is no close correlation between psoriasis and MS in South Indian patients.

Autoimmune Disease Prevalence in a Multiple Sclerosis Cohort in Argentina

PubMed Central

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

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. PMID:25170425

Study of the propensity for hemorrhage in Hispanic Americans with stroke.

PubMed

Frey, James L; Jahnke, Heidi K; Goslar, Pamela W

2008-01-01

Multiple sources document a higher proportion of intraparenchymal hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We sought an explanation for this phenomenon through analysis of multiple variables in our hospital-based stroke population. We performed univariate and multivariate analysis of risk factors in our HIS and WHI patients with stroke to identify differences that might account for a greater propensity for HEM in HIS patients. Multivariate analysis disclosed that the risk of HEM correlated significantly with untreated hypertension (HTN), HIS ethnicity, and heavy alcohol intake. A negative correlation was found for hyperlipidemia and diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN and heavy alcohol intake, with HIS men being at greatest risk. HIS patients with stroke in our hospital-based population appear relatively more prone to HEM than do WHI patients. This risk correlates with a greater likelihood of having untreated HTN and heavy alcohol intake, more so for HIS men. The explanation appears to be a relative lack of health awareness and involvement in our health care system. The possibility that HIS ethnicity itself constitutes a biological risk factor for HEM remains a matter of speculation. Validation of this work with community data should lead to remediation through a community-based effort.

A curative regimen would decrease HIV prevalence but not HIV incidence unless targeted to an ART-naïve population.

PubMed

Dimitrov, Dobromir T; Kiem, Hans-Peter; Jerome, Keith R; Johnston, Christine; Schiffer, Joshua T

2016-02-24

HIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS, and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence. The basic reproduction number was calculated to study the potential for the epidemic to be eliminated. We explored scenarios with and without the assumption that patients enrolled into HIV cure programs need to be on antiretroviral treatment (ART). In our simulations, curative regimes had limited impact on HIV incidence if only ART patients were eligible for cure. Cure implementation had a significant impact on HIV incidence if ART-untreated patients were enrolled directly into cure programs. Concurrent HIV prevention programs moderately decreased the percent of ART treated or cured patients needed to achieve elimination. We project that widespread implementation of HIV cure would decrease HIV prevalence under all scenarios but would only lower rate of new infections if ART-untreated patients were targeted. Current efforts to identify untreated HIV patients will gain even further relevance upon availability of an HIV cure.

Cross-Species Analysis of Nicotine-Induced Proteomic Alterations in Pancreatic Cells

PubMed Central

Paulo, Joao A.; Urrutia, Raul; Kadiyala, Vivek; Banks, Peter

2014-01-01

Background Toxic compounds in tobacco, such as nicotine, may have adversely affect pancreatic function. We aim to determine nicotine-induced protein alterations in pancreatic cells, which may reveal a link between nicotine exposure and pancreatic disease. Methods We compared the proteomic alterations induced by nicotine treatment in cultured pancreatic cells (mouse, rat and human stellate cells and human duct cells) using mass spectrometry-based techniques, specifically GeLC-MS/MS and spectral counting. Results We identified thousands of proteins in pancreatic cells, hundreds of which were identified exclusively or in higher abundance in either nicotine-treated or untreated cells. Inter-species comparisons of stellate cell proteins revealed several differentially-abundant proteins (in nicotine treated versus untreated cells) common among the 3 species. Proteins appearing in all nicotine-treated stellate cells include amyloid beta (A4), procollagen type VI alpha 1, integral membrane protein 2B,and Toll interacting protein. Conclusions Proteins which were differentially expressed upon nicotine treatment across cell lines, were enriched in certain pathways, including nAChR, cytokine, and integrin signaling. At this analytical depth, we conclude that similar pathways are affected by nicotine, but alterations at the protein level among stellate cells of different species vary. Further interrogation of such pathways will lead to insights into the potential effect of nicotine on pancreatic cells at the biomolecular level and the extension of this concept to the effect of nicotine on pancreatic disease. PMID:23456891

Toxicological Assessment and UV/TiO2-Based Induced Degradation Profile of Reactive Black 5 Dye

NASA Astrophysics Data System (ADS)

Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M. N.; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

2018-01-01

In this study, the toxicological and degradation profile of Reactive Black 5 (RB5) dye was evaluated using a UV/TiO2-based degradation system. Fourier transform infrared spectroscopy (FT-IR), thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) techniques were used to evaluate the degradation level of RB5. The UV-Vis spectral analysis revealed the disappearance of peak intensity at 599 nm (λmax). The FT-IR spectrum of UV/TiO2 treated dye sample manifest appearance of new peaks mainly because of the degraded product and/or disappearance of some characteristics peaks which were present in the untreated spectrum. The HPLC profile verified the RB5 degradation subject to the formation of metabolites at different retention times. A stable color removal higher than 96% with COD removal in the range of 74-82.3% was noted at all evaluated dye concentrations. The tentative degradation pathway of RB5 is proposed following a careful analysis of the intermediates identified by UPLC-MS. Toxicity profile of untreated and degraded dye samples was monitored using three types of human cell lines via MTT assay and acute toxicity testing with Artemia salina. In conclusion, the UV/TiO2-based degradation system could be effectively employed for the remediation of textile wastewater comprising a high concentration of reactive dyes.

Assessment of salivary free cortisol levels by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in patients treated with mitotane.

PubMed

Carrozza, Cinzia; Lapolla, Rosa; Gervasoni, Jacopo; Rota, Carlo Antonio; Locantore, Pietro; Pontecorvi, Alfredo; Zuppi, Cecilia; Persichilli, Silvia

2012-01-01

Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.

Metabolic syndrome in patients with prostate cancer undergoing androgen suppression.

PubMed

Morote, J; Ropero, J; Planas, J; Celma, A; Placer, J; Ferrer, R; de Torres, I

2014-06-01

Cardiovascular mortality is the leading cause of death in patients with prostate cancer (PC), metabolic syndrome (MS) being related to it. The main objective of this study was to determine the prevalence of MS in patients with CP undergoing androgen suppression (AS). We performed a retrospective study of cases and controls that included 159 patients. The study group was made up of 53 patients with PC undergoing SA for a period exceeding 12 months. The control group was formed by 53 patients with PC at the time of diagnosis and 53 patients with negative prostate biopsy. All patients were evaluated for presence of MS according to NCEP-ATPIII criteria. Prevalence of MS in patients without PC was 32.1% and in those with non-treated PC 35.8%, P = .324. In patients with PC undergoing AS, prevalence of MS was 50.9%, P < .001. When AS duration was less than 36 months, prevalence of MS was 44.0% and when greater than 36 months 57.1%, P < .001. Waist circumference and hyperglycemia were the two MS components that significantly increased. AS and its duration were independent predictors factors for the development of MS. Continuous AS therapy increases the prevalence of MS and especially waist circumference and hyperglycemia. Development of MS increases according to AS duration. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

[Epidemiological aspects of multiple sclerosis in Lublin (Poland)].

PubMed

Łobińska, Alicja; Stelmasiak, Zbigniew

2004-01-01

The objective of this paper was to present an epidemiological analysis of multiple sclerosis (MS) in Lublin, identify MS prevalence as well as characterize the population of MS patients. Information about the patients was gathered and they were examined from 1996 to the end of 2000, that is within a 5-year period. The patients' data were obtained from the neurological departments in Lublin, most often neurological (but also general and ophthalmic) clinics, as well as from the Lublin MS Society. The remaining patients' data were obtained from the doctors, family members, the Lublin MS Society members, as well as from the hospital and clinic files. The patients were interviewed in detail using a prepared questionnaire. The diagnosis and its degree of certainty were determined in accordance with the Poser's criteria. The control group included 111 healthy people who were Lublin residents on the day of examination. The obtained results were analyzed in epidemiological and statistical terms. On the prevalence day (31 December 1997) there were 204 MS cases in Lublin, including 141 women (69%) and 63 men (31%). The calculated incidence ratio was 57.3/105. The average age of MS onset was estimated to be 30.1 years. On 31 December 1997 the average duration of the illness was 15.4 years. The average age for the examined cases was 45.5 years. The average DSS (Disability Status Scale) score was 3.5. Most often the disease began with a single symptom, in 155 cases (75.9%), whereas several symptoms occurred in 37 patients (18.1%). The most common symptoms at the illness onset were sensory impairments (52 patients), optic neuritis (42 people) and pyramidal symptoms (34 patients). The most common form of the illness was a disseminated form, which was diagnosed in 131 patients (64.2%). In the examined patient population four types of MS were recognized. The relapsing-remitting MS (RR-MS) was observed in 62 patients (30.3%), the secondary progressive MS (SP-MS) in 83 patients (40.6%), and the primary progressive MS (PP-MS) was characteristic of 40 people (19.6%), while 19 patients (9.3%) experienced a benign course of MS. Our results are typical for the region of high incidence of MS. They are similar to the data achieved in other populations of that region.

Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial.

PubMed

Planchard, David; Smit, Egbert F; Groen, Harry J M; Mazieres, Julien; Besse, Benjamin; Helland, Åslaug; Giannone, Vanessa; D'Amelio, Anthony M; Zhang, Pingkuan; Mookerjee, Bijoyesh; Johnson, Bruce E

2017-10-01

BRAF V600E mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF V600E -mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF V600E -mutant metastatic NSCLC. In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF V600E -mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia. Patients received oral dabrafenib 150 mg twice per day plus oral trametinib 2 mg once per day until disease progression, unacceptable adverse events, consent withdrawal, or death. The primary endpoint was investigator-assessed overall response, defined as the percentage of patients who achieved a confirmed complete response or partial response per Response Evaluation Criteria In Solid Tumors version 1.1. The primary and safety analyses were by intention to treat in the protocol-defined population (previously untreated patients). The study is ongoing, but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Between April 16, 2014, and Dec 28, 2015, 36 patients were enrolled and treated with first-line dabrafenib plus trametinib. Median follow-up was 15·9 months (IQR 7·8-22·0) at the data cutoff (April 28, 2017). The proportion of patients with investigator-assessed confirmed overall response was 23 (64%, 95% CI 46-79), with two (6%) patients achieving a complete response and 21 (58%) a partial response. All patients had one or more adverse event of any grade, and 25 (69%) had one or more grade 3 or 4 event. The most common (occurring in more than two patients) grade 3 or 4 adverse events were pyrexia (four [11%]), alanine aminotransferase increase (four [11%]), hypertension (four [11%]), and vomiting (three [8%]). Serious adverse events occurring in more than two patients included alanine aminotransferase increase (five [14%]), pyrexia (four [11%]), aspartate aminotransferase increase (three [8%]), and ejection fraction decrease (three [8%]). One fatal serious adverse event deemed unrelated to study treatment was reported (cardiorespiratory arrest). Dabrafenib plus trametinib represents a new therapy with clinically meaningful antitumour activity and a manageable safety profile in patients with previously untreated BRAF V600E -mutant NSCLC. Novartis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of PTR-MS for Measuring Odorant Emissions from Soil Application of Manure Slurry

PubMed Central

Feilberg, Anders; Bildsoe, Pernille; Nyord, Tavs

2015-01-01

Odorous volatile organic compounds (VOC) and hydrogen sulfide (H2S) are emitted together with ammonia (NH3) from manure slurry applied as a fertilizer, but little is known about the composition and temporal variation of the emissions. In this work, a laboratory method based on dynamic flux chambers packed with soil has been used to measure emissions from untreated pig slurry and slurry treated by solid-liquid separation and ozonation. Proton-transfer-reaction mass spectrometry (PTR-MS) was used to provide time resolved data for a range of VOC, NH3 and H2S. VOC included organic sulfur compounds, carboxylic acids, phenols, indoles, alcohols, ketones and aldehydes. H2S emission was remarkably observed to take place only in the initial minutes after slurry application, which is explained by its high partitioning into the air phase. Long-term odor effects are therefore assessed to be mainly due to other volatile compounds with low odor threshold values, such as 4-methylphenol. PTR-MS signal assignment was verified by comparison to a photo-acoustic analyzer (NH3) and to thermal desorption GC/MS (VOC). Due to initial rapid changes in odorant emissions and low concentrations of odorants, PTR-MS is assessed to be a very useful method for assessing odor following field application of slurry. The effects of treatments on odorant emissions are discussed. PMID:25585103

Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

ClinicalTrials.gov

2013-06-04

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Employment among patients with multiple sclerosis-a population study.

PubMed

Bøe Lunde, Hanne Marie; Telstad, Wenche; Grytten, Nina; Kyte, Lars; Aarseth, Jan; Myhr, Kjell-Morten; Bø, Lars

2014-01-01

To investigate demographic and clinical factors associated with employment in MS. The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing -remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual 's needs in order to improve working ability among MS patients.

Recovery of peripheral muscle function from fatiguing exercise and daily physical activity level in patients with multiple sclerosis: a case-control study.

PubMed

Ickmans, Kelly; Simoens, Fauve; Nijs, Jo; Kos, Daphne; Cras, Patrick; Willekens, Barbara; Meeus, Mira

2014-07-01

Delayed recovery of muscle function following exercise has been demonstrated in the lower limbs of patients with multiple sclerosis (MS). However, studies examining this in the upper limbs are currently lacking. This study compared physical activity level (PAL) and recovery of upper limb muscle function following exercise between MS patients and healthy inactive controls. Furthermore, the relationship between PAL and muscle recovery was examined. PAL of 19 MS patients and 32 controls was measured using an accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was assessed by performing a fatiguing upper limb exercise test with subsequent recovery measures. Muscle recovery of the upper limb muscles was similar in both groups. Average activity counts were significantly lower in MS patients than in the control group. MS patients spent significantly more time being sedentary and less time on activities of moderate intensity compared with the control group. No significant correlation between PAL and recovery of muscle function was found in MS patients. Recovery of upper limb muscle function following exercise is normal in MS patients. MS patients are less physically active than healthy inactive controls. PAL and recovery of upper limb muscle function appear unrelated in MS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Earnings and Financial Compensation from Social Security Systems Correlate Strongly with Disability for Multiple Sclerosis Patients.

PubMed

Kavaliunas, Andrius; Wiberg, Michael; Tinghög, Petter; Glaser, Anna; Gyllensten, Hanna; Alexanderson, Kristina; Hillert, Jan

2015-01-01

Multiple sclerosis (MS) patients earn lower incomes and receive higher benefits. However, there is limited knowledge of how this is correlated with their disability. To elucidate sources and levels of income among MS patients with different disability, assessed with the Expanded Disability Status Scale. A total of 7929 MS patients aged 21-64 years and living in Sweden in 2010 were identified for this cross-sectional study. Descriptive statistics, logistic and truncated linear regression models were used to estimate differences between MS patients regarding earnings, disability pension, sickness absence, disability allowance, unemployment compensation, and social assistance. The average level of earnings was ten times lower and the average level of health- related benefits was four times higher when comparing MS patients with severe and mild disability. MS patients with severe disability had on average SEK 166,931 less annual income from earnings and SEK 54,534 more income from benefits compared to those with mild disability. The combined average income for MS patients was 35% lower when comparing patients in the same groups. The adjusted risk ratio for having earnings among MS patients with severe disability compared to the patients with mild disability was 0.33 (95% CI 0.29-0.39), while the risk ratio for having benefits was 1.93 (95% CI 1.90-1.94). Disease progression affects the financial situation of MS patients considerably. Correlations between higher disability and patient income were observed, suggesting that earnings and benefits could be used as measures of MS progression and proxies of disability.

Driving competences and neuropsychological factors associated to driving counseling in multiple sclerosis.

PubMed

Badenes, Dolors; Garolera, Maite; Casas, Laura; Cejudo-Bolivar, Juan Carlos; de Francisco, Jorge; Zaragoza, Silvia; Calzado, Noemi; Aguilar, Miquel

2014-05-01

Multiple Sclerosis (MS) significantly impacts daily living activities, including car driving. To investigate driving difficulties experienced with MS, we compared 50 MS patients with minor or moderate disability and 50 healthy controls (HC) using computerized driving tests (the ASDE driver test and the Useful Field of View (UFOV) test) and neuropsychological tests. Inclusion criteria included being active drivers. We evaluated whether cognitive deterioration in MS is associated with the results of driving tests by comparing MS patients without cognitive deterioration with HC. The results indicated that the MS patients performed worse than the HCs in attention, information processing, working memory and visuomotor coordination tasks. Furthermore, MS patients with cognitive impairments experienced more difficulties in the driving tests than did the non-impaired MS patients. Motor dysfunction associated with MS also played an important role in this activity. The results of this study suggest that MS should be assessed carefully and that special emphasis should be placed on visuomotor coordination and executive functions because patients with minor motor disability and subtle cognitive impairments can pass measures predictive of driving safety.

Macrophage migration inhibition test in untreated syphilis.

PubMed

Bowszyc, J

1975-01-01

Two modifications of macrophage migration inhibition test, one of George and Vaughan and the other one of Svejcar, were performed on a total of 78 cases of untreated syphilis at various stages. As specific antigens were used: Treponema Pallidum ultrasonate and cardiolipin. Inhibition of migration was observed in 87 percent patients with primary syphillis and in all patients with late and late congenital syphilis. After improving and standardisation of the technique of Treponema Pallidum antigen-the migration inhibition test may be recommended as a specific in vitro-test for detection of cell mediated immunity in syphilis.

Relationship Between Metabolic Syndrome and Clinical Features, and Its Personal-Social Performance in Patients with Schizophrenia.

PubMed

Saatcioglu, Omer; Kalkan, Murat; Fistikci, Nurhan; Erek, Sakire; Kilic, Kasim Candas

2016-06-01

The aim of this study was to evaluate the metabolic syndrome (MS) criteria and also to investigate the effects of MS on medical treatment, clinical course and personal and social performance in patients with schizophrenia. One hundred-sixteen patients with schizophrenia were included in the study. Measurements of MS were calculated in all patients. Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Personal and Social Performance Scale (PSP) were applied. The frequency of MS according to IDF criteria was 42.2 % among the patients. There was no significant difference between patients with and without MS in terms of age. The ratios of MS were 62.5 % for the group taking typical and atypical antipsychotics together and 35.7 % for the group taking two or more atypical antipsychotics together. The duration of disorder in patients with MS was higher than those without MS. Furthermore there was no significant difference between the schizophrenic patients with and without MS, in terms of PSP scores. Our findings showed that the duration of illness, high scores of BMI, use of clozapine or concurrent use of typical and atypical antipsychotics, depressive and negative symptoms of schizophrenia were significant risk factors for the development of MS.

Clinical outcomes following surgical management of coexistent cervical stenosis and multiple sclerosis: a cohort-controlled analysis.

PubMed

Lubelski, Daniel; Abdullah, Kalil G; Alvin, Matthew D; Wang, Timothy Y; Nowacki, Amy S; Steinmetz, Michael P; Ransohoff, Richard M; Benzel, Edward C; Mroz, Thomas E

2014-02-01

The presentation of myelopathy in patients with the concomitant diagnosis of cervical stenosis (CS) and multiple sclerosis (MS) complicates both diagnosis and treatment because of the similarities of presentation and disease progression. There are only a few published case series that examine this unique patient population. To define the demographic features and presenting symptoms of patients with both MS and CS and to investigate the immediate and long-term outcomes of surgery in patients with MS and CS. Matched cohort-controlled retrospective review of 77 surgical patients in the MS group and 77 surgical patients in the control group. Outcome measures were immediate and long-term postoperative neck pain, radiculopathy, and myelopathy; Nurick Disability and modified Japanese Orthopaedic Association scores were collected as well. Retrospective review was performed for all patients presenting at one institution between January 1996 and July 2011 with coexisting diagnoses of MS and CS who had presenting symptoms of myelopathy and who then underwent cervical decompression surgery. Each study patient was individually matched to a control patient of the same gender and age that did not have MS, but that did have cervical spondylotic myelopathy or myeloradiculopathy. Each control patient underwent the same surgical procedure within the same year. A total of 154 patients were reviewed, including 77 MS patients and 77 control patients, for an average follow-up of 58 months and 49 months, respectively. Patients in the control group were more likely to have preoperative neck pain (78% vs. 47%; p=.0001) and preoperative radiculopathy (90% vs. 75%; p=.03) than their counterparts in the MS group. Patients in the MS group had a significantly lower rate of postoperative resolution of myelopathic symptoms in both the short-term (39% in the MS group did not improve vs. 23% in the control group; p=.04) and the long-term (44% in the MS group did not improve vs. 19% in the control group; p=.004). Preoperative myelopathy scores were worse for the MS cohort as compared with the control cohort (1.8 vs. 1.2 in the Nurick scale, p<.0001; 13.7 vs. 15.0 in the modified Japanese Orthopaedic Association scale, p=.002). This difference in scores became even greater at the last follow-up visit with Nurick scores of 2.4 versus 0.9 (p<.0001) and modified Japanese Orthopaedic Association scores of 16.3 versus 12.4 (p<.0001) for the MS and control patients, respectively. Myelopathic patients with coexisting MS and CS improve after surgery, although at a lower rate and to a lesser degree than those without MS. Therefore, surgery should be considered for these patients. MS patients should be informed that myelopathy symptoms are less likely to be alleviated completely or may only be alleviated temporarily because of progression of MS and that surgery can help alleviate neck pain and radicular symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

PubMed

Akcali, Aylin; Zengin, Fatma; Aksoy, Sefika Nur; Zengin, Orhan

2017-07-01

Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (p<0.01). However, no difference was observed between fatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, p<0.01 and p<0.01, respectively). CLIP level was significantly low in MS patient group (p<0.01). NFI-MS scale is equally sensitive as FSS scale for assessment of MS fatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial high-energy phosphate metabolism in men.

PubMed

Schocke, Michael F; Martinek, Martin; Kremser, Christian; Wolf, Christian; Steinboeck, Peter; Lechleitner, Monika; Jaschke, Werner; Pachinger, Otmar; Metzler, Bernhard

2003-01-01

We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins have a beneficial impact on the human myocardial, high-energy, phosphate metabolism. The present study included 18 male patients (mean age 49.8 +/- 10.3) with statin-treated, familiar hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6 +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/- 12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium. Furthermore, echocardiographic evaluation and stress tests were performed in all individuals. The untreated patients with FH exhibited a significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34) compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios of the treated FH patients were in the range of the healthy controls. Our study shows for the first time an-improvement of the high-energy, phosphate metabolism in the left ventricular myocardium of patients with statin-treated FH compared with untreated FH patients.

Gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: a cross-sectional study.

PubMed

Apostolopoulou, Konstantina; Künzel, Heike E; Gerum, Sabine; Merkle, Katrin; Schulz, Sebastian; Fischer, Evelyn; Pallauf, Anna; Brand, Volker; Bidlingmaier, Martin; Endres, Stephan; Beuschlein, Felix; Reincke, Martin

2014-01-01

The renin-angiotensin-aldosterone-system (RAAS) has gained increasing attention in the investigation of the pathogenesis of depression. Primary hyperaldosteronism (PA) is associated with a marked aldosterone excess. Prior studies on PA describe an increased prevalence of anxiety and sub-threshold depressive symptoms in these patients. In a cross-sectional exploratory study we investigated 132 patients with PA. Twenty-seven patients were studied before initiation of specific treatment (U = untreated), 56 were studied 5.4 years after initiation of mineralocorticoid antagonist treatment (MRA) and 49 patients were studied 4.3 years after unilateral adrenalectomy (ADX). GAD-7 and PHQD self-rating questionnaires were used to assess symptoms for anxiety and depression. No significant difference was found between the three investigated groups. A higher prevalence for depression and anxiety compared to the normal population was found. Women of all groups had higher mean values compared to men, for depression in untreated patients this difference was found to be significant. Correlations between the psychopathology and hormones were only found for renin. Plasma renin concentration correlated significantly with anxious symptoms of untreated females. This study supports the RAAS to be involved in the pathogenesis of depression as patients with PA seem to be more depressive and anxious compared to the normal population. Gender differences in the regulation of the RAAS seem to be apparent, as females were more affected by the dysregulation than males.

Use of the scoliosis research society outcomes instrument to evaluate patient outcome in untreated idiopathic scoliosis patients in Japan: part I: comparison with nonscoliosis group: preliminary/limited review in a Japanese population.

PubMed

Watanabe, Kei; Hasegawa, Kazuhiro; Hirano, Toru; Uchiyama, Seiji; Endo, Naoto

2005-05-15

This preliminary study evaluates untreated Japanese patients with idiopathic scoliosis using the Scoliosis Research Society Outcomes Instrument (SRS-24). To determine the baseline patient outcome score using the SRS-24 for untreated Japanese scoliosis patients compared with a nonscoliosis group. The SRS instrument with 24 questions was developed to help evaluate patient-perceived outcomes of idiopathic scoliosis treatment. Evaluation of untreated Japanese idiopathic scoliosis patients using the SRS instrument has not been reported. Japanese idiopathic scoliosis patients (n = 141) (mean age, 13.6 years; range, 10-17 years) with a Cobb angle of more than 20 degrees who were not treated with a brace or surgery, were evaluated in comparison with a nonscoliosis group (healthy junior high school students; n = 72) using the SRS-24. The scoliosis group was categorized as mild deformity group with a major curve Cobb angle of less than 30 degrees, moderate deformity group with 30 degrees to 49 degrees, and severe deformity group with more than 50 degrees. The patients were evaluated using section 1 (15 questions) of the SRS-24, which was divided into four domains: total pain, general self-image, general function, and activity. Reliability, as determined by internal consistency, was validated using Cronbach's alpha for these domain scales. The severe deformity group had the lowest scores compared with the other deformity groups and the nonscoliosis group in pain (P < 0.0001) and self-image (P < 0.05) domains. The scores for questions 3 (P < 0.0001) and 5 (P < 0.0001), evaluation of self-image of back appearance, were significantly lower in the scoliosis group than those in the nonscoliosis group. This tendency was more significant in the patients with greater curve magnitude. Scores for questions 14 and 15, evaluation of general self-image, in the scoliosis group were, however, higher than those in the nonscoliosis group. Internal consistency using Cronbach's alpha was 0.57 (pain), 0.27 (general self-image), -0.08 (general function), and 0.15 (overall level of activity). Untreated scoliosis patients with severe deformity were inclined to complain of being self-conscious or distressed regarding their back appearance compared with age- and sex-matched control adolescents. The control group was inclined to have, however, a negative general self-image compared with the patients group. Internal consistency using Cronbach's alpha for all domains was considerably low. The baseline of the SRS-24 scores in the Japanese population might differ from that of the Western population because of differences in national culture. Therefore, further study is necessary to clarify the validity of the SRS-24 domains for Japanese patients.

Zinc isotope ratio imaging of rat brain thin sections from stable isotope tracer studies by LA-MC-ICP-MS.

PubMed

Urgast, Dagmar S; Hill, Sarah; Kwun, In-Sook; Beattie, John H; Goenaga-Infante, Heidi; Feldmann, Jörg

2012-10-01

Zinc stable isotope tracers (⁶⁷Zn and ⁷⁰Zn) were injected into rats at two different time points to investigate the feasibility of using tracers to study zinc kinetics at the microscale within distinct tissue features. Laser ablation coupled to multi-collector ICP-MS was used to analyse average isotope ratios in liver thin sections and to generate bio-images showing zinc isotope ratio distribution in brain thin sections. Average isotope ratios of all samples from treated animals were found to be statistically different (P < 0.05) from samples from untreated control animals. Furthermore, differing isotope ratios in physiological features of the brain, namely hippocampus, amygdala, cortex and hypothalamus, were identified. This indicates that these regions differ in their zinc metabolism kinetics. While cortex and hypothalamus contain more tracer two days after injection than 14 days after injection, the opposite is true for hippocampus and amygdala. This study showed that stable isotope tracer experiments can be combined with laser ablation MC-ICP-MS to measure trace element kinetics in tissues at a microscale level.

[Effectivity of screening, concepts and attitudes towards metabolic síndrome: a study in bipolar patients followed in Hospital Santa Maria psychiatric consultation].

PubMed

Guerreiro, Diogo Frasquilho; Navarro, Rita; Telles-Correia, Diogo; Martins, Paulo; Trigo, Elsa; Silva, Manuela; Neves, António; Góis, Carlos; Figueira, Maria Luísa

2010-01-01

The Metabolic Syndrome (MS) is constituted by a set of specific metabolic alterations being postulated that the main dysfunction is insulin resistance, associated with abdominal type obesity, hypertension, hyperglycemia and dyslipidemia. Epidemiological data indicates prevalence of MS of about 25%. Estimates point to higher prevalence of MS in bipolar (BP) patients, between 30 to 35%. Cost-effective screening methods, not recurring to blood test, have been researched. Test the viability of MS screening without using blood tests. Analyse knowledge and importance given to the issue of MS in Bipolar patients. Observational, cross-sectional, exploratory study. Random sample of 15 BP patients, in euthymic phase, between 18 and 65 years. Semi-structured interview, YMRS, HAMD were applied. MS diagnosis was investigated according to the International Diabetes Federation (IDF), including blood tests. Screening of MS was defined positive if blood pressure > or = to 130/85 or on anti-hypertensive medication and Abdominal Perimeter > 90 cm in males or > 80 cm in females. Afterwards a questionnaire about knowledge, attitudes and concerns on MS was applied. 14 patients completed the investigation protocol, 1 patient didn't do blood testing for unknown reasons. Five patients (36%) met IDF criteria for MS. Screening sensitivity was 80% and specificity 78% on our sample (1 false positive and 2 false negative). Twelve patients (80%) were overweight or obese. Mean IMC in patients that met IDF criteria for MS was 30 while in the other group mean IMC was 26, showing statistical significance. Only 3 (20%) have ever heard about MS, but the majority of the patients were concerned, in decreasing order, about weight gain, blood pressure cholesterol and hyperglycemia control. Although limited by small sample size, this study strengthens the idea that MS screening can be effective in clinical practice, it also indicates the need to educate BP patients about MS and to prevent overweight.

Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study.

PubMed

Nielsen, Nete M; Westergaard, Tine; Frisch, Morten; Rostgaard, Klaus; Wohlfahrt, Jan; Koch-Henriksen, Nils; Melbye, Mads; Hjalgrim, Henrik

2006-07-01

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. 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. Two population-based disease registers, the Danish Hospital Discharge Register and the Danish 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 Registration System. Patients with T1D and first-degree relatives of patients with MS were followed up for occurrence of MS and T1D, respectively, and the relative risks were expressed as standardized incidence ratios, that is, ratios of observed to expected numbers of outcomes based on national age, sex, and period-specific MS and T1D incidence rates. Patients with T1D were at more than 3-fold increased risk for development of MS (relative risk, 3.26; 95% confidence interval, 1.80-5.88; n = 11). First-degree relatives of patients with MS were at 63% increased risk (relative risk, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). The present nationwide cohort study demonstrates an intraindividual and, to a lesser degree, an intrafamilial co-occurrence of MS and T1D.

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families

PubMed Central

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L.; Drilling, Amy

2016-01-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was –7.5 SDs with a very delayed bone age of –13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (–5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. PMID:27244801

Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families.

PubMed

Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L; Drilling, Amy; Petryk, Anna

2016-05-01

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was -7.5 SDs with a very delayed bone age of -13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (-5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. Copyright © 2016 by the American Academy of Pediatrics.

Prevalence of metabolic syndrome among patients with depressive disorder admitted to a psychiatric inpatient unit: A comparison with healthy controls.

PubMed

Grover, Sandeep; Nebhinani, Naresh; Chakrabarti, Subho; Avasthi, Ajit

2017-06-01

This study aimed to compare the prevalence of metabolic syndrome (MS) among inpatients with depressive disorders and matched healthy controls. One hundred fifty eight patients with depressive disorders and 52 age and gender matched healthy controls were assessed for the prevalence of MS using Common Criteria for MS. Prevalence of Metabolic syndrome among inpatients with depressive disorders was 44.3%, which was significantly higher than the healthy control group (17.3%). Increased waist circumference was the most common abnormality in both the groups. Prevalence of MS among patients with recurrent depression disorder (60.3%) was almost double that seen among those with first episode depression (32.6%). Compared to healthy controls, significantly greater proportion of patients with depressive disorders had increased blood pressure, abnormal fasting blood sugar, and HDL levels. Besides the prevalence of MS in 44.3% of patients with depressive disorders, another 46% of patients fulfilled one or two criteria of MS. Significant predictors of MS were being married, obese, greater age, higher weight, higher body mass index, and multiple episodes of depression. Nearly two-fifth of depressed patients have MS and another two-fifth of patients had one or two abnormalities in the MS criteria. The prevalence of MS among patients with depressive disorders is significantly higher than the healthy controls. Hence, patients with depressive disorders should be regularly evaluated for the presence of MS and other cardiovascular risk factors and appropriate management strategies must be instituted at the earliest. Copyright © 2017 Elsevier B.V. All rights reserved.

Could Heterozygous Beta Thalassemia Provide Protection Against Multiple Sclerosis?

PubMed Central

Cikrikcioglu, Mehmet Ali; Ozcan, Muhammed Emin; Halac, Gulistan; Gultepe, Ilhami; Celik, Kenan; Sekin, Yahya; Eser, Elif Ece; Burhan, Sebnem; Cetin, Guven; Uysal, Omer

2016-01-01

Background Heterozygous beta thalassemia (HBT) has been proposed to increase the risk of developing autoimmune disease. Our aim in this study was to examine the prevalence of HBT among multiple sclerosis (MS) patients. Material/Methods HBT frequency was investigated in our MS group (243 patients with MS). Hemoglobin electrophoresis (HE) was carried out if MS patients had a mean corpuscular volume of (MCV) <80 fL and a mean corpuscular hemoglobin level of (MCH) <27 pg/L according to a complete blood count (CBC). If MCV was lower than 80 fL, MCH was lower than 27 pg/L, and Hemoglobin A2 equal to or higher than 3.5%, a diagnosis of HBT was established. The frequency of patients with HBT in our MS patient group was statistically compared with the prevalence of HBT in the city of Istanbul, where our MS patients lived. Results The HBT prevalence was 0.823% (2 patients) in the MS patient group. The prevalence of HBT in Istanbul has been reported to be 4.5%. According to the z-test, the HBT prevalence in our MS patient group was significantly lower than that in Istanbul (Z=6.3611, two-sided p value <0.0001, 95% confidence interval of prevalence of HBT in our MS patient group: 0.000998–0.029413). Conclusions Contrary to our hypothesis at the outset of study, the reduced HBT prevalence in the MS group compared to HBT frequency in the city of Istanbul might indicate that HBT is protective against MS. PMID:27941710

Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

PubMed Central

Kay, Neil E.; Geyer, Susan M.; Call, Timothy G.; Shanafelt, Tait D.; Zent, Clive S.; Jelinek, Diane F.; Tschumper, Renee; Bone, Nancy D.; Dewald, Gordon W.; Lin, Thomas S.; Heerema, Nyla A.; Smith, Lisa; Grever, Michael R.; Byrd, John C.

2007-01-01

Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity. PMID:17008537

Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition

PubMed Central

Pu, Weidan; Rolls, Edmund T.; Guo, Shuixia; Liu, Haihong; Yu, Yun; Xue, Zhimin; Feng, Jianfeng; Liu, Zhening

2014-01-01

In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity. PMID:25389520

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema.

PubMed

Gompelmann, Daniela; Lim, Hyun-Ju; Eberhardt, Ralf; Gerovasili, Vasiliki; Herth, Felix Jf; Heussel, Claus Peter; Eichinger, Monika

2016-01-01

Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema

PubMed Central

Gompelmann, Daniela; Lim, Hyun-ju; Eberhardt, Ralf; Gerovasili, Vasiliki; Herth, Felix JF; Heussel, Claus Peter; Eichinger, Monika

2016-01-01

Background Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Methods Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Finding Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Interpretation Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy. PMID:27536088

Effect of salt intake on blood pressure in patients receiving antihypertensive therapy: Shimane CoHRE Study.

PubMed

Ito, Tomoko; Takeda, Miwako; Hamano, Tsuyoshi; Kijima, Tsunetaka; Yamasaki, Masayuki; Isomura, Minoru; Yano, Shozo; Shiwaku, Kuninori; Nabika, Toru

2016-03-01

Salt intake is recognized as an important risk factor for hypertension in the general population. On the other hand, the availability of various classes of antihypertensive drugs means that it is generally not considered crucial to control the salt intake of hypertensive patients. In this study, we evaluated whether blood pressure (BP) was correlated with 24-hour salt intake in patients receiving antihypertensive therapy. A total of 1496 consecutive participants undergoing health screening examinations were recruited. Subjects were divided into two groups according to their antihypertensive medications checked on prescriptions: 1005 subjects without antihypertensive therapy (untreated subjects) and 491 subjects with antihypertensive therapy (treated subjects). The 24-hour urinary sodium excretion (24h-uNa), a surrogate marker for daily salt intake, was estimated with the formula proposed by Tanaka et al. in 2002. Univariate analysis indicated that 24h-uNa was positively correlated with the systolic BP of both untreated and treated subjects. This was confirmed by multiple linear regression analysis after adjustment for confounding factors (untreated subjects: partial regression coefficient β=1.45 ± 0.26, p<0.001; treated subjects: β=0.75 ± 0.27, p=0.01). Salt intake was also correlated with the pulse pressure in both treated subjects (β=0.55 ± 0.24, p=0.02) and untreated subjects (β=0.93 ± 0.19, p<0.001). These results suggest the importance of reducing salt intake in hypertensive patients on pharmacotherapy, as well as in the general population. Further studies of hypertensive patients employing 24-h urine collection are warranted to confirm the present findings. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Head circumference in untreated and IGF-I treated patients with Laron syndrome: comparison with untreated and hGH-treated children with isolated growth hormone deficiency.

PubMed

Laron, Zvi; Iluz, Moshe; Kauli, Rivka

2012-04-01

Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth. To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS). 20 untreated adult LS patients, aged 48.4±11.2 years and 13 LS patients treated between ages of 5.6±4 to 11.3±3 years were studied. 15 patients with congenital IGHD treated between age 6.1±4 and 13±4 by hGH served as controls. HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer. The mean HC deficit of the adult untreated LS males was -2.9±0.6 SD compared to a Ht deficit of -7.0±1.7 SDS. The HC of the LS adult females was -3.6±1 SD compared to a Ht SDS of -6.9±1.5 (p<0.001). IGF-I treatment (150-200 μg/kg once daily) increased the HC from -3.3±0.9 (m±SD) to normal values (0.87±1.8 SD) (p<0.001) in 11/13 children. The Ht SDS deficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.0±1.8 to 0.3±1.2 SD and the Ht SDS from -4.8±1.6 to 1.6±1.0. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pain Reduction in Untreated Symptomatic Irreversible Pulpitis Using Liposomal Bupivacaine (Exparel): A Prospective, Randomized, Double-blind Trial.

PubMed

Bultema, Kristy; Fowler, Sara; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2016-12-01

In the treatment of patients with symptomatic irreversible pulpitis, endodontic debridement is a predictable method to relieve pain. However, there are clinical situations in which emergency care cannot be provided immediately. An unexplored treatment option in these cases may be the use of a long-acting anesthetic to reduce pain in untreated irreversible pulpitis. Some medical studies have shown potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA) to prolong pain relief and reduce opioid use postoperatively. The Food and Drug Administration has approved Exparel only for infiltrations; therefore, the purpose of this study was to compare an infiltration of liposomal bupivacaine versus bupivacaine for pain control in untreated, symptomatic irreversible pulpitis. Ninety-five emergency patients received 2% lidocaine with 1:100,000 epinephrine via infiltration or an inferior alveolar nerve block to relieve their initial presenting pain. Patients then randomly received either 4 mL liposomal bupivacaine (13.3 mg/mL) or 4 mL 0.5% bupivacaine with 1:200,000 epinephrine by infiltration. Patients received a diary for the day of the appointment and 3 days postinjection to record soft tissue numbness, pain levels, and analgesic (non-narcotic and narcotic) use. No significant differences (P < .05) were found between the 2 anesthetic formulations for pain or the use of pain medications. A statistically higher level of soft tissue numbness was found on days 1 to 3 for the liposomal bupivacaine group. Although liposomal bupivacaine had some effect on soft tissue anesthesia, it did not reduce pain to manageable clinical levels in patients presenting with untreated, symptomatic irreversible pulpitis. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Activity of daily living for Morquio A syndrome.

PubMed

Yasuda, Eriko; Suzuki, Yasuyuki; Shimada, Tsutomu; Sawamoto, Kazuki; Mackenzie, William G; Theroux, Mary C; Pizarro, Christian; Xie, Li; Miller, Freeman; Rahman, Tariq; Kecskemethy, Heidi H; Nagao, Kyoko; Morlet, Thierry; Shaffer, Thomas H; Chinen, Yasutsugu; Yabe, Hiromasa; Tanaka, Akemi; Shintaku, Haruo; Orii, Kenji E; Orii, Koji O; Mason, Robert W; Montaño, Adriana M; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

2016-06-01

The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has four subcategories rated on a 5-point scale based on the level of assistance. The questionnaire was collected from 145 healthy controls and 82 patients with MPS IVA. The patient cohort consisted of 63 severe and 17 attenuated phenotypes (2 were undefined); 4 patients treated with hematopoietic stem cell transplantation (HSCT), 33 patients treated with enzyme replacement therapy (ERT) for more than a year, and 45 untreated patients. MPS IVA patients show a decline in ADL scores after 10years of age. Patients with a severe phenotype have a lower ADL score than healthy control subjects, and lower scores than patients with an attenuated phenotype in domains of "Movement" and "Movement with cognition." Patients, who underwent HSCT and were followed up for over 10years, had higher ADL scores and fewer surgical interventions than untreated patients. ADL scores for ERT patients (2.5years follow-up on average) were similar with the-age-matched controls below 10years of age, but declined in older patients. Surgical frequency was higher for severe phenotypic patients than attenuated ones. Surgical frequency for patients treated with ERT was not decreased compared to untreated patients. In conclusion, we have shown the utility of the proposed ADL questionnaire and frequency of surgical interventions in patients with MPS IVA to evaluate the clinical severity and therapeutic efficacy compared with age-matched controls. Copyright © 2016. Published by Elsevier Inc.

Is it necessary to treat all patients with idiopathic pulmonary fibrosis?

PubMed

Xaubet, A; Agustí, C; Luburich, P; Roca, J; Ayuso, M C; Marrades, R M; Rodriguez-Roisin, R

2001-10-01

To investigate the clinical course of untreated patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF/UIP). Forty-three patients with IPF/UIP, divided into two groups. Group I consisted of 29 patients treated at diagnosis, while Group II comprised 14 patients who did not receive treatment. The indication of treatment was established whenever patients referred to a significant progression of the degree of dyspnea during the year prior to diagnosis. At diagnosis, patients from Group I had lower FVC (mean +/- SEM, 56+/-3% vs 73+/-3%) (p = 0.0004) and a greater extent of ground glass pattern in high resolution CT scan (18+/-4% vs 4+/-1%) (p = 0.004) than those from Group II. In group I, a follow-up study was carried out on 26 patients for 24+/-4 months. Thirteen of these 26 patients (50%) died 11+/-4 months after the initial assessment. Serial pulmonary functional tests were performed on 19 patients. Thirteen patients from Group II were followed up for 23+/-3 months. Seven of these 13 patients were treated 12+/-3 months after the diagnosis because of progression of the disease. The remaining 6 patients remained untreated and with the disease stable at the end of the follow-up, representing 15% (6 out of 39) of the whole study group. No patients from this group died during the follow-up. At the end of the follow-up, there were no differences in lung function changes between treated patients (19 from Group I and 7 from Group II), and the 6 untreated patients. Some patients with IPF/UIP remain stable for extended periods of time without treatment.

Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients.

PubMed

Hoffmann, Jean-Marc; Schubert, Maria-Luisa; Wang, Lei; Hückelhoven, Angela; Sellner, Leopold; Stock, Sophia; Schmitt, Anita; Kleist, Christian; Gern, Ulrike; Loskog, Angelica; Wuchter, Patrick; Hofmann, Susanne; Ho, Anthony D; Müller-Tidow, Carsten; Dreger, Peter; Schmitt, Michael

2017-01-01

Therapy with chimeric antigen receptor T (CART) cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (T N ) vs. effector (T E ) T cells, T N cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the T N /T E ratio of CART cells. CART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL)-7/IL-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays. IL-7/IL-15 preferentially induced differentiation into T N , stem cell memory (T SCM : naive CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (T EM ), CD56+ and CD4+ T regulatory (T Reg ) CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CART N cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CART N cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CART N cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CART N cells in untreated CLL patients. Final T N /T E ratio stayed <0.3 despite stimulation condition for patients, whereas this ratio was >2 in samples from HDs stimulated with IL-7/IL-15, thus demonstrating efficient CART N expansion. Untreated CLL patients might constitute a challenge for long-lasting CART effects in vivo since only a low number of T N among the CART product could be generated. Depletion of malignant B cells before starting CART production might be considered to increase the T N /T E ratio within the CART product.

Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure.

PubMed

Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral; Sanders, Corron; Hynan, Linda S; Lee, William M

2012-05-01

The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1-21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P = 0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P = 0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, P = 0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, P < 0.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, P = 0.012] were predictors of improved transplant-free survival. Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Treatment effects of fixed functional appliances in patients with Class II malocclusion: a systematic review and meta-analysis

PubMed Central

Zymperdikas, Vasileios F.; Koretsi, Vasiliki; Papageorgiou, Spyridon N.

2016-01-01

Summary Objective: To assess the treatment effects of fixed functional appliances (FFAs) in treated versus untreated Class II patients by means of lateral cephalometric radiographs. Search methods: Unrestricted electronic search of 18 databases and additional manual searches up to October 2014. Selection criteria: Prospective randomized and non-randomized controlled trials reporting on cephalometric angular measurements of Class II patients treated with FFAs and their matched untreated controls. Data collection and analysis: Skeletal, dental, and soft tissue cephalometric data were annualized and stratified according to the time of evaluation in effects. Following risk of bias evaluation, the mean differences (MDs) and 95 % confidence intervals (CIs) were calculated with random-effects models. Patient- and appliance-related subgroup analyses and sensitivity analyses were performed with mixed-effects models. Results: Nine studies were included (244 patients; mean age: 13.5 years and 174 untreated controls; mean age: 12.8 years) reporting on cephalometric effects directly after the removal of FFAs. FFAs were found to induce a small reduction of SNA angle (MD = −0.83 degree/year, 95 % CI: −1.17 to −0.48), a small increase of SNB angle (MD = 0.87 degree/year, 95 % CI: 0.30–1.43), and moderate decrease of ANB angle (MD = −1.74 degree/year, 95 % CI: −2.50 to −0.98) compared to untreated Class II patients. FFA treatment resulted in significant dentoalveolar and soft tissue changes. Several patient- or appliance-related factors seem to affect the treatment outcome. Long-term effectiveness of FFAs could not be assessed due to limited evidence. Conclusions: According to existing evidence, FFAs seem to be effective in improving Class II malocclusion in the short term, although their effects seem to be mainly dentoalveolar rather than skeletal. PMID:25995359

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

PubMed

Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

2014-02-01

Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

“Undiagnosing” multiple sclerosis

PubMed Central

Klein, Eran P.; Bourdette, Dennis

2012-01-01

Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS). Methods: A cross-sectional Internet-based physician survey of MS specialists was performed. Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS. Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients. PMID:22581930

Employment among Patients with Multiple Sclerosis-A Population Study

PubMed Central

Bøe Lunde, Hanne Marie; Telstad, Wenche; Grytten, Nina; Kyte, Lars; Aarseth, Jan; Myhr, Kjell-Morten; Bø, Lars

2014-01-01

Objective To investigate demographic and clinical factors associated with employment in MS. Methods The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. Results After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing –remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Conclusions Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual ’s needs in order to improve working ability among MS patients. PMID:25054972

Epidemiological and clinical characteristics of multiple sclerosis in paediatric population in Slovenia: A descriptive nation-wide study.

PubMed

Bizjak, Neli; Osredkar, Damjan; Perković Benedik, Mirjana; Šega Jazbec, Saša

2017-11-01

Although multiple sclerosis usually affects young adults, paediatric-onset multiple sclerosis (pMS) is increasingly recognized in the past ten years. The aim of the present study was to evaluate the incidence of pMS in Slovenia and to characterize the clinical, laboratory and neuroradiological characteristics of pMS at the disease onset. We performed a national retrospective descriptive study including all patients diagnosed with pMS between January 1992 and June 2017. We reviewed data of all patients younger than 18 years at the first demyelinating event. The estimated incidence of pMS was 0.66/100,000 children per year. We included 61 patients (77% were female) with a median age at diagnosis of 16.3 years. In 4 patients, onset of pMS was before the age of 12 years old (childhood-onset pMS). Relapsing-remitting multiple sclerosis was most prevalent, with only 2 patients presenting a primary progressive pMS. Polysymptomatic pMS was found at onset in 59% of patients and monosymptomatic in 41%. In the cerebrospinal fluid study, 88% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (100% of patients). The clinical pattern of pMS in our cohort of patients was characterized by polysymptomatic presentation and predominantly sensory symptoms at onset, developing a relapsing-remitting pMS pattern. It is important to gather more information about the incidence of pMS and its initial presentation and clinical course to improve early recognition and appropriate initiation of immunomodulatory treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

ERIC Educational Resources Information Center

Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

2011-01-01

Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

Myeloid Sarcoma Predicts Superior Outcome in Pediatric AML; Can Cytogenetics Solve the Puzzle?

PubMed

Pramanik, Raja; Tyagi, Anudishi; Chopra, Anita; Kumar, Akash; Vishnubhatla, Sreenivas; Bakhshi, Sameer

2018-06-01

The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005). Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

Post-exercise hypotension and heart rate variability response after water- and land-ergometry exercise in hypertensive patients.

PubMed

Bocalini, Danilo Sales; Bergamin, Marco; Evangelista, Alexandre Lopes; Rica, Roberta Luksevicius; Pontes, Francisco Luciano; Figueira, Aylton; Serra, Andrey Jorge; Rossi, Emilly Martinelli; Tucci, Paulo José Ferreira; Dos Santos, Leonardo

2017-01-01

systemic arterial hypertension is the most prevalent cardiovascular disease; physical activity for hypertensive patients is related to several beneficial cardiovascular adaptations. This paper evaluated the effect of water- and land-ergometry exercise sessions on post-exercise hypotension (PEH) of healthy normotensive subjects versus treated or untreated hypertensive patients. Forty-five older women composed three experimental groups: normotensive (N, n = 10), treated hypertensive (TH, n = 15) and untreated hypertensive (UH, n = 20). The physical exercise acute session protocol was performed at 75% of maximum oxygen consumption (VO2max) for 45 minutes; systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were evaluated at rest, peak and at 15, 30, 45, 60, 75 and 90 minutes after exercise cessation. Additionally, the heart rate variability (HRV) was analyzed by R-R intervals in the frequency domain for the assessment of cardiac autonomic function. In both exercise modalities, equivalent increases in SBP were observed from rest to peak exercise for all groups, and during recovery, significant PEH was noted. At 90 minutes after the exercise session, the prevalence of hypotension was significantly higher in water- than in the land-based protocol. Moreover, more pronounced reductions in SBP and DBP were observed in the UH patients compared to TH and N subjects. Finally, exercise in the water was more effective in restoring HRV during recovery, with greater effects in the untreated hypertensive group. Our data demonstrated that water-ergometry exercise was able to induce expressive PEH and improve cardiac autonomic modulation in older normotensive, hypertensive treated or hypertensive untreated subjects when compared to conventional land-ergometry.

Dilatation by Soehendra stent retriever is feasible and effective in multiple deployment of metallic stents to malignant hilar biliary strictures.

PubMed

Kato, Hironari; Kawamoto, Hirofumi; Noma, Yasuhiro; Sonoyama, Takayuki; Tsutsumi, Koichiro; Fujii, Masakuni; Okada, Hiroyuki; Yamamoto, Kazuhide

2013-01-01

The endoscopic management of malignant hilar biliary strictures using multiple metallic stents (MS) is technically demanding, in the initial deployment of MS and the recovery from MS occlusion with deployment of multiple plastic stents (PS). We evaluated the outcomes of the application of a Soehendra stent retriever (SSR) as a dilator of intractable strictures. Fifty-nine patients with malignant hilar biliary strictures had multiple MS inserted using a partial stent-in-stent procedure. When we encountered intractable strictures, we adopted SSR to dilate the stricture and the interstice of the MS. We evaluated the success rate of MS or PS deployment after SSR application and procedural complications. Five of 59 patients (8%) were subjected to SSR application for the initial MS deployment. MS were successfully deployed in all of these patients (100%). MS occlusion was noted in 27 patients. We applied SSR to seven patients (26%) for the deployment of multiple PS after MS occlusion. In five patients (71%), successful PS deployment was achieved after the SSR application. No complications related to dilatation using SSR occurred in any patient. SSR proved to be a potent dilator of difficult strictures in the management of malignant hilar biliary strictures.

In Vitro Wound Healing Potential and Identification of Bioactive Compounds from Moringa oleifera Lam

PubMed Central

Muhammad, Abubakar Amali; Pauzi, Nur Aimi Syarina; Arulselvan, Palanisamy; Abas, Faridah; Fakurazi, Sharida

2013-01-01

Moringa oleifera Lam. (M. oleifera) from the monogeneric family Moringaceae is found in tropical and subtropical countries. The present study was aimed at exploring the in vitro wound healing potential of M. oleifera and identification of active compounds that may be responsible for its wound healing action. The study included cell viability, proliferation, and wound scratch test assays. Different solvent crude extracts were screened, and the most active crude extract was further subjected to differential bioguided fractionation. Fractions were also screened and most active aqueous fraction was finally obtained for further investigation. HPLC and LC-MS/MS analysis were used for identification and confirmation of bioactive compounds. The results of our study demonstrated that aqueous fraction of M. oleifera significantly enhanced proliferation and viability as well as migration of human dermal fibroblast (HDF) cells compared to the untreated control and other fractions. The HPLC and LC-MS/MS studies revealed kaempferol and quercetin compounds in the crude methanolic extract and a major bioactive compound Vicenin-2 was identified in the bioactive aqueous fraction which was confirmed with standard Vicenin-2 using HPLC and UV spectroscopic methods. These findings suggest that bioactive fraction of M. oleifera containing Vicenin-2 compound may enhance faster wound healing in vitro. PMID:24490175

Effect of Antibiotics and Diet on Enterolactone Concentration and Metabolome Studied by Targeted and Nontargeted LC-MS Metabolomics.

PubMed

Bolvig, Anne K; Nørskov, Natalja P; Hedemann, Mette S; Foldager, Leslie; McCarthy-Sinclair, Brendan; Marco, Maria L; Lærke, Helle N; Bach Knudsen, Knud E

2017-06-02

High plant lignan intake is associated with a number of health benefits, possibly induced by the lignan metabolite enterolactone (ENL). The gut microbiota plays a crucial role in converting dietary lignans into ENL, and epidemiological studies have shown that use of antibiotics is associated with lower levels of ENL. Here we investigate the link between antibiotic use and lignan metabolism in pigs using LC-MS/MS. The effect of lignan intake and antibiotic use on the gut microbial community and the pig metabolome is studied by 16S rRNA sequencing and nontargeted LC-MS. Treatment with antibiotics resulted in substantially lower concentrations of ENL compared with concentrations detected in untreated animals, whereas the plasma concentrations of plant lignans were unchanged. Both diet and antibiotic treatment affected the clustering of urinary metabolites and significantly altered the proportions of taxa in the gut microbiota. Diet, but not antibiotic treatment, affected the plasma lipid profile, and a lower concentration of LDL cholesterol was observed in the pigs fed a high lignan diet. This study provides solid support for the associations between ENL concentrations and use of antibiotics found in humans and indicates that the lower ENL concentration may be a consequence of the ecological changes in the microbiota.

Improved Detection of Botulinum Neurotoxin Serotype A by Endopep-MS through Peptide Substrate Modification

PubMed Central

Wang, Dongxia; Baudys, Jakub; Ye, Yiming; Rees, Jon C.; Barr, John R.; Pirkle, James L.; Kalb, Suzanne R.

2015-01-01

Botulinum neurotoxins (BoNTs) are a family of seven toxin serotypes that are the most toxic substances known to man. Intoxication with BoNT causes flaccid paralysis and can lead to death if untreated with serotype specific antibodies. Supportive care, including ventilation, may be necessary. Rapid and sensitive detection of BoNT is necessary for timely clinical confirmation of clinical botulism. Previously, our laboratory developed a fast and sensitive mass spectrometry (MS) method termed the Endopep-MS assay. The BoNT serotypes are rapidly detected and differentiated by extracting the toxin with serotype specific antibodies and detecting the unique and serotype specific cleavage products of peptide substrates that mimic the sequence of the BoNT native targets. To further improve the sensitivity of the Endopep-MS assay, we report here the optimization of the substrate peptide for the detection of BoNT/A. Modifications on the terminal groups of the original peptide substrate with acetylation and amidation significantly improved the detection of BoNT/A cleavage products. The replacement of some internal amino acid residues with single or multiple substitutions led to further improvement. An optimized peptide increased assay sensitivity five fold with toxin spiked into buffer solution or different biological matrices. PMID:23017875

[A novel protein equalizer based on single chain variable fragment display M13 phage library for nephropathy patient urine study].

PubMed

Zhao, Peng; Tao, Dingyin; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

2009-05-01

A novel protein equalizer was developed with single chain variable fragment (scFv) library displaying M13 phage covalently bonded on monolithic cryogel. Due to the great number and various kinds of displayed scFv fragments, as well as strong and specific binding capacity between scFv fragments and proteins, a new protein equalizer technology is preferable in the pretreatment of complex protein samples. After the sample dissolved in phosphate buffer solution (PBS), it was repeatedly loaded onto the equalizer for five times, the bound proteins were in sequence eluted by 2 mol/L NaCl and 50 mmol/L Gly-HC1 (pH 2.5) solution, followed by digestion with thrombin. All proteins or peptides collected from each fraction were further analyzed by high performance liquid chromatography-electrospray tandem mass spectrometry (RPLC-ESI-MS/MS) with a serially coupled long microcolumn. Compared with the untreated samples, the identified protein number was increased from 142 to 396. Furthermore, from sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis results, it was found that the protein concentration difference was reduced obviously in the eluant of direct sample loading, and most high abundance proteins were identified in the eluant of NaCl. All these results demonstrate that the novel protein equalizer with scFv display M13 phage library immobilized on cyrogel could effectively reduce the dynamic range of proteins in complex samples, enabling the identification of more low abundance proteins.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

PubMed

Taylor, R J; Wahl, R L; Sharma, P K; Bradford, C R; Terrell, J E; Teknos, T N; Heard, E M; Wolf, G T; Chepeha, D B

2001-08-01

To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

PubMed

Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

2018-01-01

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients.

PubMed

Marotta, Teodoro; Russo, Barbara F; Ferrara, L Aldo

2010-08-01

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL) >or=3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was >or=3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93-97% of group A patients and 38-51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist-to-hip ratio, total and non-HDL cholesterol than group B patients with MS. In group B, MS and non-MS patients had similar waist-to-hip ratio, blood pressure, total and non-HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 +/- 5% in group B, non-MS patients; 13.1 +/- 6% in group B, MS patients; 19.9 +/- 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r(2) = 0.227) more closely than gender, blood pressure, waist-to-hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r(2) = 0.252). Thus, TG/HDL ratio could help to characterize high-risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin-sensitive patients, identified by lower values of this parameter, is only moderately affected by MS.

Bilirubin Level is Associated with Left Ventricular Hypertrophy Independent of Blood Pressure in Previously Untreated Hypertensive Patients

PubMed Central

Ayaz, Teslime; Kocaman, Sinan Altan; Durakoğlugil, Tuğba; Erdoğan, Turan; Şahin, Osman Zikrullah; Şahin, Serap Baydur; Çiçek, Yüksel; Şatiroğlu, Ömer

2014-01-01

Background and Objectives Left ventricular hypertrophy (LVH), a sign of subclinical cardiovascular disease, is an important predictor of cardiovascular morbidity and mortality. The aim of our study was to determine the association of left ventricular mass (LVM) with possible causative anthropometric and biochemical parameters as well as carotid intima-media thickness (CIMT) and brachial flow-mediated dilation (FMD) as surrogates of atherosclerosis and endothelial dysfunction, respectively, in previously untreated hypertensive patients. Subjects and Methods Our study included 114 consecutive previously untreated hypertensive patients who underwent echocardiography and ultrasonography to evaluate their vascular status and function via brachial artery CIMT and FMD. Results Among all study parameters, age, systolic blood pressure (BP), diastolic BP, pulse pressure, plasma glucose, uric acid, total bilirubin, direct bilirubin, hemoglobin, and CIMT were positively correlated with the LVM index. Multiple logistic regression analysis revealed that office systolic BP, age, male gender, and total bilirubin were independent predictors of LVH. Conclusion Bilirubin seems to be related to LVM and LVH. The positive association of bilirubin with these parameters is novel and requires further research. PMID:25278987

Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: A combined perspective from the MS in the 21st Century Steering Group.

PubMed

Rieckmann, Peter; Centonze, Diego; Elovaara, Irina; Giovannoni, Gavin; Havrdová, Eva; Kesselring, Jurg; Kobelt, Gisela; Langdon, Dawn; Morrow, Sarah A; Oreja-Guevara, Celia; Schippling, Sven; Thalheim, Christoph; Thompson, Heidi; Vermersch, Patrick; Aston, Karen; Bauer, Birgit; Demory, Christy; Giambastiani, Maria Paz; Hlavacova, Jana; Nouvet-Gire, Jocelyne; Pepper, George; Pontaga, Maija; Rogan, Emma; Rogalski, Chrystal; van Galen, Pieter; Ben-Amor, Ali-Frédéric

2018-01-01

Patient engagement is vital in multiple sclerosis (MS) in order to optimise outcomes for patients, society and healthcare systems. It is essential to involve all stakeholders in potential solutions, working in a multidisciplinary way to ensure that people with MS (PwMS) are included in shared decision-making and disease management. To start this process, a collaborative, open environment between PwMS and healthcare professionals (HCPs) is required so that similarities and disparities in the perception of key areas in patient care and unmet needs can be identified. With this patient-centred approach in mind, in 2016 the MS in the 21st Century Steering Group formed a unique collaboration to include PwMS in the Steering Group to provide a platform for the patient voice. The MS in the 21st Century initiative set out to foster engagement through a series of open-forum joint workshops. The aims of these workshops were: to identify similarities and disparities in the perception and prioritisation in three key areas (unmet needs, the treatment burden in MS, and factors that impact patient engagement), and to provide practical advice on how the gaps in perception and understanding in these key areas could be bridged. Combined practical advice and direction are provided here as eight actions: 1. Improve communication to raise the quality of HCP-patient interaction and optimise the limited time available for consultations. 2. Heighten the awareness of 'hidden' disease symptoms and how these can be managed. 3. Improve the dialogue surrounding the benefit versus risk issues of therapies to help patients become fully informed and active participants in their healthcare decisions. 4. Provide accurate, lucid information in an easily accessible format from reliable sources. 5. Encourage HCPs and multidisciplinary teams to acquire and share new knowledge and information among their teams and with PwMS. 6. Foster greater understanding and awareness of challenges faced by PwMS and HCPs in treating MS. 7. Collaborate to develop local education, communication and patient-engagement initiatives. 8. Motivate PwMS to become advocates for self-management in MS care. Our study of PwMS and HCPs in the MS in the 21st Century initiative has highlighted eight practical actions. These actions identify how differences and gaps in unmet needs, treatment burden, and patient engagement between PwMS and HCPs can be bridged to improve MS disease management. Of particular interest now are patient-centred educational resources that can be used during time-limited consultations to enhance understanding of disease and improve communication. Actively bridging these gaps in a joint approach enables PwMS to take part in shared decision-making; with improved communication and reliable information, patients can make informed decisions with their HCPs, as part of their own personalised disease management. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Mental stress-induced ischemia in patients with coronary artery disease: echocardiographic characteristics and relation to exercise-induced ischemia.

PubMed

Stepanovic, Jelena; Ostojic, Miodrag; Beleslin, Branko; Vukovic, Olivera; Djordjevic-Dikic, Ana; Dikic, Ana Djordjevic; Giga, Vojislav; Nedeljkovic, Ivana; Nedeljkovic, Milan; Stojkovic, Sinisa; Vukcevic, Vladan; Dobric, Milan; Petrasinovic, Zorica; Marinkovic, Jelena; Lecic-Tosevski, Dusica

2012-09-01

The aims of this study were to investigate the incidence and parameters associated with myocardial ischemia during mental stress (MS) as measured by echocardiography and to evaluate the relation between MS-induced and exercise-induced myocardial ischemia. Study participants were 79 patients (63 men; mean [M] [standard deviation {SD}] age = 52 [8] years) with angiographically confirmed coronary artery disease and previous positive exercise test result. The MS protocol consisted of mental arithmetic and anger recall task. The patients performed a treadmill exercise test 15 to 20 minutes after the MS task. Data of post-MS exercise were compared with previous exercise stress test results. The frequency of echocardiographic abnormalities was 35% in response to the mental arithmetic task, compared with 61% with anger recall and 96% with exercise (p < .001, exercise versus MS). Electrocardiogram abnormalities and chest pain were substantially less common during MS than were echocardiographic abnormalities. Independent predictors of MS-induced myocardial ischemia were: wall motion score index at rest (p = .02), peak systolic blood pressure (p = .005), and increase in rate-pressure product (p = .004) during MS. The duration of exercise stress test was significantly shorter (p < .001) when MS preceded the exercise and in the case of earlier exercise (M [SD] = 4.4 [1.9] versus 6.7 [2.2] minutes for patients positive on MS and 5.7 [1.9] versus 8.0 [2.3] minutes for patients negative on MS). Echocardiography can be successfully used to document myocardial ischemia induced by MS. MS-induced ischemia was associated with an increase in hemodynamic parameters during MS and worse function of the left ventricle. MS may shorten the duration of subsequent exercise stress testing and can potentiate exercise-induced ischemia in susceptible patients with coronary artery disease.

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Soluble serum interleukin 2 receptor levels in leprosy patients

PubMed Central

Tung, K. S. K.; Umland, Edith; Matzner, P.; Nelson, K.; Schauf, Victoria; Rubin, L.; Wagner, D.; Scollard, D.; Vithayasai, Prakong; Vithayasai, Vicharn; Worobec, Sophie; Smith, T.; Suriyanond, Vinai

1987-01-01

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythrema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum. PMID:3115652

Small intestinal malabsorption in chronic alcoholism: a retrospective study of alcoholic patients by the ¹⁴C-D-xylose breath test.

PubMed

Hope, Håvar; Skar, Viggo; Sandstad, Olav; Husebye, Einar; Medhus, Asle W

2012-04-01

The ¹⁴C-D-xylose breath test was used at Ullevål University Hospital in the period from 1986 TO 1995 for malabsorption testing. The objective of this retrospective study was to reveal whether patients with chronic alcoholism may have intestinal malabsorption. The consecutive ¹⁴C-D-xylose breath test database was reviewed and patients with the diagnosis of chronic alcoholism were identified. ¹⁴C-D-xylose breath test results of the alcoholic patients were compared with the results of untreated celiac patients and patient and healthy controls. In the ¹⁴C-D-xylose breath test, ¹⁴C-D-xylose was dissolved in water and given orally after overnight fast. Breath samples were taken at 30-min intervals for 210 min, and ¹⁴CO₂ : ¹²CO₂ ratios were calculated for each time point, presenting a time curve for ¹⁴C-D-xylose absorption. Urine was collected after 210 min and the fraction of the total d-xylose passed was calculated (U%). ¹⁴CO₂ in breath and ¹⁴C-D-xylose in urine were analyzed using liquid scintillation. Both breath and urine analysis revealed a pattern of malabsorption in alcoholics comparable with untreated celiac patients, with significantly reduced absorption of d-xylose compared with patient and healthy controls. Alcoholic patients have a significantly reduced ¹⁴C-D-xylose absorption, comparable with untreated celiac patients. This indicates a reduced intestinal function in chronic alcoholism.

Temporary use of silicone stents for severe airway stenosis in untreated malignant lymphoma.

PubMed

Oki, Masahide; Saka, Hideo

2013-01-01

Airway stenting has become a popular method for palliation of airway stenosis; however, little has been reported about their use for patients with malignant lymphoma that occasionally causes a life-threatening condition. The aim of the study was to evaluate the efficacy and safety of airway stenting in chemoradiotherapy naive patients with severe airway stenosis due to malignant lymphoma. Patients who underwent airway stent placement from April 2007 to July 2011 in a single center were retrospectively reviewed. All stenting procedures were performed using rigid and flexible bronchoscopes under general anesthesia. We performed 174 airway stenting procedures (silicone stents in 154 procedures and metallic in 20 procedures) for 150 patients during the study period. Of the patients, 7 had untreated malignant lymphomas (4 diffuse large B-cell lymphomas, 2 lymphoblastic lymphomas, 1 mucosa-associated lymphoid tissue lymphoma). All patients underwent stenting using the silicone Y-stent (6 on the main carina and 1 on the primary right carina). Dyspnea was relieved immediately in 6 of 7 patients including the mechanically ventilated patient. Stents could be removed in all patients (median 90 d after stenting; range, 32 to 245 d) because of the tumor response to tumor-specific therapy. One granuloma formation and 1 mucus retention triggered the decision to remove the stents. Airway stenting using silicone stents is safe and effective in palliation of airway stenosis in patients with untreated malignant lymphoma, and permits postprocedural tumor-specific therapy. The response to tumor-specific therapy can be expected, and so removable stents should be selected.

Prevalence of metabolic syndrome among patients with schizophrenia in Palestine.

PubMed

Sweileh, Waleed M; Zyoud, Sa'ed H; Dalal, Salah A; Ibwini, Sami; Sawalha, Ansam F; Ali, Iyad

2012-12-27

Metabolic syndrome (MS) is a cluster of the most dangerous cardiac risk factors and is associated with high mortality. Ethnic differences in metabolic syndrome (MS) criteria and prevalence rates have been reported. The purpose of this study was to investigate the MS prevalence among patients with schizophrenia in Palestine. We recruited 250 patients with schizophrenia from 4 psychiatric primary healthcare centers in Northern Palestine. The MS prevalence was assessed based on National Cholesterol Education Program Adult Treatment Panel III Adapted criteria. The overall MS prevalence was 43.6%, with 39% in male and 55.9% in female patients. On average, the study patients had 2.3 ± 1.3 metabolic abnormalities. Univariate analysis showed that MS was significantly higher with older age, female gender, longer duration of the illness, smoking, abdominal obesity, high systolic and diastolic blood pressure, high triglycerides, low HDL-C, and high fasting plasma glucose. Multiple logistic regression analysis showed that only systolic blood pressure, high triglycerides, high fasting plasma glucose, and low HDL-C were significant predictors of MS in schizophrenic patients. MS is common among Arab patients with schizophrenia. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.

Long-term echocardiographic follow-up of untreated 2+ functional tricuspid regurgitation in patients undergoing mitral valve surgery.

PubMed

Kusajima, Kunio; Fujita, Tomoyuki; Hata, Hiroki; Shimahara, Yusuke; Miura, Sayaka; Kobayashi, Junjiro

2016-07-01

Concomitant tricuspid valve surgery with mitral valve surgery is recommended for patients with severe functional tricuspid regurgitation (TR). However, the treatment for 2+ TR (mild TR) remains controversial. Here, we evaluated the long-term results of untreated 2+ TR in patients undergoing mitral valve surgery. We retrospectively reviewed the records of 96 patients with untreated 2+ TR among 885 patients who underwent mitral valve surgery from 2003 to 2010. Exclusion criteria were tricuspid valve surgery (TVS), emergency surgery, primary TR and pacemaker lead through the tricuspid valve. We assessed survival and freedom from heart failure. The freedom from 3+ (moderate) or 4+ (severe) TR was investigated by echocardiographic data at pre- and postoperative week 1, then at 1, 3, 5, 7 and 10 postoperative years, which were compared with those in patients who had 2+ TR preoperatively and underwent concomitant TVS in the same period (n = 47). The mean follow-up was 7.1 ± 2.7 years. There was no 30-day mortality. The survival rate was 97.5% at 5 years and 87.5% at 10 years. The independent risk factors for mortality were age (OR 1.2, P = 0.03) and left ventricular ejection fraction (OR 0.9, P = 0.03). Untreated 2+ TR improved transiently within the first postoperative year (P < 0.001), but progressed again in the mid- to long term. Freedom from ≥3+ TR was 64.2% at 5 years and 46.7% at 10 years, which was significantly lower than that from ≥3+ TR in patients who underwent concomitant TVS (P = 0.006). The independent risk factors for TR progression (≥3 + TR) were age (OR 1.1, P = 0.005), atrial fibrillation (OR 2.2, P = 0.04) and tricuspid annular diameter (TAD) index (mm/m(2); OR 1.1, P = 0.02). Receiver operating characteristic curves showed that the optimal TAD index cut-off value was 21.0 for long-term survival [area under the curve (AUC) = 0.72] and 21.2 for TR progression (AUC = 0.64). Although untreated, 2+ TR significantly improved after mitral valve surgery, it then progressed again in the mid- to long term. Therefore, concomitant TVS should be considered in patients with 2+ TR who have dilated tricuspid annulus or atrial fibrillation, if feasible. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Metabolic syndrome cluster does not provide incremental prognostic information in patients with stable cardiovascular disease: A post hoc analysis of the AIM-HIGH trial.

PubMed

Lyubarova, Radmila; Robinson, Jennifer G; Miller, Michael; Simmons, Debra L; Xu, Ping; Abramson, Beth L; Elam, Marshall B; Brown, Todd M; McBride, Ruth; Fleg, Jerome L; Desvigne-Nickens, Patrice; Ayenew, Woubeshet; Boden, William E

Metabolic syndrome (MS) is a well-known risk factor for the development of cardiovascular (CV) disease; yet, controversy persists whether it adds incremental prognostic value in patients with established CV disease. This study was performed to determine if MS is associated with worse CV outcomes in patients with established CV disease treated intensively with statins. We performed a post hoc analysis of the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial, in which patients with established CV disease and atherogenic dyslipidemia (n = 3414) were randomly assigned to receive extended release niacin or placebo during a mean 36-month follow-up, to assess whether the presence of MS or the number of MS components contributed to CV outcomes. The composite primary end point of CV events occurred in 15.1% of patients without MS vs 13.8%, 16.9%, and 16.8% of patients with MS in the subsets with 3, 4, and 5 MS components, respectively (corresponding adjusted hazard ratios 0.9, 1.1, and 1.1 relative to patients without MS), P = .55. Comparing subgroups with 3 vs 4 or 5 MS components, there was no significant difference in either the composite primary end point or secondary end points. Patients with diabetes mellitus had higher event rates, with or without the presence of MS. The presence of MS was not associated with worse CV outcomes in the AIM-HIGH population. The rate of CV events in statin-treated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes patients with MS was not significantly influenced by the number of MS components. Copyright © 2017 National Lipid Association. All rights reserved.

Causes of death among commercially insured multiple sclerosis patients in the United States.

PubMed

Goodin, Douglas S; Corwin, Michael; Kaufman, David; Golub, Howard; Reshef, Shoshana; Rametta, Mark J; Knappertz, Volker; Cutter, Gary; Pleimes, Dirk

2014-01-01

Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes. To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients. Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the "principal" COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized. 30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs. The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide.

Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability.

PubMed

Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; Alfieri, Daniela Frizon; Flauzino, Tamires; Lopes, Josiane; de Carvalho Jennings Pereira, Wildea Lice; de Meleck Proença, Caio; Borelli, Sueli Donizete; Kaimen-Maciel, Damacio Ramón; Maes, Michael; Reiche, Edna Maria Vissoci

2017-05-01

Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.

Screening and identification of four serum miRNAs as novel potential biomarkers for cured pulmonary tuberculosis.

PubMed

Wang, Chong; Yang, Su; Liu, Chang-Ming; Jiang, Ting-Ting; Chen, Zhong-Liang; Tu, Hui-Hui; Mao, Lian-Gen; Li, Zhong-Jie; Li, Ji-Cheng

2018-01-01

Rapid and efficient methods for the determination of cured pulmonary tuberculosis (TB) are lacking. We screened serum miRNAs using the Solexa sequencing method among untreated TB patients, two-month treated TB patients, cured TB patients, and healthy controls. A total of 100 differentially expressed miRNAs were identified in cured TB patients, including 37 up-regulated (fold change >1.50, P < 0.05) and 63 down-regulated (fold change <0.60, P < 0.05) miRNAs. Gene ontology (GO) enrichment analysis revealed that most of the predicted genes were present in the nucleus with a strong protein binding function. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis strongly suggested alterations in the metabolic pathways. Following quantitative real time chain reaction (qRT-PCR), significantly reduced expression levels of miR-21-5p (0.30, P < 0.001), miR-92a-3p (0.63, P < 0.001), and miR-148b-3p (0.17, P < 0.001) were found in the cured TB patients compared with the untreated TB patients, while significantly increased expression levels of miR-21-5p (2.09, P = 0.001), miR-92a-3p (1.40, P = 0.005), and miR-148b-3p (4.80, P = 0.003) were found in the untreated TB patients compared with the healthy controls. And significantly increased level of miR-125a-5p was found between two-month treated TB patients and untreated TB patients (1.81, P = 0.004). We established a cured TB model with 83.96% accuracy by four miRNAs (miR-21-5p, miR-92a-3p, miR-148b-3p, and miR-125a-5p), and also established a diagnostic model with 70.09% accuracy. Our study provides experimental data for establishing objective indicators of cured TB, and also provides a new experimental basis to understand the pathogenesis and prognosis of TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel heparan sulfate assay by using automated high-throughput mass spectrometry: application to monitoring and screening for mucopolysaccharidoses

PubMed Central

Shimada, Tsutomu; Kelly, Joan; LaMarr, William A; van Vlies, Naomi; Yasuda, Eriko; Mason, Robert W.; Mackenzie, William; Kubaski, Francyne; Giugliani, Roberto; Chinen, Yasutsugu; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

2014-01-01

Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4–5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within ten seconds (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity in an HS assay, indicating that HT-MS/MS may be feasible for diagnosis, monitoring, and newborn screening of MPS. PMID:25092413

Earlier disability of the patients followed in Multiple Sclerosis centers compared to outpatients.

PubMed

Debouverie, M; Laforest, L; Van Ganse, E; Guillemin, F

2009-02-01

The currently published works regarding the multiple sclerosis (MS) natural history report data were collected most often on population of patients recruited in MS centers. The aim was to compare the natural history of a population of patients followed in a MS centre (MSC) with patients followed outside a MS centre (NMSC). Cases were identified through the LORSEP cohort, a network of neurologists (private ambulatory practice, hospitals, and MS centers) in France. A total of 3602 patients had been analyzed: 1036 MSC patients and 2566 NMSC patients. No difference was observed regarding gender and initial symptoms. Conversely, MSC patients were younger at MS onset and were more likely to have a primary progressive initial form. Median times (years) to the EDSS scores of 3, 4, and 6 were 5.8 (5.0-6.8), 8.4 (7.9-9.0), 16.0 (14.8-18.1) in the MSC group, respectively, whereas corresponding times were 8.4 (7.9-9.0), 12.3 (11.4-13.4), 19.1 (18.0-20.2) in the NMSC group. These differences according to the type of MS supervision were statistically significant for EDSS3 (P < 0.0001), EDSS4 (P < 0.0001), and EDSS6 (P = 0.01), respectively. These findings were confirmed in Cox multivariate models. The patients followed in a MS centre had earlier disability than patients managed otherwise. Analyses exclusively conducted in patients with MS supervised in specialized centers may falsely misestimate the times needed to reach major disability landmarks. Before using registries to study the natural history of MS, efforts should be performed to verify in how far data are exhaustive and to understand the local health care system.

[Study on the relation between Pi-deficiency pattern and metabolic syndrome in patients with polycystic ovarian syndrome].

PubMed

Wang, Xing-Juan; Jin, Hua-Liang; Liu, Ying

2010-11-01

To evaluate the relation between Pi-deficiency syndrome (PDS) pattern and metabolic syndrome (MS) in patients with polycystic ovarian syndrome (PCOS), for exploring their internal pathologic mechanism. Among the 102 PCOS patients, 22 complicated with MS (PCOS-MS) and 80 not complicated with MS (PCOS-NMS), the Chinese medicine syndrome pattern was differentiated as PDS in 50 patients and non-PDS in 52. The clinical data, in terms of fasting blood glucose (FBG), fasting insulin (FINS), waistline, body weight (BW), stature, blood pressure (BP), etc. was collected and compared and the relation between data was analyzed. Levels of FINS and homeostasis model of assessment for insulin resistence index (HOMA-IR), in PCOS-MS patients were significantly higher than those in PCOS-NMS patients, also higher in patients of PDS pattern than those of non-PDS pattern (P < 0.01); the occurrences of MS and PDS were highly positively correlated with levels of FINS and HOMA-IR (P < 0.01); incidence of MS in patients of PDS pattern was significantly higher than those in patients of non-PDS pattern (P < 0.05); presenting of PDS was positively related with the existence of MS (P < 0.05), but in case of the FINS or HOMA-IR factor being controlled, statistical meaning of the relativity between them turned to insignificant (P > 0.05). PCOS patients of PDS pattern are the high-risk population of MS, which might be related with the insulin resistance. So, early treatment of PCOS, especially on patients of PDS pattern, is of important significance for preventing the complication, as MS, of the disease.

The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.

PubMed

Atchison, Elizabeth A; Wood, Kevin M; Mattox, Cynthia G; Barry, Catherine N; Lum, Flora; MacCumber, Mathew W

2018-05-01

To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. Database study. Patients seeing an ophthalmic provider who contributes to the database. We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The IRIDICA PCR/Electrospray Ionization-Mass Spectrometry Assay on Bronchoalveolar Lavage for Bacterial Etiology in Mechanically Ventilated Patients with Suspected Pneumonia.

PubMed

Strålin, Kristoffer; Ehn, Fredrik; Giske, Christian G; Ullberg, Måns; Hedlund, Jonas; Petersson, Johan; Spindler, Carl; Özenci, Volkan

2016-01-01

We studied the diagnostic performance of the IRIDICA PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) assay applied on bronchoalveolar lavage (BAL) samples, from 51 mechanically ventilated patients with suspected pneumonia, in a prospective study. In 32 patients with X-ray verified pneumonia, PCR/ESI-MS was positive in 66% and BAL culture was positive in 38% (p = 0.045), and either of the methods was positive in 69%. The following BAL result combinations were noted: PCR/ESI-MS+/culture+, 34%; PCR/ESI-MS+/culture-, 31%; PCR/ESI-MS-/culture+, 3.1%; PCR/ESI-MS-/culture-, 31%; kappa 0.36 (95% confidence interval (CI), 0.10-0.63). In pneumonia patients without prior antibiotic treatment, optimal agreement was noted with 88% PCR/ESI-MS+/culture+ and 12% PCR/ESI-MS-/culture- (kappa 1.0). However, in patients with prior antibiotic treatment, the test agreement was poor (kappa 0.16; 95% CI, -0.10-0.44), as 10 patients were PCR/ESI-MS+/culture-. In 8/10 patients the pathogens detected by PCR/ESI-MS could be detected by other conventional tests or PCR tests on BAL. Compared with BAL culture, PCR/ESI-MS showed specificities and negative predictive values of ≥87% for all individual pathogens, an overall sensitivity of 77% and positive predictive value (PPV) of 42%. When other conventional tests and PCR tests were added to the reference standard, the overall PPV increased to 87%. The PCR/ESI-MS semi-quantitative level tended to be higher for PCR/ESI-MS positive cases with pneumonia compared with cases without pneumonia (p = 0.074). In conclusion, PCR/ESI-MS applied on BAL showed a promising performance and has potential to be clinically useful in mechanically ventilated patients with suspected pneumonia. The usefulness of the method for establishment of pneumonia etiology and selection of antibiotic therapy should be further studied.

The IRIDICA PCR/Electrospray Ionization–Mass Spectrometry Assay on Bronchoalveolar Lavage for Bacterial Etiology in Mechanically Ventilated Patients with Suspected Pneumonia

PubMed Central

Ehn, Fredrik; Giske, Christian G.; Ullberg, Måns; Hedlund, Jonas; Petersson, Johan; Spindler, Carl; Özenci, Volkan

2016-01-01

We studied the diagnostic performance of the IRIDICA PCR/electrospray ionization–mass spectrometry (PCR/ESI-MS) assay applied on bronchoalveolar lavage (BAL) samples, from 51 mechanically ventilated patients with suspected pneumonia, in a prospective study. In 32 patients with X-ray verified pneumonia, PCR/ESI-MS was positive in 66% and BAL culture was positive in 38% (p = 0.045), and either of the methods was positive in 69%. The following BAL result combinations were noted: PCR/ESI-MS+/culture+, 34%; PCR/ESI-MS+/culture-, 31%; PCR/ESI-MS-/culture+, 3.1%; PCR/ESI-MS-/culture-, 31%; kappa 0.36 (95% confidence interval (CI), 0.10–0.63). In pneumonia patients without prior antibiotic treatment, optimal agreement was noted with 88% PCR/ESI-MS+/culture+ and 12% PCR/ESI-MS-/culture- (kappa 1.0). However, in patients with prior antibiotic treatment, the test agreement was poor (kappa 0.16; 95% CI, -0.10–0.44), as 10 patients were PCR/ESI-MS+/culture-. In 8/10 patients the pathogens detected by PCR/ESI-MS could be detected by other conventional tests or PCR tests on BAL. Compared with BAL culture, PCR/ESI-MS showed specificities and negative predictive values of ≥87% for all individual pathogens, an overall sensitivity of 77% and positive predictive value (PPV) of 42%. When other conventional tests and PCR tests were added to the reference standard, the overall PPV increased to 87%. The PCR/ESI-MS semi-quantitative level tended to be higher for PCR/ESI-MS positive cases with pneumonia compared with cases without pneumonia (p = 0.074). In conclusion, PCR/ESI-MS applied on BAL showed a promising performance and has potential to be clinically useful in mechanically ventilated patients with suspected pneumonia. The usefulness of the method for establishment of pneumonia etiology and selection of antibiotic therapy should be further studied. PMID:27463099

Efficacy and Safety of Bendamustine and Ibrutinib in Previously Untreated Patients With Chronic Lymphocytic Leukemia: Indirect Comparison.

PubMed

Andrasiak, Iga; Rybka, Justyna; Knopinska-Posluszny, Wanda; Wrobel, Tomasz

2017-05-01

Bendamustine and ibrutinib are commonly used in the treatment of patients suffering from chronic lymphocytic leukemia (CLL). In this study we compare efficacy and safety bendamustine versus ibrutinib therapy in previously untreated patients with CLL. Because there are no head-to-head comparisons between bendamustine and ibrutinib, we performed indirect comparison using Bucher method. A systematic literature review was performed and 2 studies published before June 2016 were taken into analysis. Treatment with ibrutinib significantly improves PFS determined by investigator (HR of 0.3; P = .01) and OS (HR of 0.21; P < .001. Our study indicates that ibrutinib therapy improves PFS, OS and is superior in terms of safety comparing with bendamustine therapy in CLL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Higher Carotid Intima-Media Thickness in Subclinical Hypothyroidism Associated with the Metabolic Syndrome.

PubMed

França, Mariana Martins; Nogueira, Célia Regina; Hueb, João Carlos; Mendes, Adriana Lúcia; Padovani, Carlos Roberto; Mazeto, Gláucia Maria Ferreira da Silva

2016-10-01

The subclinical hypothyroidism (SH) and the metabolic syndrome (MS) have been associated with increased risk of atherosclerosis and cardiovascular disease (CVD). The measurement of carotid intima-media thickness (IMT) is capable of detecting early signs of atherosclerotic disease. The goal of the study was to compare the carotid IMT of patients with SH with and without the MS. Twenty-nine SH patients were subdivided into two groups: one with MS (SH + MS) and one without MS (SH - MS). The study also assessed a group of euthyroid patients (n = 31), also subdivided into two groups: one with MS (EU + MS) and one without MS (EU - MS). The clinical and laboratory data and the mean and maximum carotid IMT of the groups were compared. Maximum (P = 0.012) and mean (P = 0.025) IMT were higher in the SH + MS group than in the SH-MS group. Maximum IMT was higher in the SH + MS group than in the EU + MS group (P = 0.048). Maximum IMT was positively correlated with fasting glucose (FG; R = 0.621; P < 0.01) and body mass index (R = 0.258; P = 0.041) and negatively correlated with low-density lipoprotein cholesterol (LDL-C) (R = -0.297; P = 0.017). Mean IMT was positively correlated with FG (R = 0.580; P < 0.01), systolic blood pressure (R = 0.292; P = 0.02), and triglycerides (R = 0.250; P = 0.048) and negatively correlated with LDL-C (R = -0.288; P = 0.022). SH + MS patients have higher IMT than SH - MS or EU + MS patients, suggesting that SH may be one more CVD risk factor in patients with the MS.

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

PubMed

Wyles, David L; Ruane, Peter J; Sulkowski, Mark S; Dieterich, Douglas; Luetkemeyer, Anne; Morgan, Timothy R; Sherman, Kenneth E; Dretler, Robin; Fishbein, Dawn; Gathe, Joseph C; Henn, Sarah; Hinestrosa, Federico; Huynh, Charles; McDonald, Cheryl; Mills, Anthony; Overton, Edgar Turner; Ramgopal, Moti; Rashbaum, Bruce; Ray, Graham; Scarsella, Anthony; Yozviak, Joseph; McPhee, Fiona; Liu, Zhaohui; Hughes, Eric; Yin, Philip D; Noviello, Stephanie; Ackerman, Peter

2015-08-20

The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).

Effect of Valsalva's manoeuvre and hyoscinbutylbromide on the pressure gradient across the wall of oesophageal varices.

PubMed Central

Hosking, S W; Robinson, P; Johnson, A G

1987-01-01

To assess whether Valsalva's manoeuvre might cause variceal bleeding, 22 patients with oesophageal varices were studied. In 12 patients who received no previous treatment to their varices the median pressure gradient across the varix wall at rest was 19 (6-36) mmHg, and in 10 patients whose varices were thrombosed at their distal end the median pressure gradient in the proximal patent varix was 8 (1-6) mmHg. In untreated patients groups, the pressure gradient rose by 6-12 mmHg during Valsalva's manoeuvre in four patients, fell by 4-11 mmHg in five patients and was virtually unchanged in the remainder. These changes seem unlikely to cause variceal bleeding. Patients who repeated Valsalva's manoeuvre showed similar changes on each occasion. Six patients in the untreated group also received hyoscinbutylbromide 20 mg iv. No change was seen in the pressure gradient in five patients, suggesting that it is of little value in preventing variceal bleeding. PMID:3500098

The role of specialist nurses in multiple sclerosis: a rapid and systematic review.

PubMed

De Broe, S; Christopher, F; Waugh, N

2001-01-01

Multiple sclerosis (MS) is a disease of the central nervous system. The cause is unknown. There are about 80-160 people with MS per 100,000 population, with twice as many women affected as men. The management of individuals with MS includes treatment of acute relapses and chronic symptoms. The care of MS patients is provided by various healthcare professionals, such as general practitioners (GPs), neurologists, physiotherapists, occupational therapists and nurses. Some MS patients have access to an MS specialist nurse, although this provision varies geographically. The aim of this report is to assess the effectiveness and relative cost-effectiveness of MS specialist nurses in improving care and outcomes for patients with MS. A systematic review of the literature, involving a range of databases, was performed. Full details are described in the main report. Only one study was identified that tried to evaluate the benefit of MS specialist nurses. The study concluded that MS patients and their carers found the MS specialist nurse to be helpful, particularly in improving their knowledge of MS, ability to cope, mood and confidence about the future. GPs also reported finding the nurse to be helpful with their MS patients, and 40% of the GPs stated they would purchase the services of an MS specialist nurse if their practices became fundholding. However, there were considerable methodological weaknesses inherent in the study design, and it was unclear whether the results of the study could be extrapolated to other settings or to other MS patient groups. RESULTS - ONGOING RESEARCH: There are two ongoing research studies regarding MS specialist nurses. One of these studies involves the provision of MS nurses to several areas, but also has two control populations to allow evaluation of the health benefits of the nurses to MS patients and their carers. This study will help to fill the evidence gap. RESULTS - COSTS: The costs of providing MS specialist nurses consist of their yearly salary (usually NHS grade G), as well as additional costs for travelling, administration, computer and telephone use, a pension scheme, National Insurance and study leave. The MS Society of Great Britain and Northern Ireland allows a generous total yearly cost to the employer of 40,000 pounds. The present evidence does not make it possible to comment with any certainty on the value of specialist nurses in MS. The best evidence available to the authors is specialist opinion from neurologists and nurses, and comments from patients with MS; this opinion supports the provision of MS specialist nurses. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: Further research is needed before it will be feasible to make firm recommendations on the value of MS specialist nurses relative to other possible uses of funds.

Assessing the Value of Treatment to Address Various Symptoms Associated with Multiple Sclerosis: Results from a Contingent Valuation Study.

PubMed

Lin, Pei-Jung; Saret, Cayla J; Neumann, Peter J; Sandberg, Eileen A; Cohen, Joshua T

2016-12-01

Although it is well recognized that people with multiple sclerosis (MS) may experience impairments in addition to limited mobility, there has been little effort to study their relative importance to patients with the condition. The objective of this study was to assess patient preferences for addressing various MS symptoms. This study was conducted at Tufts Medical Center, Boston, Massachusetts. We developed a national online survey of MS patients and neurologists to estimate the value each group places on treating specific MS symptoms. Each respondent was presented with two randomly selected scenarios with different symptoms and treatments. MS patients were asked about their own preferences, whereas neurologists were asked to consider what a patient of theirs would do or think in each scenario. We used a bidding game approach to elicit respondents' willingness to pay (WTP) for the treatments. To treat mobility alone, WTP for MS patients averaged US$410-US$520 per month, depending on the scenario. For paired symptoms, MS patients would pay most to treat mobility and upper limb function (US$525/month) or mobility and cognition (US$514/month), somewhat less to treat mobility and eyesight (US$445/month), and least to treat mobility and fatigue (US$371/month). Patient WTP values increased with income and education. Neurologists believed their patients would be willing to pay US$216-US$249 per month to treat mobility alone, depending on the scenario. For paired symptoms, neurologists believed patients would pay most to treat mobility and fatigue (US$263/month) and least to treat mobility and upper limb function (US$177/month). Our findings suggest MS patients may value one outcome (e.g., improved arm and hand coordination) over another (e.g., less fatigue). Further, MS patients and neurologists may rank the importance of treating various symptoms differently. Given this potential mismatch, it is crucial for MS patients and their clinicians to discuss treatment priorities that take into account patient preferences.

Clinical and MRI outcomes after stopping or switching disease-modifying therapy in stable MS patients: a case series report.

PubMed

Berkovich, Regina

2017-10-01

To evaluate clinical and MRI outcomes after stopping or switching disease-modifying therapy in patients with stable MS. A retrospective chart review was conducted of stable MS patients who discontinued or switched their DMT from 2011 to 2015. Clinical and MRI outcomes were obtained at baseline and 1-year follow-up. For the DMT discontinuation group, 15 patients were included, with 67% female, 53% Caucasian, mean age of 45.3 ± 12.2 years, disease duration of 9.1 ± 4.3 years, MS type (80% RRMS, 20% SPMS), and EDSS of 3.7 ± 1.6. The average duration of stable MS course was 5.5 ± 3.7 years. Within a mean of 6.4 ± 2.2 months after DMT discontinuation, all 15 patients experienced worsening of MS disease. After re-evaluation of MS treatment options, all 15 patients were restarted on DMT, of which, 6 (40%) restarted on their prior DMT, 4 (26.7%) switched to another DMT due to adverse events on prior DMT, and 5 (33.3%) switched to a more potent DMT due to worsening of MS activity. One year follow-up showed 2 patients (13.3%) who were restarted on their prior DMT experienced a relapse and the remaining 13 patients (86.7%) had no clinical or MRI activities. For the DMT switch group, 23 patients were included, with 65% female, 61% Caucasian, a mean age of 46.9 ± 11.6 years, disease duration of 11.7 ± 5.1 years, MS Type (83% RRMS, 17% SPMS), and EDSS of 3.5 ± 0.9. After switching DMT, 9 (39.1%) patients experienced worsening of clinical or MRI outcomes at the 1-year follow-up. Of the 9 switch failures, the majority (N = 6) were due to switching to dimethyl fumarate. DMT discontinuation in stable MS patients resulted in worsening of MS disease course for all patients, which improved upon DMT restart or switch. In contrast, 39% of MS stable patients experienced worsening of MS disease course when switched to another DMT, with DMT selection potentially impacting switch outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

ClinicalTrials.gov

2018-03-19

Adult B Lymphoblastic Lymphoma; Childhood B Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Lymphoblastic Lymphoma; Down Syndrome; Stage I B Lymphoblastic Lymphoma; Stage II B Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Association of Incident Obstructive Sleep Apnea with Outcomes in a Large Cohort of US Veterans

PubMed Central

Molnar, Miklos Z; Mucsi, Istvan; Novak, Marta; Szabo, Zoltan; Freire, Amado X; Huch, Kim M; Arah, Onyebuchi A; Ma, Jennie Z; Lu, Jun L; Sim, John J; Streja, Elani; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2015-01-01

Rationale There is a paucity of large cohort studies examining the association of obstructive sleep apnea(OSA) with clinical outcomes including all-cause mortality, coronary heart disease(CHD), strokes and chronic kidney disease(CKD). Objectives We hypothesized that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes. Methods, Measurements In a nationally representative cohort of over 3 million(n=3,079,514) US veterans(93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73m2, we examined the association between the diagnosis of incident OSA, treated and untreated with continuous positive airway pressure(CPAP), and: 1) all-cause mortality, 2) incident CHD, 3) incident strokes, 4)incident CKD defined as eGFR<60 ml/min/1.73m2, and 5)slopes of eGFR. Main Results Compared to OSA negative patients, untreated and treated OSA was associated with 86% higher mortality risk,(adjusted hazard ratio and 95% confidence interval: 1.86(1.81-1.91)) and 35% (1.35(1.21-1.51)), respectively. Similarly, untreated and treated OSA was associated with 3.5 times(3.54(3.40-3.69)) and 3 times(3.06(2.62-3.56)) higher risk of incident CHD; 3.5 times higher risk of incident strokes(3.48(3.28-3.64) and 3.50(2.92-4.19)) for untreated and treated OSA, respectively. The risk of incident CKD was also significantly higher in untreated(2.27(2.19-2.36)) and treated(2.79(2.48-3.13)) OSA patients. The median (interquartile range) of the eGFR slope was −0.41(−2.01 - 0.99), −0.61(−2.69 - 0.93) and −0.87(−3.00 - 0.70)ml/min/1.73m2 in OSA negative, untreated and treated OSA positive patients, respectively. Conclusions In this large and contemporary cohort of more than 3 million US veterans, a diagnosis of incident OSA was associated with higher mortality, incident CHD, stroke and CKD and with faster kidney function decline. PMID:26038534

On-the-road driving performance and driving-related skills in older untreated insomnia patients and chronic users of hypnotics.

PubMed

Leufkens, T R M; Ramaekers, J G; de Weerd, A W; Riedel, W J; Vermeeren, A

2014-07-01

Many older adults report sleep problems and use of hypnotics. Several studies have shown that hypnotics can have acute adverse effects on driving the next morning. It is unclear however whether driving of chronic hypnotic users is impaired. Therapeutic effects on insomnia and development of tolerance may reduce the residual effects on driving. The present study aimed to compare actual driving performance and driving-related skills of chronic hypnotic users to good sleepers. To determine whether insomnia itself affects driving performance, driving and driving-related skills were compared between insomnia patients who do not or infrequently use hypnotics and good sleepers. Twenty-two frequent users of hypnotics (using hypnotics ≥ 4 nights per week for more than 3 months), 20 infrequent users (using hypnotics ≤ 3 nights per week), and 21 healthy, age-matched controls participated in this study. On the night before testing, all subjects were hospitalized for an 8-h sleep recorded by polysomnography. Frequent hypnotic users used their regular medication at bedtime (2330 hours), while infrequent users and controls received no medication. Cognitive performance (word learning, digit span, tracking, divided attention, vigilance, and inhibitory control) was assessed 8.5 h and driving performance between 10 and 11 h after bedtime and dosing. Polysomnographic recordings did not significantly differ between the groups, but the insomnia patients, treated or untreated, still reported subjective sleep complaints. Results show no differences in driving performance and driving-related skills between both groups of insomnia patients and controls. Driving performance in chronic users of hypnotics and untreated insomnia patients is not impaired. For chronic users, this may be due to prescription of relatively safe drugs and low doses. For untreated insomniacs, this corroborates previous findings showing an absence of neuropsychological deficits in this group of patients.

[The glaucoma pharmacological treatment and biomechanical properties of the cornea].

PubMed

Liehneová, I; Karlovská, S

2014-10-01

To evaluate and compare the impact of long-term use of intraocular pressure lowering medication on the biomechanical properties of the cornea. Group of 305 eyes of 154 patients newly diagnosed with primary open angle glaucoma (POAG, n = 68) or ocular hypertension (OH, n = 6) was enrolled in prospective cohort study. The control group was established of 80 untreated eyes of 40 patients with ocular hypertension and 80 eyes of 40 patients with no ocular pathology. Following parameters were evaluated: intraocular pressure (IOPg,IOPcc), hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT). The parameters were evaluated at baseline (untreated) and in follow up periods of 3, 6, 9 and 12 months. The same schedule was used for eyes in the control group. Eyes with POAG or OH were sorted into two groups depending on the type of applied medication: prostaglandin analogues, carboanhydrase inhibitors alone or combined with betablockers. We did not prove any statistically significant difference in hysteresis in patients with newly diagnosed POAG (yet untreated) in comparison with normal eyes in control group (p = 0.238). We proved significantly higher values of CRF (p = 0.032) and CCT (p = 0.013) in the control group of untreated patients with ocular hypertension. This result confirms higher number of patients with stiffer and thicker corneas. Statistically significant difference of CH and CRF was proved (p < 0.0001) in eyes treated by prostaglandin analogues during follow up period. In these eyes we also demonstrated reduction of CCT (p < 0.001). We did not record any other statistically significant change in remaining followed parameters. Increase of CH and CRF can show change of biomechanical properties of the cornea after long-term use of prostaglandin analogues. The biomechanical properties of the cornea were not impacted by carboanhydrase inhibitors. Further studies are required to establish the effect of long-term use prostaglandin analogues on accuracy of IOP measurements.

Impact of overt and subclinical hypothyroidism on exercise tolerance: a systematic review.

PubMed

Lankhaar, Jeannette A C; de Vries, Wouter R; Jansen, Jaap A C G; Zelissen, Pierre M J; Backx, Frank J G

2014-09-01

This systematic review describes the state of the art of the impact of hypothyroidism on exercise tolerance and physical performance capacity in untreated and treated patients with hypothyroidism. A systematic computer-aided search was conducted using biomedical databases. Relevant studies in English, German, and Dutch, published from the earliest date of each database up to December 2012, were identified. Out of 116 studies, a total of 38 studies with 1,379 patients fulfilled the inclusion criteria. These studies emphasize the multifactorial causes of exercise intolerance in untreated patients by the impact of limitations in different functional systems, with cardiovascular, cardiopulmonary, musculoskeletal, neuromuscular, and cellular metabolic systems acting in concert. Moreover, the studies affirm that exercise intolerance in patients is not always reversible during adequate hormone replacement therapy. As a consequence, despite a defined euthyroid status, there remains a significant group of treated patients with persistent complaints related to exercise intolerance who are suffering from limitations in daily and sport activities, as well as an impaired quality of life. An explanation for this phenomenon is lacking. Only 2 studies investigated the effects of a physical training program, and they showed inconsistent effects on the performance capacity in untreated patients with subclinical hypothyroidism. A limited body of knowledge exists concerning exercise tolerance in treated patients with hypothyroidism, and there is an insufficient amount of quantitative studies on the effects of a physical training program. To enhance exercise and sports participation for this specific group, more research in this forgotten area is warranted.

Brain activation by music in patients in a vegetative or minimally conscious state following diffuse brain injury.

PubMed

Okumura, Yuka; Asano, Yoshitaka; Takenaka, Shunsuke; Fukuyama, Seisuke; Yonezawa, Shingo; Kasuya, Yukinori; Shinoda, Jun

2014-01-01

The aim of this study was to objectively evaluate the brain activity potential of patients with impaired consciousness in a chronic stage of diffuse brain injury (DBI) using functional MRI (fMRI) following music stimulation (MS). Two patients in a minimally conscious state (MCS) and five patients in a vegetative state (VS) due to severe DBI were enrolled along with 21 healthy adults. This study examined the brain regions activated by music and assessed topographical differences of the MS-activated brain among healthy adults and these patients. MS was shown to activate the bilateral superior temporal gyri (STG) of both healthy adults and patients in an MCS. In four of five patients in a VS, however, no significant activation in STG could be induced by the same MS. The remaining patient in a VS displayed the same MS-induced brain activation in STG as healthy adults and patients in an MCS and this patient's status also improved to an MCS 4 months after the study. The presence of STG activation by MS may predict a possible improvement of patients in a VS to MCS and fMRI employing MS may be a useful modality to objectively evaluate consciousness in these patients.

The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction.

PubMed

Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O'Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

2017-01-01

Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment.

The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

PubMed Central

Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O’Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

2017-01-01

Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. PMID:28053511

Season of birth and multiple sclerosis in Tunisia.

PubMed

Sidhom, Youssef; Kacem, Imen; Bayoudh, Lamia; Ben Djebara, Mouna; Hizem, Yosr; Ben Abdelfettah, Sami; Gargouri, Amina; Gouider, Riadh

2015-11-01

Recent studies on date of birth of multiple sclerosis (MS) patients showed an association between month of birth and the risk of developing MS. This association has not been investigated in an African country. We aimed to determine if the risk of MS is associated with month of birth in Tunisia. Data concerning date of birth for MS patients in Tunisia (n = 1912) was obtained. Birth rates of MS patients were compared with all births in Tunisia matched by year of birth (n = 11,615,912). We used a chi-squared analysis and the Hewitt's non-parametric test for seasonality. The distribution of births among MS patients compared with the control population was not different when tested by the chi-squared test. The Hewitt's test for seasonality showed an excess of births between May and October among MS patients (p = 0.03). The peak of Births of MS patients in Tunisia was in July and the nadir in December. Our data does support the seasonality hypothesis of month of birth as risk factor for MS in Tunisia. Low vitamin D levels during pregnancy could be a possible explanation that needs further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of interferon β-1b on gut microbiota composition in patients with multiple sclerosis.

PubMed

Castillo-Álvarez, F; Pérez-Matute, P; Oteo, J A; Marzo-Sola, M E

2018-06-09

The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce. We performed a descriptive, cross-sectional study comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon β-1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing. Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon β-1b than in untreated patients, with levels resembling those observed in the healthy control group. We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon β-1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon β-1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

A North Central Cancer Treatment Group Phase II trial of 9-aminocamptothecin in previously untreated patients with measurable metastatic colorectal carcinoma.

PubMed

Pitot, H C; Knost, J A; Mahoney, M R; Kugler, J; Krook, J E; Hatfield, A K; Sargent, D J; Goldberg, R M

2000-10-15

Topoisomerase I inhibitors have demonstrated clinical activity in patients with metastatic colorectal carcinoma. The authors performed a Phase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated patients with measurable recurrent metastatic colorectal carcinoma. Fifty-one patients were registered. One schedule evaluated 9-AC given at 1100 microgram/m(2)/24 hours by continuous infusion for 72 hours along with granulocyte-colony stimulating factor at 5 microgram/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 microgram/m(2)/24 hours by continuous infusion for 120 hours on Days 1, 8, and 15 given every 4 weeks. Forty-eight of 51 patients (94%) were evaluable (28 patients who received 72-hour infusion and 20 patients who received 120-hour infusion) for response and toxicity. Significant hematologic toxicities were encountered, especially with the 72-hour infusion schedule, in which 43% (12 of 28) and 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxicity Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutropenia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on the 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. Seventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencing Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedule. Three patients died of chemotherapy-related toxicity. One response was observed in 48 evaluable patients (2%). 9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic colorectal carcinoma. Copyright 2000 American Cancer Society.

Is the risk of primary hyperparathyroidism increased in patients with untreated breast cancer?

PubMed

Belardi, V; Fiore, E; Giustarini, E; Muller, I; Sabatini, S; Rosellini, V; Seregni, E; Agresti, R; Marcocci, C; Vitti, P; Giani, C

2013-05-01

An increased frequency of primary hyperparathyroidism (PHP) has been reported in patients with treated breast cancer (BC). PHP has been found in about 7% of BC patients after surgery and radio-, chemio- or hormonal therapy. To evaluate the frequency of PHP in untreated BC patients. We evaluated 186 women with BC and 233 women with thyroid cancer (TC, no.=122) or benign thyroid diseases (BTD, no.=111). In all patients, serum calcium, albumin, PTH, and 25-hydroxyvitamin D (25-OH vitD) were measured before any treatment. Serum calcium concentrations were significantly higher in BC than in TC and BTD groups (median values 9.5 mg/dl, 9.3 mg/dl and 9.3 mg/dl, respectively) but, according to a logistic regression model, calcium was not significantly different between the 3 groups when age was taken into account. In all patients, serum calcium was in the normal range, indicating that no case of overt PHP was present. Five patients (1 in BC, 2 in TC, and 2 in BDT groups) had serum calcium close to the upper limit of normal range, high PTH and low 25-OH vitD, indicating a possible PHP with hypercalcemia masked by concomitant 25-OH vitD deficiency. In untreated BC group, no patient had overt PHP and 1/186 (0.5%) presented a possible PHP masked by 25-OH vitD deficiency, a PHP frequency much lower than that observed in treated BC patients. These data suggest that the treatments of BC may be responsible for the increased frequency of PHP reported in previous studies.

Patients with multiple sclerosis do not necessarily consume more alcohol or tobacco than the general population.

PubMed

Fragoso, Yara Dadalti; Gomes, Sidney; Goncalves, Marcus Vinicius M; Machado, Suzana C Nunes; Morales, Rogerio de Rizo; Oliveira, Francisco Tomas M de; Oliveira, João Filipe de; Olmo, Neide R Simoes; Parolin, Monica K Fiuza; Siquineli, Fabio; Stoney, Patrick N

2015-10-01

Purpose Recent papers suggest that patients with multiple sclerosis (MS) are prone to alcohol misuse. This may be due to the combination of a lifelong and disabling disease with a psychiatric profile typical of MS. The objective of the present study was to assess these findings in a culturally different population of patients with MS.Method The present case-control transversal study assessed 168 patients with MS and 168 control subjects from Brazil.Results There were no evidence that patients with MS drank more alcohol or, smoked more than did controls. In fact, control subjects had a significantly higher alcohol consumption. The only trait associated to higher alcohol consumption was anxiety, both for patients and controls.Conclusion Unlike previous reports in the literature, patients with MS in our study did not drink or smoked more than a control population.

Supervised resistance training results in changes in postural control in patients with multiple sclerosis.

PubMed

Huisinga, Jessie M; Filipi, Mary L; Stergiou, Nicholas

2012-01-01

Postural disturbances are one of the first reported symptoms in patients with Multiple Sclerosis (MS). The purpose of this study was to investigate the effect of supervised resistance training on postural control in MS patients. Postural control was assessed using amount of sway variability [Root Mean Square (RMS)] and temporal structure of sway variability [Lyapunov Exponent (LyE)] from 15 MS patients. Posture was evaluated before and after completion of three months of resistance training. There were significant differences between MS patients pretraining and healthy controls for both LyE (p = .000) and RMS (p = .002), but no differences between groups after training. There was a significant decrease in RMS (p = .025) and a significant increase in LyE (p = .049) for MS patients pre- to posttraining. The findings suggested that postural control of MS patients could be affected by a supervised resistance training intervention.

High prevalence of sickness absence and disability pension among multiple sclerosis patients: a nationwide population-based study.

PubMed

Tinghög, Petter; Hillert, Jan; Kjeldgård, Linnea; Wiberg, Michael; Glaser, Anna; Alexanderson, Kristina

2013-12-01

Although multiple sclerosis (MS) often implies substantial disability, there is little knowledge about sick leave and disability pension among MS patients. The purpose of this study was to estimate the prevalence rates of sick leave and disability pension among MS patients and to explore how socio-demographics are associated with such rates. The register data of all people who lived in Sweden in 2005 and were 16-64 years old was used to identify 9721 MS patients and matched controls. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and effect modifications were evaluated with Wald X(2) tests. In 2005, 61.7% of the MS patients were on partial or full disability pension compared to 14.2% among the controls. Of the others, 36.8% had ≥ 1 sick-leave spell for >14 days during that year. Socio-demographics were similarly associated with sick leave and disability pension among MS patients and controls, with the noteworthy exceptions that female gender and immigration status were less potent risk factors in the MS population (p<0.05). In spite of widespread access to modern health care including disease-modifying drugs, the majority of MS patients of working ages were on a disability pension. Strategies enabling MS patients to retain their footing in the labour market are needed.

[Physical activity in patients with symptoms of metabolic syndrome reduces the concentration of plasma antioxidant vitamins - protective effect of vitamin C].

PubMed

Godala, Małgorzata; Materek-Kuśmierkiewicz, Izabela; Moczulski, Dariusz; Rutkowski, Maciej; Szatko, Franciszek; Gaszyńska, Ewelina; Tokarski, Sławomir; Kowalski, Jan

2015-05-01

Patients with cardiovascular diseases, including those with the symptoms of metabolic syndrome (MS), are recommended regular exercise but many studies indicate its role in the production of reactive oxygen species. Vitamin C supplementation may enhance the antioxidant barrier in MS patients. The aim of the study was to assess the impact of regular physical activity (PA)and vitamin C supplementation on plasma vitamin A, C and E levels in patients with MS. The study included 62 patients with MS according to International Diabetes Federation criteria, 32 men and 30 women, aged 38-57 years (mean age 51,24 ± 5,29 years). The patients were divided in two groups: group I (MS+PA) - 31 patients with recommended regular physical activity; group II ( MS+PA+C) - 31 patients with recommended regular physical activity and vitamin C supplementation per os. The control group consisted of 23 healthy individuals without MS, 17 men and 6 women, aged 49-56 years (mean age 53,21 ± 3,6 years), who were not recommended any vitamin supplementation nor physical activity. Plasma vitamin A, C and E levels were estimated in MS patients with spectrophotometry using T60V spectrophotometer (PG Instruments) before and after regular exercise with and without vitamin C supplementation. In the control group plasma levels of antioxidant vitamins were assessed only once. The plasma vitamin A, C and E levels were significantly lower (p<0,05) in MS patients than in the control group. After 6 weeks of regular physical activity a significant fall in plasma levels of antioxidant vitamins was observed in MS patients. In the group of patients with regular physical activity and vitamin C supplementation there was detected a significant rise in the level of all the tested vitamins close to the levels in control group. Regular physical activity enhances the decrease in plasma antioxidant vitamin level in patients with MS. Vitamin C supplementation conducted in parallel with regular physical activity normalize plasma vitamin A, C and E levels in these patients. © 2015 MEDPRESS.

Verbal episodic memory in 426 multiple sclerosis patients: impairment in encoding, retrieval or both?

PubMed

Brissart, H; Morele, E; Baumann, C; Debouverie, M

2012-10-01

Episodic memory is frequently impaired in multiple sclerosis (MS) patients but the exact nature of the disorder is controversial. It was initially thought to be due to a retrieval deficit but some studies have demonstrated an encoding deficit, which could be linked to a slowing of information processing speed or to a deficit in elaboration of strategies. The main objective of this study is to assess the prevalence and the nature of verbal episodic memory (VEM) impairment in MS patients. We retrieved memory performances of 426 patients [314 F-112 M; mean age: 46.1 years; median Expanded Disability Status Scale (EDSS) score: 3.1] from a neuropsychological data base. VEM was assessed using the 16 words RL-RI 16 test. 66% MS patients present at least one recall impaired in VEM (37.2% from 2 to 5 recall). 14.2% MS patients present an impairment in encoding phase. We observed that 5% of patients presented recognition difficulties. Correlations were observed between VEM performances and EDSS, and disease duration but no group effect (ANOVA) is observed between form of MS and VEM performances. These results confirm the high prevalence of VEM impairment in MS patients. Deficits affect mainly information retrieval in early stage MS patients and are then linked to encoding as disability increases. Storage disorders are infrequent, so cognitive rehabilitation with mental imaging could be effective in MS patients.

Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database.

PubMed

Auerbach, Scott R; Kukreja, Manisha; Gilbert, Deborah; Bastardi, Heather; Feingold, Brian; Knecht, Kenneth; Kaufman, Beth D; Brown, Robert N; Miyamoto, Shelley D

2015-08-01

Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes. All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups. Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively). MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Impulsivity traits in patients with multiple sclerosis.

PubMed

Toro, Jaime; Blanco, Luisa; Orozco-Cabal, Luis Felipe; Díaz, Camilo; Reyes, Saúl; Burbano, Lisseth; Cuéllar-Giraldo, David Felipe; Duque, Alejandra; Patiño, Jorge; Cortés, Fabián

2018-05-01

Multiple sclerosis (MS) is a demyelinating disease with a lifetime prevalence of 4.41/100000 in Bogota, Colombia. It is known that it can be related with neuropsychiatric disorders, increasing by a factor of three the prevalence of depression in MS patients compared to general population. However, less attention has been given to the association between MS and impulsive behavior. This cross-sectional study compared the levels of impulsivity controlling for the presence of MS. 60 patients with MS and 60 sex- and age-matched subjects without MS were included. In order to assess depression and impulsivity, participants completed the 13-item short form of the Beck Depression Inventory (BDI-SF), the self-report Barratt Impulsiveness Scale version 11 (BIS-11) and the Immediate and Delayed Memory Tasks (IMT-DMT) as an objective measure of impulsive behavior. Total scores, motor and cognitive subscales on the BIS-11 were significantly higher in the MS group. However, median BDI-SF score was also higher in MS patients than in subjects without MS (p < 0.001). To rule out depression as a confounding factor, stratification was performed using the BDI-SF score. In the subgroup of individuals with a BDI-SF< 8, the BIS-11 cognitive subscale scores were significantly higher in patients with MS than in subjects without MS (p = 0.041). In the IMT/DMT test, subjects with MS had a fewer number of correct detections than did subjects without MS, after controlling for BDI-SF score (p = 0.0001/p = 0.003). The ratio of commission errors to correct detections in the IMT was significantly higher in the MS group (p = 0.011). Patients with MS showed higher levels of cognitive impulsivity than subjects without MS. Objective measures for impulsiveness further support this finding. Impulsiveness scales scores might be biased by depression, which should be considered when assessing impulsivity in MS. Copyright © 2018 Elsevier B.V. All rights reserved.

Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients.

PubMed

Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D'Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria

2016-11-30

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.

Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients

PubMed Central

Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D’Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria

2016-01-01

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis. PMID:27916909

Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1*06:02?

PubMed

Lorenzoni, Paulo José; Werneck, Lineu Cesar; Crippa, Ana Christina de Souza; Zanatta, Alessandra; Kay, Cláudia S Kamoi; Silvado, Carlos Eduardo S; Scola, Rosana Herminia

2017-06-01

We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.

Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension.

PubMed

Supasyndh, Ouppatham; Wang, Jian'an; Hafeez, Kudsia; Zhang, Ying; Zhang, Jack; Rakugi, Hiromi

2017-11-06

Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001); similarly, reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan. At week 14, despite more patients requiring up-titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated. Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Numeracy of multiple sclerosis patients: A comparison of patients from the PERCEPT study to a German probabilistic sample.

PubMed

Gaissmaier, Wolfgang; Giese, Helge; Galesic, Mirta; Garcia-Retamero, Rocio; Kasper, Juergen; Kleiter, Ingo; Meuth, Sven G; Köpke, Sascha; Heesen, Christoph

2018-01-01

A shared decision-making approach is suggested for multiple sclerosis (MS) patients. To properly evaluate benefits and risks of different treatment options accordingly, MS patients require sufficient numeracy - the ability to understand quantitative information. It is unknown whether MS affects numeracy. Therefore, we investigated whether patients' numeracy was impaired compared to a probabilistic national sample. As part of the larger prospective, observational, multicenter study PERCEPT, we assessed numeracy for a clinical study sample of German MS patients (N=725) with a standard test and compared them to a German probabilistic sample (N=1001), controlling for age, sex, and education. Within patients, we assessed whether disease variables (disease duration, disability, annual relapse rate, cognitive impairment) predicted numeracy beyond these demographics. MS patients showed a comparable level of numeracy as the probabilistic national sample (68.9% vs. 68.5% correct answers, P=0.831). In both samples, numeracy was higher for men and the highly educated. Disease variables did not predict numeracy beyond demographics within patients, and predictability was generally low. This sample of MS patients understood quantitative information on the same level as the general population. There is no reason to withhold quantitative information from MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic syndrome in patients with peripheral arterial disease.

PubMed

Estirado, E; Lahoz, C; Laguna, F; García-Iglesias, F; González-Alegre, M T; Mostaza, J M

2014-11-01

The prevalence of metabolic syndrome (MS) in patients with peripheral arterial disease (PAD) and coronary or cerebrovascular disease is increasing, but it is not known whether this association also exists in patients with isolated PAD. The aim of the current study was to assess the prevalence of MS in patients with PAD who had no coronary or cerebrovascular disease, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals in patients with PAD and with and without MS. Multicenter, cross-sectional study of 3.934 patients aged ≥ 45 years with isolated PAD who were treated in primary care and specialized outpatient clinics during 2009. A diagnosis of PAD was reached for ankle brachial indices <0.9, a previous history of amputation or revascularization. In the overall population, the mean age was 67.6 years, 73.8% were males and 63% had MS (95% CI 61.5-64.3%). Patients with MS had a higher prevalence of cardiovascular risk factors and comorbidities, more severe PAD and higher prescription rate of evidence-based cardiovascular therapies. After adjusting for risk factors and comorbidity, there was a more frequent use of renin-angiotensin system blockers, beta-blockers, diuretics and statins among the patients with MS. A lower percentage of patients with MS achieved the therapeutic goals for blood pressure (22% vs. 41.5%, p<0.001). Similarly, a lower percentage of patients with diabetes achieved the glycated hemoglobin goals (44% vs. 53.1%, p<0.001), with no differences in LDL-cholesterol levels (29.8% vs. 39.1%, p=0.265). Patients with PAD have a high prevalence of MS. Patients with MS do not attain therapeutic goals as frequently as those without, despite taking more cardiovascular drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy.

PubMed

Pfeifer, M A; Ross, D R; Schrage, J P; Gelber, D A; Schumer, M P; Crain, G M; Markwell, S J; Jung, S

1993-08-01

To investigate why, in spite of a vast variety of treatment agents, the alleviation of pain in patients with diabetic neuropathy is difficult. Previous studies have not used a treatment algorithm based on anatomic site and neuropathophysiological source of the neuropathic pain. A model that categorizes the types of pain into three groups (superficial, deep, and muscular) was applied in 75 diabetic patients with chronic (> 12 mo) painful distal symmetrical polyneuropathy in a controlled case series. Twenty-two patients were untreated and 53 patients were treated with imipramine +/- mexiletine for deep pain, capsaicin for superficial pain, and stretching exercises and metaxalone +/- piroxican for muscular pain. Each type of pain was scored separately on a scale of 0 (none) to 19 (worst), and the total of all three types was used as an index of overall pain. Ability to sleep through the night was scored by a scale of 1 (never) to 5 (always). No significant differences were observed in initial pain scores, sleep scores, demographics, biochemistries, or physical findings between the two groups. After 3 mo a significant improvement in scores was noted in the treated but not the untreated patients. In addition, a significant difference was found in the change of scores between the treated and untreated patients: total pain (-18 +/- 2 vs. 0 +/- 2), deep pain (-7 +/- 1 vs. 0 +/- 1), superficial pain (-5 +/- 1 vs. 0 +/- 1), muscular pain (-6 +/- 1 vs. 0 +/- 1), and sleep (1.2 +/- 0.2 vs. 0.2 +/- 0.2), all P < 0.0001. In treated patients 21% became pain-free (total pain < 2), 66% had improvement (decrease in total pain > 5, but not total elimination of painful symptoms), and 13% were considered treatment failures (a decrease in total pain of < or = 5). This compares with 0 (P < 0.02), 10 (P < 0.0001), and 90% (P < 0.0001), respectively, in the untreated patients. This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy. It uniquely bases the treatment algorithm on the types and sources of the pain.

Prevalence of metabolic syndrome among patients with Schizophrenia in Palestine

PubMed Central

2012-01-01

Background Metabolic syndrome (MS) is a cluster of the most dangerous cardiac risk factors and is associated with high mortality. Ethnic differences in metabolic syndrome (MS) criteria and prevalence rates have been reported. The purpose of this study was to investigate the MS prevalence among patients with schizophrenia in Palestine. Methods We recruited 250 patients with schizophrenia from 4 psychiatric primary healthcare centers in Northern Palestine. The MS prevalence was assessed based on National Cholesterol Education Program Adult Treatment Panel III Adapted criteria. Results The overall MS prevalence was 43.6%, with 39% in male and 55.9% in female patients. On average, the study patients had 2.3 ± 1.3 metabolic abnormalities. Univariate analysis showed that MS was significantly higher with older age, female gender, longer duration of the illness, smoking, abdominal obesity, high systolic and diastolic blood pressure, high triglycerides, low HDL-C, and high fasting plasma glucose. Multiple logistic regression analysis showed that only systolic blood pressure, high triglycerides, high fasting plasma glucose, and low HDL-C were significant predictors of MS in schizophrenic patients. Conclusions MS is common among Arab patients with schizophrenia. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors. PMID:23270504

The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis

PubMed Central

Holloman, Jameson P; Ho, Calvin C; Hukki, Arushi; Huntley, Jennifer L; Gallicano, G Ian

2013-01-01

This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity—with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. PMID:23862098

Down-regulated resistin level in consequence of decreased neutrophil counts in untreated Grave's disease.

PubMed

Peng, Ying; Qi, Yicheng; Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu

2016-11-29

Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients.

Is there a prognostic relevance of electrophysiological studies in bundle branch block patients?

PubMed

Bogossian, Harilaos; Frommeyer, Gerrit; Göbbert, Kornelius; Hasan, Fuad; Nguyen, Quy Suu; Ninios, Ilias; Mijic, Dejan; Bandorski, Dirk; Hoeltgen, Reinhard; Seyfarth, Melchior; Lemke, Bernd; Eckardt, Lars; Zarse, Markus

2017-08-01

The present European guidelines suggest a diagnostic electrophysiological (EP) study to determine indication for cardiac pacing in patients with bundle branch block and unexplained syncope. We evaluated the prognostic relevance of an EP study for mortality and the development of permanent complete atrioventricular (AV) block in patients with symptomatic bifascicular block and first-degree AV block. The HV interval is a poor prognostic marker to predict the development of permanent AV block in patients with symptomatic bifascicular block (BFB) and AV block I°. Thirty consecutive patients (mean age, 74.8 ± 8.6 years; 25 males) with symptomatic BFB and first-degree AV block underwent an EP study before device implantation, according to current guidelines. For 53 ± 31 months, patients underwent yearly follow-up screening for syncope or higher-degree AV block. Thirty patients presented with prolonged HV interval during the EP study (mean, 82.2 ± 20.1 ms; range, 57-142 ms), classified into 3 groups: group 1, <70 ms (mean, 62 ± 4 ms; range, 57-67 ms; n = 7), group 2, >70 to ≤100 ms (mean, 80 ± 8 ms; range, 70-97 ms; n = 18), and group 3, >100 ms (mean, 119 ± 14 ms; range, 107-142 ms; n = 5). According to the guidelines, patients in groups 2 and 3 received a pacemaker. The length of the HV interval was not associated with the later development of third-degree AV block or with increased mortality. Our present study suggests that an indication for pacemaker implantation based solely on a diagnostic EP study with prolongation of the HV interval is not justified. © 2017 Wiley Periodicals, Inc.

Imaging the cortical effect of lamotrigine in patients with idiopathic generalized epilepsy: a low-resolution electromagnetic tomography (LORETA) study.

PubMed

Clemens, Béla; Piros, Pálma; Bessenyei, Mónika; Tóth, Márton; Hollódy, Katalin; Kondákor, István

2008-10-01

Anatomical localization of the cortical effect of lamotrigine (LTG) in patients with idiopathic generalized epilepsy (IGE). 19 patients with untreated IGE were investigated. EEG was recorded in the untreated condition and 3 months later when LTG treatment abolished the seizures. 19-channel EEG was recorded, and a total of 2min artifact-free, waking EEG was processed to low-resolution electromagnetic tomography (LORETA) analysis. Activity (that is, current source density, A/m(2)) was computed in four frequency bands (delta, theta, alpha, and beta), for 2394 voxels that represented the cortical gray matter and the hippocampi. Group differences between the untreated and treated conditions were computed for the four bands and all voxels by multiple t-tests for interdependent datasets. The results were presented in terms of anatomical distribution and statistical significance. p<0.01 (uncorrected) changes (decrease of activity) emerged in the theta and the alpha bands. Theta activity decreased in a large cluster of voxels including parts of the temporal, parietal, occipital cortex bilaterally, and in the transverse temporal gyri, insula, hippocampus, and uncus on the right side. Alpha activity decreased in a relatively smaller cortical area involving the right temporo-parietal junction and surrounding parts of the cortex, and part of the insula on the right side. LTG decreased theta activity in several cortical areas where abnormally increased theta activity had been found in a prior study in another cohort of untreated IGE patients [Clemens, B., Bessenyei, M., Piros, P., Tóth, M., Seress, L., Kondákor, I., 2007b. Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy. Epilepsia 48, 941-949]. These LTG-related changes might be related to the decrease of seizure propensity in IGE.

Parental administration of antipyretics to children with upper respiratory tract infections without consultation with a physician

PubMed Central

Andabaka, Tea; Globočnik, Tina; Vukelić, Dalibor; Esposito, Susanna; Baršić, Bruno

2011-01-01

Aim To evaluate the administration of antipyretics to children with upper respiratory tract infections (URTI) by their parents or guardians without consultation with physicians, and compare epidemiological and clinical characteristics of patients who received antipyretics and of untreated patients. Methods A prospective observational study was performed in three pediatric clinics in Zagreb, Croatia, from March to June 2002. A total of 171 children aged from 2 to 14 years with symptoms and signs of URTI lasting more than 2 days and fever above 38°C lasting more than 2 days were included in the study. Data were collected on the usage of antipyretics, patients’ demographic and epidemiological characteristics, and clinical signs and symptoms. Results Antipyretics, predominantly paracetamol, were used in 29.8% of patients. Their usage was less frequent in children attending day-care centers (49% of treated and 70% of untreated children, P = 0.014) and in children with reiterated URTIs (33.3% of treated and 55.8% of untreated children, P = 0.008). However, it was more frequent in children with recent URTIs in the family (33.3% of treated and 7.5% of untreated children, P < 0.001). Overall, most clinical signs and symptoms of URTI were notably less pronounced in patients treated with antipyretics. Conclusions Antipyretics use correlated with less pronounced clinical signs and symptoms of infection, which indicates their anti-inflammatory activity, but also with negative effects such as lethargy. It is necessary to educate parents on the positive and negative aspects of antipyretics use and on the optimal choice of an antipyretic drug. PMID:21328720

Post-exercise hypotension and heart rate variability response after water- and land-ergometry exercise in hypertensive patients

PubMed Central

Bocalini, Danilo Sales; Bergamin, Marco; Evangelista, Alexandre Lopes; Rica, Roberta Luksevicius; Pontes, Francisco Luciano; Figueira, Aylton; Serra, Andrey Jorge; Rossi, Emilly Martinelli; Tucci, Paulo José Ferreira

2017-01-01

Background systemic arterial hypertension is the most prevalent cardiovascular disease; physical activity for hypertensive patients is related to several beneficial cardiovascular adaptations. This paper evaluated the effect of water- and land-ergometry exercise sessions on post-exercise hypotension (PEH) of healthy normotensive subjects versus treated or untreated hypertensive patients. Methods Forty-five older women composed three experimental groups: normotensive (N, n = 10), treated hypertensive (TH, n = 15) and untreated hypertensive (UH, n = 20). The physical exercise acute session protocol was performed at 75% of maximum oxygen consumption (VO2max) for 45 minutes; systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were evaluated at rest, peak and at 15, 30, 45, 60, 75 and 90 minutes after exercise cessation. Additionally, the heart rate variability (HRV) was analyzed by R-R intervals in the frequency domain for the assessment of cardiac autonomic function. Results In both exercise modalities, equivalent increases in SBP were observed from rest to peak exercise for all groups, and during recovery, significant PEH was noted. At 90 minutes after the exercise session, the prevalence of hypotension was significantly higher in water- than in the land-based protocol. Moreover, more pronounced reductions in SBP and DBP were observed in the UH patients compared to TH and N subjects. Finally, exercise in the water was more effective in restoring HRV during recovery, with greater effects in the untreated hypertensive group. Conclusion Our data demonstrated that water-ergometry exercise was able to induce expressive PEH and improve cardiac autonomic modulation in older normotensive, hypertensive treated or hypertensive untreated subjects when compared to conventional land-ergometry. PMID:28658266

Resting-state connectivity of pre-motor cortex reflects disability in multiple sclerosis.

PubMed

Dogonowski, A-M; Siebner, H R; Soelberg Sørensen, P; Paulson, O B; Dyrby, T B; Blinkenberg, M; Madsen, K H

2013-11-01

To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing-remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8 between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity of left PMd showed a positive linear relation with clinical disability in patients with MS. This effect was stronger when considering the group of patients with RR-MS alone, whereas patients with SP-MS showed no increase in coupling strength between left PMd and the motor resting-state network with increasing clinical disability. No significant relation between motor resting-state connectivity of the right PMd and clinical disability was detected in MS. The increase in functional coupling between left PMd and the motor resting-state network with increasing clinical disability can be interpreted as adaptive reorganization of the motor system to maintain motor function, which appears to be limited to the relapsing-remitting stage of the disease. © 2013 John Wiley & Sons A/S.

Behçet's disease patients with multiple sclerosis-like features: discriminative value of Barkhof criteria.

PubMed

Akman-Demir, Gulsen; Mutlu, Melike; Kiyat-Atamer, Asli; Shugaiv, Erkingul; Kurtuncu, Murat; Tugal-Tutkun, Ilknur; Tuzun, Erdem; Eraksoy, Mefkure; Bahar, Sara

2015-01-01

Behçet's disease (BD) is a systemic auto-inflammatory disorder of unknown cause, which may affect the central nervous system in around 5% of the patients [neuro-BD (NBD)], usually causing large lesions encompassing brainstem, diencephalon and basal ganglia regions. Occasionally NBD patients present with white matter lesions necessitating differential diagnosis from multiple sclerosis (MS). In this study, the efficacy of Barkhof criteria was tested in diagnostic differentiation of NBD and MS. Charts and MRIs of 84 NBD patients were retrospectively evaluated. Clinical and radiological features of NBD patients fulfilling (Barkhof+) and not fulfilling Barkhof criteria (Barkhof-) were compared. While the Barkhof- patients (n=73) mostly displayed typical large lesions covering brainstem, diencephalon and basal ganglia regions and neurological findings consistent with brainstem involvement, all Barkhof+ (n=11) patients demonstrated MS-like white matter lesions, fulfilled McDonald's criteria and showed reduced frequency of brainstem symptoms and increased frequency of hemiparesis, hemihypesthesia and spinal cord symptoms. Moreover, the Barkhof+ group had more female patients, increased number of attacks, higher rate of oligoclonal band positivity and less patients with cerebrospinal fluid pleocytosis. A subgroup of BD patients with neurological complaints displays MS-like lesions, fulfills the clinical and radiological criteria of MS and presents with clinical and laboratory features resembling those of MS rather than NBD. These results suggest that Barkhof+ patients are either an overlapping group between NBD and MS, or they represent MS patients with concomitant systemic findings of BD, rather than NBD. Barkhof criteria appear to be effective in discriminating these patients.

Physiological consequences of CPAP therapy withdrawal in patients with obstructive sleep apnoea-an opportunity for an efficient experimental model.

PubMed

Schwarz, Esther I; Stradling, John R; Kohler, Malcolm

2018-01-01

Randomised controlled trials (RCTs) of continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are time consuming, and their findings often inconclusive or limited due to suboptimal CPAP adherence in CPAP-naïve patients with OSA. Short-term CPAP withdrawal in patients with prior optimal CPAP adherence results in recurrence of OSA and its consequences. Thus, this experimental model serves as an efficient tool to investigate both the consequences of untreated OSA, and potential treatment alternatives to CPAP. The CPAP withdrawal protocol has been thoroughly validated, and applied in several RCTs focusing on cardiovascular and metabolic consequences of untreated OSA, as well as the assessment of treatment alternatives to CPAP.

Physiological consequences of CPAP therapy withdrawal in patients with obstructive sleep apnoea—an opportunity for an efficient experimental model

PubMed Central

Stradling, John R.; Kohler, Malcolm

2018-01-01

Randomised controlled trials (RCTs) of continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are time consuming, and their findings often inconclusive or limited due to suboptimal CPAP adherence in CPAP-naïve patients with OSA. Short-term CPAP withdrawal in patients with prior optimal CPAP adherence results in recurrence of OSA and its consequences. Thus, this experimental model serves as an efficient tool to investigate both the consequences of untreated OSA, and potential treatment alternatives to CPAP. The CPAP withdrawal protocol has been thoroughly validated, and applied in several RCTs focusing on cardiovascular and metabolic consequences of untreated OSA, as well as the assessment of treatment alternatives to CPAP. PMID:29445525

Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients.

PubMed

Wattjes, Mike P; Wijburg, Martijn T; Vennegoor, Anke; Witte, Birgit I; Roosendaal, Stefan D; Sanchez, Esther; Liu, Yaou; Martins Jarnalo, Carine O; Richert, Nancy D; Uitdehaag, Bernard Mj; Barkhof, Frederik; Killestein, Joep

2016-08-01

In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML). To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability. In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions (n = 21) or new MS lesions (n = 20) or no new lesions (n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated. Overall sensitivity and specificity for the detection of new lesions, regardless of the nature of the lesions, were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate. The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate. © The Author(s), 2015.

The Natural History of Epilepsy in 163 Untreated Patients: Looking for “Oligoepilepsy”

PubMed Central

Gasparini, Sara; Ferlazzo, Edoardo; Leonardi, Cinzia Grazia; Cianci, Vittoria; Mumoli, Laura; Sueri, Chiara; Labate, Angelo; Gambardella, Antonio; Aguglia, Umberto

2016-01-01

The clinical evolution of untreated epilepsy has been rarely studied in developed countries, and the existence of a distinct syndrome characterized by rarely repeated seizures (oligoepilepsy) is debated. The aim of this study is to assess the natural history of 163 untreated patients with epilepsy in order to evaluate whether oligoepilepsy retains specific features. We retrospectively evaluated 7344 patients with ≥2 unprovoked seizures. Inclusion criteria: sufficient anamnestic/EEG data, disease duration ≥10 years, follow-up ≥3 years. Exclusion criteria: psychogenic seizures, natural history of disease <5 years. The 163 included subjects were divided into 2 groups according to seizure frequency: oligoepilepsy (≤1/year; 47 subjects) and controls (>1/year; 116 subjects). We also evaluated seizure frequency during the natural history. There were no differences between groups regarding duration of natural history, family history of epilepsy/febrile seizures, interictal EEG. Subjects with oligoepilepsy differed from controls in terms of sex (females 38% vs. 58%, p = 0.03) and drug resistance (6% vs 28%; p = 0.003). Juvenile myoclonic epilepsy was more frequent in controls (9.5% vs 0%, p = 0.04). Patients with oligoepilepsy, differently from controls, had stable seizure frequency. Oligoepilepsy represents a favourable evolution of different epileptic syndromes and keeps a stable seizure frequency over time. PMID:27657542

Information processing characteristics in subtypes of multiple sclerosis.

PubMed

De Sonneville, L M J; Boringa, J B; Reuling, I E W; Lazeron, R H C; Adèr, H J; Polman, C H

2002-01-01

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps. Copyright 2002 Elsevier Science Ltd.

Practices of US health insurance companies concerning MS therapies interfere with shared decision-making and harm patients.

PubMed

Bourdette, Dennis N; Hartung, Daniel M; Whitham, Ruth H

2016-04-01

The US Food and Drug Administration has registered 13 multiple sclerosis (MS) disease-modifying therapies (DMTs). The medications are not interchangeable as they vary in route of administration, efficacy, and safety profile. Selecting the appropriate MS DMT for individual patients requires shared decision-making between patients and neurologists. To reduce costs, insurance companies acting through pharmacy benefit companies restrict access to MS DMTs through tiered coverage and other regulations. We discuss how policies established by insurance companies that limit access to MS DMTs interfere with the process of shared decision-making and harm patients. We present potential actions that neurologists can take to change how insurance companies manage MS DMTs.

Prognostic value of metabolic syndrome for the development of cardiovascular disease in a cohort of premenopausal women with systemic lupus erythematosus.

PubMed

García-Villegas, Elsy Aidé; Lerman-Garber, Israel; Flores-Suárez, Luis Felipe; Aguilar-Salinas, Carlos; Márquez González, Horacio; Villa-Romero, Antonio Rafael

2015-04-08

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE. Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD). The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD. We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

PubMed

Arrighi, James A; Burg, Matthew; Cohen, Ira S; Soufer, Robert

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS. These data indicate the feasibility of simultaneous assessment of perfusion and function responses during MS. Flow and function responses to MS are frequently not concordant. These data suggest that MS-induced changes in perfusion may represent a different phenomenon than MS-induced changes in left ventricular function (either globally or regionally).

Deficiency in Mental Rotation of Upper and Lower-Limbs in Patients With Multiple Sclerosis and Its Relation With Cognitive Functions.

PubMed

Azin, Mahdieh; Zangiabadi, Nasser; Moghadas Tabrizi, Yousef; Iranmanesh, Farhad; Baneshi, Mohammad Reza

2016-08-01

Mental rotation is a cognitive motor process which was impaired in different neurologic disorders. We investigated whether there were deficits in response pattern, reaction time and response accuracy rate of mental rotation in multiple sclerosis (MS) patients compared to healthy subjects and whether cognitive dysfunctions in MS patients were correlated with mental rotation deficits. Moreover, we showed whether there was a difference between upper and lower-limbs mental rotation in MS patients. Thirty-five MS patients and 25 healthy subjects performed hand mental rotation (HMR) and foot mental rotation (FMR) tasks. Visual information processing speed, spatial learning and memory ability, and visuospatial processing were assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and Judgment of Line Orientation Test (JLO) respectively in MS patients. Reaction time for both hand and foot stimuli increased, and response accuracy rate for hand stimuli decreased in MS patients compared to healthy subjects, but response pattern of mental rotation in MS patients persisted. Similar to healthy subjects, MS patients performed upper-limbs mental rotation more easily than a lower-limbs mental rotation with more speed and response accuracy rate. Reaction time and response accuracy rate were correlated with the mentioned cognitive functions. MS patients made use of the correct response pattern for problem solving of increasing orientation from upright stimuli. Reaction time and response accuracy rate altered in these patients and this alteration might occur along with impairment in motor planning. Subjects' better responding to hand stimuli was due to more familiarity with hand stimuli. The correlation of mental rotation ability with cognitive functions indicates the possible role of cognitive functions in mental rotation.

Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2018-05-24

Acute Myeloid Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Human intestinal mucosal mast cells: expanded population in untreated coeliac disease.

PubMed Central

Strobel, S; Busuttil, A; Ferguson, A

1983-01-01

Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6826106

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review.

PubMed

Thiebaut, Mathilde; Launay, David; Rivière, Sébastien; Mahévas, Thibault; Bellakhal, Syrine; Hachulla, Eric; Fain, Olivier; Mekinian, Arsène

2018-06-01

To describe safety and efficacy of rituximab in patients with systemic sclerosis. We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8; 18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage.

PubMed

Morel, Agnieszka; Bijak, Michał; Miller, Elżbieta; Rywaniak, Joanna; Miller, Sergiusz; Saluk, Joanna

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 (-∙) in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

PubMed Central

Bijak, Michał; Miller, Elżbieta; Miller, Sergiusz

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 −∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets. PMID:26064417

Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management.

PubMed

Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Giovannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G

2018-05-01

The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines. © 2018 EAN.

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

A more in-depth interpretation of MMPI-2 in MS patients by using Harris and Lingoes subscales.

PubMed

Incerti, Chiara C; Argento, Ornella; Pisani, Valerio; Magistrale, Giuseppe; Sabatello, Ugo; Caltagirone, Carlo; Nocentini, Ugo

2017-01-01

Multiple Sclerosis (MS) is frequently associated with neuropsychiatric abnormalities. The aim of our study was to discriminate between psychosomatic disturbances and MS physically-related symptoms using the Harris-Lingoes subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Forty-six MS out-patients (35 females; mean age = 44.5); and 82 healthy volunteers (62 females; mean age = 46.5) were evaluated with MMPI-2 questionnaire. The frequency distribution of MMPI-2 clinical scales with high scores (> = 65) and the related Harris-Lingoes subscales were analyzed for both MS patients and healthy control subjects. Data analysis showed elevated scores in 47.8% of the patients mainly on MMPI-2 clinical scales 1, 2, and 3. The Harris-Lingoes subscales analysis allowed us to isolate and identify physical symptoms contributing to elevation of MMPI-2 clinical scales, reduce the occurrence of false positives (MMPI-2 clinical scales elevations mainly due to MS physical disability) and provide a more detailed description of psycho-emotional symptoms of MS patients. In conclusion, our study shows the utility of Harris-Lingoes subscales analysis when MMPI-2 is used for psychological assessment of MS patients.

A wireless body measurement system to study fatigue in multiple sclerosis.

PubMed

Yu, Fei; Bilberg, Arne; Stenager, Egon; Rabotti, Chiara; Zhang, Bin; Mischi, Massimo

2012-12-01

Fatigue is reported as the most common symptom by patients with multiple sclerosis (MS). The physiological and functional parameters related to fatigue in MS patients are currently not well established. A new wearable wireless body measurement system, named Fatigue Monitoring System (FAMOS), was developed to study fatigue in MS. It can continuously measure electrocardiogram, body-skin temperature, electromyogram and motions of feet. The goal of this study is to test the ability of distinguishing fatigued MS patients from healthy subjects by the use of FAMOS. This paper presents the realization of the measurement system including the design of both hardware and dedicated signal processing algorithms. Twenty-six participants including 17 MS patients with fatigue and 9 sex- and age-matched healthy controls were included in the study for continuous 24 h monitoring. The preliminary results show significant differences between fatigued MS patients and healthy controls. In conclusion, the FAMOS enables continuous data acquisition and estimation of multiple physiological and functional parameters. It provides a new, flexible and objective approach to study fatigue in MS, which can distinguish between fatigued MS patients and healthy controls. The usability and reliability of the FAMOS should however be further improved and validated through larger clinical trials.

Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes

NASA Technical Reports Server (NTRS)

Vrtovec, Bojan; Sinkovec, Matjaz; Starc, Vito; Radovancevic, Branislav; Schlegel, Todd T.

2005-01-01

Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-min high-resolution resting electrocardiograms (ECG) in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender- matched apparently healthy subjects (Controls). Using leads I and II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if a 350% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than Controls (SDNN(QT): 15.81+/-7.22 ms vs. 8.94+/-6.04 ms; P <0.001, rMSSD(QT): 21.02k7.07 ms vs. 11.18k7.45 ms; P <0.001). VRD in diabetic patients with negative angiograms did not differ from VRD in Controls (SDNN(QT): 8.94+/-6.04 ms vs. 7.44+/-5.72 ms; P=0.67, rMSSD(QT): 11.18+/-7.45 ms vs. 10.22+/-5.35 ms; P=O. 82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than to diabetes per se.

The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis.

PubMed

van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H

2015-08-12

Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians, psychologists and other professionals working in the field of occupational health.

The efficacy of targeted Health Agents education to reduce the duration of untreated psychosis in a rural population

PubMed Central

Padilla, Eduardo; Molina, Juan; Kamis, Danielle; Calvo, Maria; Stratton, Lee; Strejilevich, Sergio; Aleman, Gabriela Gonzalez; Guerrero, Gonzalo; Bourdieu, Mercedes; Conesa, Horacio A.; Escobar, Javier I.; de Erausquin, Gabriel A.

2014-01-01

The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis. PMID:25439394

Duration of untreated psychosis and pathway to care in Riyadh, Saudi Arabia.

PubMed

Al Fayez, Hanan; Lappin, Julia; Murray, Robin; Boydell, Jane

2017-02-01

Recent studies of 'duration of untreated psychosis' (DUP) indicate that some patients remain untreated in the community for some time. Considerable emphasis has been placed on reducing the DUP. However, most studies investigating DUP have been conducted in Western countries, where well-developed primary care systems are available. This study aims to describe DUP and its association with both demographic factors and pathways to care in Riyadh, Saudi Arabia. A retrospective study of 421 new case records of all Saudi schizophrenia patients over a 2-year period in six governmental hospitals in Riyadh, Saudi Arabia. The median DUP was 1.41 years (interquartile range 0.35-2.81 years). The longest time to contact was 9.86 years but 90% had a DUP shorter than 5 years. Older age at onset, single marital status and higher educational level were associated with shorter DUP. Long DUP was associated with help seeking from traditional healers. In Saudi Arabia, it usually takes longer for patients to seek help from psychiatric services after their first psychosis onset than it does in Western countries. The results suggest that the DUP is influenced by both demographic factors and pathways to care. © 2015 Wiley Publishing Asia Pty Ltd.

The progression of coeliac disease: its neurological and psychiatric implications.

PubMed

Campagna, Giovanna; Pesce, Mirko; Tatangelo, Raffaella; Rizzuto, Alessia; La Fratta, Irene; Grilli, Alfredo

2017-06-01

The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.

Cerebrospinal Fluid in a Small Cohort of Patients with Multiple Sclerosis Was Generally Free of Microbial DNA

PubMed Central

Jovel, Juan; O'keefe, Sandra; Patterson, Jordan; Bording-Jorgensen, Michael; Wang, Weiwei; Mason, Andrew L.; Warren, Kenneth G.; Wong, Gane Ka-Shu

2017-01-01

Multiple sclerosis (MS) is a common cause of non-traumatic neurologic disability with high incidence in many developed countries. Although the etiology of the disease remains elusive, it is thought to entail genetic and environmental causes, and microbial pathogens have also been envisioned as contributors to the phenotype. We conducted a metagenomic survey in cerebrospinal fluid (CSF) from 28 MS patients and 15 patients suffering other type of neurological conditions. We detected bacterial reads in eight out of the 15 non-MS patients and in a single MS patient, at an abundance >1% of total classified reads. Two patients were of special interest: one non-MS patient harbored ~73% bacterial reads, while an MS patient had ~83% bacterial reads. In the former case, Veillonella parvula, a bacterium occasionally found associated with meningitis was the predominant species, whilst Kocuria flava, apparently an environmental bacterium, predominated in the latter case. Thirty-four out of 43 samples contained <1% bacterial reads, which we regard as cross- or environmental contamination. A few viral reads corresponding to Epstein-Barr virus, cytomegalovirus, and parvovirus were also identified. Our results suggest that CSF of MS patients is often (but not always) free of microbial DNA. PMID:28111617

Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

PubMed

Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

2016-07-07

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

Exercise prescription for patients with multiple sclerosis; potential benefits and practical recommendations.

PubMed

Halabchi, Farzin; Alizadeh, Zahra; Sahraian, Mohammad Ali; Abolhasani, Maryam

2017-09-16

Multiple sclerosis (MS) can result in significant mental and physical symptoms, specially muscle weakness, abnormal walking mechanics, balance problems, spasticity, fatigue, cognitive impairment and depression. Patients with MS frequently decrease physical activity due to the fear from worsening the symptoms and this can result in reconditioning. Physicians now believe that regular exercise training is a potential solution for limiting the reconditioning process and achieving an optimal level of patient activities, functions and many physical and mental symptoms without any concern about triggering the onset or exacerbation of disease symptoms or relapse. Appropriate exercise can cause noteworthy and important improvements in different areas of cardio respiratory fitness (Aerobic fitness), muscle strength, flexibility, balance, fatigue, cognition, quality of life and respiratory function in MS patients. Aerobic exercise training with low to moderate intensity can result in the improvement of aerobic fitness and reduction of fatigue in MS patients affected by mild or moderate disability. MS patients can positively adapt to resistance training which may result in improved fatigue and ambulation. Flexibility exercises such as stretching the muscles may diminish spasticity and prevent future painful contractions. Balance exercises have beneficial effects on fall rates and better balance. Some general guidelines exist for exercise recommendation in the MS population. The individualized exercise program should be designed to address a patient's chief complaint, improve strength, endurance, balance, coordination, fatigue and so on. An exercise staircase model has been proposed for exercise prescription and progression for a broad spectrum of MS patients. Exercise should be considered as a safe and effective means of rehabilitation in MS patients. Existing evidence shows that a supervised and individualized exercise program may improve fitness, functional capacity and quality of life as well as modifiable impairments in MS patients.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

PubMed

Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie

2014-04-01

The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

Relation of QRS duration to mortality in a community-based cohort with hypertrophic cardiomyopathy.

PubMed

Bongioanni, Sergio; Bianchi, Francesca; Migliardi, Alessandro; Gnavi, Roberto; Pron, Paolo Giay; Casetta, Marzia; Conte, Maria Rosa

2007-08-01

A prolonged QRS duration on the standard electrocardiogram is associated with an increased risk of cardiovascular death in cardiomyopathies of different origin. However, the relation between QRS duration and prognosis in hypertrophic cardiomyopathy (HC) remains undefined. We assessed the relation between QRS duration and cardiovascular death in 241 consecutive patients with HC. The study cohort was divided into 2 groups according to QRS duration: <120 and > or =120 ms. Of the 241 patients, 191 (79%) had a QRS duration <120 ms and 50 (21%) a QRS duration > or =120 ms. During a mean follow-up of 7.9 +/- 5.1 years, 35 patients died of cardiovascular causes related to HC. Of these 35 patients, 13 (6%) had a QRS duration <120 ms and 22 (43%) had a QRS duration > or =120 ms (p <0.01). Risk of cardiovascular death was significantly higher in patients with a QRS duration > or =120 ms than in those with a QRS duration <120 ms (relative risk 5.2, p <0.0001). At 8-year follow-up, cumulative risks of HC-related death were 7.1% in patients with a QRS duration <120 ms and 55% in those with a QRS duration > or =120 ms. Multivariate analysis confirmed that a QRS duration > or =120 ms was independently associated with an increased risk of cardiovascular death (hazard ratio 3.2, p = 0.007). New York Heart Association functional class III/IV was the only other clinical variable significantly and independently associated with an increased risk of cardiovascular death. In conclusion, in patients with HC, QRS duration on standard electrocardiogram is directly related to cardiovascular mortality, and a QRS duration > or =120 ms is a strong and independent predictor of prognosis.

Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Rodríguez-Vallejo, J M; González-Esteban, J; Miranda, G; Torrubia, F

1999-07-01

The development of benign prostatic hyperplasia (BPH) is an androgen-dependent process which may be mediated by a number of locally produced growth factors. One of these, the basic fibroblast growth factor (bFGF or FGF2), has a mitogenic effect on prostatic stroma. High expression levels of bFGF have been reported in BPH. FGFR1 and FGFR2 receptors, that exhibit affinity for bFGF, have been identified in normal and hyperplastic prostate. Finasteride, a 5alpha-reductase inhibitor, is an effective drug in the treatment of BPH, inducing regressive changes in the prostate of treated patients, even though its mechanisms of action are not yet completely elucidated. This study was designed to assess the effects of finasteride on the expression levels of bFGF, FGFR1, and FGFR2 in patients with BPH. The expression levels of bFGF, FGFR1, and FGFR2 in 9 patients with prostatic hyperplasia treated with finasteride were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA expression and were compared with those of 9 control patients with untreated BPH. Immunohistochemistry showed strong bFGF immunoreactivity in the prostatic stroma of untreated patients, this being somewhat weaker in the epithelium. In treated patients, epithelial immunoreactivity was practically negative, and a considerable reduction in stromal immunoreactivity was seen. These findings were also confirmed by RT-PCR. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR2 exhibited strong stromal immunoreactivity, becoming weaker in the basal epithelium. No differences were seen in the expression of both receptors between the groups of treated and untreated patients. A marked reduction in bFGF levels is seen in BPH treated with finasteride in comparison to untreated BPH. In our opinion, finasteride may act as a negative regulator of bFGF expression, counteracting the role of bFGF in the development of BPH.

Electrophysiological Evaluation of Dysphagia in the Mild or Moderate Patients with Multiple Sclerosis: A Concept of Subclinical Dysphagia.

PubMed

Beckmann, Yesim; Gürgör, Nevin; Çakır, Ahmet; Arıcı, Şehnaz; İncesu, Tülay Kurt; Seçil, Yaprak; Ertekin, Cumhur

2015-06-01

Swallowing mechanism and neurogenic dysphagia in MS have been rarely studied by electromyographical (EMG) methods. This study aims to evaluate the presence of subclinical dysphagia in patients with mild multiple sclerosis (MS) using electrophysiological methods. A prospective study of 51 patients with relapsing remitting multiple sclerosis and 18 age-matched healthy adults was investigated. We used electromyography to measure the activity of the submental muscles during swallowing. Electrophysiological recordings of patients were obtained during relapse, after relapse, and at any time in remission period. Clinical dysphagia was found in 12% of MS patients, while electrophysiological swallowing abnormalities were encountered in 33% of patients. Subclinical dysphagia was determined in 35% of patients during an MS relapse, in 20% of patients after a relapse, and in 25% of all 51 patients in the remission period based on EMG findings. Duration of swallowing signal of submental muscles in all MS patients was found to be longer than in normal subjects (p = 0.001). During swallowing of 50 ml of sequential water, the compensatory respiratory cycles occurred more often in MS patients than normal subjects, especially during a relapse (p = 0.005). This is the first study investigating swallowing abnormalities and subclinical dysphagia from the electrophysiological aspect in MS patients with mild disability. The electrophysiological tests described in this study are useful to uncover subclinical dysphagia since they have the advantage of being rapid, easy to apply, non-invasive, and without risk for the patients.

ECG parameters predict left ventricular conduction delay in patients with left ventricular dysfunction.

PubMed

Pastore, Gianni; Maines, Massimiliano; Marcantoni, Lina; Zanon, Francesco; Noventa, Franco; Corbucci, Giorgio; Baracca, Enrico; Aggio, Silvio; Picariello, Claudio; Lanza, Daniela; Rigatelli, Gianluca; Carraro, Mauro; Roncon, Loris; Barold, S Serge

2016-12-01

Estimating left ventricular electrical delay (Q-LV) from a 12-lead ECG may be important in evaluating cardiac resynchronization therapy (CRT). The purpose of this study was to assess the impact of Q-LV interval on ECG configuration. One hundred ninety-two consecutive patients undergoing CRT implantation were divided electrocardiographically into 3 groups: left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (IVCD). The IVCD group was further subdivided into 81 patients with left (L)-IVCD and 15 patients with right (R)-IVCD (resembling RBBB, but without S wave in leads I and aVL). The Q-LV interval in the different groups and the relationship between ECG parameters and the maximum Q-LV interval were analyzed. Patients with LBBB presented a long Q-LV interval (147.7 ± 14.6 ms, all exceeding cutoff value of 110 ms), whereas RBBB patients presented a very short Q-LV interval (75.2 ± 16.3 ms, all <110 ms). Patients with an IVCD displayed a wide range of Q-LV intervals. In L-IVCD, mid-QRS notching/slurring showed the strongest correlation with a longer Q-LV interval, followed, in decreasing order, by QRS duration >150 ms and intrinsicoid deflection >60 ms. Isolated mid-QRS notching/slurring predicted Q-LV interval >110 ms in 68% of patients. The R-IVCD group presented an unexpectedly longer Q-LV interval (127.0 ± 12.5 ms; 13/15 patients had Q-LV >110 ms). Patients with LBBB have a very prolonged Q-LV interval. Mid-QRS notching in lateral leads strongly predicts a longer Q-LV interval in L-IVCD patients. Patients with R-IVCD constitute a subgroup of patients with a long Q-LV interval. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Linguistic and psychometric validation of the MSSS-88 questionnaire for patients with multiple sclerosis and spasticity in Germany.

PubMed

Henze, Thomas; von Mackensen, Sylvia; Lehrieder, Gerald; Zettl, Uwe K; Pfiffner, Carmen; Flachenecker, Peter

2014-08-01

Multiple sclerosis (MS) is an inflammatory disease where many of the patients suffer from spasticity impacting their quality-of-life. The purpose of this paper was to linguistically validate and psychometrically test the Multiple Sclerosis Spasticity Scale (MSSS-88) in German speaking MS patients. The study had two stages: 1) forward/backward translations of the original MSSS-88 scale into German, discussions with MS-experts and cognitive debriefings with MS patients; 2) psychometric evaluation of the German version. Data collection took part in an observational multi-centre study in Germany (MOVE2). The German translation of the MSSS-88 scale was discussed with three MS-experts; followed by two cognitive debriefing sessions with 12 MS patients. For psychometric evaluation the MSSS-88 was filled in by 87 MS patients with a mean age of 50.2 ± 10.4 years; 26.4% of them had severe spasticity. Data quality was acceptable. Missing data for items of the MSSS-88 were low (range 0-5.75%). Psychometric testing of the MSSS-88 revealed excellent values for reliability and validity. Significant differences between groups regarding severity, grading, type and self-ratings of MS-spasticity and sleep disturbances were found. Sensitivity to change could be demonstrated for the MSSS-88 in the group of MS patients treated with cannabinoid oromucosal spray vs. non-treated patients. In the treated group significant changes with a moderate effect size were found for 'muscle spasms', 'emotional health' and 'pain/discomfort'. No significant changes could be detected in the non-treated group. Preliminary evidence from this small study supports reliability, validity, and responsiveness of the German version of the MSSS-88 for measuring the impact of spasticity in MS.

The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats.

PubMed

Cowan, C S M; Callaghan, B L; Richardson, R

2016-05-31

Recently, scientific interest in the brain-gut axis has grown dramatically, particularly with respect to the link between gastrointestinal and psychiatric dysfunction. However, the role of gut function in early emotional dysregulation is yet to be examined, despite the prevalence and treatment resistance of early-onset psychiatric disorders. The present studies utilized a developmental rodent model of early-life stress (ELS) to explore this gap. Rats were exposed to maternal separation (MS) on postnatal days 2-14. Throughout MS, dams received either vehicle or a probiotic formulation (previously shown to reduce gastrointestinal dysfunction) in their drinking water. Replicating past research, untreated MS infants exhibited an adult-like profile of long-lasting fear memories and fear relapse following extinction. In contrast, probiotic-exposed MS infants exhibited age-appropriate infantile amnesia and resistance to relapse. These effects were not mediated by changes in pups' or dams' anxiety at the time of training, nor by maternal responsiveness. Overall, probiotics acted as an effective and non-invasive treatment to restore normal developmental trajectories of emotion-related behaviors in infant rats exposed to ELS. These results provide promising initial evidence for this novel approach to reduce the risk of mental health problems in vulnerable individuals. Future studies are needed to test this treatment in humans exposed to ELS and to elucidate mechanisms for the observed behavioral changes.

The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats

PubMed Central

Cowan, C S M; Callaghan, B L; Richardson, R

2016-01-01

Recently, scientific interest in the brain–gut axis has grown dramatically, particularly with respect to the link between gastrointestinal and psychiatric dysfunction. However, the role of gut function in early emotional dysregulation is yet to be examined, despite the prevalence and treatment resistance of early-onset psychiatric disorders. The present studies utilized a developmental rodent model of early-life stress (ELS) to explore this gap. Rats were exposed to maternal separation (MS) on postnatal days 2–14. Throughout MS, dams received either vehicle or a probiotic formulation (previously shown to reduce gastrointestinal dysfunction) in their drinking water. Replicating past research, untreated MS infants exhibited an adult-like profile of long-lasting fear memories and fear relapse following extinction. In contrast, probiotic-exposed MS infants exhibited age-appropriate infantile amnesia and resistance to relapse. These effects were not mediated by changes in pups’ or dams’ anxiety at the time of training, nor by maternal responsiveness. Overall, probiotics acted as an effective and non-invasive treatment to restore normal developmental trajectories of emotion-related behaviors in infant rats exposed to ELS. These results provide promising initial evidence for this novel approach to reduce the risk of mental health problems in vulnerable individuals. Future studies are needed to test this treatment in humans exposed to ELS and to elucidate mechanisms for the observed behavioral changes. PMID:27244232

At the Intersection of Urbanization, Water, and Food Security: Determination of Select Contaminants of Emerging Concern in Mussels and Oysters from Hong Kong.

PubMed

Burket, S Rebekah; Sapozhnikova, Yelena; Zheng, J S; Chung, Shan Shan; Brooks, Bryan W

2018-05-23

Aquaculture, which is growing 3-5 times faster than terrestrial agriculture, will play an important role to meet future global food production needs. However, over 80% of global sewage production is returned to the environment untreated or poorly treated. In developing nations, these nontraditional waters of diverse quality are being recycled for aquaculture, yet chemical residues are differentially studied. Here, we examined pharmaceuticals, pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and flame retardants in marine bivalves using isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) and low-pressure gas chromatography-tandem mass spectrometry (LP GC-MS/MS). Green-lipped mussels from the field and oysters from aquaculture net pens, which are harvested as food products, were collected adjacent to point source municipal wastewater and landfill leachate effluent discharges, respectively, in Hong Kong, the fourth most densely populated country in the world. Multiple classes of pharmaceutical, pesticides, PAHs, and phosphorus-based flame retardants were detected at low μg/kg levels. Acceptable servings per week indicated minimal risk for a number of chemicals; however, such calculations could not be performed for other contaminants of emerging concern. Future efforts are needed to better understand contaminant influences on marine bivalve populations and aquaculture product safety, particularly in rapidly urbanizing regions of developing countries with limited wastewater infrastructure.

Hydrothermal pretreatment of microalgae for production of pyrolytic bio-oil with a low nitrogen content.

PubMed

Du, Zhenyi; Mohr, Michael; Ma, Xiaochen; Cheng, Yanling; Lin, Xiangyang; Liu, Yuhuan; Zhou, Wenguang; Chen, Paul; Ruan, Roger

2012-09-01

Microalgae can be converted to an energy-dense bio-oil via pyrolysis; however, the relatively high nitrogen content of this bio-oil presents a challenge for its direct use as fuels. Therefore, hydrothermal pretreatment was employed to reduce the N content in Nannochloropsis oculata feedstock by removing proteins without requiring significant energy inputs. The effects of reaction conditions on the yield and composition of pretreated algae were investigated by varying the temperature (150-225°C) and reaction time (10-60 min). Compared with untreated algae, pretreated samples had higher carbon contents and enhanced heating values under all reaction conditions and 6-42% lower N contents at 200-225°C for 30-60 min. The pyrolytic bio-oil from pretreated algae contained less N-containing compounds than that from untreated samples and the bio-oil contained mainly (44.9% GC-MS peak area) long-chain fatty acids (C14-C18) which can be more readily converted into hydrocarbon fuels in the presence of simple catalysts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prevalence and predictors of dysphagia in Iranian patients with multiple sclerosis

PubMed Central

Tarameshlu, Maryam; Azimi, Amir Reza; Ghelichi, Leila; Ansari, Noureddin Nakhostin

2017-01-01

Background: Dysphagia is frequently observed in patients with multiple sclerosis (MS). Dysphagia and its complications are common causes of morbidity and mortality in final stages of MS disease. This study aimed at determining the prevalence of dysphagia in Iranian patients with MS and identifying predictors associated with dysphagia. Methods: A total of 230 MS patients were enrolled in this cross-sectional study. Dysphagia was evaluated using Mann Assessment of Swallowing Ability (MASA). Demographic characteristics (age and gender), duration of the disease, disease course, and Expanded Disability Status Scale (EDSS) were recorded for all participants. Results: In total, dysphagia was found in 85 participants (37%) with mild to severe dysphagia (mild 50.6%; moderate 29.4%; and severe 20%). The logistic regression model demonstrated that disability status in EDSS (OR= 2.1; 95% CI 0.5-1.2) and disease duration (OR= 2.3; 95% CI 0.4-1.1) predicts a high risk for dysphagia in MS patients. Conclusion: Dysphagia is prevalent in Iranian patients with MS. Disability level and disease duration are significant predictors of dysphagia after MS.

Epidemiology of multiple sclerosis in Qom: Demographic study in Iran.

PubMed

Rezaali, Saeed; Khalilnezhad, Ahad; Naser Moghadasi, Abdorreza; Chaibakhsh, Samira; Sahraian, Mohammad Ali

2013-01-01

Recent studies have demonstrated controversial results and somewhat increased frequency of multiple sclerosis (MS). We reevaluated the files of MS patients from Qom Province of Iran in order to investigate the epidemiology of the disease. Demographic and clinical records of 592 MS patients were reviewed, which included; age, sex, date of birth, marital and occupation status, presenting symptoms, time of onset, type and family history of MS, and history of autoimmune or other diseases. At the time of our study, 11 patients had died, and 581 were alive with a total female-to-male ratio of 3.4. The mean age of onset of the disease was 34.25 ± 9.01 for all the patients. 11.2% of patients had positive family history of MS. The majority of patients (80.1%) showed relapsing-remitting (RR) pattern. The prevalence of MS was calculated as 50.4/100000 for Qom. Qom is located within a high risk zone of MS. Although we found evidences about the role of environmental factors, geographical distribution, and etcetera, many more studies need to be performed in this respect.

Need for symptomatic management in advanced multiple sclerosis.

PubMed

Rønning, O M; Tornes, K D

2017-05-01

A majority of patients with advanced multiple sclerosis (MS) need symptomatic treatment. Many MS-related symptoms may not be recognized and thus are not treated. We conducted a study to estimate the prevalence of inadequate symptomatic treatment of patients with advanced MS. Patients with advanced MS admitted to a specialist MS rehabilitation clinic were included in this study. Severity was assessed using the Expanded Disability Status Scale (EDSS). The information we collected included age of onset, initial course, time to sustained disability, pharmacological treatment, degree of spasticity, pain and bladder dysfunction, and unmet needs of symptomatic treatment. In total, we assessed demographic and clinical characteristics in 129 patients with a mean age of 56 years and a median EDSS of 7.5. The proportion with inadequate symptom treatment was regarding spasticity 46%, pain 28%, and bladder dysfunction 23%. This study showed that a large proportion of patients with advanced MS had lack of symptomatic treatment. These patients probably underuse neurological specialist services. Better symptomatic treatment could contribute to improving quality of life of people with MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of anger on the health-related quality of life of multiple sclerosis patients.

PubMed

Labiano-Fontcuberta, Andrés; Mitchell, Alex J; Moreno-García, Sara; Puertas-Martín, Verónica; Benito-León, Julián

2015-04-01

There is evidence of the presence of a disturbed pattern of anger in multiple sclerosis (MS). Emotion changes, including anger, are thought to influence health-related quality of life (HRQoL). However, although deleterious consequences of anger on physical health have been well reported, there are no studies that have analysed the effects of anger on the HRQoL in patients with MS. Our purpose was to assess the extent to which anger impacts on the HRQoL of a cohort of MS patients. One hundred and fifty-seven consecutive MS patients were enrolled in the study. Participants were administered affective trait measures (Beck Depression Inventory, Beck Anxiety Inventory) and anger measures (the Spanish adapted version of the State-Trait Anger Expression Inventory-2). HRQoL was quantified using the Functional Assessment of MS. Linear regression analyses revealed that even after controlling for socio-demographic and clinical variables, higher levels of anger expression-in (tendency to handle anger by keeping it inside) independently predicted worse overall HRQoL of MS patients (β = -0.15, p = 0.04). We further found that this relationship was moderated by gender, showing that anger expression-in is a more influential predictor of the HRQoL in women with MS. The present study provides evidence that anger negatively affects the HRQoL of MS patients. Our results may have implications for those involved in treating emotional complications of MS and especially regarding psychotherapeutic interventions to improve HRQoL of MS patients. © The Author(s), 2014.

29 Year Old Man with Multiple Sclerosis and Schizophrenia: A Case Report.

PubMed

Noorani, Nahid; Hadi, Fateme; Ahmadkhaniha, Hamid Reza

2016-12-01

Multiple sclerosis (MS) is the most common debilitating neurological disease that affects adults, whether young adults or middle-aged. Although, most attention is toward the neurological signs of the disease, the neuropsychiatric signs are not uncommon. This case report presents a 29 year old male with a record of obsessive-compulsive disorder (OCD) without psychotic disorder, which coincides with the diagnosis MS, has been stricken to auditory hallucinations and reference delusion. The patient received some antipsychotic drugs such as Haloperidol and Perphenazine irregularly, but any psychotic signs of the patient were never in control. During this period he had several active episodes of MS disease, wherein the symptoms had subsided due to hospitalization and received corticosteroids pulse. The first time the patient was submitted to the emergency unit of Rasoul Akram Hospital, there was the possibility of schizophrenia which was confirmed in subsequent visits. The signs of the patient were not controllable for a long time and finally fully controlled by a combination of Aripiprazole (abilizol), Risperidone and Sertraline, and currently, for almost 3 years, both psychotic symptoms and MS disease have been under control. Our patient seems to catch the MS disease and schizophrenia simultaneously. There was no relation between MS and psychosis episodes and the MS attacks. Since the onset the patient had several acute MS attacks of MS, and hospitalization several times. These findings and characteristics regarding our patient made him completely different from other reported cases of MS along with neuropsychiatric signs which may help doctors in diagnosis and managment of similar cases.

Urine Multi-drug Screening with GC-MS or LC-MS-MS Using SALLE-hybrid PPT/SPE.

PubMed

Lee, Junhui; Park, Jiwon; Go, Ahra; Moon, Heesung; Kim, Sujin; Jung, Sohee; Jeong, Wonjoon; Chung, Heesun

2018-05-14

To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.

Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up.

PubMed

Füchtbauer, Laila; Olsson, Daniel S; Bengtsson, Bengt-Åke; Norrman, Lise-Lott; Sunnerhagen, Katharina S; Johannsson, Gudmundur

2017-08-01

Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. Prospective observational study. Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis ( n  = 48), 1 year after surgery ( n  = 29) and after long-term follow-up (median 11 years) ( n  = 24). Results were compared to healthy subjects. Untreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively. Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased. © 2017 European Society of Endocrinology.

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

PubMed

Spalletta, Gianfranco; Musicco, Massimo; Padovani, Alesandro; Rozzini, Luca; Perri, Roberta; Fadda, Lucia; Canonico, Vincenzo; Trequattrini, Alberto; Pettenati, Carla; Caltagirone, Carlo; Palmer, Katie

2010-11-01

Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.

The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis

PubMed Central

Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

2018-01-01

Purpose This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. Patients and methods One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Results Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion. PMID:29731642

Growth inhibitory response and ultrastructural modification of oral-associated candidal reference strains (ATCC) by Piper betle L. extract

PubMed Central

Nordin, Mohd-Al-Faisal; Wan Harun, Wan Himratul-Aznita; Abdul Razak, Fathilah; Musa, Md Yusoff

2014-01-01

Candida species have been associated with the emergence of strains resistant to selected antifungal agents. Plant products have been used traditionally as alternative medicine to ease mucosal fungal infections. This study aimed to investigate the effects of Piper betle extract on the growth profile and the ultrastructure of commonly isolated oral candidal cells. The major component of P. betle was identified using liquid chromatography-mass spectrophotometry (LC-MS/MS). Seven ATCC control strains of Candida species were cultured in yeast peptone dextrose broth under four different growth environments: (i) in the absence of P. betle extract; and in the presence of P. betle extract at respective concentrations of (ii) 1 mg⋅mL−1; (iii) 3 mg⋅mL−1; and (iv) 6 mg⋅mL−1. The growth inhibitory responses of the candidal cells were determined based on changes in the specific growth rates (µ). Scanning electron microscopy (SEM) was used to observe any ultrastructural alterations in the candida colonies. LC-MS/MS was performed to validate the presence of bioactive compounds in the extract. Following treatment, it was observed that the µ-values of the treated cells were significantly different than those of the untreated cells (P<0.05), indicating the fungistatic properties of the P. betle extract. The candidal population was also reduced from an average of 13.44×106 to 1.78×106 viable cell counts (CFU)⋅mL−1. SEM examination exhibited physical damage and considerable morphological alterations of the treated cells. The compound profile from LC-MS/MS indicated the presence of hydroxybenzoic acid, chavibetol and hydroxychavicol in P. betle extract. The effects of P. betle on candida cells could potentiate its antifungal activity. PMID:24406634

Growth inhibitory response and ultrastructural modification of oral-associated candidal reference strains (ATCC) by Piper betle L. extract.

PubMed

Nordin, Mohd-Al-Faisal; Wan Harun, Wan Himratul-Aznita; Abdul Razak, Fathilah; Musa, Md Yusoff

2014-03-01

Candida species have been associated with the emergence of strains resistant to selected antifungal agents. Plant products have been used traditionally as alternative medicine to ease mucosal fungal infections. This study aimed to investigate the effects of Piper betle extract on the growth profile and the ultrastructure of commonly isolated oral candidal cells. The major component of P. betle was identified using liquid chromatography-mass spectrophotometry (LC-MS/MS). Seven ATCC control strains of Candida species were cultured in yeast peptone dextrose broth under four different growth environments: (i) in the absence of P. betle extract; and in the presence of P. betle extract at respective concentrations of (ii) 1 mg⋅mL(-1); (iii) 3 mg⋅mL(-1); and (iv) 6 mg⋅mL(-1). The growth inhibitory responses of the candidal cells were determined based on changes in the specific growth rates (µ). Scanning electron microscopy (SEM) was used to observe any ultrastructural alterations in the candida colonies. LC-MS/MS was performed to validate the presence of bioactive compounds in the extract. Following treatment, it was observed that the µ-values of the treated cells were significantly different than those of the untreated cells (P<0.05), indicating the fungistatic properties of the P. betle extract. The candidal population was also reduced from an average of 13.44×10(6) to 1.78×10(6) viable cell counts (CFU)⋅mL(-1). SEM examination exhibited physical damage and considerable morphological alterations of the treated cells. The compound profile from LC-MS/MS indicated the presence of hydroxybenzoic acid, chavibetol and hydroxychavicol in P. betle extract. The effects of P. betle on candida cells could potentiate its antifungal activity.

Intravitreal Injection of Proinsulin-Loaded Microspheres Delays Photoreceptor Cell Death and Vision Loss in the rd10 Mouse Model of Retinitis Pigmentosa.

PubMed

Isiegas, Carolina; Marinich-Madzarevich, Jorge A; Marchena, Miguel; Ruiz, José M; Cano, María J; de la Villa, Pedro; Hernández-Sánchez, Catalina; de la Rosa, Enrique J; de Pablo, Flora

2016-07-01

The induction of proinsulin expression by transgenesis or intramuscular gene therapy has been shown previously to retard retinal degeneration in mouse and rat models of retinitis pigmentosa (RP), a group of inherited conditions that result in visual impairment. We investigated whether intraocular treatment with biodegradable poly (lactic-co-glycolic) acid microspheres (PLGA-MS) loaded with proinsulin has cellular and functional neuroprotective effects in the retina. Experiments were performed using the Pde6brd10 mouse model of RP. Methionylated human recombinant proinsulin (hPI) was formulated in PLGA-MS, which were administered by intravitreal injection on postnatal days (P) 14 to 15. Retinal neuroprotection was assessed at P25 by electroretinography, and by evaluating outer nuclear layer (ONL) cellular preservation. The attenuation of photoreceptor cell death by hPI was determined by TUNEL assay in cultured P22 retinas, as well as Akt phosphorylation by immunoblotting. We successfully formulated hPI PLGA-MS to deliver the active molecule for several weeks in vitro. The amplitude of b-cone and mixed b-waves in electroretinographic recording was significantly higher in eyes injected with hPI-PLGA-MS compared to control eyes. Treatment with hPI-PLGA-MS attenuated photoreceptor cell loss, as revealed by comparing ONL thickness and the number of cell rows in this layer in treated versus untreated retinas. Finally, hPI prevented photoreceptor cell death and increased AktThr308 phosphorylation in organotypic cultured retinas. Retinal degeneration in the rd10 mouse was slowed by a single intravitreal injection of hPI-PLGA-MS. Human recombinant proinsulin elicited a rapid and effective neuroprotective effect when administered in biodegradable microspheres, which may constitute a future potentially feasible delivery method for proinsulin-based treatment of RP.

Quantification of 19-nortestosterone sulphate and boldenone sulphate in urine from male horses using liquid chromatography/tandem mass spectrometry.

PubMed

Grace, Philip B; Drake, Erica C; Teale, Philip; Houghton, Edward

2008-10-01

Following administration of the anabolic steroid 19-nortestosterone or its esters to the horse, a major urinary metabolite is 19-nortestosterone-17beta-sulphate. The detection of 19-nortestosterone in urine from untreated animals has led to it being considered a naturally occurring steroid in the male horse. Recently, we have demonstrated that the majority of the 19-nortestosterone found in extracts of 'normal' urine from male horses arises as an artefact through decarboxylation of the 19-carboxylic acid of testosterone. The aim of this investigation was to establish if direct analysis of 19-nortestosterone-17beta-sulphate by liquid chromatography/tandem mass spectrometry (LC/MS/MS) had potential for the detection of 19-nortestosterone misuse in the male horse. The high concentrations of sulphate conjugates of the female sex hormones naturally present in male equine urine were overcome by selective hydrolysis of the aryl sulphates using glucuronidase from Helix pomatia; this was shown to have little or no activity for alkyl sulphates such as 19-nortestosterone-17beta-sulphate. The 'free' phenolic steroids were removed by solid-phase extraction (SPE) prior to LC/MS/MS analysis. The method also allowed for the quantification of the sulphate conjugate of boldenone, a further anabolic steroid endogenous in the male equine with potential for abuse in sports. The method was applied to the quantification of these analytes in a population of samples. This paper reports the results of that study along with the development and validation of the LC/MS/MS method. The results indicate that while 19-nortestosterone-17beta-sulphate is present at low levels as an endogenous substance in urine from 'normal' male horses, its use as an effective threshold substance may be viable.

Analysis of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues in chlorine-treated water by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS).

PubMed

Planas, Carles; Ventura, Francesc; Caixach, Josep; Martín, Jordi; Boleda, M Rosa; Paraira, Miquel

2015-11-01

A simple, selective and sensitive method for the analysis of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and its brominated analogues (BMXs) in chlorine-treated water has been developed. The method is based on gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS), previous liquid-liquid extraction (LLE) of a smaller sample volume compared to other methods and on-line derivatization with a silylation reactive. GC-QqQ-MS/MS has been raised as an alternative easier to perform than gas chromatography coupled to high resolution mass spectrometry (GC-HRMS) for the analysis of MX and BMXs, and it allows to achieve low LODs (0.3 ng/L for MX and 0.4-0.9 ng/L for BMXs). This technique had not been previously described for the analysis of MX and BMXs. Quality parameters were calculated and real samples related to 3 drinking water treatment plants (DWTPs), tap water and both untreated and chlorinated groundwater were analyzed. Concentrations of 0.3-6.6 ng/L for MX and 1.0-7.3 ng/L for BMXs were detected. Results were discussed according to five of the main factors affecting MX and BMXs formation in chlorine-treated water (organic precursors, influence of bromide ions, evolution of MX and BMXs in the drinking water distribution system, groundwater chlorination and infiltration of water coming from chlorination processes in groundwater). Copyright © 2015 Elsevier B.V. All rights reserved.

Divided visual attention: A comparison of patients with multiple sclerosis and controls, assessed with an optokinetic nystagmus suppression task.

PubMed

Williams, Isla M; Schofield, Peter; Khade, Neha; Abel, Larry A

2016-12-01

Multiple sclerosis (MS) frequently causes impairment of cognitive function. We compared patients with MS with controls on divided visual attention tasks. The MS patients' and controls' stare optokinetic nystagmus (OKN) was recorded in response to a 24°/s full field stimulus. Suppression of the OKN response, judged by the gain, was measured during tasks dividing visual attention between the fixation target and a second stimulus, central or peripheral, static or dynamic. All participants completed the Audio Recorded Cognitive Screen. MS patients had lower gain on the baseline stare OKN. OKN suppression in divided attention tasks was the same in MS patients as in controls but in both groups was better maintained in static than in dynamic tasks. In only dynamic tasks, older age was associated with less effective OKN suppression. MS patients had lower scores on a timed attention task and on memory. There was no significant correlation between attention or memory and eye movement parameters. Attention, a complex multifaceted construct, has different neural combinations for each task. Despite impairments on some measures of attention, MS patients completed the divided visual attention tasks normally. Copyright © 2016 Elsevier Ltd. All rights reserved.

Epstein-Barr virus in multiple sclerosis.

PubMed

Abdelrahman, Hisham S; Selim, Heba S; Hashish, Mona H; Sultan, Lobna I

2014-08-01

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Many diseases are associated with Epstein-Barr virus (EBV) infection, such as infectious mononucleosis and many types of malignancies, and it is thought to be related to some diseases of autoimmune origin, such as rheumatoid arthritis, systemic lupus erythematosis, and others. The present study aimed to assess EBV in patients with MS. This case-control study was conducted from October 2012 to September 2013 on 75 MS patients and non-MS controls. Both were tested quantitatively for immunoglobulin G (IgG) antibodies against Epstein-Barr nuclear antigen-1 (EBNA1) and viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique. Seventy MS patients (93.3%) were positive for EBNA1 IgG compared with 68 controls (90.7%). In MS patients, the mean EBNA1 IgG serum level was 310.91 (±131.05) U/ml; meanwhile, among controls the mean serum EBNA IgG level was 177.81 (±104.98) U/ml.All patients with MS were positive for VCA IgG, whereas only 60 (80.0%) controls were positive. In the MS group, the VCA IgG mean level was 302.19 (±152.11) U/ml compared with 167.94 (±111.79) U/ml in controls. The differences in the serum levels of both markers between the two groups were statistically significant (P<0.001). EBV proved to have a unique immunological pattern in MS patients when compared with non-MS controls. Further studies for more confirmation of the relation between EBV and MS on a large scale are recommended.

The Italian validation of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) and the application of the Cognitive Impairment Index scoring procedure in MS patients.

PubMed

Argento, Ornella; Incerti, Chiara C; Quartuccio, Maria E; Magistrale, Giuseppe; Francia, Ada; Caltagirone, Carlo; Pisani, Valerio; Nocentini, Ugo

2018-04-27

Cognitive dysfunction occurs in almost 50-60% of patients with multiple sclerosis (MS) even in early stages of the disease and affects different aspects of patient's life. Aims of the present study were (1) to introduce and validate an Italian version of the minimal assessment of cognitive functions in MS (MACFIMS) battery and (2) to propose the use of the Cognitive Impairment Index (CII) as a scoring procedure to define the degree of impairment in relapsing-remitting (RRMS) and secondary-progressive (SPMS) patients. A total of 240 HC and 123 MS patients performed the Italian version of the MACFIMS composed by the same tests as the original except for the Paced Auditory Serial Addition Test. The CII was derived for each score of the 11 scales for participants of both groups. The results of the study show that cognitive impairment affects around 50% of our sample of MS patients. In RRMS group, only the 15.7% of patients reported a severe impairment, while in the group of SPMS, the 51.4% of patients felt in the "severely impaired" group. Results are in line with previously reported percentages of impairment in MS patients, showing that the calculation of the CII applied to the Italian version of the MACFIMS is sensitive and reliable in detecting different degrees of impairment in MS patients.

Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis

PubMed Central

Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

2015-01-01

Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56bright/CD56dim) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56bright and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease. PMID:25565222

Carotid artery intima-media thickness and erectile dysfunction in patients with metabolic syndrome.

PubMed

Unal, Mustafa; Aksoy, Duygu Yazgan; Aydın, Yusuf; Tanriover, Mine Durusu; Berker, Dilek; Karakaya, Jale; Guler, Serdar

2014-05-29

Metabolic syndrome (MS) has become a pandemic in Turkey, as is the case globally. Increase in carotid artery intima-media thickness (CIMT) and erectile dysfunction (ED) may be evident before the clinical signs of cardiovascular disease appear. We aimed to investigate the prevalence of increased CIMT and ED as markers of atherosclerotic disease in patients with MS. Thirty-two patients with MS and 29 healthy controls were included. Anthropometric and biochemical parameters, along with total testosterone (TT), high sensitive C-reactive protein (hs-CRP), were recorded. Carotid artery intima-media thickness was measured. Erectile dysfunction was assessed with International Index of Erectile Function. Patients with MS had higher BMI, fasting plasma glucose, post-prandial plasma glucose, insulin, HOMA-IR, total cholesterol, triglycerides, hs-CRP, and CIMT, whereas TT levels were lower (p<0.0001). The prevalence and severity of erectile dysfunction were higher in patients with MS (p<0.0001). Erectile dysfunction scores correlated inversely with CIMT. MS patients with ED were older and had higher CIMT compared to those without ED. Increase in age and HOMA and decrease in TT increased the risk of ED. When KIMT exceeding the 95th percentile of healthy controls was accepted as a risk factor for CVD, presence of ED was the only determinant for this increase. Erectile dysfunction was more prevalent and severe in patients with MS and correlated with subclinical endothelial dysfunction. Total testosterone deficiency was prominent among MS patients. Presence of ED points to an increased risk of cardiovascular disease when MS is present.

Patients with multiple sclerosis present low levels of empathy.

PubMed

Almeida, Marcos Barbosa de; Going, Luana Carramilo; Fragoso, Yara Dadalti

2016-12-01

This is a single center, cross-sectional study, of 34 patients with MS and 34 matched control subjects. A specific questionnaire (empathy quotient) was used. Patients with MS showed significantly lower levels of empathy. This finding was not correlated with disease duration, degree of disability, drugs for treating MS or lesion load on resonance magnetic imaging. Decreased empathy is a frequent condition in patients with MS and should be addressed in order to diminish the psychosocial burden of this neurological disease.

Myeloproliferative neoplasms in five multiple sclerosis patients☆

PubMed Central

Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis; Hasselbalch, Hans Carl

2013-01-01

The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007–2012. We describe the patients' history and treatment. A potential link between MS and MPNs has not been previously recognized. This observation calls attention to potential environmental factors and/or previously unrecognized genetic factors predisposing these patients to both MS and MPNs. PMID:24371783

Metabolic syndrome and obesity in peritoneal dialysis.

PubMed

Lo, Wai Kei

2016-03-01

Metabolic syndrome (MS) refers to clustering of features related to increased risk of cardiovascular disease, which include obesity or central obesity, dyslipidemia, diabetes mellitus or insulin resistance, together with hypertension. The prevalence of MS in end-stage renal failure patients on peritoneal dialysis is quite common, ranging from 40% to 60%, depending on the population studied and the definition used. However, there are controversies about the clinical outcome of patients with MS, particularly in the area of obesity. Whether peritoneal dialysis predisposes patients to MS is another unsolved issue. Despite these controversies, preventing patients from developing MS is important, at least from a theoretical point of view.

Cognition in older patients with multiple sclerosis compared to patients with amnestic mild cognitive impairment and healthy older adults.

PubMed

Roth, Alexandra K; Denney, Douglas R; Burns, Jeffrey M; Lynch, Sharon G

2018-06-25

Progress in the treatment of multiple sclerosis (MS) has resulted in larger numbers of patients living to an advanced age, but little is known about the cognitive status of these individuals. The primary purpose of this study was to identify differences in the cognitive performance between elderly individuals with MS and those with amnestic mild cognitive impairment (aMCI). Three groups ranging in age from 60 to 80 were compared: patients with MS (n = 64), patients with aMCI (n = 58), and healthy adults (n = 70). All participants completed a standard neuropsychological test battery that evaluated domains of attention, processing speed, executive function, memory, language, and visual spatial function. Compared to age- and gender-matched healthy controls, elderly MS patients exhibited a pattern of cognitive impairment centering on information processing speed and memory that was consistent with the deficits observed in other studies of MS patients regardless of age. Compared to aMCI patients, the MS patients exhibited worse performance on measures of processing speed, but better performance on a measure of memory under cued conditions (Selective Reminding Test), a nonspeeded measure of language (Boston Naming Test), and measures of executive function with processing speed statistically controlled (Trail Making Test, Stroop Test). Differences on neuropsychological measures can serve to distinguish aMCI from MS-related cognitive impairment in older patients, but it is essential that these measures control for the deficit in processing speed that is such a primary feature of MS. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Salicylic Acid Induces Changes in Mango Fruit that Affect Oviposition Behavior and Development of the Oriental Fruit Fly, Bactrocera dorsalis

PubMed Central

Roy, Tapas Kumar; Shivashankara, Kodthalu Seetharamaiah; Verghese, Abraham

2015-01-01

The Oriental fruit fly, Bactrocera dorsalis (Hendel) is an important quarantine pest around the globe. Although measures for its control are implemented worldwide through IPM and male annihilation, there is little effect on their population. Hence, there is a need for new strategies to control this minacious pest. A strategy that has received negligible attention is the induction of ‘natural plant defenses’ by phytohormones. In this study, we investigated the effect of salicylic acid (SA) treatment of mango fruit (cv. Totapuri) on oviposition and larval development of B. dorsalis. In oviposition choice assays, gravid females laid significantly less eggs in SA treated compared to untreated fruit. Headspace volatiles collected from SA treated fruit were less attractive to gravid females compared to volatiles from untreated fruit. GC-MS analysis of the headspace volatiles from SA treated and untreated fruit showed noticeable changes in their chemical compositions. Cis-ocimene and 3-carene (attractants to B. dorsalis) were reduced in the headspace volatiles of treated fruit. Further, reduced pupae formation and adult emergence was observed in treated fruit compared to control. Increased phenol and flavonoid content was recorded in treated fruit. We also observed differential expression of anti-oxidative enzymes namely catalase (CAT), polyphenoloxidase (PPO) and peroxidase (POD). In summary, the results indicate that SA treatment reduced oviposition, larval development and adult emergence of B. dorsalis and suggest a role of SA in enhancing mango tolerance to B. dorsalis. PMID:26422203

The relationship between event-related potentials, stress perception and personality type in patients with multiple sclerosis without cognitive impairment: A pilot study.

PubMed

Waliszewska-Prosół, Marta; Nowakowska-Kotas, Marta; Kotas, Roman; Bańkowski, Tomasz; Pokryszko-Dragan, Anna; Podemski, Ryszard

2018-06-08

The clinical course of multiple sclerosis (MS) can vary significantly among patients and is affected by exogenous and endogenous factors. Among these, stress and personality type have been gaining more attention. The aim of this study was to investigate the parameters of event-related potentials (ERPs) with regards to stress perception and personality type, as well as cognitive performance in MS patients. The study group consisted of 30 MS patients and 26 healthy controls. Auditory ERPs were performed in both groups, including an analysis of P300 and N200 response parameters. The Perceived Stress Scale (PSS) was used in the MS group to measure the perception of stress. The D-type Scale (DS14) scale was used to determine the features of Type D personality, characterized by social inhibition and negative affectivity. The score on the PSS corresponded with a moderate or high level of stress perception in 63% of MS patients, while 23% of patients presented with a Type D personality. P300 latencies were significantly longer (p = 0.001), N200 amplitudes were significantly higher (p = 0.004), and N200 latencies were longer in MS patients than in the controls. Strong positive correlations were found between N200 and P300 amplitudes, as well as between the DS14 and PSS results. Most MS patients experience moderate to severe stress. ERP abnormalities were found in MS patients who did not have overt cognitive impairment and showed correlations with stress levels and negative affectivity. Event-related potentials may be useful in assessing the influence of stress and emotions on the course of MS.

Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

PubMed Central

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

2015-01-01

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

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2008-08-15

To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

[Cardiac structure and function in patients with obstructive sleep apnea syndrome and co-prevalent arterial hypertension. Influence of CPAP therapy].

PubMed

Duchna, Hans-Werner; Myslinski, Wojciech; Dichmann, Manuel; Rasche, Kurt; Schultze-Werninghaus, Gerhard; Orth, Maritta

2006-01-15

30% of patients with arterial hypertension (AH) are supposed to have a co-prevalent obstructive sleep apnea syndrome (OSAS). Hence, the influence of CPAP (continuous positive airway pressure) therapy on cardiac structure and function was investigated in medically treated patients with AH and co-prevalent OSAS. In all patients AH was treated for at least 5 years. Matched pairs concerning anthropometric data, medical therapy and duration of AH, and severity of OSAS were investigated: 20 patients with untreated OSAS were compared to 20 patients with CPAP therapy for at least 6 months. Further cardiopulmonary diseases were excluded. Cardiac structure and function were assessed echocardiographically. Patients under CPAP therapy had significantly better diastolic left ventricular function, a lower left ventricular mass index, and significantly less frequent signs of left ventricular (eccentric) hypertrophy than patients with untreated OSAS. Furthermore, differences were significant concerning right ventricular wall thickness and mean pulmonary artery pressure. CPAP therapy positively influences left and right cardial structure and function in addition to antihypertensive medication in patients with AH and co-prevalent OSAS.

Does famotidine induce thrombocytopenia in neurosurgical patients?

PubMed

Ecker, Robert D; Wijdicks, Eelco F M; Wix, Kelly; McClelland, Robyn

2004-10-01

The incidence of thrombocytopenia in neurosurgical patients prescribed famotidine is unknown. Using hospital records of neurosurgery patients treated between July 2001 and July 2002, a retrospective cohort study was performed comparing platelet counts in patients treated with famotidine with a similar group of patients who were not prescribed an H2 antagonist. Patients were excluded if: 1) platelets were less than 150,000 prior to famotidine administration; 2) pre-drug and post-drug platelets were not drawn; 3) they were concurrently taking a potential thrombocytopenic inducing drug; or 4) disseminated intravascular coagulation, thrombocytopenic purpura, or any other confounding hematologic disorder developed. Seventeen of 50 (34%) patients on famotidine developed thrombocytopenia compared with 11 of 98 (11.2%) of those untreated (P = 0.002). In this retrospective study, neurosurgical patients on famotidine developed thrombocytopenia statistically significantly more often than those untreated. Although no clinically significant sequelae developed as a result of the thrombocytopenia, if these findings are confirmed by a prospective study, proton pump inhibitors and sucralfate, with their similar efficacy, may be a better choice for gastrointestinal prophylaxis in neurosurgical patients.

Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study in the Asia-Pacific Region (MUSIC OS-AP): Design of a multinational, prospective, observational study examining the impact of gastrointestinal events on osteoporosis management in postmenopausal women.

PubMed

Modi, Ankita; Ebeling, Peter R; Lee, Mel S; Min, Yong-Ki; Mithal, Ambrish; Yang, Xiaoqin; Sajjan, Shiva

2015-12-01

The burden of osteoporosis in the Asia-Pacific region is not well characterized. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study in the Asia-Pacific Region (MUSIC OS-AP) was designed to better understand the association of gastrointestinal events with patient-reported outcomes in postmenopausal women of this region. MUSIC OS-AP is a prospective, multinational, observational cohort study of postmenopausal women ≥ 50 years of age diagnosed with osteoporosis. The study was conducted in five Asia-Pacific countries: Australia, New Zealand, Taiwan, Korea, and India. MUSIC OS-AP has three components: a physician questionnaire, a retrospective chart review, and a prospective cohort study. The physician questionnaire investigated the role of gastrointestinal events in physicians' pharmacologic management of osteoporosis. The retrospective chart review, also completed by physicians, recorded rate of osteoporosis treatment and the types of osteoporosis medications prescribed to osteoporosis patients. The prospective cohort study investigated the associations between gastrointestinal events and patient-reported outcomes among patients taking oral medications for osteoporosis as well as reasons for non-treatment in patients who remained untreated. The prospective cohort study enrolled two groups of patients: untreated, and treated with oral osteoporosis medications. Untreated patients completed only the baseline surveys, providing information on gastrointestinal event rates, quality of life, health care resource use, and reasons for non-treatment. Treated patients, who were either new to osteoporosis medication or continuing an ongoing medication course, completed surveys at baseline and 3, 6, and 12 months post-baseline. The evaluations recorded patient characteristics, gastrointestinal events, health-related and osteoporosis-specific quality of life, health care resource use, medication adherence, and satisfaction with treatment. Physicians at 59 sites completed the physician questionnaire, and data for 300 patients from 26 sites were abstracted for the retrospective chart review. Enrollment and baseline data collection for the prospective cohort study were conducted between July 2013 and August 2014 for 301 untreated and 3287 treated patients, of whom 1416 were new users and 1871 were experienced users of oral osteoporosis medications. The results of MUSIC OS-AP will highlight the association of gastrointestinal events with patient-reported outcomes among postmenopausal women with osteoporosis and elucidate physicians' management of gastrointestinal events among this patient population in the Asia-Pacific region.

Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis.

PubMed

Schoser, Benedikt; Stewart, Andrew; Kanters, Steve; Hamed, Alaa; Jansen, Jeroen; Chan, Keith; Karamouzian, Mohammad; Toscano, Antonio

2017-04-01

A number of studies have assessed the efficacy of alglucosidase alfa as an enzyme replacement therapy (ERT) on motor and respiratory endpoints in patients with late-onset Pompe disease (LOPD). A previous review evaluated the clinical efficacy and safety of alglucosidase alfa; however, it is difficult to draw inferences from individual studies due to small patient populations, particularly in evaluating the benefit on survival. To evaluate the current evidence on the long-term efficacy of alglucosidase alfa with regard to survival, motor, and respiratory function in patients with LOPD in relation to the natural progression of the disease, a new systematic literature review was performed identifying studies that assessed either mortality, percent predicted forced vital capacity (% FVC), or the 6-min walk test (6MWT) among treated and untreated LOPD patients. Patient overlap was avoided by removing smaller studies or ensuring the use of only one conflicting study per outcome. Mortality was modeled using Poisson models for each treatment group. Outcomes were modeled using first- and second-order fractional polynomial meta-analysis with fixed- and random-effects. Meta-regression was used to explore sources of heterogeneity. Twenty-two publications pertaining to 19 studies/trials were selected, including 438 patients when accounting for overlaps, with the average study duration being 45.7 months. Patients treated with alglucosidase alfa in these studies had a nearly five-fold lower mortality rate than untreated patients (rate ratio: 0.21; 95 % credible interval: 0.11, 0.41). On average, % FVC declined consistently among untreated patients, including a 2.3 % decline after 12 months follow-up and 6.2 % decline after 48 months. This is in contrast to alglucosidase alfa-treated patients, who, on average, improved rapidly, with an increase of 1.4 % FVC after 2 months, followed by a slow regression back to baseline over a three-year period. Nonetheless, the relative difference between those treated and not grew over time, from 4.5 % FVC after 12 months to 6 % FVC after 48 months. In the 6MWT, alglucosidase alfa-treated patients on average had the largest improvement over the first 20 months of treatment of approximately 50 meters increase over baseline, with its substantial stabilization in the following years. By comparison, untreated patients do not show 6MWT improvement over time. Alglucosidase alfa has a beneficial effect in LOPD patients as demonstrated by improvements in survival and ambulation maintained over time, as well as prevention of deterioration in respiratory function.

Reevaluation of the role of duration of morning stiffness in the assessment of rheumatoid arthritis activity.

PubMed

Khan, Nasim A; Yazici, Yusuf; Calvo-Alen, Jaime; Dadoniene, Jolanta; Gossec, Laure; Hansen, Troels M; Huisman, Margriet; Kallikorm, Riina; Muller, Raili; Liveborn, Margareth; Oding, Rolf; Luchikhina, Elena; Naranjo, Antonio; Rexhepi, Sylejman; Taylor, Peter; Tlustochowich, Witold; Tsirogianni, Afrodite; Sokka, Tuulikki

2009-11-01

To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

[Impact of metabolic syndrome on CRP levels].

PubMed

Rodilla, E; Costa, J A; Mares, S; Miralles, A; González, C; Sánchez, C; Pascual, J M

2006-09-01

C-reactive protein (CRP) is considered a marker of subclinical atherosclerosis. The aim of the study was to assess whether the metabolic syndrome (MS) and parameters involved in its diagnosis might influence serum CRP values. Cross-sectional study in outpatients of a HTA and Vascular Risk clinic. MS was diagnosed according to National Cholesterol Educational Program ATP-III guidelines, and hs-CRP was analyzed by nephelometry. A total of 1,969 patients (47% male) were evaluated and distributed into four groups: 1) 1,220 non-diabetics without MS; 2) 384 non-diabetics with MS; 3) 153 diabetics without MS, and 4) 212 diabetics with MS. Patients with MS had higher CRP in both non-diabetic 3.0 (1.7-4.4) mg/l vs. 1.7 (0.9-3.4) mg/l; p=0.001 (MW), and diabetic patients: 2.8 (1.5-4.6) mg/l vs. 2.2 (0.9-4.3) mg/l; p=0.01 (MW). Diabetic patients without MS had CRP values not different to non-diabetic without MS. CRP values increased in relation to the number of parameters included in the MS from 1.7 (2.2) mg/l, in patients without any parameters, to 4.2 (2.8) mg/l in patients who fulfilled five parameters (p=0.001) (KW). In multiple regression analysis abdominal obesity (p=0.001), TG (p=0.001) and glucose (p=0.02) were associated with CRP levels after correcting for other factors. Abdominal obesity (OR: 1.9; 95% CI: 1.5-2.4; p=0.001) and TG (OR: 1.4; 95% CI: 1.1 -1.7; p=0.003), but not glucose were independent factors related to the presence of high levels of CRP (>3 mg/l) in a logistic regression analysis. Diabetic and non-diabetic patients with MS have high CRP levels. Of the five components of MS, the most closely related to CRP is abdominal obesity.

Phase I study of 3-weekly combination chemotherapy using epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer.

PubMed

Sym, Sun Jin; Hong, Junsik; Jung, Minkyu; Park, Jinny; Cho, Eun Kyung; Lee, Woon Ki; Chung, Min; Kim, Hyung-Sik; Lee, Jae Hoon; Shin, Dong Bok

2012-08-01

This study was performed to determine the recommended dose (RD) and dose-limiting toxicity (DLT) associated with epirubicin, oxaliplatin, and S-1 (EOS) combination therapy in patients with previously untreated advanced gastric cancer (AGC). Previously untreated patients with histologically proven metastatic AGC, with an ECOG performance status of 0-2, were enrolled in this study. A fixed dose of epirubicin (50 mg/m(2)) and oxaliplatin (130 mg/m(2)) was intravenously administered on day 1 of treatment, followed by oral S-1 administration twice daily on days 1-14. The S-1 dose was escalated according to the following schedule: level I, 35 mg/m(2); level II, 40 mg/m(2); level III, 45 mg/m(2); Level IV, 50 mg/m(2). Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment. Nineteen patients with a median age of 53 years (range, 40-71 years) were enrolled in this study. One case of DLT (grade 4 neutropenia lasting more than 5 days) developed from among the six dose level II patients, while 2 DLTs (grade 3 diarrhea and nausea) were observed among the 4 dose level III patients. Based on these results, dose level II was determined as the RD. Of the 13 patients with measurable lesions, eight achieved partial response, three showed stable disease, and the objective response rate was 61.5 % (95 % confidence interval (CI), 13.3-66.6 %). The median progression-free survival and overall survival of all patients was 6.8 months (95 % CI, 1.4-9.5 months) and 13.3 months (95 % CI, 1.9-24.6 months), respectively. The RD of the EOS regimen in patients with previously untreated AGC was 50 mg/m(2) of epirubicin and 130 mg/m(2) of oxaliplatin on day 1, with administration of 40 mg/m(2) of S-1 twice a day on days 1-14 for each 21-day cycle. The EOS regimen described produced promising results.

Coexistence of systemic lupus erythematosus and multiple sclerosis. A case report and literature review.

PubMed

Jácome Sánchez, Elisa Carolina; García Castillo, María Ariana; González, Victor Paredes; Guillén López, Fernando; Correa Díaz, Edgar Patricio

2018-01-01

Multiple sclerosis (MS) and systemic lupus erythematous (SLE) are autoimmune diseases, the coexistence of which is uncommon in patients. Owing to the rarity of this condition, the distinction between MS and SLE is a diagnostic challenge for neurologists. We present a case report in which MS and SLE were present in the same patient. There are few case reports in the world on the association between MS and SLE. The following case report is the first of its kind in which both MS and SLE are present in a patient from a country with low prevalence of MS such as Ecuador.

Adaptive Personalized Training Games for Individual and Collaborative Rehabilitation of People with Multiple Sclerosis

PubMed Central

2014-01-01

Any rehabilitation involves people who are unique individuals with their own characteristics and rehabilitation needs, including patients suffering from Multiple Sclerosis (MS). The prominent variation of MS symptoms and the disease severity elevate a need to accommodate the patient diversity and support adaptive personalized training to meet every patient's rehabilitation needs. In this paper, we focus on integrating adaptivity and personalization in rehabilitation training for MS patients. We introduced the automatic adjustment of difficulty levels as an adaptation that can be provided in individual and collaborative rehabilitation training exercises for MS patients. Two user studies have been carried out with nine MS patients to investigate the outcome of this adaptation. The findings showed that adaptive personalized training trajectories have been successfully provided to MS patients according to their individual training progress, which was appreciated by the patients and the therapist. They considered the automatic adjustment of difficulty levels to provide more variety in the training and to minimize the therapists involvement in setting up the training. With regard to social interaction in the collaborative training exercise, we have observed some social behaviors between the patients and their training partner which indicated the development of social interaction during the training. PMID:24982862

The patient's perspective: How to create awareness for improving access to care and treatment of MS patients?

PubMed

Vermersch, Patrick; Faller, Andreas; Czarnota-Szałkowska, Dominika; Meesen, Bianca; Thalheim, Christoph

2016-08-01

There is currently no known cure for multiple sclerosis (MS). Four stakeholders play a major role in MS: healthcare professionals, regulators, payers and patients. In Europe, patients are represented by the European Multiple Sclerosis Platform (EMSP), which aims to improve MS management and patients' quality of life. The EMSP has recently shown that there are major disparities in Europe in terms of access to care and treatment. Implementing the Code of Good Practice and a standardised MS nurse training may be useful in harmonising MS management across Europe. Additionally, the burden for novel therapeutic options to be approved by regulatory agencies has to decrease in order to provide faster access of treatment to patients. Data collection (e.g. national registers) also appears crucial to help research and shape the most effective policy in each country. Finally, people with MS should get appropriate (financial) support in order to complete their studies and find a job, as their active participation in society requires proper access to education and employment. Moreover, as they are the ones affected by MS, they seem to be best placed to represent themselves and their needs and should be consulted more often during decision-making processes by policy makers, regulators and payers. © The Author(s), 2016.

Metabolic syndrome and psoriasis severity in South-East Asian patients: An investigation of potential association using current and chronological assessments.

PubMed

Chularojanamontri, Leena; Wongpraparut, Chanisada; Silpa-Archa, Narumol; Chaweekulrat, Pichanee

2016-12-01

Although studies regarding prevalence of metabolic syndrome (MS) in Asian psoriatic patients are limited and show varying results, a previous report describes a significant increase in prevalence of MS in Thai psoriatic patients, as compared with rates in the general population. However, no significant association between MS and psoriasis severity using the Psoriasis Area and Severity Index (PASI) was found, which differs from the findings of Korean and Japanese studies. This study aimed at re-evaluating the association between MS and psoriasis severity in Thai patients using current assessment (PASI) and chronological assessment (historical course and interventions). A total of 273 psoriatic patients were recruited. After controlling for age and sex, 96 patients were assigned to the MS group and 96 patients to the non-MS group. Similar to the previous study, no significant differences were identified between metabolic and non-metabolic patients regarding PASI, age of onset, disease duration and family history of psoriasis. However, the numbers of hospitalizations (P = 0.018) and interventions (P = 0.028) were significantly higher in metabolic patients than in non-metabolic patients. Further, a greater number of metabolic components was significantly associated with a higher number of hospitalizations (P = 0.012), pustular or erythrodermic psoriasis episodes (P = 0.049), and interventions (P = 0.005). Body mass index of 23 kg/m 2 or more, abdominal obesity and high blood pressure were associated with an increased risk of treatment failure. Using chronological assessment, our study supported that MS negatively affects psoriasis severity and treatment outcomes. Screening for MS is highly recommended for psoriatic patients. © 2016 Japanese Dermatological Association.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision.

PubMed

Morrison, Cecily; D'Souza, Marcus; Huckvale, Kit; Dorn, Jonas F; Burggraaff, Jessica; Kamm, Christian Philipp; Steinheimer, Saskia Marie; Kontschieder, Peter; Criminisi, Antonio; Uitdehaag, Bernard; Dahlke, Frank; Kappos, Ludwig; Sellen, Abigail

2015-06-24

Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients' level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Perspectives from the Patient and the Healthcare Professional in Multiple Sclerosis: Social Media and Patient Education.

PubMed

Kantor, Daniel; Bright, Jeremy R; Burtchell, Jeri

2018-06-01

A diagnosis of multiple sclerosis (MS) is life-altering. Because the course of MS is heterogeneous, patients may face uncertainty in terms of long-term physical and cognitive challenges, potential loss of employment, and the risk of social isolation. Patients often turn to the Internet and social media for information about MS and its management, and to seek out fellow patients and support groups. Here, we examine the use of social media and the Internet among patients with MS, considering its impact on patient education. We consider the access that these conduits provide not only to other patients with MS but also to a wealth of disease-related information online. These themes are further illustrated with first-hand experiences of the patient author and her physician. We also explore the impact of the Internet and social media on the education and support of patients with MS from the healthcare professional's (HCP's) perspective, including opportunities for HCPs to promote disease education among their patients, and the advantages that arise from patients being better informed about their disease. The rise of the Internet and social media has changed the patient experience, helping patients to support each other, to educate themselves proactively about their condition, and to participate more actively in decisions relating to disease management than perhaps was the case historically. Funding Novartis Pharmaceuticals Corporation.

Islamic fasting and multiple sclerosis

PubMed Central

2014-01-01

Background Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. Discussion In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. Summary These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient. PMID:24655543

Islamic fasting and multiple sclerosis.

PubMed

Jahromi, Soodeh Razeghi; Sahraian, Mohammad Ali; Ashtari, Fereshteh; Ayromlou, Hormoz; Etemadifar, Massoud; Ghaffarpour, Majid; Mohammadianinejad, Ehsan; Nafissi, Shahriar; Nickseresht, Alireza; Shaygannejad, Vahid; Togha, Mansoreh; Torabi, Hamid Reza; Ziaie, Shadi

2014-03-22

Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.

Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

PubMed

Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2016-11-01

Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis.

PubMed

Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen; Olsson, Tomas; Jensen, Poul Erik; Sørensen, Per Soelberg; Sellebjerg, Finn

2013-06-01

The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS. Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased. CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.

"Cure" for multiple sclerosis (MS)-Evolving views of therapy goals in patients on different stages of the disease: A pilot study in a cohort of Polish MS patients.

PubMed

Chacińska, Weronika; Brzostowska, Marta; Nojszewska, Monika; Podlecka-Piętowska, Aleksandra; Jędrzejczak, Wiesław W; Snarski, Emilian

2017-06-01

New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients' acceptance for risks connected with the MS treatment. The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the "cure" for MS and crucial goals in the treatment. One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years ( SD  = 10.29). The MS forms were as follows: relapsing-remitting (65%), secondary progressive (14%), primary progressive (10%), and other (11%), with mean EDSS score of 3 points ( SD  = 2.6). For 50% of the patients, relief of symptoms such as fatigue (72%), paresis (66%), and balance disorders (65%) was synonymous with "cure." The patients with faster progression of the disease were likely to accept risky "curative" treatments-with average 68% accepted mortality risk ( p  = .003). Over 81% of patients accepted mortality rates over 1% for the treatment that achieves self-defined cure. The study shows that the MS patients are likely to accept even very risky treatments as long as they promise patient-defined "cure."

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

PubMed Central

Santos, Antônio Carlos; Lana-Peixoto, Marco Aurélio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antônio; Barreira, Amilton Antunes; Simões, Aguinaldo Luiz

2013-01-01

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. PMID:23527051

The Association Between Major Depressive Disorder and Outcomes in Older Veterans Hospitalized With Pneumonia.

PubMed

DeWaters, Ami L; Chansard, Matthieu; Anzueto, Antonio; Pugh, Mary Jo; Mortensen, Eric M

2018-01-01

Major depressive disorder ("depression") has been identified as an independent risk factor for mortality for many comorbid conditions, including heart failure, cancer and stroke. Major depressive disorder has also been linked to immune suppression by generating a chronic inflammatory state. However, the association between major depression and pneumonia has not been examined. The aim of this study was to examine the association between depression and outcomes, including mortality and intensive care unit admission, in Veterans hospitalized with pneumonia. We conducted a retrospective national study using administrative data of patients hospitalized at any Veterans Administration acute care hospital. We included patients ≥65 years old hospitalized with pneumonia from 2002-2012. Depressed patients were further analyzed based on whether they were receiving medications to treat depression. We used generalized linear mixed effect models to examine the association of depression with the outcomes of interest after controlling for potential confounders. Patients with depression had a significantly higher 90-day mortality (odds ratio 1.12, 95% confidence interval 1.07-1.17) compared to patients without depression. Patients with untreated depression had a significantly higher 30-day (1.11, 1.04-1.20) and 90-day (1.20, 1.13-1.28) mortality, as well as significantly higher intensive care unit admission rates (1.12, 1.03-1.21), compared to patients with treated depression. For older veterans hospitalized with pneumonia, a concurrent diagnosis of major depressive disorder, and especially untreated depression, was associated with higher mortality. This highlights that untreated major depressive disorder is an independent risk factor for mortality for patients with pneumonia. Published by Elsevier Inc.

The relationship between 25-hydroxyvitamin D levels and ambulatory arterial stiffness index in newly diagnosed and never-treated hypertensive patients.

PubMed

Malçok Gürel, Özgül; Bilgiç, Ayşe; Demirçelik, Bora; Özaydin, Meltem; Bozduman, Fadime; Aytürk, Zübeyde; Yilmaz, Hakki; Atar, Asli; Selçoki, Yusuf; Eryonucu, Beyhan

2016-02-01

Vitamin D insufficiency has been shown to be associated with cardiac dysfunctions, such as cardiac hypertrophy and hypertension, in animal studies. Arterial stiffness is a prognostic marker for cardiovascular disease. Previous studies have demonstrated that 25-hydroxyvitamin D [25(OH)D] levels were negatively correlated with arterial stiffness index. The aim of this study was to investigate the relationship between 25(OH)D levels and arterial stiffness, which is evaluated using an ambulatory arterial stiffness index (AASI), in patients who have untreated and newly diagnosed essential hypertension. A total of 123 consecutive patients with newly diagnosed and untreated essential hypertension were included. Patients were divided into two groups according to their 25(OH)D levels. Vitamin D insufficiency was defined by 25(OH)D levels less than 20 ng/ml. All patients were referred for ambulatory blood pressure monitoring. The regression slope of diastolic and systolic blood pressure was computed for each individual on the basis of ambulatory blood pressure readings. AASI was described as one minus the respective regression slope. The mean AASI was significantly higher in patients with 25(OH)D levels less than 20 as compared with patients with 25(OH)D levels greater than or equal to 20 (0.50±0.20 vs. 0.34±0.17, P<0.001). In Pearson's correlation analysis, AASI had a significantly strong negative correlation with vitamin D levels (r=-0.385, P<0.001). In multivariate linear regression analysis, vitamin D levels were found to be significantly and independently associated with AASI (β=-0.317, P=0.035). Arterial stiffness measured by AASI in newly diagnosed and untreated patients with essential hypertension were significantly related to vitamin D levels.

Salivary hormone measurement using LC/MS/MS: specific and patient-friendly tool for assessment of endocrine function.

PubMed

Higashi, Tatsuya

2012-01-01

Saliva has recently been attracting attention as a patient-friendly available bio-fluid and an alternative to serum/plasma for hormone tests. LC coupled with atmospheric pressure ionization-MS/MS, especially electrospray ionization (ESI)-MS/MS, has been recently valued as a highly specific method in the analysis of salivary hormones. In this article, LC/ESI-MS/MS assays for salivary hormones are overviewed according to the papers that have been published during the last 5 years. Practical derivatization to enhance the detectabilities of hormones in ESI-MS/MS is also discussed, because a major disadvantage of using saliva is low hormone concentrations.

The impact of treatment adherence on clinical and economic outcomes in multiple sclerosis: Real world evidence from Alberta, Canada.

PubMed

Gerber, Brittany; Cowling, Tara; Chen, Guanmin; Yeung, Michael; Duquette, Pierre; Haddad, Paola

2017-11-01

Approximately 1 in 400 Albertans has multiple sclerosis (MS). The current study objective was to determine the real-world impact of adherence to disease-modifying therapies (DMTs) on healthcare utilization and costs among MS patients utilizing administrative data from the Alberta health system in Canada. MS patients were identified using a validated case definition (≥ 1 inpatient record or ≥ 5 practitioner claims within 2 years) and the study index DMT was defined as the first claim for a DMT between 1 April 2011 and 31 March 2014. Treatment adherence was calculated using medication possession ratio (MPR), and patients with MPR ≥ 80% were considered adherent; healthcare utilization and costs were explored using multivariable negative binominal regression and logistic regression models. The majority of the 2864 MS patients identified were females, aged 35-55 years old. Overall, 66% of patients were adherent. Compared to non-adherent patients, adherent patients had fewer ambulatory care visits (all-cause: 8.8 vs 10.9, p = 0.0012; MS-related: 4.3 vs 5.3; p = 0.001), physician visits (all-cause: 15.1 vs 18.2, p = 0.0001; MS-related: 3.6 vs 4.4; p = 0.0001), and hospitalizations (all-cause: 5.2% vs 10.2%, p < 0.0001; MS-related: 1.2% vs 2.5%, p = 0.0088). After adjusting for potential confounding factors adherent patients had approximately 20% less physician visits (MS-related: IRR 0.82 (0.79,0.86), p < 0.0001; all-cause: IRR 0.83 (0.81,0.85), p < 0.0001) and ambulatory care visits (MS-related IRR 0.80 (0.77,0.84), p < 0.0001; all-cause: IRR 0.82 (0.80,0.84), p < 0.0001) and approximately 50% fewer hospitalizations (MS-related: OR 0.50 (0.28-0.89), p < 0.0001; all-cause: OR 0.48 (0.35-0.64), p < 0.0001) than non-adherent patients. The current study found a significant impact of non-adherence to MS therapy on increased health system utilization. These findings demonstrate the importance of treatment adherence on clinical decision-making for patients with MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation.

PubMed

Sciarra, Luigi; Golia, Paolo; Palamà, Zefferino; Scarà, Antonio; De Ruvo, Ermenegildo; Borrelli, Alessio; Martino, Anna Maria; Minati, Monia; Fagagnini, Alessandro; Tota, Claudia; De Luca, Lucia; Grieco, Domenico; Delise, Pietro; Calò, Leonardo

Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within -30° and +90°) or LAD (within -30° and -90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Thirty patients (mean age 70.6years; 19 males) were included. Mean left ventricular ejection fraction was 0.28±0.06. Mean QRS duration was 172.5±13.9ms. Fifteen patients showed LBBB with LAD (QRS duration 173±14; EF 0.27±0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172±14; EF 0.29±0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201±46ms, inferior 242±58ms, lateral 267±45ms, anterior 302±50ms; p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228±65ms, inferior 250±64ms, lateral 328±98ms, anterior 291±86ms; p<0.0001). Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

APOE epsilon4 is associated with impaired verbal learning in patients with MS.

PubMed

Koutsis, G; Panas, M; Giogkaraki, E; Potagas, C; Karadima, G; Sfagos, C; Vassilopoulos, D

2007-02-20

To investigate the effect of APOE epsilon4 on different cognitive domains in a population of Greek patients with multiple sclerosis (MS). A total of 125 patients with MS and 43 controls were included in this study and underwent neuropsychological assessment with Rao's Brief Repeatable Battery. All patients with MS were genotyped for APOE. The effect of APOE epsilon4 on different cognitive domains was investigated. Fifty-one percent of patients with MS were cognitively impaired. E4 carriers had a sixfold increase in the relative risk of impairment in verbal learning vs noncarriers (OR 6.28, 95% CI 1.74 to 22.69). This effect was domain-specific and was not observed in other cognitive domains assessed by the battery. We found an association of APOE epsilon4 with impaired verbal learning in patients with multiple sclerosis.

Amylolytic activity of IgM and IgG antibodies from patients with multiple sclerosis.

PubMed

Saveliev, Andrew N; Ivanen, Dina R; Kulminskaya, Anna A; Ershova, Nadezhda A; Kanyshkova, Tat'yana G; Buneva, Valentina N; Mogelnitskii, Alexander S; Doronin, Boris M; Favorova, Olga O; Nevinsky, Georgy A; Neustroev, Kirill N

2003-05-01

IgG and IgM antibodies from the sera of patients with multiple sclerosis (MS) were found to possess amylolytic activity hydrolyzing alpha-(1-->4)-glucosyl linkages of maltooligosaccharides, glycogen, and several artificial substrates. Individual IgM fractions isolated from 54 analyzed patients with the clinically definite diagnoses of MS had approximately three orders of magnitude higher specific amylolytic activity than that for healthy donors, whereas IgG from only a few patients had high amylolytic activity. Strict criteria were used to prove that the amylolytic activity of IgMs and IgGs is their intrinsic property and is not due to any enzyme contamination. Fab fragments produced from IgM and IgG fractions of the MS patients displayed the same amylolytic activity. IgMs from various patients demonstrated different modes of action in hydrolyzing maltooligosaccharides.

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

PubMed Central

Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles

2016-01-01

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

Survival in commercially insured multiple sclerosis patients and comparator subjects in the U.S.

PubMed

Kaufman, D W; Reshef, S; Golub, H L; Peucker, M; Corwin, M J; Goodin, D S; Knappertz, V; Pleimes, D; Cutter, G

2014-05-01

Compare survival in patients with multiple sclerosis (MS) from a U.S. commercial health insurance database with a matched cohort of non-MS subjects. 30,402 MS patients and 89,818 non-MS subjects (comparators) in the OptumInsight Research (OIR) database from 1996 to 2009 were included. An MS diagnosis required at least 3 consecutive months of database reporting, with two or more ICD-9 codes of 340 at least 30 days apart, or the combination of 1 ICD-9-340 code and at least 1 MS disease-modifying treatment (DMT) code. Comparators required the absence of ICD-9-340 and DMT codes throughout database reporting. Up to three comparators were matched to each patient for: age in the year of the first relevant code (index year - at least 3 months of reporting in that year were required); sex; region of residence in the index year. Deaths were ascertained from the National Death Index and the Social Security Administration Death Master File. Subjects not identified as deceased were assumed to be alive through the end of 2009. Annual mortality rates were 899/100,000 among MS patients and 446/100,000 among comparators. Standardized mortality ratios compared to the U.S. population were 1.70 and 0.80, respectively. Kaplan-Meier analysis yielded a median survival from birth that was 6 years lower among MS patients than among comparators. The results show, for the first time in a U.S. population, a survival disadvantage for contemporary MS patients compared to non-MS subjects from the same healthcare system. The 6-year decrement in lifespan parallels a recent report from British Columbia. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells

PubMed Central

Tao, Hou-Quan; Zou, Shou-Chun

2002-01-01

AIM: To study the effects of preoperative regional artery chemotherapy (PRACT) in inducing growth inhibition and apoptosis of gastric carcinoma (GC) cells. METHODS: TUNEL (terminal-deoxynucleotidyl-transferase TdT-mediated dUTP-fluorescein and labeling) method and immunohistochemical techniques were used to detect the state of apoptosis and proliferation of GC cells in histopathologic sections. A total of 110 cases of GC and 68 cases of metastatic lymph node with or without PRACT were adopted. Correlations between apoptosis index (AI), proliferation index (PI) and PRACT and prognosis were analysed. RESULTS: The apoptosis index (AI) was significantly higher in the PRACT group (12.5‰ ± 4.33‰) than in the untreated group (7.1‰ ± 3.43‰, P < 0.001), whereas the proliferation index (PI) in the PRACT group (33.8% ± 8.8%) was significantly lower than that in untreated group (43.6% ± 12.8%, P < 0.01). Both AI and PI were correlated to the differentiation degree of GC in PRACT group, the AI in the differentiated group was higher than that in undifferentiated group (P < 0.001), but the PI was lower in the differentiated group than that of the undifferentiated group (P < 0.01). The AI of GC cells in metastatic lymph node was also significantly higher in the PRACT group (7.9‰ ± 3.41‰) than in the untreated group (3.6‰ ± 2.93‰, P < 0.01), though the PI of GC cells in metastatic lymph nodes in the PRACT group (17.2% ± 6.8%) was significantly lower than that in the untreated group (26.7% ± 9.3%, P < 0.01). The severity of histopathologic changes was significantly higher in the PRACT group than in the untreated group (P < 0.05). In addition, postoperative surveys demonstrated that the 5-year survival rate of GC patients in the PRACT group was significantly higher than that of patients in the untreated group (P < 0.01). CONCLUSION: Preoperative regional artery chemotherapy (PRACT) showed inhibitory action on the growth of GC cells mainly through inhibiting proliferation and inducing the apoptosis of tumor cells. PRACT can improve the prognosis of GC patients also. PMID:12046068

Skeletal, dental and soft tissue changes in Class III patients treated with fixed appliances and lower premolar extractions.

PubMed

Abu Alhaija, Elham S J; Al-Khateeb, Susan N

2011-05-01

Mild Class III malocciusions can be treated by upper incisor proclination and lower incisor retroclination following extraction of the lower first premolars. To compare the skeletal, dental and soft tissue changes in Class III patients treated with fixed appliances, Class III traction and lower first premolar extractions with the changes in a group of untreated Class III patients. The Treatment group consisted of 30 Class III patients (Mean age 13.69 +/- 1.48 years) who were treated by upper and lower fixed appliances, Class III intermaxillary traction and lower first premolar extractions for 2.88 +/- 1.12 years. The Control group consisted of 20 untreated Class III patients (Mean age 13.51 +/- 0.95) matched for age and gender. The T1 to T2 changes in the treated and untreated groups were compared using a paired t-test while differences between the two groups were compared with an independent t-test. During treatment, the upper incisors were proclined about 1 degree and the lower incisors were retroclined 8 degrees. Small, but statistically significant changes in SNB, Wits and the overlying soft tissues accompanied the changes in incisor inclination. At the end of treatment a positive overbite and overjet were achieved. The increase in lower facial height in the Treatment group was comparable with the change in the Control group. A range of mild to moderate Class III malocclusions can be treated by dentoalveolar compensation.

Do Improved Patient Recall and the Provision of Memory Support Enhance Treatment Adherence?

PubMed Central

Dong, Lu; Lee, Jason Y.; Harvey, Allison G.

2017-01-01

Background and Objectives Patient adherence to psychosocial treatment is an important but understudied topic. The aim of this study was to examine whether better patient recall of treatment contents and therapist use of memory support (MS) were associated with better treatment adherence. Methods Data were drawn from a pilot randomized controlled trial. Participants were 48 individuals (mean age = 44.27 years, 29 females) with Major Depressive Disorder randomized to receive either Cognitive Therapy (CT) with an adjunctive Memory Support Intervention (CT+Memory Support) or CT-as-usual. Therapist and patient ratings of treatment adherence were collected during each treatment session. Patient recall was assessed at mid-treatment. Therapist use of MS was manually coded for a random selection of sessions. Results Patient recall was significantly associated with better therapist and patient ratings of adherence. Therapist use of Application, a specific MS strategy, predicted higher therapist ratings of adherence. Attention Recruitment, another specific MS strategy, appeared to attenuate the positive impact of session number on patient ratings of adherence. Treatment groups, MS summary scores and other specific MS strategies were not significantly associated with adherence. Limitations The measure for treatment adherence is in the process of being formally validated. Results were based on small sample. Conclusions These results support the importance of patient recall in treatment adherence. Although collectively the effects of MS on treatment adherence were not significant, the results support the use of certain specific MS strategy (i.e., application) as a potential pathway to improve treatment adherence. Larger-scale studies are needed to further examine these constructs. PMID:27614662

Do improved patient recall and the provision of memory support enhance treatment adherence?

PubMed

Dong, Lu; Lee, Jason Y; Harvey, Allison G

2017-03-01

Patient adherence to psychosocial treatment is an important but understudied topic. The aim of this study was to examine whether better patient recall of treatment contents and therapist use of memory support (MS) were associated with better treatment adherence. Data were drawn from a pilot randomized controlled trial. Participants were 48 individuals (mean age = 44.27 years, 29 females) with Major Depressive Disorder randomized to receive either Cognitive Therapy (CT) with an adjunctive Memory Support Intervention (CT + Memory Support) or CT-as-usual. Therapist and patient ratings of treatment adherence were collected during each treatment session. Patient recall was assessed at mid-treatment. Therapist use of MS was manually coded for a random selection of sessions. Patient recall was significantly associated with better therapist and patient ratings of adherence. Therapist use of Application, a specific MS strategy, predicted higher therapist ratings of adherence. Attention Recruitment, another specific MS strategy, appeared to attenuate the positive impact of session number on patient ratings of adherence. Treatment groups, MS summary scores and other specific MS strategies were not significantly associated with adherence. The measure for treatment adherence is in the process of being formally validated. Results were based on small sample. These results support the importance of patient recall in treatment adherence. Although collectively the effects of MS on treatment adherence were not significant, the results support the use of certain specific MS strategy (i.e., application) as a potential pathway to improve treatment adherence. Larger-scale studies are needed to further examine these constructs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

PubMed

Li, L P H; Shiao, A S; Chen, L F; Niddam, D M; Chang, S Y; Lien, C F; Lee, S K; Hsieh, J C

2006-08-01

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

The Relationship of Carotid Arterial Stiffness and Left Ventricular Concentric Hypertrophy in Hypertension.

PubMed

Jaroch, Joanna; Łoboz-Grudzień, Krystyna; Magda, Stefania; Florescu, Maria; Bociąga, Zbigniew; Ciobanu, Andrea O; Kruszyńska, Ewa; Dudek, Krzysztof; Vinereanu, Dragos

2016-01-01

Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the β stiffness index (β), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVβ) and the wave reflection augmentation index (AI). Univariate analysis showed that the following variables are significant in determining CH: β > 8.4, Ep > 136 kPa, PWVβ > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVβ > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence of systolic blood pressure and diabetes.

Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

PubMed

Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

2017-03-01

In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Challenges in randomized controlled trials and emerging multiple sclerosis therapeutics.

PubMed

Huang, DeRen

2015-12-01

The remarkable global development of disease-modifying therapies (DMTs) specific for multiple sclerosis (MS) has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials (RCTs) for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica (NMO) and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.

Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

PubMed

Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

2015-05-01

Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Obstructive sleep apnea in normal weight patients: characteristics and comparison with overweight and obese patients.

PubMed

Dacal Quintas, Raquel; Tumbeiro Novoa, Manuel; Alves Pérez, María Teresa; Santalla Martínez, Mari Luz; Acuña Fernández, Adela; Marcos Velázquez, Pedro

2013-12-01

To determine the frequency of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) in normal weight patients and their characteristics, and to compare these with overweight and obese patients. We studied all patients with suspected OSA referred to the sleep laboratory from January to December 2009. OSA was diagnosed when the apnoea-hypopnoea index (AHI) was >5 and symptoms were present. MS was diagnosed according to International Diabetes Federation (IDF) criteria. The patients were distributed into 3 groups according to body mass index (BMI): normal weight (<25kg/m(2)), overweight (25-29.9kg/m(2)) and obese (≥30kg/m(2)). We studied 475 patients: 7.60% normal weight and 56.4% obese. Most patients in the normal weight group were women, snorers, non-smokers, non-drinkers and were significantly younger and with a smaller neck and waist circumference than obese and overweight patients. OSA was diagnosed in 90.10%: 77.70% normal weight. OSA in these patients was mostly mild, and there were differences between the diagnosis of OSA and the BMI classified. MS was diagnosed in 64.40%: 33.33% normal weight. There was a higher probability of MS as the BMI increased. OSA and MS frequency in normal weight patients was 22% and in obese patients was 70.52%. OSA in normal weight patients was related with gender and age. There was no relationship between OSA and MS, or between otorhinolaryngological malformations and OSA in normal weight patients. Eight normal weight patients with OSA were treated with continuous positive airway pressure (CPAP) therapy. The frequency of OSA in normal weight patients was lower than in overweight and obese patients. The frequency of concomitant OSA and MS was lower in normal weight patients than in obese subjects. Normal weight patients were mostly women, younger and had no toxic habits. In normal weight patients, age and gender were predictive factors for OSA, but OSA and MS were not related. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Metabonomics study of the therapeutic mechanism of fenugreek galactomannan on diabetic hyperglycemia in rats, by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

PubMed

Jiang, Wenyue; Gao, Lu; Li, Pengdong; Kan, Hong; Qu, Jiale; Men, Lihui; Liu, Zhiqiang; Liu, Zhongying

2017-02-15

Fenugreek is a traditional plant for the treatment of diabetes. Galactomannan, an active major component in fenugreek seeds, has shown hypoglycemic activity. The present study was performed to investigate the therapeutic mechanism underlying fenugreek galactomannan (F-GAL) in treating diabetes, using a metabonomics approach based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The F-GAL used for study was highly purified, and its yield, purity, and galactose/mannose ratio were characterized by capillary zone electrophoresis (CZE) and a modified phenol-sulfuric acid method. After treatment of streptozotocin (STZ)-induced diabetic rats with F-GAL for 28days, urine and serum samples were analyzed by UPLC-QTOF/MS. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish the non-diabetic/untreated, diabetic/untreated, and diabetic/F-GAL-treated groups. Then, potential biomarkers were identified that may help elucidate the underlying therapeutic mechanism of F-GAL in diabetes. The results demonstrated that there was a clear separation among the three groups in the PCA model. Fourteen potential biomarkers were identified by OPLS-DA, and they were determined to be produced in response to the therapeutic effects of F-GAL. These biomarkers were involved in histidine metabolism, tryptophan metabolism, energy metabolism, phenylalanine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. In conclusion, our study demonstrates that a metabonomics approach is a powerful, novel tool that can be used to evaluate the underlying therapeutic mechanisms of herb extracts. Copyright © 2016 Elsevier B.V. All rights reserved.

Profiling modifications for glioblastoma proteome using ultra-tolerant database search: Are the peptide mass shifts biologically relevant or chemically induced?

PubMed

Tarasova, Irina A; Chumakov, Peter M; Moshkovskii, Sergei A; Gorshkov, Mikhail V

2018-05-17

Peptide mass shifts were profiled using ultra-tolerant database search strategy for shotgun proteomics data sets of human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The main objective of this profiling was revealing the cell response to IFN treatment at the level of protein modifications. To achieve this objective, statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples were analyzed. Detailed analysis of MS/MS spectra allowed further interpretation of the observed mass shifts and differentiation between post-translational and artifact modifications. Malignant cells typically acquire increased sensitivity to viruses due to the deregulated antiviral mechanisms. Therefore, a viral therapy is considered as one of the promising approaches to treat cancer. However, recent studies have demonstrated that malignant cells can preserve intact antiviral mechanisms, e.g. interferon signaling, and develop resistance to virus infection in response to interferon treatment. Post translational modifications, e.g. tyrosine phosphorylation, are the interferon signaling drivers. Thus, comprehensive characterization of modifications is crucially important, yet, most challenging problem in cancer proteomics. Here, we report on the application of the recently introduced ultra-tolerant search strategy for profiling peptide modifications in the human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The specific aim of the study was identification of statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples, as well as determination of whether these shifts represent the biologically relevant modification. Copyright © 2018 Elsevier B.V. All rights reserved.

Single chain variable fragment displaying M13 phage library functionalized magnetic microsphere-based protein equalizer for human serum protein analysis.

PubMed

Zhu, Guijie; Zhao, Peng; Deng, Nan; Tao, Dingyin; Sun, Liangliang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

2012-09-18

Single chain variable fragment (scFv) displaying the M13 phage library was covalently immobilized on magnetic microspheres and used as a protein equalizer for the treatment of human serum. First, scFv displaying M13 phage library functionalized magnetic microspheres (scFv@M13@MM) was incubated with a human serum sample. Second, captured proteins on scFv@M13@MM were eluted with 2 M NaCl, 50 mM glycine-hydrochloric acid (Gly-HCl), and 20% (v/v) acetonitrile with 0.5% (v/v) trifluoroacetic acid in sequence. Finally, the tightly bonded proteins were released by the treatment with thrombin. The eluates were first analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with silver staining. Results indicated that the difference of protein concentration was reduced obviously in NaCl and Gly-HCl fractions compared with untreated human serum sample. The eluates were also digested with trypsin, followed by online 2D-strong cation exchange (SCX)-RPLC-ESI-MS/MS analysis. Results demonstrated that the number of proteins identified from an scFv@M13@MM treated human serum sample was improved 100% compared with that from the untreated sample. In addition, the spectral count of 10 high abundance proteins (serum albumin, serotransferrin, α-2-macroglobulin, α-1-antitrypsin, apolipoprotein B-100, Ig γ-2 chain C region, haptoglobin, hemopexin, α-1-acid glycoprotein 1, and α-2-HS-glycoprotein) decreased evidently after scFv@M13@MM treatment. All these results demonstrate that scFv@M13@MM could efficiently remove high-abundance proteins, reduce the protein concentration difference of human serum, and result in more protein identification.

Occurrence and diversity of antibiotic resistance in untreated hospital wastewater.

PubMed

Wang, Qiang; Wang, Panliang; Yang, Qingxiang

2018-04-15

Antibiotics, antibiotic-resistant bacteria (ARB), antibiotic-resistance genes (ARGs), and mobile genetic elements (MGEs) have been reported in many environments. However, the investigation of their occurrence and diversity in untreated hospital wastewater is still insufficient. High concentrations of antibiotic residues were found in hospital wastewater using solid-phase extraction and UPLC-MS/MS analysis. The concentrations of six of 14 antibiotics reached μg/L levels in the hospital wastewater, which is higher than reported in other aquatic environments. Results of high-throughput sequencing analysis indicated that sequences affiliated to genera Escherichia and Acinetobacter were the predominant in the cultivable multiple-antibiotic-resistant bacteria (CMARB) recovered from the wastewater of three hospitals in China, with compositions of 34%-74%. Notably, several genera containing clinically pathogenic or opportunistic CMARB (e.g., Escherichia, Acinetobacter, Aeromonas, Myroides, Enterococcus, Proteus, Pseudomonas, and Streptococcus) were detected at high relative abundances in the wastewaters of the three hospitals. High-capacity quantitative PCR showed that 131-139 unique ARGs of the 178 targeted genes were detected in the hospital wastewaters. The high prevalence of five MGEs and 12 ARGs was confirmed with qPCR, and some positive correlations between ARGs and MGEs were identified, such as between intI1 and qnrD, intI2 and sul3, intI3 and tetX, Tn916/Tn1545 and sul2, and ISCR1 and sul3. These results suggest that highly abundant antibiotic-resistant pathogens and highly mobile ARGs already exist in the human body, and that their release from hospitals without effective treatment poses high risks to environments and human health. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple sclerosis: evaluation of purine nucleotide metabolism in central nervous system in association with serum levels of selected fat-soluble antioxidants.

PubMed

Kuračka, Lubomír; Kalnovičová, Terézia; Kucharská, Jarmila; Turčáni, Peter

2014-01-01

In the pathogenesis of demyelinating diseases including multiple sclerosis (MS) an important role is played by oxidative stress. Increased energy requirements during remyelination of axons and mitochondria failure is one of the causes of axonal degeneration and disability in MS. In this context, we analyzed to what extent the increase in purine catabolism is associated with selected blood lipophilic antioxidants and if there is any association with alterations in serum levels of coenzyme Q10. Blood serum and cerebrospinal fluid (CSF) samples from 42 patients with diagnosed MS and 34 noninflammatory neurologic patients (control group) were analyzed. Compared to control group, MS patients had significantly elevated values of all purine nucleotide metabolites, except adenosine. Serum lipophilic antioxidants γ -tocopherol, β -carotene, and coenzyme Q10 for the vast majority of MS patients were deficient or moved within the border of lower physiological values. Serum levels of TBARS, marker of lipid peroxidation, were increased by 81% in the MS patients. The results indicate that the deficit of lipophilic antioxidants in blood of MS patients may have a negative impact on bioenergetics of reparative remyelinating processes and promote neurodegeneration.

Composition of fatty acids in plasma and erythrocytes and eicosanoids level in patients with metabolic syndrome

PubMed Central

2011-01-01

Background Disturbances of the fatty acids composition in plasma and red blood cells and eicosanoid synthesis play an important role in the metabolic syndrome (MS) formation. Methods The observation group included 61 people with metabolic syndrome (30 patients with MS and normal levels of insulin, 31 people with MS and insulin resistance - IR). The parameters of carbohydrate and lipid metabolism in blood serum were examined. The composition of nonesterified fatty acids (NEFA), fatty acid (FA) of red blood cells lipids was analyzed by gas-liquid chromatography. Eicosanoids level in MS patients blood serum was studied by enzyme immunoassay. Results In MS patients in the absence of glucose-insulin homeostasis disturbances and in patients with IR the accumulation of polyunsaturated fatty acids (18:2 n6, 18:3 n3, 22:4 n6) and lower pool of saturated FA (12:0, 14:0, 16: 0, 17:0) in plasma were discovered. A deficit of polyunsaturated FA (18:3 n3, 20:4 n6) with a predominance of on-saturated FA (14:0, 18:0) in erythrocyte membranes was revealed. In MS patients regardless of the carbohydrate metabolism status high levels of leukotriene B4 and 6-keto-prostaglandin-F1α in serum were found. The development of IR in MS patients leads to increased synthesis of thromboxane A2. Conclusion The results revealed a disturbance in nonesterified fatty acids of plasma lipids and red blood cells, eicosanoid synthesis in MS patients. The breach of the plasma and cell membranes fatty acids compositions, synthesis of vasoactive and proinflammatory eicosanoids is an important pathogenetic part of the MS development. PMID:21595891

P-wave dispersion and maximum duration are independently associated with insulin resistance in metabolic syndrome.

PubMed

Wang, Weiwei; Zhang, Feilong; Xhen, Jianhua; Chen, Xuehai; Fu, Fayuan; Tang, Mirong; Chen, Lianglong

2014-07-01

Metabolic syndrome (MS) is an important risk factor for atrial fibrillation. P-wave indices, including P-wave dispersion (PWD) and P-wave duration, can be used as non-invasive markers of heterogeneous atrial conduction. The aim of our study was to evaluate the relationship between P-wave indices and insulin resistance in patients with MS. Seventy-four patients with MS (44 men, 30 women) and 81 patients without MS (48 men, 33 women) were enrolled in the study. A diagnosis of MS was made as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. P-wave maximum duration (Pmax) and P-wave minimum duration (Pmin) were calculated on a 12-lead electrocardiogram, and the difference between the Pmax and the Pmin was defined as PWD. Patients with MS had a longer PWD and a higher Pmax compared with patients without MS (PWD, 35.65±4.36 vs. 26.27±4.04, P<0.001; Pmax, 117.12±10.77 vs. 105.98±9.02, P<0.001), whereas no difference was found between Pmin values from MS patients and controls (81.47±9.54 vs. 79.70±8.76, P=0.231). Stepwise multivariate analysis revealed only the HOMA index to be an independent predictor of PWD (β=3.115, P<0.001) and Pmax (β=7.175, P<0.001). This study suggests that patients with MS have a prolonged PWD and Pmax. The increase in these parameters may be an indicator for identification of patients at an increased risk for atrial fibrillation. Copyright © 2014. Published by Elsevier Masson SAS.

Healthcare resource use and costs of multiple sclerosis patients in Germany before and during fampridine treatment.

PubMed

Ziemssen, Tjalf; Prosser, Christine; Haas, Jennifer Scarlet; Lee, Andrew; Braun, Sebastian; Landsman-Blumberg, Pamela; Kempel, Angela; Gleißner, Erika; Patel, Sarita; Huang, Ming-Yi

2017-03-27

Multiple sclerosis (MS) patients often suffer from gait impairment and fampridine is indicated to medically improve walking ability in this population. Patient characteristics, healthcare resource use, and costs of MS patients on fampridine treatment for 12 months in Germany were analyzed. A retrospective claims database analysis was conducted including MS patients who initiated fampridine treatment (index date) between July 2011 and December 2013. Continuous insurance enrollment during 12 months pre- and post-index date was required, as was at least 1 additional fampridine prescription in the fourth quarter after the index date. Patient characteristics were evaluated and pre- vs post-index MS-related healthcare utilization and costs were compared. A total of 562 patients were included in this study. The mean (standard deviation [SD]) age was 50.5 (9.8) years and 63% were female. In the treatment period, almost every patient had at least 1 MS-related outpatient visit, 24% were hospitalized due to MS, and 79% utilized MS-specific physical therapy in addition to the fampridine treatment. Total MS-related healthcare costs were significantly higher in the fampridine treatment period than in the period prior to fampridine initiation (€17,392 vs €10,960, P < 0.001). While this difference was driven primarily by prescription costs, MS-related inpatient costs were lower during fampridine treatment (€1,333 vs €1,565, P < 0.001). Physical therapy is mainly used concomitant to fampridine treatment. While healthcare costs were higher during fampridine treatment compared to the pre-treatment period, inpatient costs were lower. Further research is necessary to better understand the fampridine influence.

Differential Changes in QTc Duration during In-Hospital Haloperidol Use

PubMed Central

Blom, Marieke T.; Bardai, Abdennasser; van Munster, Barbara C.; Nieuwland, Mei-Ing; de Jong, Hendrik; van Hoeijen, Daniel A.; Spanjaart, Anne M.; de Boer, Anthonius; de Rooij, Sophia E.; Tan, Hanno L.

2011-01-01

Aims To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. Methods In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. Results Patients with normal before-haloperidol QTc duration (male ≤430 ms, female ≤450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male ≥450 ms, female ≥470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430–450 ms, female 450–470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (ORadj 34.9, p = 0.009) and before-haloperidol QTc duration (ORadj 0.94, p = 0.004). Conclusion QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongation. PMID:21961030

Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis.

PubMed

Wattjes, Mike P; Harzheim, Michael; Lutterbey, Götz G; Bogdanow, Manuela; Schmidt, Stephan; Schild, Hans H; Träber, Frank

2008-02-01

The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS.

Memory Support Strategies and Bundles: A Pathway to Improving Cognitive Therapy for Depression?

PubMed Central

Dong, Lu; Lee, Jason Y.; Harvey, Allison G.

2017-01-01

Objective Therapist use of memory support (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of treatment contents, has been of recent interest as a novel pathway to improve treatment outcome. The Memory Support Intervention involves treatment providers’ using eight specific MS strategies to promote patient memory for treatment. The present study examines to what extent therapist use of MS strategies and bundles improves patient recall of treatment contents and treatment outcome. Methods The data were drawn from a pilot randomized controlled trial reported elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with major depressive disorder (MDD), randomized to receive 14 sessions of either CT+Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded using the Memory Support Rating Scale. Patient memory and treatment outcomes were assessed at baseline, mid-treatment (patient recall only), post-treatment, and 6-month follow-up. Results Participants in CT+Memory Support received significantly higher amount of MS relative to CT-as-usual. Though not reaching statistical significance, small-to-medium effects were observed between MS strategies and patient recall in the expected direction. Although MS variables were not significantly associated with changes in continuous depressive symptoms, MS was associated with better global functioning. MS also exhibited small to medium effects on treatment response and recurrence in the expected direction but not on remission, though these effects did not reach statistical significance. Conclusions These results provide initial empirical evidence supporting an active method for therapists to implement MS strategies. PMID:28221056

Memory support strategies and bundles: A pathway to improving cognitive therapy for depression?

PubMed

Dong, Lu; Lee, Jason Y; Harvey, Allison G

2017-03-01

Therapist use of memory support (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of treatment contents, has been of recent interest as a novel pathway to improve treatment outcome. The memory support intervention (MSI) involves treatment providers' using 8 specific MS strategies to promote patient memory for treatment. The present study examines to what extent therapist use of MS strategies and bundles improves patient recall of treatment contents and treatment outcome. The data were drawn from a pilot RCT reported elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with major depressive disorder (MDD), randomized to receive 14 sessions of either CT + Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded using the Memory Support Rating Scale. Patient memory and treatment outcomes were assessed at baseline, midtreatment (patient recall only), posttreatment, and 6-month follow-up. Participants in CT + Memory Support received significantly higher amount of MS relative to CT-as-usual. Although not reaching statistical significance, small-to-medium effects were observed between MS strategies and patient recall in the expected direction. Although MS variables were not significantly associated with changes in continuous depressive symptoms, MS was associated with better global functioning. MS also exhibited small to medium effects on treatment response and recurrence in the expected direction but not on remission, though these effects did not reach statistical significance. These results provide initial empirical evidence supporting an active method for therapists to implement MS strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A comparison between the pathophysiology of multiple sclerosis and normal pressure hydrocephalus: is pulse wave encephalopathy a component of MS?

PubMed

Bateman, Grant A; Lechner-Scott, Jeannette; Lea, Rodney A

2016-09-22

It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matter. Limited data exists indicating there is an alteration in pulse wave propagation within the craniospinal cavity in MS, similar to the findings in normal pressure hydrocephalus (NPH). It is hypothesized MS may harbor pulse wave encephalopathy. The purpose of this study is to compare blood flow and pulse wave measurements in MS patients with a cohort of NPH patients and control subjects, to test this hypothesis. Twenty patients with MS underwent magnetic resonance (MR) flow quantification techniques. Mean blood flow and stroke volume were measured in the arterial inflow and venous out flow from the sagittal (SSS) and straight sinus (ST). The arteriovenous delay (AVD) was defined. The results were compared with both age-matched controls and NPH patients. In MS there was a 35 % reduction in arteriovenous delay and a 5 % reduction in the percentage of the arterial inflow returning via the sagittal sinus compared to age matched controls. There was an alteration in pulse wave propagation, with a 26 % increase in arterial stroke volume but 30 % reduction in SSS and ST stroke volume. The AVD and blood flow changes were in the same direction to those of NPH patients. There are blood flow and pulsation propagation changes in MS patients which are similar to those of NPH patients. The findings would be consistent with an underlying pulse wave encephalopathy component in MS.

Abundant extracellular myelin in the meninges of patients with multiple sclerosis.

PubMed

Kooi, E-J; van Horssen, J; Witte, M E; Amor, S; Bø, L; Dijkstra, C D; van der Valk, P; Geurts, J J G

2009-06-01

In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. Formalin-fixed brain tissue containing meninges from 29 MS patients, 9 non-neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double-labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non-neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.

Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

ClinicalTrials.gov

2016-05-18

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction

PubMed Central

Jimenez-Balderas, F Javier; Tapia-Serrano, Rosario; Fonseca, M Eugenia; Arellano, Jorge; Beltran, Arturo; Yañez, Patricia; Camargo-Coronel, Adolfo; Fraga, Antonio

2001-01-01

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels. PMID:11714390

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis.

PubMed

Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

2018-01-01

This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion.

Development and pilot phase of a European MS register.

PubMed

Flachenecker, Peter; Khil, Laura; Bergmann, Sverrir; Kowalewski, Mariusz; Pascu, Ion; Pérez-Miralles, Francisco; Sastre-Garriga, Jaume; Zwingers, Thomas

2010-10-01

The MS-ID (Multiple Sclerosis Information Dividend) project was initiated by the European Multiple Sclerosis Platform (EMSP) in 2007 in order to identify and address major inequalities of MS treatment and care and thus eliminate disparities across the EU. One major approach to reach these goals in the longer term is the implementation of a European MS register for MS. The feasibility of an EU MS register was piloted among five countries (Germany, Iceland, Poland, Romania and Spain). Each country liaised with one documentation centre. Countries and test centres were both chosen in a way that a heterogeneous health care structure was provided. After reaching consensus about the data set, comprehension and acceptability of the two questionnaires-representing both the physician's and the patient's perspective-were tested with 20 MS patients in each country. In a 6-month data collection period, data from 547 patients were recorded. Most sections of the questionnaires were available for more than 90% of patients. The results obtained from the pilot phase of the European MS register indicate that it is feasible to collect standardized data across Europe. Thus, the European MS register may be a valuable instrument to compare treatment and care of MS across countries, estimate the cost of MS in Europe and monitor the implementation of and adherence to guidelines. It may help to reduce the disparities in MS care and treatment throughout Europe and eventually improve the quality of life of people with MS.

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.

PubMed

Guthrie, T C; Nelson, D A

1995-03-01

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures. Over 80% of MS patients develop a panoply of neurological signs during hyperthermia, 60% of which are "new" to that patient. The literature contains a number of unexplained paradoxical responses of MS patients during induced hyperthermia. These challenge the current hypothesis that, in MS, hyperthermia induces a heat-linked neuro-blockade of partially demyelinated axons. Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending. Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent neurological deficits after hyperthermia. The etiology of HR may be multifactorial. This includes heat itself, effects of serum calcium, blockade of ion channels, circulatory changes, heat shock proteins, and unidentified humoral substances. Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of demyelination.

On the role of the amygdala for experiencing fatigue in patients with multiple sclerosis.

PubMed

Hanken, Katrin; Francis, Yoselin; Kastrup, Andreas; Eling, Paul; Klein, Jan; Hildebrandt, Helmut

2018-02-01

Recently, we proposed a model explaining the origin of fatigue in multiple sclerosis (MS) patients. This model assumes that the feeling of fatigue results from inflammation-induced information processing within interoceptive brain areas. To investigate the association between self-reported cognitive fatigue and structural integrity of interoceptive brain areas in MS patients. 95 MS patients and 28 healthy controls participated in this study. All participants underwent diffusion tensor MRI and fractional anisotropy data were calculated for the amygdala, the stria terminalis and the corpus callosum, a non-interoceptive brain area. Based on the cognitive fatigue score of the Fatigue Scale for Motor and Cognition, patients were divided into moderately cognitively fatigued (cognitive fatigue score ≥ 28) and cognitively non-fatigued (cognitive fatigue score < 28) MS patients. Healthy controls were recruited as a third group. Repeated measures analyses of covariance, controlling for age, depression and brain atrophy, were performed to investigate whether the factor Group had a significant effect on the fractional anisotropy data. A significant effect of Group was observed for the amygdala (F = 3.389, p = 0.037). MS patients without cognitive fatigue presented lower values of the amygdala than MS patients with cognitive fatigue and healthy controls. For the stria terminalis and the corpus callosum, no main effect of Group was observed. The structural integrity of the amygdala in non-fatigued MS patients appears to be reduced. According to our model this might indicate that the absence of fatigue in non-fatigued MS patients might result from disturbed inflammation-induced information processing in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome.

PubMed

Huss, André M; Halbgebauer, Steffen; Öckl, Patrick; Trebst, Corinna; Spreer, Annette; Borisow, Nadja; Harrer, Andrea; Brecht, Isabel; Balint, Bettina; Stich, Oliver; Schlegel, Sabine; Retzlaff, Nele; Winkelmann, Alexander; Roesler, Romy; Lauda, Florian; Yildiz, Özlem; Voß, Elke; Muche, Rainer; Rauer, Sebastian; Bergh, Florian Then; Otto, Markus; Paul, Friedemann; Wildemann, Brigitte; Kraus, Jörg; Ruprecht, Klemens; Stangel, Martin; Buttmann, Mathias; Zettl, Uwe K; Tumani, Hayrettin

2016-12-01

The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.

Correlation between chronotropic incompetence and metabolic equivalents in patients with type 2 diabetes mellitus and concomitant metabolic syndrome.

PubMed

Gao, M; Chen, W; Gong, Z K; Han, L; Zhang, L

2015-09-01

The aim of the study was to examine the relationship between chronotropic incompetence and motor ability in patient with type 2 diabetes mellitus and concomitant metabolic syndrome (MS) in order to facilitate exercise prescriptions for these patients. A total of 120 patients with type 2 diabetes mellitus were randomly enrolled and divided into study groups with (N.=64) or without MS (N.=56). All patients completed the electrocardiographic exercise testing, after which ratio of heart rate (rHR) and heart rate reserve (HRR) were calculating to assess chronotropic incompetence. In addition, maximum metabolic equivalents (maxMETs) were calculated to assess the motor ability. The MS group had significantly higher indicators of chronotropic incompetence (rHR and HRR) as well as maxMETs than patients without MS (all P<0.05). Further, maxMETs significantly correlated with rHR (r=0.81, P=0.003) and HRR (r=0.78, P<0.001). Patients with type 2 diabetes mellitus and concomitant MS have higher chronotropic incompetence and maxMETs compared with those without MS. METs or perceived level of exertion can be used in patients in whom heart rate is not available during the exercise.

Growth of Untreated Unruptured Small-sized Aneurysms (≺7mm): Incidence and Related Factors.

PubMed

Choi, Hyun Ho; Cho, Young Dae; Jeon, Jin Pyeong; Yoo, Dong Hyun; Moon, Jusun; Lee, Jeongjun; Kang, Hyun-Seung; Cho, Won-Sang; Kim, Jeong Eun; Zhang, Li; Han, Moon Hee

2018-06-01

The need to treat small (<7 mm) unruptured aneurysms is still controversial, despite data collected through several large cohort studies. Such lesions typically are incidental findings, usually followed for potential growth through serial imaging. For this study, growth estimates for untreated unruptured small-sized aneurysms were generated, examining incidence and related risk factors. A cohort of 135 consecutive patients harboring 173 untreated unruptured small-sized aneurysms (<7 mm) was subjected to extended monitoring (mean, 73.1 ± 30.0 months). Growth was defined as a 1-mm increase at minimum in one or more aneurysmal dimensions or as a significant change in shape. Medical records and radiological data were reviewed. Cumulative growth rate and related risk factors were analyzed via Cox proportional hazards regression and Kaplan-Meier product-limit estimator. A total of 28 aneurysms (16.2%) displayed growth during continued surveillance (1054.1 aneurysm-years). The annual growth rate was 2.65% per aneurysm-year, with 15 surfacing within 60 months and 13 after 60 months. Multivariate analysis indicated that bifurcation type was the sole significant risk factor (hazard ratio HR = 7.64; p < 0.001) in terms of growth. Cumulative survival rates without growth were significantly lower in subjects with bifurcation aneurysms than with side-wall aneurysms (p < 0.001). During the follow-up period, one patient suffered a subarachnoid hemorrhage and then aneurysm growth was detected. Most (83.8%) untreated unruptured small-sized aneurysms (<7 mm) remained stable and devoid of growth in long-term follow-up. Because bifurcation aneurysms were prone to eventual growth, careful long-term monitoring at regular intervals is advised if left untreated.

The efficacy of targeted health agents education to reduce the duration of untreated psychosis in a rural population.

PubMed

Padilla, Eduardo; Molina, Juan; Kamis, Danielle; Calvo, Maria; Stratton, Lee; Strejilevich, Sergio; Aleman, Gabriela Gonzalez; Guerrero, Gonzalo; Bourdieu, Mercedes; Conesa, Horacio A; Escobar, Javier I; de Erausquin, Gabriel A

2015-02-01

The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

PubMed

Kim, Bo Eun; Koh, Kyung-Nam; Suh, Jin Kyung; Im, Ho Joon; Song, Joon Sup; Lee, Ji Won; Kang, Hyoung Jin; Park, Kyung Duck; Shin, Hee Young; Choi, Hyoung Soo; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Jung, Hye Lim; Chung, Nak-Gyun; Cho, Bin; Kim, Hack Ki; Lyu, Chuhl Joo; Baek, Hee Jo; Kook, Hoon; Park, Jun Eun; Park, Hyeon Jin; Park, Byung-Kiu; Yoo, Eun Sun; Ryu, Kyung Ha; Lee, Kun Soo; Kim, Heung Sik; Lee, Jae Min; Park, Eun Sil; Yoon, Hoi Soo; Lee, Kwang Chul; Lee, Mee Jeong; Lim, Young Tak; Kim, Hwang Min; Park, Sang Kyu; Park, Jeong-A; Kim, Soon Ki; Park, Meerim; Lim, Yeon-Jung; Lee, Young Ho; Seo, Jong Jin

2014-03-01

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

The most important psychological and psychosocial needs of Polish multiple sclerosis patients and their significant others.

PubMed

Potemkowski, Andrzej; Brola, Waldemar; Ratajczak, Anna; Ratajczak, Marcin; Kowalewski, Mariusz; Lewita, Małgorzata; Kapica-Topczewska, Katarzyna; Tarasiuk, Joanna; Stępień, Adam; Gocyła-Dudar, Katarzyna; Zaborski, Jacek; Bartosik-Psujek, Halina

2017-01-01

People with multiple sclerosis (MS) and their relatives often have multiple, complex needs which require support from a wide range of services. The aim of the study, the first of its kind in Poland, was to identify the most important needs of patients with MS and their significant others (SO). A questionnaire developed from focus groups consisting of 20 needs-related statements was administered in seven MS centers to 573 MS patients and 220 SO. The mean age of the patients was 42.61 years old; the mean MS duration was 9.43 years. The respondents were asked to rate the needs statements according to their importance on an 11-point scale. The questionnaire was similar for the MS patients and their SO. The most important needs in the patient group were: to feel needed and efficient in life; to have easy access to professional rehabilitation; and to be sure that doctors are interested in my condition. The three most important needs in the SO group were: to know that relatives/friends feel needed and efficient in life; to have good living conditions; and to be sure that doctors are interested in my relative's/friend's condition. Correlation analysis revealed that in the patients group, there was a positive correlation between patient's age and the importance of factors such as the need for support and interest in their disease from the family doctor ( P <0.004), receiving educational materials from an MS clinic ( P <0.011), interest from the clinic in life issues of the patient ( P <0.001), and the need for access to self-rehabilitation ( P <0.003); while the need to continue working part-time was inversely correlated with age ( P <0.009). The needs of the MS patients and SO were similar. The data validate the importance of interdisciplinary care for the MS population.

Factors affecting bone mineral density in multiple sclerosis patients

PubMed Central

Ayatollahi, Azin; Mohajeri-Tehrani, Mohammad Reza

2013-01-01

Background Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD). Methods 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years) participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA). The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS). The patient's quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29). Results Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI) of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs) pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001), but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL), disease duration and BMD of both site. Conclusion As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients’ treatment protocols. PMID:24250892

Identification of avocado (Persea americana) pulp proteins by nano-LC-MS/MS via combinatorial peptide ligand libraries.

PubMed

Esteve, Clara; D'Amato, Alfonsina; Marina, María Luisa; García, María Concepción; Righetti, Pier Giorgio

2012-09-01

Avocado (Persea americana) proteins have been scarcely studied despite their importance, especially in food related allergies. The proteome of avocado pulp was explored in depth by extracting proteins with capture by combinatorial peptide ligand libraries at pH 7.4 and under conditions mimicking reverse-phase capture at pH 2.2. The total number of unique gene products identified amounts to 1012 proteins, of which 174 are in common with the control, untreated sample, 190 are present only in the control and 648 represent the new species detected via combinatorial peptide ligand libraries of all combined eluates and likely represent low-abundance proteins. Among the 1012 proteins, it was possible to identify the already known avocado allergen Pers a 1 and different proteins susceptible to be allergens such as a profilin, a polygalacturonase, a thaumatin-like protein, a glucanase, and an isoflavone reductase like protein. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry using Poly(dimethylsiloxane) Microchips with Monolithically Integrated Emitters

PubMed Central

Sun, Xuefei; Kelly, Ryan T.; Tang, Keqi; Smith, Richard D.

2010-01-01

Summary Poly(dimethylsiloxane) (PDMS) is a widely used substrate for microfluidic devices, as it enables facile fabrication and has other distinctive properties. However, for applications requiring highly sensitive nanoelectrospray ionization mass spectrometry (nanoESI-MS) detection, the use of PDMS microdevices has been hindered by a large chemical background in the mass spectra that originates from the leaching of uncross-linked oligomers and other contaminants from the substrate. A more general challenge is that microfluidic devices containing monolithically integrated electrospray emitters are frequently unable to operate stably in the nanoflow regime where the best sensitivity is achieved. In this report, we extracted the contaminants from PDMS substrates using a series of solvents, eliminating the background observed when untreated PDMS microchips are used for nanoESI-MS, such that peptides at concentrations of 1 nM were readily detected. Optimization of the integrated emitter geometry enabled stable operation at flow rates as low as 10 nL/min. PMID:20617264

The effect of exogenous 24-epibrassinolide on the ecdysteroid content in the leaves of Spinacia oleracea L.

PubMed

Kamlar, Marek; Rothova, Olga; Salajkova, Sarka; Tarkowska, Dana; Drasar, Pavel; Kocova, Marie; Harmatha, Juraj; Hola, Dana; Kohout, Ladislav; Macek, Tomas

2015-05-01

The aim of this study was to show whether/how the application of exogenous 24-epibrassinolide can affect the content of ecdysteroids in spinach leaves. Brassinosteroids and ecdysteroids, structurally related phytosterols, show effect on a range of processes in plants. Brassinosteroids increase biomass yield in some species, photosynthesis and resistance to stress, and ecdysteroids show effect on proteins responsible for binding of CO2 or water cleavage. The mutual interaction of these sterols in plants is unclear. The UPLC-(+)ESI-MS/MS analyses of extracts of treated and untreated spinach (Spinacia oleracea L.) leaves show that the application of exogenous 24-epibrassinolide does influence the ecdysteroid content in plant tissues. The response differs for the major ecdysteroids and also differs from that for the minor ones and is dependent on the developmental stage of the leaves within the same plant or the 24-epibrassinolide concentration applied. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC.

PubMed

Hu, Jianxia; Liu, Xiaoyi; Chi, Jingwei; Che, Kui; Feng, Yan; Zhao, Shihua; Wang, Zhongchao; Wang, Yangang

2018-01-01

Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (P< 0.01). The expression levels of IGF-1 and ERK in MS patients with CRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (P< 0.01). Expression levels of ERK, IGF-1, GLUT4 were associated with clinical characteristics of CRC, including tumor size, distant metastasis and advanced stages (III/IV) (P< 0.05). Expressions of IGF-1, ERK and GLUT4 in greater omental adipose tissues might be useful biomarkers and predictive targets in the diagnosis of CRC.

Short-term, high-dose glucocorticoid treatment does not contribute to reduced bone mineral density in patients with multiple sclerosis.

PubMed

Olsson, A; Oturai, D B; Sørensen, P S; Oturai, P S; Oturai, A B

2015-10-01

Patients with multiple sclerosis (MS) are at increased risk of reduced bone mineral density (BMD). A contributing factor might be treatment with high-dose glucocorticoids (GCs). The objective of this paper is to assess bone mass in patients with MS and evaluate the importance of short-term, high-dose GC treatment and other risk factors that affect BMD in patients with MS. A total of 260 patients with MS received short-term high-dose GC treatment and had their BMD measured by dual x-ray absorptiometry. BMD was compared to a healthy age-matched reference population (Z-scores). Data regarding GCs, age, body mass index (BMI), serum 25(OH)D, disease duration and severity were collected retrospectively and analysed in a multiple linear regression analysis to evaluate the association between each risk factor and BMD. Osteopenia was present in 38% and osteoporosis in 7% of the study population. Mean Z-score was significantly below zero, indicating a decreased BMD in our MS patients. Multiple linear regression analysis showed no significant association between GCs and BMD. In contrast, age, BMI and disease severity were independently associated with both lumbar and femoral BMD. Reduced BMD was prevalent in patients with MS. GC treatment appears not to be the primary underlying cause of secondary osteoporosis in MS patients. © The Author(s), 2015.

Prevalence and Outcomes of Mitral Stenosis in Patients Undergoing Transcatheter Aortic Valve Replacement: Findings From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry.

PubMed

Joseph, Lee; Bashir, Mohammad; Xiang, Qun; Yerokun, Babatunde A; Matsouaka, Roland Albert; Vemulapalli, Sreekanth; Kapadia, Samir; Cigarroa, Joaquin E; Zahr, Firas

2018-04-09

This study sought to examine the prevalence of mitral stenosis (MS) and its impact on in-hospital and 1-year clinical outcomes among patients undergoing transcatheter aortic valve replacement (TAVR). Patients with coexisting severe aortic stenosis and MS are increasingly being considered for TAVR. The study cohort included 44,755 patients (age ≥18 years) who underwent TAVR during November 1, 2011, to September 30, 2015, and were registered in Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies (TVT) Registry. One-year outcomes were assessed by linking TVT registry data of this cohort to patient-specific Centers for Medicare & Medicaid Services administrative claims data (n = 31,453). The primary outcome was the composite of death, stroke, heart failure-related hospitalization, and mitral valve intervention at 1 year. MS was present in 11.6% of cohort (mean age, 82 years; 52% males), being severe in 2.7%. Severe MS was associated with higher in-hospital mortality rates (5.6% vs. 3.9% for nonsevere MS and 4.1% for no MS; p = 0.02). In contrast to those without MS, severe MS group had significantly higher risk for the primary outcome, mortality (1 year), and heart failure-related hospitalization (1 year) (adjusted hazard ratio: 1.2 [95% confidence interval (CI): 1.1 to 1.4], 1.2 [95% CI: 1.0 to 1.4], and 1.3 [95% CI: 1.1 to 1.5], respectively; p < 0.05 for all). Approximately one-tenth of patients undergoing TAVR have concomitant MS. Severe MS is an independent predictor of 1-year adverse clinical outcomes following TAVR. The higher risk for long-term adverse events must be considered when evaluating patients with combined aortic stenosis and MS for TAVR. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome after radical gastrectomy.

PubMed

Sun, Li; Zhou, Pingping; Hua, Qingli; Jin, Changming; Guo, Chunling; Song, Bing

2018-06-01

This study aimed to investigate the effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome (MS) after radical gastrectomy. A total of 150 patients with gastric cancer, who were treated in Daqing Longnan Hospital from November, 2015 to May, 2017, were enrolled in this study. The patients were divided into the MS group (80 cases) and non-MS group (70 cases). Patients in the MS group were given corresponding drugs to control blood pressure, blood lipids and blood glucose, while patients in the non-MS group were not treated with those drugs. Patients in the MS group were divided into the normal and abnormal groups according to the levels of blood glucose, blood lipids and blood pressure. Moreover, occurrences of complications were compared between the normal and abnormal groups. Before surgery, blood glucose, blood lipids and blood pressure in the MS group were significantly higher than those in the non-MS group (p<0.05). One month after operation, blood glucose, blood lipids and blood pressure of the MS group decreased significantly compared to those before operation (p<0.05). Incidence of complications at 1 and 3 months after operation was significantly lower in the normal groups than that in the corresponding abnormal groups (p<0.05). Postoperative recovery was significantly better in the normal groups than that in the corresponding abnormal groups (p<0.05). Logistic regression analysis showed that the incidence of postoperative complications was related to fasting blood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin, total triglycerides (TGs), LDL, mean blood pressure and BMI (p<0.05). The results show that, control of blood glucose, blood lipids and blood pressure in patients with gastric cancer complicated with MS after radical gastrectomy can reduce the incidence of postoperative complications and promote postoperative recovery.

Assessment of atrial electromechanical delay and P-wave dispersion in patients with psoriasis.

PubMed

Yildiz, Abdulkadir; Ucmak, Derya; Oylumlu, Mustafa; Akkurt, Meltem Z; Yuksel, Murat; Akil, Mehmet Ata; Acet, Halit; Polat, Nihat; Aydin, Mesut; Bilik, M Zihni

2014-10-01

In this study, we sought to evaluate atrial electromechanical properties and conduction homogeneity by tissue Doppler imaging and electrocardiography in patients with psoriasis. Thirty-four patients with psoriasis and 30 age- and gender-matched healthy controls were included in the study. Atrial electromechanical coupling intervals were assessed by means of tissue Doppler echocardiography and P-wave dispersion (Pd) was calculated from electrocardiogram. A total of 64 subjects (33 male) with a mean age of 36.8 ± 11.9 years were included in the study. Basal characteristics were similar between 2 groups. Intra-atrial (15 ± 7 ms vs. 12 ± 5 ms, P = 0.009) and inter-atrial (28 ± 7 ms vs. 23 ± 7 ms, P = 0.002) electromechanical delays were significantly higher in patients with psoriasis compared with control groups. P-maximum (112 ± 16 ms vs. 103 ± 8 ms, P = 0.006) and Pd (35 ± 9 ms vs. 20 ± 6 ms, P < 0.001) were also prolonged in patients with psoriasis. This study demonstrated that atrial electromechanical coupling intervals and P-wave dispersion were prolonged in patients with psoriasis, which may cause an increased risk of atrial fibrillation in this patient group. © 2014, Wiley Periodicals, Inc.

Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea.

PubMed

Barceló, A; Piérola, J; de la Peña, M; Esquinas, C; Fuster, A; Sanchez-de-la-Torre, M; Carrera, M; Alonso-Fernandez, A; Ladaria, A; Bosch, M; Barbé, F

2011-06-01

Obesity and metabolic syndrome (MS) occur frequently in patients with obstructive sleep apnoea syndrome (OSAS). We hypothesised that circulating free fatty acids (FFAs) are elevated in OSAS patients independently of obesity. This elevation may contribute to the development of MS in these patients. We studied 119 OSAS patients and 119 controls. Participants were recruited and studied at sleep unit of our institution (Hospital Universitari Son Dureta, Palma de Mallorca, Spain) and were matched for sex, age and body mass index (BMI). The occurrence of MS was analysed by clinical criteria. Serum levels of FFAs, glucose, triglycerides, cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, C-reactive protein and 8-isoprostanes were determined. Prevalence of MS was higher in OSAS than in the control group (38 versus 21%; p=0.006). OSAS patients had higher FFAs levels than controls (mean±sd 12.2±4.9 versus 10.5±5.0 mg·dL(-1); p=0.015). Among subjects without MS, OSAS patients (OSAS+ MS-) showed higher levels of FFAs than controls (OSAS- MS-) (11.6±4.7 versus 10.0±4.4 mg·dL(-1); p=0.04). In a multiple regression model, after adjustment for age, sex, BMI and the presence of MS, FFAs were significantly associated with apnoea/hypopnoea index (p=0.04). This study shows that FFAs are elevated in OSAS and could be one of the mechanisms involved in the metabolic complications of OSAS.

Expiratory and phonation times as measures of disease severity in patients with Multiple Sclerosis. A case-control study.

PubMed

Nordio, Sara; Bernitsas, Evanthia; Meneghello, Francesca; Palmer, Katie; Stabile, Maria Rosaria; Dipietro, Laura; Di Stadio, Arianna

2018-04-21

Speech disorders are common in patients with Multiple Sclerosis (MS). They can be assessed with several methods, which are however expensive, complex, and not easily accessible to physicians during routine clinic visits. This study aimed at measuring maximum phonation times, maximum expiratory times, and articulation abilities scores in patients with MS compared to healthy subjects and at investigating if any of these parameters could be used as a measure of MS progression. 50 MS patients and 50 gender- and age-matched healthy controls were enrolled in the study. Maximum expiratory times and maximum phonation times were collected from both groups. Articulation abilities were evaluated using the articulation subtest from the Fussi assessment (dysarthria scores). MS patients were evaluated with the Expanded Disability Status Scale (EDSS). Correlations between EDSS scores and maximum expiratory times, maximum phonation times, and dysarthria scores were calculated. EDSS scores of MS patients ranged from 4.5 to 7.5. In MS patients, maximum expiratory times, maximum phonation times, and dysarthria scores were significantly altered compared to healthy controls. Moreover, the EDSS scores were correlated with the maximum expiratory times; the maximum expiratory times were correlated with the maximum phonation times, and the maximum phonation times were correlated with the dysarthria scores. As the expiratory times were significantly correlated with the EDSS scores, they could be used to measure the severity of MS and to monitor its progression. Copyright © 2018 Elsevier B.V. All rights reserved.

The MS Choices Survey: findings of a study assessing physician and patient perspectives on living with and managing multiple sclerosis

PubMed Central

Riñon, Alberto; Buch, Mandy; Holley, Derek; Verdun, Elisabetta

2011-01-01

Background Treatment of multiple sclerosis (MS) with disease-modifying drugs (DMDs) can reduce relapse frequency and delay disability progression. Although adherence to DMDs is difficult to measure accurately, evidence suggests that poor adherence is common and can compromise treatment success. There are likely to be multiple factors underlying poor adherence. To better understand these factors, the global MS Choices Survey investigated patient and physician perspectives regarding key aspects of MS diagnosis, treatment adherence and persistence, and disease management. Methods The survey was conducted in seven countries and involved patients with MS (age 18–60 years; MS diagnosis for ≥1 year; current treatment with a DMD) and physicians (neurologist for 3–30 years; treating ≥15 patients with MS per average month; >60% of time spent in clinical practice). Separate questionnaires were used for physicians and patients, each containing approximately 30 questions. Results Questionnaires were completed by 331 patients and 280 physicians. Several differences were observed between the responses of patients and physicians, particularly for questions relating to treatment adherence. Overall, the proportion of patients reporting taking a treatment break (31%) was almost twice that estimated by physicians (on average 17%). The reasons cited for poor adherence also differed between patients and physicians. For example, more physicians cited side effects as the main reason for poor patient adherence (82%), than responding patients (42%). Conclusions Physicians may underestimate the scale of poor adherence to DMDs, which could impact on their assessment of treatment efficacy and result in inappropriate treatment escalation. In addition, disparities were identified between patient and physician responses regarding the underlying reasons for poor adherence. Improvements in the dialog between patients and neurologists may increase adherence to DMDs. PMID:22259240

Multiple sclerosis in pregnancy: prevalence, sociodemographic features, and obstetrical outcomes.

PubMed

Fong, Alex; Chau, Cindy T; Quant, Cara; Duffy, Jennifer; Pan, Deyu; Ogunyemi, Dotun A

2018-02-01

We sought to describe the prevalence, sociodemographic features, and antenatal/peripartum outcomes of multiple sclerosis (MS) in pregnancy. A retrospective cohort study was performed using deliveries in California from 2001 to 2009. Cases of MS as well as other morbidities were identified via ICD-9-CM code. Logistic regression was performed to adjust for potential confounders. About 1185 out of 4,424,049 deliveries were complicated by MS. MS prevalence increased with maternal age, with Caucasians comprising a higher proportion of MS subjects. MS subjects were older and more likely to have private insurance. Women with MS were more likely to have preexisting medical conditions such as asthma, chronic hypertension, thyroid disease, or cardiac disease. However, no significant antepartum and peripartum morbidities were found to be increased in patients with MS. Urinary tract infection, cesarean delivery, and induction of labor were slightly increased in MS patients. MS is a rare condition which is more likely to affect older Caucasian women of higher socioeconomic status and is associated with several preexisting medical conditions. MS, however, does not appear to pose significant increases in adverse pregnancy outcome. This suggests that pregnant patients with MS may likely experience an uneventful pregnancy.

Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population.

PubMed

Lin, Na; Ye, Jun; Qiu, Wenjuan; Han, Lianshu; Zhang, Huiwen; Gu, Xuefan

2013-01-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population. A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method. The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment. The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.

Genetic Variation near IRF8 is Associated with Serologic and Cytokine Profiles in Systemic Lupus Erythematosus and Multiple Sclerosis

PubMed Central

Chrabot, Beverly S.; Kariuki, Silvia N.; Zervou, Maria I.; Feng, Xuan; Arrington, Jasmine; Jolly, Meenakshi; Boumpas, Dimitrios T.; Reder, Anthony T.; Goulielmos, George N.; Niewold, Timothy B.

2013-01-01

Alleles of IRF8 are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). While high type I interferon (IFN) is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles which have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-dsDNA autoantibodies in SLE patients (meta-analysis OR=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in PBMC from anti-dsDNA negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance. PMID:23965942

Impact of multiple sclerosis on quality of life: Comparison with systemic lupus erythematosus.

PubMed

Carnero Contentti, Edgar; Genco, Néstor David; Hryb, Javier Pablo; Caspi, Mercedes; Chiganer, Edson; Di Pace, José Luis; López, Pablo Adrián; Lessa, Carmen; Caride, Alejandro; Perassolo, Mónica

2017-12-01

To report the impact of multiple sclerosis (MS) on patients' quality of life (QoL) compared to systemic lupus erythematosus (SLE) using the 36-Item Short Form (SF-36) health questionnaire in Argentina. Cross-sectional study. All consecutive MS patients, SLE and healthy controls (HC) were included. Demographics, clinical and radiological aspects, EDSS and SF-36 were assessed. A total of 191 subjects were included (MS=74, SLE=30 and HC=87). When we compared, using 2 standard deviations below the normal mean, the SF-36 subscales scores between MS and SLE, we found that MS patients experienced significant deterioration in general health (p<0.0001), vitality (p=0.009), current health (p<0.0001) and previous year health perception (p=0.003). Additional evaluated areas did not show significant differences. MS patients scored significantly lower in all categories compared to HC, except for bodily pain. An inverse correlation between EDSS and SF-36 total (R 2 =0.59, β -11.08, p<0.0001) and subscale scores was observed after applying regression analysis. MS behaves as a systemic disease from the functional point of view. Patient-reported QoL scales scores provide comprehensive additional prognostic information beyond the EDSS score. Therefore, adding the SF-36 questionnaire in clinical practice might be useful for the assessment and follow-up of MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain volume in early MS patients with and without IgG oligoclonal bands in CSF.

PubMed

Fenu, G; Lorefice, L; Sechi, V; Loi, L; Contu, F; Cabras, F; Coghe, G; Frau, J; Secci, M A; Melis, C; Schirru, L; Costa, G; Melas, V; Arru, M; Barracciu, M A; Marrosu, M G; Cocco, E

2018-01-01

Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of intravenous amiodarone on QT and T peak-T end dispersions in patients with nonischemic heart failure treated with cardiac resynchronization-defibrillator therapy and electrical storm.

PubMed

Ogiso, Masataka; Suzuki, Atsushi; Shiga, Tsuyoshi; Nakai, Kenji; Shoda, Morio; Hagiwara, Nobuhisa

2015-02-01

The effect of intravenous amiodarone on spatial and transmural dispersion of ventricular repolarization in patients receiving cardiac resynchronization therapy (CRT) remains unclear. We studied 14 patients with nonischemic heart failure who received CRT with a defibrillator, experienced electrical storm and were treated with intravenous amiodarone. Each patient underwent 12-lead electrocardiography (ECG) and 187-channel repolarization interval-difference mapping electrocardiography (187-ch RIDM-ECG) before and during the intravenous administration of amiodarone infusion. A recurrence of ventricular tachyarrhythmia was observed in 2 patients during the early period of intravenous amiodarone therapy. Intravenous amiodarone increased the corrected QT interval (from 470±52 ms to 508±55 ms, P=0.003), but it significantly decreased the QT dispersion (from 107±35 ms to 49±27 ms, P=0.001), T peak-T end (Tp-e) dispersion (from 86±17 ms to 28±28 ms, P=0.001), and maximum inter-lead difference between corrected Tp-e intervals as measured by using the 187-ch RIDM-ECG (from 83±13 ms to 50±19 ms, P=0.001). Intravenous amiodarone suppressed the electrical storm and decreased the QT and Tp-e dispersions in patients treated by using CRT with a defibrillator.

Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne.

PubMed

Ben-Amitai, D; Laron, Z

2011-08-01

The role of growth hormone, insulin, and insulin-like growth factor-1 (IGF-1) in the development of acne is incompletely understood. To study the effect of the absence of IGF-1 and its pharmacologic replacement on the occurrence of acne vulgaris. Laron syndrome (LS) is characterized by congenital IGF-1 deficiency. The study group consisted of 21 patients with classical LS, who underwent puberty: 13 (8 male, 5 female) untreated and under regular follow-up until age 20?48 years; and 8 (2 male, 6 female) treated with IGF-1 (70-200 μg/kg/day), including 6 adults (2 male, treated at age 14.5-29 years and 4 female, treated at age 30-37 years) and 2 adolescents (2 female, treated at age 3.5-16 years). The medical files were reviewed for occurrence of acne and the corresponding sex hormone levels, and the findings were compared between the treated and untreated patients. Puberty was delayed in all untreated patients. Only one patient had slight acne at age 22 years, when he reached full puberty. Among the 2 IGF-1 treated male patients, none acquired acne. Among the 6 treated female patients, 3 had signs of hyperandrogenism (oligo-amenorrhea) and acne during IGF-1 over-dosage. On reduction of the IGF-1 dose (to 50 μg/kg/day) or cessation of treatment, the acne disappeared in all 3 patients. This study demonstrates for the first time that serum IGF-1 deficiency prevents the occurrence of acne. The findings suggest that an interaction between IGF-1 and androgens is necessary for the development of acne. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PubMed

Choo, R; DeBoer, G; Klotz, L; Danjoux, C; Morton, G C; Rakovitch, E; Fleshner, N; Bunting, P; Kapusta, L; Hruby, G

2001-07-01

To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Prevalence and clinical characteristics of white-coat hypertension based on different definition criteria in untreated and treated patients.

PubMed

de la Sierra, Alejandro; Vinyoles, Ernest; Banegas, José R; Segura, Julián; Gorostidi, Manuel; de la Cruz, Juan J; Ruilope, Luis M

2017-12-01

The prevalence and associated risks of white-coat hypertension (WCH) are still a matter of debate. We aimed to assess differences in prevalence and associated conditions of WCH defined on the basis of the normality of all daytime, night-time, and 24-h blood pressure (BP), only daytime, or only 24-h BP. We selected 115 708 patients (45 020 untreated and 70 688 treated) from the Spanish Ambulatory BP Monitoring Registry. WCH was estimated in patients with elevated office BP (≥140 and/or 90 mmHg) by using normal daytime (<135/85) BP, normal 24-h BP (<130/80), or normal daytime, night-time (<120/70) and 24-h BP. Demographic and clinical data (associated risk factors and organ damage) were compared among groups. Prevalence of WCH was 41.3, 35.2, and 26.1% in untreated, and 45.8, 38.9, and 27.2% in treated patients with elevated office BP, by using the criteria of daytime, 24-h, or all ambulatory periods. Compared with the normotensive group, WCH defined by normal daytime, night-time, and 24-h BP did not significantly differ in terms of other cardiovascular risk factors or organ damage. In contrast, patients from other groups (either only normal daytime BP or 24-h BP) had significantly more prevalence of diabetes, dyslipidaemia, microalbuminuria, left ventricular hypertrophy, reduced renal function, and previous history of cardiovascular disease. Prevalence of WCH is dependent on definition criteria. Only diagnostic criteria which considers the normality of all ambulatory periods identifies patients with cardiovascular risk similar to normotensive patients. These results support using such criteria for a more accurate definition of WCH.

Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection.

PubMed

Hagberg, Lars; Cinque, Paola; Gisslen, Magnus; Brew, Bruce J; Spudich, Serena; Bestetti, Arabella; Price, Richard W; Fuchs, Dietmar

2010-06-03

HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients.In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.

Prospective memory impairment in multiple sclerosis: a review.

PubMed

Rouleau, Isabelle; Dagenais, Emmanuelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2017-08-04

Multiple sclerosis (MS) is a progressive disease of the central nervous system affecting information processing speed, episodic memory, attention, and executive functions. MS patients also often report prospective memory (PM) failures that directly impact their functional autonomy, including professional and social life. The purpose of this paper was to review the literature concerning the assessment and remediation of PM deficits in MS. The literature pertaining to PM impairment in MS was carefully reviewed using PubMed, PsyINFO, and Google Scholar, as well as cross-references from the articles published on this topic. Since PM rehabilitation in MS patients is still in its infancy, this review mainly focuses on studies that have directly assessed PM through various measures including questionnaires, standardized clinical tests, and experimental procedures. This literature review confirms the presence of PM deficits in MS patients, even in the early stages of the disease. A further need for controlled studies on PM assessment and PM interventions in patients with MS is stressed.

Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients.

PubMed

Atya, Hanaa B; Ali, Sahar A; Hegazy, Mohamed I; El Sharkawi, Fathia Z

2018-04-01

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

Causes of death in critically ill multiple sclerosis patients.

PubMed

Karamyan, A; Brandtner, H; Grinzinger, S; Chroust, V; Bacher, C; Otto, F; Reisp, M; Hauer, L; Sellner, J

2017-10-01

Patients with multiple sclerosis (MS) experience higher mortality rates as compared to the general population. While the risk of intensive care unit (ICU) admission is also reported to be higher, little is known about causes of death CoD in critically ill MS patients. To study the causes of death (CoD) in the series of critically ill patients with MS verified by autopsy. We reviewed hospital electronic charts of MS patients treated at the neurological ICU of a tertiary care hospital between 2000 and 2015. We compared clinical and pathological CoD for those who were autopsied. Overall, 10 patients were identified (seven female; median age at death 65 years, range 27-80), and six of them were autopsied. The median MS duration prior to ICU admission was 27.5 years (range 1-50), and the median EDSS score at the time of ICU admission was 9 (range 5-9.5). The median length of ICU stay was 3 days (range 2-213). All the individuals in our series had experienced respiratory insufficiency during their ICU stay. The autopsy examination of brain tissue did not reveal evidences of MS lesions in one patient. In another patient, Lewy bodies were found on brain immunohistochemistry. Mortality in critically ill MS patients is largely driven by respiratory complications. Sporadic disparities between clinical and pathological findings can be expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The challenges of healthcare delivery to people with multiple sclerosis in Iran.

PubMed

Yazdannik, Ahmadreza; Abolhassani, Shahla; Taleghani, Fariba; Zamani, Ahmadreza

2015-01-01

Multiple sclerosis (MS) is a chronic disease prevalent in young and middle-aged people. Patients with MS often have numerous complicated needs and, consequently, require a broad range of health services. Results of a number of studies indicate that patients' needs are only partially met. This study was conducted to explore the challenges of healthcare delivery to patients with MS in Iran. In this qualitative case study, 43 participants selected through purposeful sampling were interviewed using semi-structured method in the cities of Isfahan and Tehran in 2012-2013. Besides the interview, documentations relevant to healthcare delivery were collected from different sources, including websites of all Iranian universities of medical sciences, insurance organizations, patients' weblogs, news agencies, the MS Center forum for MS patients, and MS Payam bimonthly. The data were analyzed through the constant comparative analysis. The data were categorized into four main categories, including functional challenges (diagnosis problems, failure to pay attention to patient needs, failure to follow-up, and miscommunication), administrative challenges (resource allocation and supervision), policy-making challenges (lack of comprehensive services, bureaucracy, and problems in provision of medications), and structural challenges (difficult access to services, lack of comprehensive centers, space limit, and long wait). Despite all attempts of governmental and nongovernmental organizations for healthcare delivery to MS patients, these services cannot satisfy all needs of the patients. In this regard, service providers and administrators should pay more attention to the needs and expectations of patients and their families.

Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity).

PubMed

Laron, Zvi; Ginsberg, Shira; Lilos, Pearl; Arbiv, Mira; Vaisman, Nahum

2006-07-01

To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. Lifelong congenital IGF-I deficiency leads to extreme adiposity.

Quantitative analysis of hepatitis C virus activity in vivo in different groups of untreated patients.

PubMed

Manzin, A; Solforosi, L; Giostra, F; Bianchi, F B; Bruno, S; Rossi, S; Gabrielli, A; Candela, M; Petrelli, E; Clementi, M

1997-01-01

Highly sensitive competitive PCR (cPCR) and competitive reverse transcription PCR (cRT-PCR) methodologies were recently developed and applied for quantifying viral DNA and RNA species (including HCV RNA) present in clinical samples at low concentration. In this study, we used cRT-PCR to compare the viral load of 118 untreated patients with HCV infection and different clinical conditions (80 patients with chronic hepatitis, 18 infected subjects with persistently normal ALT levels and various degrees of liver injury, 10 HCV infected subjects that tested positive for anti-LKM1 antibodies, and 10 patients with HCV infection and cryoglobulinemia). The results indicate that while great individual variability of HCV viremia is detectable even among patients with similar clinical conditions, the mean HCV RNA copy number in samples from patients with different clinical conditions was similar in all groups with the single exception of patients that tested positive for anti-liver-kidney microsomal auto-antibodies type 1 (anti-LKM1); interestingly, lower HCV viremia levels were revealed in these anti-LKM1-positive cases with liver disease of uncertain pathogenesis.

Voice-related quality of life (V-RQOL) following type I thyroplasty for unilateral vocal fold paralysis.

PubMed

Hogikyan, N D; Wodchis, W P; Terrell, J E; Bradford, C R; Esclamado, R M

2000-09-01

Unilateral vocal fold paralysis is a common clinical problem which frequently causes severe dysphonia. Various treatment options exist for this condition, with the type I thyroplasty being one of the more commonly performed surgical procedures for vocal rehabilitation. The Voice-Related Quality of Life (V-RQOL) Measure is a validated outcomes instrument for voice disorders. This study measured the V-RQOL of patients with unilateral vocal fold paralysis who had undergone a type I thyroplasty and compared these scores to those of patients with untreated and uncompensated unilateral vocal fold paralysis and to normals. Treated patients had significantly higher domain and overall V-RQOL scores than untreated patients, but also scored lower than normals. These differences were true across gender and age. Patients who were more distant from surgery had lower V-RQOL scores than those who had more recently been treated. It is concluded that type I thyroplasty leads to a significantly higher V-RQOL for patients with unilateral vocal fold paralysis. This study also demonstrates further the utility of patient-oriented measures of treatment outcome.

[The analysis of epidemiology, clinical symptoms, serological tests in the course of borreliosis].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Leśniak, Maciej; Garlicki, Aleksander; Mach, Tomasz

2010-01-01

Lyme disease is an animal-borne disease, caused by spirochetes of the Borrelia burgdorferi (Bb). The infection is transmitted by ticks of the Ixodes ricinus species. Humans are infected through a tick bite to the skin. The aim of the study was evaluation of epidemiology, symptoms and serologic factors in Lyme disease. We have enrolled 39 patients from Malopołska region in the study treated for Lyme borreliosis. History of tick biting, clinical signs and symptoms and serological tests were evaluated. The most common symptoms were headaches and pain of the large joints. Patients with untreated erithema migrans (EM) more often developed symptoms from nervous system (83%) than joints (54%). We found abnormalities which confirmed inflammation in CSF in 24.3% of patients. Patients with positive IgG antibodies against Bb in CSF and confirmed their intrathecal synthesis had never had EM in the past. There is low percentage of the patients who were treated due to EM. Patients with untreated EM more often developed symptoms from nervous system than joints. The most common symptoms among our patients were headaches and pain of large joints.

Exercise-induced pulse wave velocity changes in untreated patients with essential hypertension: the effect of an angiotensin receptor antagonist.

PubMed

Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Nikolaidou, Barbara; Triantafyllou, George; Douma, Stella

2014-07-01

This study investigates arterial stiffness changes after acute exercise in young patients with untreated, recently diagnosed grade I essential hypertension (UH) compared with normotensive (NT) individuals and the effect of antihypertensive treatment on this phenomenon. Study 1 consisted of 25 UH and 15 NT patients. UH patients who received treatment were included in study 2 and were followed-up after a 3-month treatment period with an angiotensin II receptor blocker. Aortic pulse wave velocity (PWV) was assessed at baseline, at maximal exercise, and at 10, 30, and 60 minutes later. In UH patients, PWV increased significantly at maximal exercise and 10 and 30 minutes of recovery, despite blood pressure fall to baseline levels. No significant PWV changes were observed in NT patients. Post-treatment PWV levels were significantly decreased and similar to those of NT patients. Arterial stiffness is impaired following high-intensity acute exercise even in the early stages of hypertension. Antihypertensive treatment ameliorates these effects. ©2014 Wiley Periodicals, Inc.

Who benefits most from THC:CBD spray? Learning from clinical experience.

PubMed

Koehler, Jürgen

2014-01-01

Patients with multiple sclerosis (MS) represent a diverse and heterogeneous population varying in terms of disease type, its severity and variable progression/time-course, and with regard to the wide range of presenting symptoms. Consequently, detailed experience with individual patients is important to provide examples of therapy to specific patient types. In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) in patients with moderate to severe spasticity resistant to usual therapy will be presented. Three common clinical scenarios will be considered: MS patients with resistance to usual spasticity therapies; patients with impairment in MS spasticity symptoms; MS patients with relevant impairment in quality of life/activities of daily living (QoL/ADL). These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC:CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies, within the frame of use approved after large clinical trial results. Perhaps the most important finding is the possibility of obtaining relevant improvements in QoL/ADL in some patients with resistant MS spasticity, allowing them to engage back in physical and social activities. © 2014 S. Karger AG, Basel.

[Prevalence of metabolic syndrome in elderly patients].

PubMed

Castro Vilela, María Elena; Quílez Pina, Raquel María; Bonafonte Marteles, José Luis; Morlanes Navarro, Teresa; Calvo Gracia, Fernando

2014-01-01

To determine the prevalence of metabolic syndrome (MS) according to the definitions of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the International Diabetes Federation (IDF) and its relation to cardiovascular disease (CVD) in hospitalized elderly patients. This descriptive and prospective study (February-March 2011) included 200 consecutive patients hospitalized in a Geriatric Department. Sociodemographic, clinical and biochemical data was collected. The prevalence of MS was 65% (NCEP-ATP III) and 67.5% (IDF) and was greater in women (NCEP-ATP III=72.8%, IDF=73.6%) than in men (NCEP-ATP III=50.7%; IDF=56.3%). The mean age of patients diagnosed with MS by both diagnostic criteria were similar: 84.7 years. MS was not associated with an increased prevalence of CVD. MS is highly prevalent in elderly hospitalized patients, being higher in women, with both diagnostic criteria (NCEP- ATP III and IDF). In our population the MS was not associated with an increased prevalence of CVD. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

PubMed Central

van Agtmaal, Maaike; van Os, Gera J.; Hol, W.H. Gera; Hundscheid, Maria P.J.; Runia, Willemien T.; Hordijk, Cornelis A.; de Boer, Wietse

2015-01-01

There is increasing evidence that microbial volatiles (VOCs) play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial community composition would affect the production by soils of VOCs suppressing the plant-pathogenic oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we compared the composition of bacterial communities in sandy soils that had been exposed to anaerobic disinfestation (AD), a treatment used to kill harmful soil organisms, with the composition in untreated soils. Three months after the AD treatment had been finished, there was still a clear legacy effect of the former anaerobic stress on bacterial community composition with a strong increase in relative abundance of the phylum Bacteroidetes and a significant decrease of the phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi, and Chlorobi. This change in bacterial community composition coincided with loss of production of Pythium suppressing soil volatiles (VOCs) and of suppression of Pythium impacts on Hyacinth root development. One year later, the composition of the bacterial community in the AD soils was reflecting that of the untreated soils. In addition, both production of Pythium-suppressing VOCs and suppression of Pythium in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS analysis identified several VOCs, among which compounds known to be antifungal, that were produced in the untreated soils but not in the AD soils. These compounds were again produced 15 months after the AD treatment. Our data indicate that soils exposed to a drastic stress can temporarily lose pathogen suppressive characteristics and that both loss and return of these suppressive characteristics coincides with shifts in the soil bacterial community composition. Our data are supporting the suggested importance of microbial VOCs in the natural buffer of soils against diseases caused by soil-borne pathogens. PMID:26217330

Ursodeoxycholic acid after bile duct stone removal and risk factors for recurrence: a randomized trial.

PubMed

Yamamoto, Ryuichi; Tazuma, Susumu; Kanno, Keishi; Igarashi, Yoshinori; Inui, Kazuo; Ohara, Hirotaka; Tsuyuguchi, Toshio; Ryozawa, Shomei

2016-02-01

Currently, no established pharmacologic treatment exists for the prevention of recurrent common bile duct (CBD) stones. Here, we present a multi-center randomized trial that compared the CBD recurrence rate after bile duct stone removal between patients given ursodeoxycholic acid (UDCA) and the untreated group. A total of 36 patients were randomly assigned to either the UDCA (n = 15) or the untreated group (n = 21). The primary end-point was the recurrence rate of CBD stones. The recurrence rate of CBD stones was 6.6% in the UDCA group and 18.6% in the untreated group (P = 0.171). A multivariate analysis found that not receiving UDCA was an independent risk factor for stone recurrence. The recurrence rates of CBD stones did not differ by sex, past history of cholecystectomy, or the presence of gallstones. Our findings indicate that UDCA may be a novel treatment strategy to prevent the recurrence of CBD stones. However, further evaluation of UDCA in a larger number of subjects will be required to confirm the applicability of these results. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

PubMed Central

Dorn, Jonas F; Burggraaff, Jessica; Kamm, Christian Philipp; Steinheimer, Saskia Marie; Kontschieder, Peter; Criminisi, Antonio; Uitdehaag, Bernard; Dahlke, Frank; Kappos, Ludwig; Sellen, Abigail

2015-01-01

Background Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment. PMID:27025782

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

[Frequency of the metabolic syndrome among overweight and obese patients in a primary health care facility in northern Mexico].

PubMed

Zonana-Nacach, Abraham; Castillón-Chapa, Mario Arturo

2006-01-01

Assess the frequency of the metabolic syndrome (MS) among overweight and obese subjects attending a primary health care clinic in Tijuana, Baja California, Mexico. Male and female patients over 20 years of age attending a primary health care setting during April-Sept 2004 were selected to participate in the study. Metabolic syndrome was defined using the Adult Treatment Panel III criteria (NCEP III). Three-hundred twenty one patients with a mean age 47.9 years were assessed. The MS frequency was 44% for those patients without previous history of diabetes mellitus or hypertension (n = 281). The MS was present in 30% and 53% of overweight and obese patients respectively. Being an older male who had not been born in Baja California State were significantly associated with the presence of MS. The frequency of MS in a selected group of patients was common and higher than the national prevalence. The high frequency of MS in our study could be associated with a high prevalence of diabetes and obesity in the northwest population of Mexico.

Disease modifying drugs modulate endogenous secretory receptor for advanced glycation end-products, a new biomarker of clinical relapse in multiple sclerosis.

PubMed

Sternberg, Zohara; Sternberg, Daniel; Drake, Allison; Chichelli, Trevor; Yu, Jinhee; Hojnacki, David

2014-09-15

This study is one in a series measuring RAGE axis (receptor for advanced glycation end products, its isoforms, and ligands) and its potential as a biomarker in multiple sclerosis (MS). We evaluated serum levels of the endogenous secretory RAGE (esRAGE) in MS patients and assessed the relationship between esRAGE levels and the use of disease modifying drugs (DMDs), and between esRAGE levels and indicators of MS disease severity. esRAGE serum levels were compared between 98 MS patients and 34 healthy controls (HCs) using ELISA. esRAGE serum levels were similar between MS and HCs. DMD-treated patients had higher esRAGE serum levels than DMD-naïve patients (395.7±38.6pg/ml vs. 299.2±20.1pg/ml, P=0.02). DMD-naïve, primary progressive (PP) patients had higher esRAGE serum levels, than relapsing remitting (RR) (P=0.02) and secondary progressive (SP) (P=0.04) patients; RRMS patients in clinical relapse had lower esRAGE serum levels than clinically stable patients (219.7±30.0pg/ml vs. 338.2±31.6pg/ml, P=0.02). In a univariate regression analysis of DMD-naïve MS patients, esRAGE serum levels inversely correlated with the rate of clinical relapse (r=-0.44, P=0.006), MS severity scale (MSSS) (r=-0.32, P=0.03), and expanded disability status scale (EDSS) (r=-0.251, P=0.07). esRAGE serum levels are modulated by DMDs. The serum levels may be a useful biomarker of MS clinical relapse. Published by Elsevier B.V.

Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients

PubMed Central

Paroni Sterbini, Francesco; Palladini, Alessandra; Masucci, Luca; Cannistraci, Carlo Vittorio; Pastorino, Roberta; Ianiro, Gianluca; Bugli, Francesca; Martini, Cecilia; Ricciardi, Walter; Gasbarrini, Antonio; Cammarota, Giovanni; Posteraro, Brunella

2016-01-01

ABSTRACT Besides being part of anti-Helicobacter pylori treatment regimens, proton pump inhibitors (PPIs) are increasingly being used to treat dyspepsia. However, little is known about the effects of PPIs on the human gastric microbiota, especially those related to H. pylori infection. The goal of this study was to characterize the stomach microbial communities in patients with dyspepsia and to investigate their relationships with PPI use and H. pylori status. Using 16S rRNA gene pyrosequencing, we analyzed the mucosa-associated microbial populations of 24 patients, of whom 12 were treated with the PPI omeprazole and 9 (5 treated and 4 untreated) were positive for H. pylori infection. The Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria phyla accounted for 98% of all of the sequences, with Helicobacter, Streptococcus, and Prevotella ranking among the 10 most abundant genera. H. pylori infection or PPI treatment did not significantly influence gastric microbial species composition in dyspeptic patients. Principal-coordinate analysis of weighted UniFrac distances in these communities revealed clear but significant separation according to H. pylori status only. However, in PPI-treated patients, Firmicutes, particularly Streptococcaceae, were significantly increased in relative abundance compared to those in untreated patients. Consistently, Streptococcus was also found to significantly increase in relation to PPI treatment, and this increase seemed to occur independently of H. pylori infection. Our results suggest that Streptococcus may be a key indicator of PPI-induced gastric microbial composition changes in dyspeptic patients. Whether the gastric microbiota alteration contributes to dyspepsia needs further investigation. IMPORTANCE Although PPIs have become a popular treatment choice, a growing number of dyspeptic patients may be treated unnecessarily. We found that patients treated with omeprazole showed gastric microbial communities that were different from those of untreated patients. These differences regarded the abundances of specific taxa. By understanding the relationships between PPIs and members of the gastric microbiota, it will be possible to envisage new strategies for better managing patients with dyspepsia. PMID:27590821

Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacini, F.; Gasperi, M.; Fugazzola, L.

1994-09-01

The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients hadmore » an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.« less

Social aspects of multiple sclerosis for Iranian individuals.

PubMed

Abolhassani, Shahla; Yazdannik, Ahmadreza; Taleghani, Fariba; Zamani, Ahmadreza

2015-01-01

This study aimed to determine the social aspects of multiple sclerosis (MS) in the Iranian individuals. A qualitative case study approach was used for this study, which is a part of a larger qualitative study about health care delivery system of MS. Participants were selected on the basis of purposive sampling method. Semi-structured interviews regarding the social aspects of MS were conducted with 18 MS patients, 6 family members and 7 health care providers. Besides interviews with the participants, documents related to the aim of the study, including weblogs, MS magazines, special websites of individuals with MS and news agencies. Data analysis was performed using the qualitative content analysis technique. Data obtained has been categorised into five main categories, including confronting stigma symbols, the outcome of stigma, walling-in due to stigma, disturbance in normal life and concern about job. There are multiple social effects of MS on the afflicted individuals, which affect various dimensions of their life. Policy makers and health care providers must also consider these effects of MS on other dimensions of the individuals' life. Implications for Rehabilitation Multiple sclerosis (MS) is a disease which restricts social life for patients, in addition to physical impacts. Individuals with MS experienced stigma as well as problems with employment and marital life, due to improper information about MS in society. We recommend that health care workers offer proper information about MS to patients and their family members to minimise the social problems faced by them. We recommend that mass media offers proper information about MS to people in society to disseminate the correct picture of MS. We recommend that the rehabilitation team offers psychological support to patients and their families for their empowerment, to facilitate dealing with the impacts of the disease. We recommend that health care providers teach the family members about patient support and communication skills.

Changing composition of renal calculi in patients with musculoskeletal anomalies.

PubMed

Gnessin, Ehud; Mandeville, Jessica A; Handa, Shelly E; Lingeman, James E

2011-09-01

Calculi from patients with musculoskeletal (MS) anomalies who are largely immobile and prone to urinary infections have been traditionally composed primarily of struvite and carbonate apatite. Because of substantial improvements in the care of these patients in recent decades, stone etiology may have shifted from infectious to metabolic. We assessed the composition of renal calculi and metabolic characteristics in a contemporary cohort of patients with MS anomalies who underwent percutaneous nephrolithotomy (PCNL). Retrospective analysis of patients who underwent PCNL between April 1999 and June 2009 and had follow-up 24-hour urine studies was performed. Patients with MS anomalies included spinal cord injury, myelomeningocele, muscular dystrophy, multiple sclerosis, cerebral palsy, or other clinical syndromes causing kyphoscoliosis and contractures. Our cohort included 33 patients with MS anomalies and 334 consecutive patients as a control group who underwent PCNL and had metabolic workup. Stones were infectious in etiology in 18.4% and 6.2% in MS and control groups, respectively. Thus, most patients harbored stones of metabolic origin. Metabolic stones in the MS group were composed of 52.7% hydroxyapatite, 10.5% calcium oxalate, 7.9% brushite, 2.6% uric acid, 0% cystine, and 7.9% other. Metabolic stones in the control group were 50.5% calcium oxalate, 16.4% hydroxyapatite, 11.5% brushite, 10.8% uric acid, 4.3% cystine, and 0.3% other. Mean 24-hour urine values for patients with metabolic stones in MS/control groups were volume 2.18/1.87 L/d, pH 6.78/6.05, calcium to creatinine ratio 220/151 mg/g, and oxalate 44.8/39.5 mg/d. Although patients with MS anomalies are traditionally thought to harbor infection-related calculi, most will be found to have calculi of metabolic etiology. The incidence of calcium phosphate stones is high in this group of patients, perhaps reflecting their high urinary pH.

Sensitivity and specificity of Frontal Assessment Battery in newly diagnosed and untreated obstructive sleep apnea patients.

PubMed

Ladera, Valentina; Sargento, Paulo; Perea, Victoria; Faria, Miguel; Garcia, Ricardo

2018-02-01

Executive dysfunction (ED) is often observed in subjects diagnosed with obstructive sleep apnea (OSA), but their assessment requires facilities that are not always available. We aim to evaluate the extent to which Frontal Assessment Battery (FAB) discriminates ED in newly diagnosed, untreated, and without-comorbidity OSA patients. Sixty subjects participated in the study. Of these, 40 (31 males and 9 females) were newly diagnosed for OSA through full-night polysomnography (apnea/hypopnea index; M = 39.01, SD = 27.16), untreated, with a mean age of 54.50 years (SD = 8.90), while the remaining 20 (15 males and 5 females) had no symptoms of OSA (M = 51.60 years, SD = 10.70). The instruments used were the following: Questionnaire for Sleep Apnea Risk, Epworth Sleepiness Scale, Mini-Mental State Examination, and FAB. The group with OSA exhibited significantly lower values in the FAB global score (p = 0.003) and in Conceptualization (p = 0.001) and Mental Flexibility (p = 0.009) subtests. ROC analysis showed adequate discriminative capacity for the FAB global score (AUC = 0.74) and for Conceptualization (AUC = 0.75) and Mental Flexibility (AUC = 0.70) scores. The FAB is a short and no-time-consuming tool that can be used to investigate the presence of ED in untreated OSA patients with no comorbidities, providing clinicians with a simple and effective way of detecting the presence of this dysfunction and allowing a more informed decision for the need of a full neuropsychological assessment. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-Term Effects of Untreated Adolescent Idiopathic Scoliosis: A Review of the Literature

PubMed Central

Karavidas, Nikos; Moramarco, Marc; Moramarco, Kathryn

2016-01-01

Currently, adolescent idiopathic scoliosis (AIS) is principally regarded as benign, but some researchers have cited serious or extreme effects, including severe pain, cardiopulmonary compromise, social isolation, and even early death. Therefore, exploration of the long-term effects of AIS, the most common type of idiopathic scoliosis, is warranted. The purpose of this review was to examine the long-term studies on the natural history of AIS and/or reviews concerning the long-term effects of untreated AIS. A PubMed search was conducted using the key words idiopathic scoliosis, long-term effects and idiopathic scoliosis, natural history. For further analysis, references cited in those studies were reviewed for additional, related evidence not retrieved in the initial PubMed search. A review of the pertinent bibliography showed that older natural history studies did not distinguish between late-onset scoliosis (referred to in this paper as AIS) and early-onset scoliosis (EOS). The more recent studies offer such important distinction and reach to the general conclusion that untreated AIS does not lead to severe consequences with respect to signs and symptoms of scoliosis. It is possible that earlier studies may have included patient populations with EOS, leading to the perception of untreated scoliosis as having an unusually high morbidity rate. Studies on the long-term effects of AIS that specifically excluded EOS patients conclude that AIS is a benign disorder. This indicates that for research and reporting purposes, it is important to distinguishing between AIS and EOS. This will allow the practitioner and patient and their families to decide on an optimal treatment plan based on the most appropriate prognosis. PMID:27994795

Managed approaches to multiple sclerosis in special populations.

PubMed

Sperandeo, Kara; Nogrady, Lisa; Moreo, Kathleen; Prostko, Chris R

2011-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system that is classified as an immune-mediated inflammatory disease. In managed care, patients with MS can be managed through care coordination that engages an interprofessional approach to a comprehensive spectrum of preventive, medical, rehabilitative, cognitive, and long-term health care services. In addition, the management paradigm for MS is currently in a stage of rapid evolution, with a number of new agents, including more oral drugs, expected to become available in the near future. Pharmacy and therapeutic committees may soon be faced with evaluating a hierarchy of new scientific data to differentiate the safety and efficacy of these new agents. Decisions will need to be made regarding the utility of these potential new agents among existing therapies with longer-term safety and efficacy data available in the scientific literature. For those MS patients managed under Medicaid, formulary and medication management decisions may be further impacted by psychosocial, cultural, educational, attitudinal, and/or economic factors that may be unique to the Medicaid population. The need to maximize immediate and long-term resource utilization is usually an important consideration when managing a Medicaid population. There is also an increasing focus on quality measures and quality outcomes by the Centers for Medicare and Medicaid Services. Many managed care professionals can be involved in establishing quality measures and quality improvement processes to effectively appropriate and manage the resources required for Medicaid patients with MS. As a result, medication and medical management of this special population can involve a comprehensive approach by managed care professionals. For purposes of this article, the term "special populations" applies to patients with MS who are managed under Medicaid plans. To review (a) particular challenges managed care organizations (MCOs) encounter when managing special populations of Medicaid patients with MS, (b) recent efficacy and safety data for oral therapies for relapsing forms of MS, (c) costs of current MS therapies, and (d) potential strategies for managed care to improve care of their MS patient population and optimize clinical and economic outcomes. Review of recent published literature, abstracts related to MS presented at major medical conferences, and recommendations from key organizations including the U.S. Department of Health and Human Services and the National Multiple Sclerosis Society. The health economics of MS are a central issue for MCOs managing Medicaid patient populations. Additional challenges include the anticipated expansion of the marketplace to include several new oral agents and the lack of consensus guidelines for management of patients with MS. The benefit-risk profile of new agents will need to be considered in the context of established first-line parenteral drugs. Management of patients with MS should include an individualized approach for each patient as part of a shared decision-making process. In the overall management of special patient populations, case management and collaborative practice models in managed care may help to ensure that critical benchmarks are achieved.

Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

ClinicalTrials.gov

2017-09-05

Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Recommendations and Extraction of Clinical Variables of Pediatric Multiple Sclerosis Using Common Data Elements.

PubMed

Newland, Pamela; Newland, John M; Hendricks-Ferguson, Verna L; Smith, Judith M; Oliver, Brant J

2018-06-01

The purpose of this article was to demonstrate the feasibility of using common data elements (CDEs) to search for information on the pediatric patient with multiple sclerosis (MS) and provide recommendations for future quality improvement and research in the use of CDEs for pediatric MS symptom management strategies Methods: The St. Louis Children's Hospital (SLCH), Washington University (WU) pediatrics data network was evaluated for use of CDEs identified from a database to identify variables in pediatric MS, including the key clinical features from the disease course of MS. The algorithms used were based on International Classification of Diseases, Ninth/Tenth Revision, codes and text keywords to identify pediatric patients with MS from a de-identified database. Data from a coordinating center of SLCH/WU pediatrics data network, which houses inpatient and outpatient records consisting of patients (N = 498 000), were identified, and detailed information regarding the clinical course of MS were located from the text of the medical records, including medications, presence of oligoclonal bands, year of diagnosis, and diagnosis code. There were 466 pediatric patients with MS, with a few also having the comorbid diagnosis of anxiety and depression. St. Louis Children's Hospital/WU pediatrics data network is one of the largest databases in the United States of detailed data, with the ability to query and validate clinical data for research on MS. Nurses and other healthcare professionals working with pediatric MS patients will benefit from having common disease identifiers for quality improvement, research, and practice. The increased knowledge of big data from SLCH/WU pediatrics data network has the potential to provide information for intervention and decision-making that can be personalized to the pediatric MS patient.

Elevated serum uric acid levels are associated with endothelial dysfunction in HIV patients receiving highly-active antiretroviral therapy.

PubMed

Pirro, Matteo; Bianconi, Vanessa; Schiaroli, Elisabetta; Francisci, Daniela; Mannarino, Massimo R; Bagaglia, Francesco; Sahebkar, Amirhossein; Merriman, Tony; Baldelli, Franco

2018-05-01

Elevated serum uric acid (SUA) levels may be associated with endothelial dysfunction. Increased rates of metabolic syndrome (MS) and elevated SUA levels were described in human immunodeficiency virus (HIV) infected patients. We investigated whether SUA levels are associated with endothelial dysfunction in HIV positive patients receiving highly-active antiretroviral therapy (HAART) irrespective of MS. In this cross-sectional study of 250 HIV positive patients receiving stable HAART, we evaluated the relationship between MS, SUA levels and endothelial function. SUA levels and brachial artery flow-mediated dilation (bFMD) were measured. The relationship between logarithmic (LG)-transformed SUA levels and bFMD was evaluated after correction for MS. MS was detected in 28.4% of patients and elevated SUA levels (≥6 mg/dL) in 25.2%. MS was associated with higher LG-SUA levels (age-, gender- and glomerular filtration rate-adjusted beta = 0.204, p = 0.001). The crude linear association between LG-SUA levels and LG-bFMD (beta = -0.166, p = 0.008) was abolished after correction for MS (beta = -0.089, p = 0.172). When SUA levels were used as a categorical variable (≥6 mg/dL or <6 mg/dL and SUA quartiles, respectively), the association between LG-SUA levels and LG-bFMD remained significant after adjustment for MS (beta = -0.142, p = 0.022 and beta = -0.163, p = 0.010, respectively). MS significantly affects SUA levels in HAART-treated HIV infected patients. The negative association between SUA and bFMD is independent of MS only for elevated SUA levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

PubMed Central

Füvesi, Judit; Hanrieder, Jörg; Bencsik, Krisztina; Rajda, Cecilia; Kovács, S. Krisztián; Kaizer, László; Beniczky, Sándor; Vécsei, László; Bergquist, Jonas

2012-01-01

Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. PMID:22837721